WorldWideScience

Sample records for ankyrin repeat domain

  1. 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.

  2. Notch ankyrin repeat domain variation influences leukemogenesis and Myc transactivation.

    Directory of Open Access Journals (Sweden)

    Jon C Aster

    Full Text Available BACKGROUND: The functional interchangeability of mammalian Notch receptors (Notch1-4 in normal and pathophysiologic contexts such as cancer is unsettled. We used complementary in vivo, cell-based and structural analyses to compare the abilities of activated Notch1-4 to support T cell development, induce T cell acute lymphoblastic leukemia/lymphoma (T-ALL, and maintain T-ALL cell growth and survival. PRINCIPAL FINDINGS: We find that the activated intracellular domains of Notch1-4 (ICN1-4 all support T cell development in mice and thymic organ culture. However, unlike ICN1-3, ICN4 fails to induce T-cell acute lymphoblastic leukemia/lymphoma (T-ALL and is unable to rescue the growth of Notch1-dependent T-ALL cell lines. The ICN4 phenotype is mimicked by weak gain-of-function forms of Notch1, suggesting that it stems from a failure to transactivate one or more critical target genes above a necessary threshold. Experiments with chimeric receptors demonstrate that the Notch ankyrin repeat domains differ in their leukemogenic potential, and that this difference correlates with activation of Myc, a direct Notch target that has an important role in Notch-associated T-ALL. CONCLUSIONS/SIGNIFICANCE: We conclude that the leukemogenic potentials of Notch receptors vary, and that this functional difference stems in part from divergence among the highly conserved ankyrin repeats, which influence the transactivation of specific target genes involved in leukemogenesis.

  3. 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.

  4. 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.

  5. 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.

  6. Structures of the spectrin-ankyrin interaction binding domains

    Energy Technology Data Exchange (ETDEWEB)

    Ipsaro, Jonathan J.; Huang, Lei; Mondragón, Alfonso; (NWU)

    2010-01-07

    As key components of the erythrocyte membrane skeleton, spectrin and ankyrin specifically interact to tether the spectrin cytoskeleton to the cell membrane. The structure of the spectrin binding domain of ankyrin and the ankyrin binding domain of spectrin have been solved to elucidate the structural basis for ankyrin-spectrin recognition. The structure of repeats 14 and 15 of spectrin shows that these repeats are similar to all other spectrin repeats. One feature that could account for the preference of ankyrin for these repeats is the presence of a conserved, negatively charged patch on one side of repeat 14. The structure of the ankyrin ZU5 domain shows a novel structure containing a {beta} core. The structure reveals that the canonical ZU5 consensus sequence is likely to be missing an important region that codes for a {beta} strand that forms part of the core of the domain. In addition, a positively charged region is suggestive of a binding surface for the negatively charged spectrin repeat 14. Previously reported mutants of ankyrin that map to this region lie mostly on the surface of the protein, although at least one is likely to be part of the core.

  7. 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.

  8. Functional Dynamics of the Folded Ankyrin Repeats of IκBα Revealed by Nuclear Magnetic Resonance†

    OpenAIRE

    Cervantes, Carla F.; Phineus R L Markwick; Sue, Shih-Che; McCammon, J. Andrew; Dyson, H Jane; Komives, Elizabeth A.

    2009-01-01

    Inhibition of nuclear factor κB (NF-κB) is mainly accomplished by IκBα, which consists of a signal response sequence at the N-terminus, a six-ankyrin repeat domain (ARD) that binds NF-κB, and a C-terminal PEST sequence. Previous studies with the ARD revealed that the fifth and sixth repeats are only partially folded in the absence of NF-κB. Here we report NMR studies of a truncated version of IκBα, containing only the first four ankyrin repeats, IκBα(67−206). This four-repeat segment is well-...

  9. 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.

  10. Analyses of Physcomitrella patens Ankyrin Repeat Proteins by Computational Approach

    Science.gov (United States)

    Mahmood, Niaz; Tamanna, Nahid

    2016-01-01

    Ankyrin (ANK) repeat containing proteins are evolutionary conserved and have functions in crucial cellular processes like cell cycle regulation and signal transduction. In this study, through an entirely in silico approach using the first release of the moss genome annotation, we found that at least 54 ANK proteins are present in P. patens. Based on their differential domain composition, the identified ANK proteins were classified into nine subfamilies. Comparative analysis of the different subfamilies of ANK proteins revealed that P. patens contains almost all the known subgroups of ANK proteins found in the other angiosperm species except for the ones having the TPR domain. Phylogenetic analysis using full length protein sequences supported the subfamily classification where the members of the same subfamily almost always clustered together. Synonymous divergence (dS) and nonsynonymous divergence (dN) ratios showed positive selection for the ANK genes of P. patens which probably helped them to attain significant functional diversity during the course of evolution. Taken together, the data provided here can provide useful insights for future functional studies of the proteins from this superfamily as well as comparative studies of ANK proteins.

  11. Structurally Similar but Functionally Diverse ZU5 Domains in Human Erythrocyte Ankyrin

    Energy Technology Data Exchange (ETDEWEB)

    Yasunaga, Mai; Ipsaro, Jonathan J.; Mondragón, Alfonso (NWU)

    2014-10-02

    The metazoan cell membrane is highly organized. Maintaining such organization and preserving membrane integrity under different conditions are accomplished through intracellular tethering to an extensive, flexible protein network. Spectrin, the principal component of this network, is attached to the membrane through the adaptor protein ankyrin, which directly bridges the interaction between {beta}-spectrin and membrane proteins. Ankyrins have a modular structure that includes two tandem ZU5 domains. The first domain, ZU5A, is directly responsible for binding {beta}-spectrin. Here, we present a structure of the tandem ZU5 repeats of human erythrocyte ankyrin. Structural and biophysical experiments show that the second ZU5 domain, ZU5B, does not participate in spectrin binding. ZU5B is structurally similar to the ZU5 domain found in the netrin receptor UNC5b supramodule, suggesting that it could interact with other domains in ankyrin. Comparison of several ZU5 domains demonstrates that the ZU5 domain represents a compact and versatile protein interaction module.

  12. Identification of the ankyrin repeat proteins ANKRA and RFXANK as novel partners of class IIa histone deacetylases.

    Science.gov (United States)

    Wang, Audrey H; Grégoire, Serge; Zika, Eleni; Xiao, Lin; Li, Cathy S; Li, Hongwei; Wright, Kenneth L; Ting, Jenny P; Yang, Xiang-Jiao

    2005-08-12

    Eighteen human histone deacetylases (HDACs) have been identified, and according to their sequence similarity to yeast homologs, these enzymes are grouped into distinct classes. Within class II, HDAC4, HDAC5, HDAC7, and HDAC9 share similar domain organization both within the N-terminal extension and the C-terminal catalytic domain, thus forming a subclass known as class IIa. These HDACs function as signal-responsive transcriptional corepressors. To gain further insight into their function and regulation, we utilized an N-terminal fragment of HDAC4 as bait in yeast two-hybrid screens, which uncovered myocyte enhancer factor 2C, 14-3-3zeta, and ankyrin repeat family A protein (ANKRA). ANKRA is a poorly characterized protein with an ankyrin repeat domain similar to RFXANK, a subunit of the trimeric transcription factor RFX. Mutations on genes of the RFX subunits and the coactivator CIITA are responsible for the bare lymphocyte syndrome, an immunodeficiency disorder attributed to the lack of major histocompatibility complex class II (MHCII) antigens. Through its ankyrin repeat domain, RFXANK interacted with HDAC4. Two RFXANK-binding sites were found on HDAC4 with one located within residues 118-279 and another within residues 448-666. Interestingly, this deacetylase also interacted with CIITA. Consistent with the physical interaction with RFXANK and CIITA, HDAC4 and homologs repressed MHCII expression. These results identify ANKRA, RFXANK, and CIITA as novel targets of class IIa HDACs and suggest that these deacetylases play a role in regulating MHCII expression.

  13. Genome-wide characterization of the ankyrin repeats gene family under salt stress in soybean.

    Science.gov (United States)

    Zhang, Dayong; Wan, Qun; He, Xiaolan; Ning, Lihua; Huang, Yihong; Xu, Zhaolong; Liu, Jia; Shao, Hongbo

    2016-10-15

    Ankyrin repeats (ANK) gene family are common in diverse organisms and play important roles in cell growth, development and response to environmental stresses. Recently, genome-wide identification and evolutionary analyses of the ANK gene family have been carried out in Arabidopsis, rice and maize. However, little is known about the ANK genes in the whole soybean genome. In this study, we described the identification and structural characterization of 162ANK genes in soybean (GmANK). Then, comprehensive bioinformatics analyses of GmANK genes family were performed including gene locus, phylogenetic, domain composition analysis, chromosomal localization and expression profiling. Domain composition analyses showed that GmANK proteins formed eleven subfamilies in soybean. In sicilo expression analysis of these GmANK genes demonstrated that GmANK genes show a diverse/various expression pattern, suggesting that functional diversification of GmANK genes family. Based on digital gene expression profile (DGEP) data between cultivated soybean and wild type under salt treatment, some GmANKs related to salt/drought response were investigated. Moreover, the expression pattern and subcellular localization of GmANK6 were performed. The results will provide important clues to explore ANK genes expression and function in future studies in soybean. PMID:27335162

  14. Interaction between a plasma membrane-localized ankyrin-repeat protein ITN1 and a nuclear protein RTV1

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Hikaru [Department of Bioproduction, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri-shi, Hokkaido 093-2422 (Japan); Sakata, Keiko; Kusumi, Kensuke [Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Kojima, Mikiko; Sakakibara, Hitoshi [RIKEN Plant Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 (Japan); Iba, Koh, E-mail: koibascb@kyushu-u.org [Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer ITN1, a plasma membrane ankyrin protein, interacts with a nuclear DNA-binding protein RTV1. Black-Right-Pointing-Pointer The nuclear transport of RTV1 is partially inhibited by interaction with ITN1. Black-Right-Pointing-Pointer RTV1 can promote the nuclear localization of ITN1. Black-Right-Pointing-Pointer Both overexpression of RTV1 and the lack of ITN1 increase salicylic acids sensitivity in plants. -- Abstract: The increased tolerance to NaCl 1 (ITN1) protein is a plasma membrane (PM)-localized protein involved in responses to NaCl stress in Arabidopsis. The predicted structure of ITN1 is composed of multiple transmembrane regions and an ankyrin-repeat domain that is known to mediate protein-protein interactions. To elucidate the molecular functions of ITN1, we searched for interacting partners using a yeast two-hybrid assay, and a nuclear-localized DNA-binding protein, RTV1, was identified as a candidate. Bimolecular fluorescence complementation analysis revealed that RTV1 interacted with ITN1 at the PM and nuclei in vivo. RTV1 tagged with red fluorescent protein localized to nuclei and ITN1 tagged with green fluorescent protein localized to PM; however, both proteins localized to both nuclei and the PM when co-expressed. These findings suggest that RTV1 and ITN1 regulate the subcellular localization of each other.

  15. Distribution of an Ankyrin-repeat Protein on the Endoplasmic Reticulum in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Liqin Wei; Yan Li

    2009-01-01

    There are many ankyrin-repeat proteins in plant cells. However, the distribution and function of these proteins are mostly unclear. By reverse transcription-polymerase chain reaction, a gene encoding an ankyrin-like protein was cloned from Arabidopsis and named AtANK1 (GenBank accession no. NM_120340). The 6-His-tagged AtAnk1-N fusion protein was affinity-purified and its rabbit polyclonal antibody was obtained. Immuno-blotting with the purified anti-AtAnk1-N polyclonal antibody revealed that the relative molecular weight of the AtANK1 protein was about 76 kDa. By immunofluorescence labeling and immuno-gold labeling with the purified anti-AtAnk1-N polyclonal antibody, coupled with confocal and transmission electron microscopy observation, AtANK1 was found to be distributed on the membrane of the endoplaamic reticulum in Arabidopsis cells. Based on these results, we suggested that AtANK1 might be involved in endoplasmic reticulum-related protein localization and sorting in plant cells.

  16. Generation of Fluorogen-Activating Designed Ankyrin Repeat Proteins (FADAs) as Versatile Sensor Tools.

    Science.gov (United States)

    Schütz, Marco; Batyuk, Alexander; Klenk, Christoph; Kummer, Lutz; de Picciotto, Seymour; Gülbakan, Basri; Wu, Yufan; Newby, Gregory A; Zosel, Franziska; Schöppe, Jendrik; Sedlák, Erik; Mittl, Peer R E; Zenobi, Renato; Wittrup, K Dane; Plückthun, Andreas

    2016-03-27

    Fluorescent probes constitute a valuable toolbox to address a variety of biological questions and they have become irreplaceable for imaging methods. Commonly, such probes consist of fluorescent proteins or small organic fluorophores coupled to biological molecules of interest. Recently, a novel class of fluorescence-based probes, fluorogen-activating proteins (FAPs), has been reported. These binding proteins are based on antibody single-chain variable fragments and activate fluorogenic dyes, which only become fluorescent upon activation and do not fluoresce when free in solution. Here we present a novel class of fluorogen activators, termed FADAs, based on the very robust designed ankyrin repeat protein scaffold, which also readily folds in the reducing environment of the cytoplasm. The FADA generated in this study was obtained by combined selections with ribosome display and yeast surface display. It enhances the fluorescence of malachite green (MG) dyes by a factor of more than 11,000 and thus activates MG to a similar extent as FAPs based on single-chain variable fragments. As shown by structure determination and in vitro measurements, this FADA was evolved to form a homodimer for the activation of MG dyes. Exploiting the favorable properties of the designed ankyrin repeat protein scaffold, we created a FADA biosensor suitable for imaging of proteins on the cell surface, as well as in the cytosol. Moreover, based on the requirement of dimerization for strong fluorogen activation, a prototype FADA biosensor for in situ detection of a target protein and protein-protein interactions was developed. Therefore, FADAs are versatile fluorescent probes that are easily produced and suitable for diverse applications and thus extend the FAP technology. PMID:26812208

  17. CD4-specific designed ankyrin repeat proteins are novel potent HIV entry inhibitors with unique characteristics.

    Directory of Open Access Journals (Sweden)

    Andreas Schweizer

    2008-07-01

    Full Text Available Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins-high physical stability, specificity and low production costs-with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development.

  18. Designed ankyrin repeat proteins: a new approach to mimic complex antigens for diagnostic purposes?

    Directory of Open Access Journals (Sweden)

    Stefanie Hausammann

    Full Text Available Inhibitory antibodies directed against coagulation factor VIII (FVIII can be found in patients with acquired and congenital hemophilia A. Such FVIII-inhibiting antibodies are routinely detected by the functional Bethesda Assay. However, this assay has a low sensitivity and shows a high inter-laboratory variability. Another method to detect antibodies recognizing FVIII is ELISA, but this test does not allow the distinction between inhibitory and non-inhibitory antibodies. Therefore, we aimed at replacing the intricate antigen FVIII by Designed Ankyrin Repeat Proteins (DARPins mimicking the epitopes of FVIII inhibitors. As a model we used the well-described inhibitory human monoclonal anti-FVIII antibody, Bo2C11, for the selection on DARPin libraries. Two DARPins were selected binding to the antigen-binding site of Bo2C11, which mimic thus a functional epitope on FVIII. These DARPins inhibited the binding of the antibody to its antigen and restored FVIII activity as determined in the Bethesda assay. Furthermore, the specific DARPins were able to recognize the target antibody in human plasma and could therefore be used to test for the presence of Bo2C11-like antibodies in a large set of hemophilia A patients. These data suggest, that our approach might be used to isolate epitopes from different sets of anti-FVIII antibodies in order to develop an ELISA-based screening assay allowing the distinction of inhibitory and non-inhibitory anti-FVIII antibodies according to their antibody signatures.

  19. The structure of the ankyrin-binding site of [beta]-spectrin reveals how tandem spectrin-repeats generate unique ligand-binding properties

    Energy Technology Data Exchange (ETDEWEB)

    Stabach, Paul R.; Simonovic, Ivana; Ranieri, Miranda A.; Aboodi, Michael S.; Steitz, Thomas A.; Simonovic, Miljan; Morrow, Jon S.; (Yale); (HHMI)

    2009-09-02

    Spectrin and ankyrin participate in membrane organization, stability, signal transduction, and protein targeting; their interaction is critical for erythrocyte stability. Repeats 14 and 15 of {beta}I-spectrin are crucial for ankyrin recognition, yet the way spectrin binds ankyrin while preserving its repeat structure is unknown. We have solved the crystal structure of the {beta}I-spectrin 14,15 di-repeat unit to 2.1 {angstrom} resolution and found 14 residues critical for ankyrin binding that map to the end of the helix C of repeat 14, the linker region, and the B-C loop of repeat 15. The tilt (64{sup o}) across the 14,15 linker is greater than in any published di-repeat structure, suggesting that the relative positioning of the two repeats is important for ankyrin binding. We propose that a lack of structural constraints on linker and inter-helix loops allows proteins containing spectrin-like di-repeats to evolve diverse but specific ligand-recognition sites without compromising the structure of the repeat unit. The linker regions between repeats are thus critical determinants of both spectrin's flexibility and polyfunctionality. The putative coupling of flexibility and ligand binding suggests a mechanism by which spectrin might participate in mechanosensory regulation.

  20. Novel interactions of ankyrins-G at the costameres: The muscle-specific Obscurin/Titin-Binding-related Domain (OTBD) binds plectin and filamin C

    Energy Technology Data Exchange (ETDEWEB)

    Maiweilidan, Yimingjiang; Klauza, Izabela; Kordeli, Ekaterini, E-mail: ekaterini.kordeli@inserm.fr

    2011-04-01

    Ankyrins, the adapters of the spectrin skeleton, are involved in local accumulation and stabilization of integral proteins to the appropriate membrane domains. In striated muscle, tissue-dependent alternative splicing generates unique Ank3 gene products (ankyrins-G); they share the Obscurin/Titin-Binding-related Domain (OTBD), a muscle-specific insert of the C-terminal domain which is highly conserved among ankyrin genes, and binds obscurin and titin to Ank1 gene products. We previously proposed that OTBD sequences constitute a novel domain of protein-protein interactions which confers ankyrins with specific cellular functions in muscle. Here we searched for muscle proteins binding to ankyrin-G OTBD by yeast two hybrid assay, and we found plectin and filamin C, two organizing elements of the cytoskeleton with essential roles in myogenesis, muscle cell cytoarchitecture, and muscle disease. The three proteins coimmunoprecipitate from skeletal muscle extracts and colocalize at costameres in adult muscle fibers. During in vitro myogenesis, muscle ankyrins-G are first expressed in postmitotic myocytes undergoing fusion to myotubes. In western blots of subcellular fractions from C2C12 cells, the majority of muscle ankyrins-G appear associated with membrane compartments. Occasional but not extensive co-localization at nascent costameres suggested that ankyrin-G interactions with plectin and filamin C are not involved in costamere assembly; they would rather reinforce stability and/or modulate molecular interactions in sarcolemma microdomains by establishing novel links between muscle-specific ankyrins-G and the two costameric dystrophin-associated glycoprotein and integrin-based protein complexes. These results report the first protein-protein interactions involving the ankyrin-G OTBD domain and support the hypothesis that OTBD sequences confer ankyrins with a gain of function in vertebrates, bringing further consolidation and resilience of the linkage between sarcomeres

  1. Tandem-repeat protein domains across the tree of life

    Directory of Open Access Journals (Sweden)

    Kristin K. Jernigan

    2015-01-01

    Full Text Available Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20–40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM and tetratricopeptide (TPR repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species.

  2. Development of the designed ankyrin repeat protein (DARPin) G3 for HER2 molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, Robert; Livanos, Maria; Bhavsar, Gaurav; Rashid, Mohammed; Miranda, Enrique; Tolner, Berend; Meyer, Tim; Chester, Kerry [UCL Cancer Institute, London (United Kingdom); Sosabowski, Jane; Leyton, Julius; Mather, Stephen [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom); Vigor, Kim [Clare Hall Laboratories, Biotherapeutics Development Unit, Cancer Research UK, South Mimms (United Kingdom); Nagy-Davidescu, Gabriela; Plueckthun, Andreas [Universitaet Zuerich, Biochemisches Institut, Zuerich (Switzerland); Yeung, Jenny [UCL Cancer Institute, London (United Kingdom); UCL Institute of Child Health, London (United Kingdom)

    2014-11-13

    Human epidermal growth factor receptor-2 (HER2) overexpression is a predictor of response to anti-HER2 therapy in breast and gastric cancer. Currently, HER2 status is assessed by tumour biopsy, but this may not be representative of the larger tumour mass or other metastatic sites, risking misclassification and selection of suboptimal therapy. The designed ankyrin repeat protein (DARPin) G3 binds HER2 with high affinity at an epitope that does not overlap with trastuzumab and is biologically inert. We hypothesized that radiolabelled DARPin G3 would be capable of selectively imaging HER2-positive tumours, and aimed to identify a suitable format for clinical application. G3 DARPins tagged with hexahistidine (His{sub 6}) or with histidine glutamate (HE){sub 3} and untagged G3 DARPins were manufactured using a GMP-compatible Pichia pastoris protocol and radiolabelled with {sup 125}I, or with {sup 111}In via DOTA linked to a C-terminal cysteine. BALB/c mice were injected with radiolabelled G3 and tissue biodistribution was evaluated by gamma counting. The lead construct ((HE){sub 3}-G3) was assessed in mice bearing HER2-positive human breast tumour (BT474) xenografts. For both isotopes, (HE){sub 3}-G3 had significantly lower liver uptake than His{sub 6}-G3 and untagged G3 counterparts in non-tumour-bearing mice, and there was no significantly different liver uptake between His{sub 6}-G3 and untagged G3. (HE){sub 3}-G3 was taken forward for evaluation in mice bearing HER2-positive tumour xenografts. The results demonstrated that radioactivity from {sup 111}In-(HE){sub 3}-G3 was better maintained in tumours and cleared faster from serum than radioactivity from {sup 125}I-(HE){sub 3}-G3, achieving superior tumour-to-blood ratios (343.7 ± 161.3 vs. 22.0 ± 11.3 at 24 h, respectively). On microSPECT/CT, {sup 111}In-labelled and {sup 125}I-labelled (HE){sub 3}-G3 could image HER2-positive tumours at 4 h after administration, but there was less normal tissue uptake of

  3. Poxviral Ankyrin Proteins

    Directory of Open Access Journals (Sweden)

    Michael H. Herbert

    2015-02-01

    Full Text Available Multiple repeats of the ankyrin motif (ANK are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range.

  4. Diabetes-Related Ankyrin Repeat Protein (DARP/Ankrd23 Modifies Glucose Homeostasis by Modulating AMPK Activity in Skeletal Muscle.

    Directory of Open Access Journals (Sweden)

    Yoshiaki Shimoda

    Full Text Available Skeletal muscle is the major site for glucose disposal, the impairment of which closely associates with the glucose intolerance in diabetic patients. Diabetes-related ankyrin repeat protein (DARP/Ankrd23 is a member of muscle ankyrin repeat proteins, whose expression is enhanced in the skeletal muscle under diabetic conditions; however, its role in energy metabolism remains poorly understood. Here we report a novel role of DARP in the regulation of glucose homeostasis through modulating AMP-activated protein kinase (AMPK activity. DARP is highly preferentially expressed in skeletal muscle, and its expression was substantially upregulated during myotube differentiation of C2C12 myoblasts. Interestingly, DARP-/- mice demonstrated better glucose tolerance despite similar body weight, while their insulin sensitivity did not differ from that in wildtype mice. We found that phosphorylation of AMPK, which mediates insulin-independent glucose uptake, in skeletal muscle was significantly enhanced in DARP-/- mice compared to that in wildtype mice. Gene silencing of DARP in C2C12 myotubes enhanced AMPK phosphorylation, whereas overexpression of DARP in C2C12 myoblasts reduced it. Moreover, DARP-silencing increased glucose uptake and oxidation in myotubes, which was abrogated by the treatment with AICAR, an AMPK activator. Of note, improved glucose tolerance in DARP-/- mice was abolished when mice were treated with AICAR. Mechanistically, gene silencing of DARP enhanced protein expression of LKB1 that is a major upstream kinase for AMPK in myotubes in vitro and the skeletal muscle in vivo. Together with the altered expression under diabetic conditions, our data strongly suggest that DARP plays an important role in the regulation of glucose homeostasis under physiological and pathological conditions, and thus DARP is a new therapeutic target for the treatment of diabetes mellitus.

  5. NUC-2, a component of the phosphate-regulated signal transduction pathway in Neurospora crassa, is an ankyrin repeat protein.

    Science.gov (United States)

    Poleg, Y; Aramayo, R; Kang, S; Hall, J G; Metzenberg, R L

    1996-10-28

    In response to phosphorus limitation, the fungus Neurospora crassa synthesizes a number of enzymes that function to bring more phosphate into the cell. The NUC-2 protein appears to sense the availability of phosphate and transmits the signal downstream to the regulatory pathway. The nuc-2+ gene has been cloned by its ability to restore growth of a nuc-2 mutant under restrictive conditions of high pH and low phosphate concentration. We mapped the cloned gene to the right arm of linkage group II, consistent with the chromosomal position of the nuc-2 mutation as determined by classical genetic mapping. The nuc-2' open reading frame is interrupted by five introns and codes for a protein of 1066 amino acid residues. Its predicted amino acid sequence has high similarity to that of its homolog in Saccharomyces cerevisiae, PHO81. Both proteins contain six ankyrin repeats, which have been implicated in the cyclin-dependent kinase inhibitory activity of PHO81. The phenotypes of a nuc-2 mutant generated by repeat-induced point mutation and of a strain harboring a UV-induced nuc-2 allele are indistinguishable. Both are unable to grow under the restrictive conditions, a phenotype which is to some degree temperature dependent. The nuc-2+ gene is transcriptionally regulated. A 15-fold increase in the level of the nuc-2+ transcript occurs in response to a decrease in exogenous phosphate concentration.

  6. An Adaptable Spectrin/Ankyrin-Based Mechanism for Long-Range Organization of Plasma Membranes in Vertebrate Tissues.

    Science.gov (United States)

    Bennett, Vann; Lorenzo, Damaris N

    2016-01-01

    Ankyrins are membrane-associated proteins that together with their spectrin partners are responsible for micron-scale organization of vertebrate plasma membranes, including those of erythrocytes, excitable membranes of neurons and heart, lateral membrane domains of columnar epithelial cells, and striated muscle. Ankyrins coordinate functionally related membrane transporters and cell adhesion proteins (15 protein families identified so far) within plasma membrane compartments through independently evolved interactions of intrinsically disordered sequences with a highly conserved peptide-binding groove formed by the ANK repeat solenoid. Ankyrins are coupled to spectrins, which are elongated organelle-sized proteins that form mechanically resilient arrays through cross-linking by specialized actin filaments. In addition to protein interactions, cellular targeting and assembly of spectrin/ankyrin domains also critically depend on palmitoylation of ankyrin-G by aspartate-histidine-histidine-cysteine 5/8 palmitoyltransferases, as well as interaction of beta-2 spectrin with phosphoinositide lipids. These lipid-dependent spectrin/ankyrin domains are not static but are locally dynamic and determine membrane identity through opposing endocytosis of bulk lipids as well as specific proteins. A partnership between spectrin, ankyrin, and cell adhesion molecules first emerged in bilaterians over 500 million years ago. Ankyrin and spectrin may have been recruited to plasma membranes from more ancient roles in organelle transport. The basic bilaterian spectrin-ankyrin toolkit markedly expanded in vertebrates through gene duplications combined with variation in unstructured intramolecular regulatory sequences as well as independent evolution of ankyrin-binding activity by ion transporters involved in action potentials and calcium homeostasis. In addition, giant vertebrate ankyrins with specialized roles in axons acquired new coding sequences by exon shuffling. We speculate that

  7. An Adaptable Spectrin/Ankyrin-Based Mechanism for Long-Range Organization of Plasma Membranes in Vertebrate Tissues.

    Science.gov (United States)

    Bennett, Vann; Lorenzo, Damaris N

    2016-01-01

    Ankyrins are membrane-associated proteins that together with their spectrin partners are responsible for micron-scale organization of vertebrate plasma membranes, including those of erythrocytes, excitable membranes of neurons and heart, lateral membrane domains of columnar epithelial cells, and striated muscle. Ankyrins coordinate functionally related membrane transporters and cell adhesion proteins (15 protein families identified so far) within plasma membrane compartments through independently evolved interactions of intrinsically disordered sequences with a highly conserved peptide-binding groove formed by the ANK repeat solenoid. Ankyrins are coupled to spectrins, which are elongated organelle-sized proteins that form mechanically resilient arrays through cross-linking by specialized actin filaments. In addition to protein interactions, cellular targeting and assembly of spectrin/ankyrin domains also critically depend on palmitoylation of ankyrin-G by aspartate-histidine-histidine-cysteine 5/8 palmitoyltransferases, as well as interaction of beta-2 spectrin with phosphoinositide lipids. These lipid-dependent spectrin/ankyrin domains are not static but are locally dynamic and determine membrane identity through opposing endocytosis of bulk lipids as well as specific proteins. A partnership between spectrin, ankyrin, and cell adhesion molecules first emerged in bilaterians over 500 million years ago. Ankyrin and spectrin may have been recruited to plasma membranes from more ancient roles in organelle transport. The basic bilaterian spectrin-ankyrin toolkit markedly expanded in vertebrates through gene duplications combined with variation in unstructured intramolecular regulatory sequences as well as independent evolution of ankyrin-binding activity by ion transporters involved in action potentials and calcium homeostasis. In addition, giant vertebrate ankyrins with specialized roles in axons acquired new coding sequences by exon shuffling. We speculate that

  8. Identification of amino acid residues of a designed ankyrin repeat protein potentially involved in intermolecular interactions with CD4: analysis by molecular dynamics simulations.

    Science.gov (United States)

    Nimmanpipug, Piyarat; Khampa, Chalermpon; Lee, Vannajan Sanghiran; Nangola, Sawitree; Tayapiwatana, Chatchai

    2011-11-01

    We applied molecular dynamics simulations to investigate the binding properties of a designed ankyrin repeat protein, the DARPin-CD4 complex. DARPin 23.2 has been reported to disturb the human immunodeficiency virus (HIV) viral entry process by Schweizer et al. The protein docking simulation was analysed by comparing the specific ankyrin binder (DARPin 23.2) to an irrelevant control (2JAB) in forming a composite with CD4. To determine the binding free energy of both ankyrins, the MM/PBSA and MM/GBSA protocols were used. The free energy decomposition of both complexes were analysed to explore the role of certain amino acid residues in complex configuration. Interestingly, the molecular docking analysis of DARPin 23.2 revealed a similar CD4 interaction regarding the gp120 theoretical anchoring motif. In contrast, the binding of control ankyrin to CD4 occurred at a different location. This observation suggests that there is an advantage to the molecular modification of DARPin 23.2, an enhanced affinity for CD4. PMID:21962990

  9. The Ankyrin-Repeat Transmembrane Protein BDA1 Functions Downstream of the Receptor-Like Protein SNC2 to Regulate Plant Immunity1[C][OA

    Science.gov (United States)

    Yang, Yuanai; Zhang, Yaxi; Ding, Pingtao; Johnson, Kaeli; Li, Xin; Zhang, Yuelin

    2012-01-01

    Plants utilize a large number of immune receptors to recognize pathogens and activate defense responses. A small number of these receptors belong to the receptor-like protein family. Previously, we showed that a gain-of-function mutation in the receptor-like protein SNC2 (for Suppressor of NPR1, Constitutive2) leads to constitutive activation of defense responses in snc2-1D mutant plants. To identify defense signaling components downstream of SNC2, we carried out a suppressor screen in the snc2-1D mutant background of Arabidopsis (Arabidopsis thaliana). Map-based cloning of one of the suppressor genes, BDA1 (for bian da; “becoming big” in Chinese), showed that it encodes a protein with amino-terminal ankyrin repeats and carboxyl-terminal transmembrane domains. Loss-of-function mutations in BDA1 suppress the dwarf morphology and constitutive defense responses in snc2-1D npr1-1 (for nonexpressor of pathogenesis-related genes1,1) and also result in enhanced susceptibility to bacterial pathogens. In contrast, a gain-of-function allele of bda1 isolated from a separate genetic screen to search for mutants with enhanced pathogen resistance was found to constitutively activate cell death and defense responses. These data suggest that BDA1 is a critical signaling component that functions downstream of SNC2 to regulate plant immunity. PMID:22740615

  10. Multifunctional protein:cardiac ankyrin repeat protein%心锚重复蛋白的研究进展

    Institute of Scientific and Technical Information of China (English)

    Na ZHANG; Xiao-jie XIE; Jian-an WANG‡

    2016-01-01

    概心锚重复蛋白(CARP)是一个双重定位的蛋白,既可以在胞浆中作为肌节的结构组成蛋白,又定位于细胞核中作为转录共刺激因子调节其他基因的表达。研究发现CARP在多种心血管疾病及肌肉疾病中表达升高,但其在疾病中的作用尚存在争议。本文就CARP的研究进展进行综述,概述CARP的发现过程和结构,并对CARP在疾病中的作用的争议进行总结分析。%Cardiac ankyrin repeat protein (CARP) not only serves as an important component of muscle sarcomere in the cytoplasm, but also acts as a transcription co-factor in the nucleus. Previous studies have demonstrated that CARP is up-regulated in some cardiovascular disorders and muscle diseases;however, its role in these diseases remains controversial now. In this review, we wil discuss the continued progress in the research related to CARP, including its discovery, structure, and the role it plays in cardiac development and heart diseases.

  11. The cell signaling adaptor protein EPS-8 is essential for C. elegans epidermal elongation and interacts with the ankyrin repeat protein VAB-19.

    Directory of Open Access Journals (Sweden)

    Mei Ding

    Full Text Available The epidermal cells of the C. elegans embryo undergo coordinated cell shape changes that result in the morphogenetic process of elongation. The cytoskeletal ankyrin repeat protein VAB-19 is required for cell shape changes and localizes to cell-matrix attachment structures. The molecular functions of VAB-19 in this process are obscure, as no previous interactors for VAB-19 have been described.In screens for VAB-19 binding proteins we identified the signaling adaptor EPS-8. Within C. elegans epidermal cells, EPS-8 and VAB-19 colocalize at cell-matrix attachment structures. The central domain of EPS-8 is necessary and sufficient for its interaction with VAB-19. eps-8 null mutants, like vab-19 mutants, are defective in epidermal elongation and in epidermal-muscle attachment. The eps-8 locus encodes two isoforms, EPS-8A and EPS-8B, that appear to act redundantly in epidermal elongation. The function of EPS-8 in epidermal development involves its N-terminal PTB and central domains, and is independent of its C-terminal SH3 and actin-binding domains. VAB-19 appears to act earlier in the biogenesis of attachment structures and may recruit EPS-8 to these structures.EPS-8 and VAB-19 define a novel pathway acting at cell-matrix attachments to regulate epithelial cell shape. This is the first report of a role for EPS-8 proteins in cell-matrix attachments. The existence of EPS-8B-like isoforms in Drosophila suggests this function of EPS-8 proteins could be conserved among other organisms.

  12. Expansion and Function of Repeat Domain Proteins During Stress and Development in Plants.

    Science.gov (United States)

    Sharma, Manisha; Pandey, Girdhar K

    2015-01-01

    The recurrent repeats having conserved stretches of amino acids exists across all domains of life. Subsequent repetition of single sequence motif and the number and length of the minimal repeating motifs are essential characteristics innate to these proteins. The proteins with tandem peptide repeats are essential for providing surface to mediate protein-protein interactions for fundamental biological functions. Plants are enriched in tandem repeat containing proteins typically distributed into various families. This has been assumed that the occurrence of multigene repeats families in plants enable them to cope up with adverse environmental conditions and allow them to rapidly acclimatize to these conditions. The evolution, structure, and function of repeat proteins have been studied in all kingdoms of life. The presence of repeat proteins is particularly profuse in multicellular organisms in comparison to prokaryotes. The precipitous expansion of repeat proteins in plants is presumed to be through internal tandem duplications. Several repeat protein gene families have been identified in plants. Such as Armadillo (ARM), Ankyrin (ANK), HEAT, Kelch-like repeats, Tetratricopeptide (TPR), Leucine rich repeats (LRR), WD40, and Pentatricopeptide repeats (PPR). The structure and functions of these repeat proteins have been extensively studied in plants suggesting a critical role of these repeating peptides in plant cell physiology, stress and development. In this review, we illustrate the structural, functional, and evolutionary prospects of prolific repeat proteins in plants. PMID:26793205

  13. Structural basis for spectrin recognition by ankyrin

    Energy Technology Data Exchange (ETDEWEB)

    Ipsaro, Jonathan J.; Mondragón, Alfonso (NWU)

    2010-10-19

    Maintenance of membrane integrity and organization in the metazoan cell is accomplished through intracellular tethering of membrane proteins to an extensive, flexible protein network. Spectrin, the principal component of this network, is anchored to membrane proteins through the adaptor protein ankyrin. To elucidate the atomic basis for this interaction, we determined a crystal structure of human {beta}I-spectrin repeats 13 to 15 in complex with the ZU5-ANK domain of human ankyrin R. The structure reveals the role of repeats 14 to 15 in binding, the electrostatic and hydrophobic contributions along the interface, and the necessity for a particular orientation of the spectrin repeats. Using structural and biochemical data as a guide, we characterized the individual proteins and their interactions by binding and thermal stability analyses. In addition to validating the structural model, these data provide insight into the nature of some mutations associated with cell morphology defects, including those found in human diseases such as hereditary spherocytosis and elliptocytosis. Finally, analysis of the ZU5 domain suggests it is a versatile protein-protein interaction module with distinct interaction surfaces. The structure represents not only the first of a spectrin fragment in complex with its binding partner, but also that of an intermolecular complex involving a ZU5 domain.

  14. MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection

    Directory of Open Access Journals (Sweden)

    Gelfi Jacqueline

    2010-03-01

    Full Text Available Abstract Myxoma virus (MYXV, a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus. Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has drawn considerable attention for its potential role in modulating the host ubiquitin-proteasome system during viral infection. To date, many members of this novel protein family have been shown to interact with SCF components, in vitro. Here, we focus on MNF gene, which has been shown to express a nuclear protein presenting nine ANK repeats, one of which has been identified as a nuclear localization signal. In transfection, MNF has been shown to colocalise with the transcription factor NF-κB in the nucleus of TNFα-stimulated cells. Functionally, MNF is a critical virulence factor since its deletion generates an almost apathogenic virus. In this study, to pursue the investigation of proteins interacting with MNF and of its mechanism of action, we engineered a recombinant MYXV expressing a GFP-linked MNF under the control of MNF native promoter. Infection of rabbits with MYXV-GFPMNF recombinant virus provided the evidence that the GFP fusion does not disturb the main function of MNF. Hence, cells were infected with MYXV-GFPMNF and immunoprecipitation of the GFPMNF fusion protein was performed to identify MNF's partners. For the first time, endogenous components of SCF (Cullin-1 and Skp1 were co-precipitated with an ANK myxoma virus protein, expressed in an infectious context, and without over-expression of any protein.

  15. MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection.

    Science.gov (United States)

    Blanié, Sophie; Gelfi, Jacqueline; Bertagnoli, Stéphane; Camus-Bouclainville, Christelle

    2010-01-01

    Myxoma virus (MYXV), a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor) and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has drawn considerable attention for its potential role in modulating the host ubiquitin-proteasome system during viral infection. To date, many members of this novel protein family have been shown to interact with SCF components, in vitro. Here, we focus on MNF gene, which has been shown to express a nuclear protein presenting nine ANK repeats, one of which has been identified as a nuclear localization signal. In transfection, MNF has been shown to colocalise with the transcription factor NF-kappaB in the nucleus of TNFalpha-stimulated cells. Functionally, MNF is a critical virulence factor since its deletion generates an almost apathogenic virus. In this study, to pursue the investigation of proteins interacting with MNF and of its mechanism of action, we engineered a recombinant MYXV expressing a GFP-linked MNF under the control of MNF native promoter. Infection of rabbits with MYXV-GFPMNF recombinant virus provided the evidence that the GFP fusion does not disturb the main function of MNF. Hence, cells were infected with MYXV-GFPMNF and immunoprecipitation of the GFPMNF fusion protein was performed to identify MNF's partners. For the first time, endogenous components of SCF (Cullin-1 and Skp1) were co-precipitated with an ANK myxoma virus protein, expressed in an infectious context, and without over-expression of any protein. PMID:20211013

  16. Protein Interaction Screening for the Ankyrin Repeats and Suppressor of Cytokine Signaling (SOCS) Box (ASB) Family Identify Asb11 as a Novel Endoplasmic Reticulum Resident Ubiquitin Ligase

    DEFF Research Database (Denmark)

    Andresen, Christina Aaen; Smedegaard, Stine; Sylvestersen, Kathrine Beck;

    2014-01-01

    The Ankyrin and SOCS (Suppressor of Cytokine Signaling) box (ASB) family of proteins function as the substrate recognition subunit in a subset of Elongin-Cullin-SOCS (ECS) E3 ubiquitin ligases. Despite counting with 18 members in humans, the identity of the physiological targets of the Asb protei...... in vivo. In summary, we provide a comprehensive protein-protein interaction data resource that can aid the biological and functional characterization of ASB ubiquitin ligases....

  17. Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma.

    Science.gov (United States)

    Deering-Rice, Cassandra E; Shapiro, Darien; Romero, Erin G; Stockmann, Chris; Bevans, Tatjana S; Phan, Quang M; Stone, Bryan L; Fassl, Bernhard; Nkoy, Flory; Uchida, Derek A; Ward, Robert M; Veranth, John M; Reilly, Christopher A

    2015-12-01

    Inhaled irritants activate transient receptor potential ankyrin-1 (TRPA1), resulting in cough, bronchoconstriction, and inflammation/edema. TRPA1 is also implicated in the pathogenesis of asthma. Our hypothesis was that particulate materials activate TRPA1 via a mechanism distinct from chemical agonists and that, in a cohort of children with asthma living in a location prone to high levels of air pollution, expression of uniquely sensitive forms of TRPA1 may correlate with reduced asthma control. Variant forms of TRPA1 were constructed by mutating residues in known functional elements and corresponding to single-nucleotide polymorphisms in functional domains. TRPA1 activity was studied in transfected HEK-293 cells using allyl-isothiocynate, a model soluble electrophilic agonist; 3,5-ditert butylphenol, a soluble nonelectrophilic agonist and a component of diesel exhaust particles; and insoluble coal fly ash (CFA) particles. The N-terminal variants R3C and R58T exhibited greater, but not additive, activity with all three agonists. The ankyrin repeat domain-4 single nucleotide polymorphisms E179K and K186N exhibited decreased response to CFA. The predicted N-linked glycosylation site residues N747A and N753A exhibited decreased responses to CFA, which were not attributable to differences in cellular localization. The pore-loop residue R919Q was comparable to wild-type, whereas N954T was inactive to soluble agonists but not CFA. These data identify roles for ankyrin domain-4, cell surface N-linked glycans, and selected pore-loop domain residues in the activation of TRPA1 by insoluble particles. Furthermore, the R3C and R58T polymorphisms correlated with reduced asthma control for some children, which suggest that TRPA1 activity may modulate asthma, particularly among individuals living in locations prone to high levels of air pollution.

  18. Towards Development of a Dermal Pain Model: In Vitro Activation of Rat and Human Transient Receptor Potential Ankyrin Repeat 1 and Safe Dermal Injection of o-Chlorobenzylidene Malononitrile to Rat.

    Science.gov (United States)

    Annas, Anita; Berg, Anna-Lena; Nyman, Eva; Meijer, Thomas; Lundgren, Viveka; Franzén, Bo; Ståhle, Lars

    2015-12-01

    During clinical development of analgesics, it is important to have access to pharmacologically specific human pain models. o-Chlorobenzylidene malononitrile (CS) is a selective and potent agonist of the transient receptor potential ankyrin repeat 1 (TRPA1), which is a transducer molecule in nociceptors sensing reactive chemical species. While CS has been subject to extensive toxicological investigations in animals and human beings, its effects on intradermal or subcutaneous injection have not previously been reported. We have investigated the potential of CS to be used as an agonist on TRPA1 in human experimental pain studies. A calcium influx assay was used to confirm the capacity of CS to activate TRPA1 with >100,000 times the selectivity over the transient receptor potential vanilloid receptor 1. CS dose-dependently (EC50 0.9 μM) released calcitonin gene-related peptide in rat dorsal root ganglion cultures, supporting involvement in pain signalling. In a local tolerance study, injection of a single intradermal dose of 20 mM CS to rats resulted in superficial, circular crusts at the injection sites after approximately 4 days. The histopathology evaluation revealed a mild, acute inflammatory reaction in the epidermis and dermis at the intradermal CS injection site 1 day after administration. After 14 days, the epidermal epithelium was fully restored. The symptoms were not considered to be adverse, and it is suggested that doses up to 20 μL of 20 mM CS can be safely administered to human beings. In conclusion, our data support development of a CS human dermal pain model. PMID:26046936

  19. The crystal structures of dystrophin and utrophin spectrin repeats: implications for domain boundaries.

    Directory of Open Access Journals (Sweden)

    Muralidharan Muthu

    Full Text Available Dystrophin and utrophin link the F-actin cytoskeleton to the cell membrane via an associated glycoprotein complex. This functionality results from their domain organization having an N-terminal actin-binding domain followed by multiple spectrin-repeat domains and then C-terminal protein-binding motifs. Therapeutic strategies to replace defective dystrophin with utrophin in patients with Duchenne muscular dystrophy require full-characterization of both these proteins to assess their degree of structural and functional equivalence. Here the high resolution structures of the first spectrin repeats (N-terminal repeat 1 from both dystrophin and utrophin have been determined by x-ray crystallography. The repeat structures both display a three-helix bundle fold very similar to one another and to homologous domains from spectrin, α-actinin and plectin. The utrophin and dystrophin repeat structures reveal the relationship between the structural domain and the canonical spectrin repeat domain sequence motif, showing the compact structural domain of spectrin repeat one to be extended at the C-terminus relative to its previously defined sequence repeat. These structures explain previous in vitro biochemical studies in which extending dystrophin spectrin repeat domain length leads to increased protein stability. Furthermore we show that the first dystrophin and utrophin spectrin repeats have no affinity for F-actin in the absence of other domains.

  20. Domain Modeling: NP_060174.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_060174.2 chr11 Asn-hydroxylation stabilises the ankyrin repeat domain fold c2zgga_ chr11/NP_060174.2.../NP_060174.2_holo_73-160.pdb blast 80W,81A,84K,85N,86R,119G,120H _CD,CMO 0 ...

  1. Molecular cloning and characterization of a gene encoding RING zinc finger ankyrin protein from drought-tolerant Artemisia desertorum

    Indian Academy of Sciences (India)

    Xiuhong Yang; Chao Sun; Yuanlei Hun; Zhongping Lin

    2008-03-01

    A RING zinc finger ankyrin protein gene, designated AdZFP1, was isolated from drought-tolerant Artemisia desertorum Spreng by mRNA differential display and RACE. Its cDNA was 1723 bp and encoded a putative protein of 445 amino acids with a predicted molecular mass of 47.9 kDa and an isoelectric point (pI) of 7.49. A typical C3HC4-type RING finger domain was found at the C-terminal region of the AdZFP1 protein, and several groups of ankyrin repeats were found at the N-terminal region. Alignments of amino acid sequence showed that AdZFP1 was 66% identical to the Arabidopsis thaliana putative RING zinc finger ankyrin protein AAN31869. Transcriptional analysis showed that AdZFP1 was inducible under drought stress in root, stem and leaf of the plant. Semi-quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis showed that the transcript of AdZFP1 was strongly induced by exogenous abscisic acid (ABA) and also by salinity, cold and heat to some extent. Overexpression of the AdZFP1 gene in transgenic tobacco enhanced their tolerance to drought stress.

  2. Nonlinear analysis of sequence repeats of multi-domain proteins

    International Nuclear Information System (INIS)

    Many multi-domain proteins have repetitive three-dimensional structures but nearly-random amino acid sequences. In the present paper, by using a modified recurrence plot proposed by us previously, we show that these amino acid sequences have hidden repetitions in fact. These results indicate that the repetitive domain structures are encoded by the repetitive sequences. This also gives a method to detect the repetitive domain structures directly from amino acid sequences

  3. Ankyrin-G Inhibits Endocytosis of Cadherin Dimers.

    Science.gov (United States)

    Cadwell, Chantel M; Jenkins, Paul M; Bennett, Vann; Kowalczyk, Andrew P

    2016-01-01

    Dynamic regulation of endothelial cell adhesion is central to vascular development and maintenance. Furthermore, altered endothelial adhesion is implicated in numerous diseases. Therefore, normal vascular patterning and maintenance require tight regulation of endothelial cell adhesion dynamics. However, the mechanisms that control junctional plasticity are not fully understood. Vascular endothelial cadherin (VE-cadherin) is an adhesive protein found in adherens junctions of endothelial cells. VE-cadherin mediates adhesion through trans interactions formed by its extracellular domain. Trans binding is followed by cis interactions that laterally cluster the cadherin in junctions. VE-cadherin is linked to the actin cytoskeleton through cytoplasmic interactions with β- and α-catenin, which serve to increase adhesive strength. Furthermore, p120-catenin binds to the cytoplasmic tail of cadherin and stabilizes it at the plasma membrane. Here we report that induced cis dimerization of VE-cadherin inhibits endocytosis independent of both p120 binding and trans interactions. However, we find that ankyrin-G, a protein that links membrane proteins to the spectrin-actin cytoskeleton, associates with VE-cadherin and inhibits its endocytosis. Ankyrin-G inhibits VE-cadherin endocytosis independent of p120 binding. We propose a model in which ankyrin-G associates with and inhibits the endocytosis of VE-cadherin cis dimers. Our findings support a novel mechanism for regulation of VE-cadherin endocytosis through ankyrin association with cadherin engaged in lateral interactions. PMID:26574545

  4. Enhanced antibody-dependent cellular phagocytosis by chimeric monoclonal antibodies with tandemly repeated Fc domains.

    Science.gov (United States)

    Nagashima, Hiroaki; Ootsubo, Michiko; Fukazawa, Mizuki; Motoi, Sotaro; Konakahara, Shu; Masuho, Yasuhiko

    2011-04-01

    We previously reported that chimeric monoclonal antibodies (mAbs) with tandemly repeated Fc domains, which were developed by introducing tandem repeats of Fc domains downstream of 2 Fab domains, augmented binding avidities for all Fcγ receptors, resulting in enhanced antibody (Ab)-dependent cellular cytotoxicity. Here we investigated regarding Ab-dependent cellular phagocytosis (ADCP) mediated by these chimeric mAbs, which is considered one of the most important mechanisms that kills tumor cells, using two-color flow cytometric methods. ADCP mediated by T3-Ab, a chimeric mAb with 3 tandemly repeated Fc domains, was 5 times more potent than that by native anti-CD20 M-Ab (M-Ab hereafter). Furthermore, T3-Ab-mediated ADCP was resistant to competitive inhibition by intravenous Ig (IVIG), although M-Ab-mediated ADCP decreased in the presence of IVIG. An Fcγ receptor-blocking study demonstrated that T3-Ab mediated ADCP via both FcγRIA and FcγRIIA, whereas M-Ab mediated ADCP exclusively via FcγRIA. These results suggest that chimeric mAbs with tandemly repeated Fc domains enhance ADCP as well as ADCC, and that Fc multimerization may significantly enhance the efficacy of therapeutic Abs. PMID:21215693

  5. Localization and Structure of the Ankyrin-binding Site on [beta] [subscript 2]-Spectrin

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Lydia; Abdi, Khadar; Machius, Mischa; Brautigam, Chad; Tomchick, Diana R.; Bennett, Vann; Michaely, Peter; (HHMI); (UTSMC)

    2009-06-08

    Spectrins are tetrameric actin-cross-linking proteins that form an elastic network, termed the membrane skeleton, on the cytoplasmic surface of cellular membranes. At the plasma membrane, the membrane skeleton provides essential support, preventing loss of membrane material to environmental shear stresses. The skeleton also controls the location, abundance, and activity of membrane proteins that are critical to cell and tissue function. The ability of the skeleton to modulate membrane stability and function requires adaptor proteins that bind the skeleton to membranes. The principal adaptors are the ankyrin proteins, which bind to the {beta}-subunit of spectrin and to the cytoplasmic domains of numerous integral membrane proteins. Here, we present the crystal structure of the ankyrin-binding domain of human {beta}{sub 2}-spectrin at 1.95 {angstrom} resolution together with mutagenesis data identifying the binding surface for ankyrins on {beta}{sub 2}-spectrin.

  6. Ankyrin 3: genetic association with bipolar disorder and relevance to disease pathophysiology

    Directory of Open Access Journals (Sweden)

    Leussis Melanie P

    2012-10-01

    Full Text Available Abstract Bipolar disorder (BD is a multi-factorial disorder caused by genetic and environmental influences. It has a large genetic component, with heritability estimated between 59-93%. Recent genome-wide association studies (GWAS using large BD patient populations have identified a number of genes with strong statistical evidence for association with susceptibility for BD. Among the most significant and replicated genes is ankyrin 3 (ANK3, a large gene that encodes multiple isoforms of the ankyrin G protein. This article reviews the current evidence for genetic association of ANK3 with BD, followed by a comprehensive overview of the known biology of the ankyrin G protein, focusing on its neural functions and their potential relevance to BD. Ankyrin G is a scaffold protein that is known to have many essential functions in the brain, although the mechanism by which it contributes to BD is unknown. These functions include organizational roles for subcellular domains in neurons including the axon initial segment and nodes of Ranvier, through which ankyrin G orchestrates the localization of key ion channels and GABAergic presynaptic terminals, as well as creating a diffusion barrier that limits transport into the axon and helps define axo-dendritic polarity. Ankyrin G is postulated to have similar structural and organizational roles at synaptic terminals. Finally, ankyrin G is implicated in both neurogenesis and neuroprotection. ANK3 and other BD risk genes participate in some of the same biological pathways and neural processes that highlight several mechanisms by which they may contribute to BD pathophysiology. Biological investigation in cellular and animal model systems will be critical for elucidating the mechanism through which ANK3 confers risk of BD. This knowledge is expected to lead to a better understanding of the brain abnormalities contributing to BD symptoms, and to potentially identify new targets for treatment and intervention

  7. The BARD1 C-Terminal Domain Structure and Interactions with Polyadenylation Factor CstF-50

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, Ross A.; Lee, Megan S.; Tsutakawa, Susan E.; Williams, R. Scott; Tainer, John A.; Glover, J. N. Mark

    2009-07-13

    The BARD1 N-terminal RING domain binds BRCA1 while the BARD1 C-terminal ankyrin and tandem BRCT repeat domains bind CstF-50 to modulate mRNA processing and RNAP II stability in response to DNA damage. Here we characterize the BARD1 structural biochemistry responsible for CstF- 50 binding. The crystal structure of the BARD1 BRCT domain uncovers a degenerate phosphopeptide binding pocket lacking the key arginine required for phosphopeptide interactions in other BRCT proteins.Small angle X-ray scattering together with limited proteolysis results indicates that ankyrin and BRCT domains are linked by a flexible tether and do not adopt a fixed orientation relative to one another. Protein pull-down experiments utilizing a series of purified BARD1 deletion mutants indicate that interactions between the CstF-50 WD-40 domain and BARD1 involve the ankyrin-BRCT linker but do not require ankyrin or BRCT domains. The structural plasticity imparted by the ANK-BRCT linker helps to explain the regulated assembly of different protein BARD1 complexes with distinct functions in DNA damage signaling including BARD1-dependent induction of apoptosis plus p53 stabilization and interactions. BARD1 architecture and plasticity imparted by the ANK-BRCT linker are suitable to allow the BARD1 C-terminus to act as a hub with multiple binding sites to integrate diverse DNA damage signals directly to RNA polymerase.

  8. 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.

  9. 心肌锚定重复序列蛋白基因心脏特异敲除小鼠模型构建与鉴定%Construction and identification of mice model with cardiac disruption of cardiac ankyrin repeat protein

    Institute of Scientific and Technical Information of China (English)

    许家林; 李艳凤; 朱大海

    2011-01-01

    目的 构建心肌锚定重复序列蛋白(CARP)基因心脏特异敲除小鼠模型,为研究CARP基因与心脏疾病的关系奠定基础.方法 构建CARP基因条件打靶载体pL253-CARP-LoxP电转入小鼠胚胎干细胞(ES)细胞,G418和GANC药物筛选阳性细胞克隆,Southern blot确定CARP基在条件打靶载体转染成功.胚胎注射ES细胞入小鼠囊胚,获得嵌合体小鼠与心脏特异启动子Cre小鼠(α-MHC-Cre)杂交.结果 得到6只嵌合体小鼠,与α-MHC-Cre小鼠杂交获得CARP基因心脏特异敲除小鼠(CARP-KO),半定量RT-PCR和Westem blot确定CARP基因在CARP-KO小鼠心脏缺失.该小鼠早期胚胎发育和个体生长、心脏发育正常,但心肌肥厚标志基因β-MHC和ANF显著升高(分别为2.25±0.04和1.45 +0.03)(P<0.05).结论 成功构建CARP基因心脏特异敲除小鼠,CARP基因缺失对小鼠胚胎发育、个体生长和心脏发育没有显著影响.%Objective To establish a mouse model with cardiac disruption of cardiac ankyrin repeat protein (CARP) and to develop reliable tools for studying the function of CARP gene in heart related diseases. Methods Construct the conditional target plasmid of pL253-CARP-LoxP and transfect to 129 embryonic stem cells. Positive clones selected by G418 and GANC were checked by Southern blot to confirm conditional disruption of CARP gene, and then injected to the blastula. Chimeras were got and crossed with a-MHC-Cre transgenic mice, which expressed recombinase specifically in heart. Results Six chimeras were developed, and cardiac disruption of cardiac ankyrin repeat protein mice (CARP-KO) were obtained after crossing with a-MHC-Cre mice. CARP gene disruption was confirmed in the heart of CARP-KO mice by semi-quantitative RT-PCR and Western blot. These mice displayed normal in embryonic development, body growth, and heart development. However the expression of hypertrophic genes of β-MHC and ANF increased significantly in CARP-KO mice (2. 25 ±0. 04 and 1. 45

  10. 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.

  11. Variation of the neurofilament medium KSP repeat sub-domain across mammalian species: implications for altering axonal structure.

    Science.gov (United States)

    Barry, D M; Carpenter, C; Yager, C; Golik, B; Barry, K J; Shen, H; Mikse, O; Eggert, L S; Schulz, D J; Garcia, M L

    2010-01-01

    The evolution of larger mammals resulted in a corresponding increase in peripheral nerve length. To ensure optimal nervous system functionality and survival, nerve conduction velocities were likely to have increased to maintain the rate of signal propagation. Increases of conduction velocities may have required alterations in one of the two predominant properties that affect the speed of neuronal transmission: myelination or axonal diameter. A plausible mechanism to explain faster conduction velocities was a concomitant increase in axonal diameter with evolving axonal length. The carboxy terminal tail domain of the neurofilament medium subunit is a determinant of axonal diameter in large caliber myelinated axons. Sequence analysis of mammalian orthologs indicates that the neurofilament medium carboxy terminal tail contains a variable lysine-serine-proline (KSP) repeat sub-domain flanked by two highly conserved sub-domains. The number of KSP repeats within this region of neurofilament medium varies among species. Interestingly, the number of repeats does not change within a species, suggesting that selective pressure conserved the number of repeats within a species. Mapping KSP repeat numbers onto consensus phylogenetic trees reveals independent KSP expansion events across several mammalian clades. Linear regression analyses identified three subsets of mammals, one of which shows a positive correlation in the number of repeats with head-body length. For this subset of mammals, we hypothesize that variations in the number of KSP repeats within neurofilament medium carboxy terminal tail may have contributed to an increase in axonal caliber, increasing nerve conduction velocity as larger mammals evolved. PMID:20008369

  12. 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.

  13. 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. PMID:27182946

  14. 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.

  15. 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.

  16. 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.

  17. Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8.

    Science.gov (United States)

    Lux, S E; Tse, W T; Menninger, J C; John, K M; Harris, P; Shalev, O; Chilcote, R R; Marchesi, S L; Watkins, P C; Bennett, V

    1990-06-21

    Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic anaemias. HS red cells from both autosound dominant and recessive variants are spectrin-deficient, which correlates with the severity of the disease. Some patients with recessive HS have a mutation in the spectrin alpha-2 domain (S.L.M. et al., unpublished observations), and a few dominant HS patients have an unstable beta-spectrin that is easily oxidized, which damages the protein 4.1 binding site and weakens spectrin-actin interactions. In most patients, however, the cause of spectrin deficiency is unknown. The alpha- and beta-spectrin loci are on chromosomes 1 and 14 respectively. The only other genetic locus for HS is SPH2, on the short arm of chromosome 8 (8p11). This does not correspond to any of the known loci of genes for red cell membrane proteins including protein 4.1 (1p36.2-p34), the anion exchange protein (AE1, band 3; 17q21-qter), glycophorin C (2q14-q21), and beta-actin (7pter-q22). Human erythrocyte ankyrin, which links beta-spectrin to the anion exchange protein, has recently been cloned. We now show that the ankyrin gene maps to chromosome 8p11.2, and that one copy is missing from DNA of two unrelated children with severe HS and heterozygous deletions of chromosome 8 (del(8)(p11-p21.1)). Affected red cells are also ankyrin-deficient. The data suggest that defects or deficiency or ankyrin are responsible for HS at the SPH2 locus.

  18. 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.

  19. Ligand-Binding Properties of the Carboxyl-Terminal Repeat Domain of Streptococcus mutans Glucan-Binding Protein A

    OpenAIRE

    Haas, Wolfgang; Banas, Jeffrey A.

    2000-01-01

    Streptococcus mutans glucan-binding protein A (GbpA) has sequence similarity in its carboxyl-terminal domain with glucosyltransferases (GTFs), the enzymes responsible for catalyzing the synthesis of the glucans to which GbpA and GTFs can bind and which promote S. mutans attachment to and accumulation on the tooth surface. It was predicted that this C-terminal region, comprised of what have been termed YG repeats, represents the GbpA glucan-binding domain (GBD). In an effort to test this hypot...

  20. 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

  1. 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.

  2. GPU-enabled molecular dynamics simulations of ankyrin kinase complex

    Science.gov (United States)

    Gautam, Vertika; Chong, Wei Lim; Wisitponchai, Tanchanok; Nimmanpipug, Piyarat; Zain, Sharifuddin M.; Rahman, Noorsaadah Abd.; Tayapiwatana, Chatchai; Lee, Vannajan Sanghiran

    2014-10-01

    The ankyrin repeat (AR) protein can be used as a versatile scaffold for protein-protein interactions. It has been found that the heterotrimeric complex between integrin-linked kinase (ILK), PINCH, and parvin is an essential signaling platform, serving as a convergence point for integrin and growth-factor signaling and regulating cell adhesion, spreading, and migration. Using ILK-AR with high affinity for the PINCH1 as our model system, we explored a structure-based computational protocol to probe and characterize binding affinity hot spots at protein-protein interfaces. In this study, the long time scale dynamics simulations with GPU accelerated molecular dynamics (MD) simulations in AMBER12 have been performed to locate the hot spots of protein-protein interaction by the analysis of the Molecular Mechanics-Poisson-Boltzmann Surface Area/Generalized Born Solvent Area (MM-PBSA/GBSA) of the MD trajectories. Our calculations suggest good binding affinity of the complex and also the residues critical in the binding.

  3. Sequence-specific 1H, 13C and 15N backbone resonance assignments of the plakin repeat domain of human envoplakin.

    Science.gov (United States)

    Jeeves, Mark; Fogl, Claudia; Al-Jassar, Caezar; Chidgey, Martyn; Overduin, Michael

    2016-04-01

    The plakin repeat domain is a distinctive hallmark of the plakin superfamily of proteins, which are found within all epithelial tissues. Plakin repeat domains mediate the interactions of these proteins with the cell cytoskeleton and are critical for the maintenance of tissue integrity. Despite their biological importance, no solution state resonance assignments are available for any homologue. Here we report the essentially complete (1)H, (13)C and (15)N backbone chemical shift assignments of the singular 22 kDa plakin repeat domain of human envoplakin, providing the means to investigate its interactions with ligands including intermediate filaments. PMID:26590577

  4. Tandem repeat of a seven-bladed beta-propeller domain in oligoxyloglucan reducing-end-specific cellobiohydrolase.

    Science.gov (United States)

    Yaoi, Katsuro; Kondo, Hidemasa; Noro, Natsuko; Suzuki, Mamoru; Tsuda, Sakae; Mitsuishi, Yasushi

    2004-07-01

    Oligoxyloglucan reducing-end-specific cellobiohydrolase (OXG-RCBH; EC 3.2.1.150) is an exoglucanase that recognizes the reducing end of oligoxyloglucan and releases two glucosyl residue segments from the main chain. The X-ray crystal structure of OXG-RCBH determined at 2.2 A resolution reveals a unique feature of this enzyme; OXG-RCBH consists of a tandem repeat of two similar domains, which are both folded into seven-bladed beta-propeller structures. The sequence alignment of the propeller blades, based on the structure, indicates that a weak repeat of the amino acid sequence occurred seven times to construct each domain. There is a cleft that can accommodate the substrate oligosaccharide between the two domains, which is a putative substrate binding subsite. Mutation of either Asp35 or Asp465, located in the putative catalytic center, to Asn resulted in a protein with no detectable catalytic activity, indicating the critical role of these amino acids in catalysis. PMID:15242597

  5. Alternate utilization of two regulatory domains within the Moloney murine sarcoma virus long terminal repeat.

    OpenAIRE

    Graves, B J; Eisenberg, S P; Coen, D M; McKnight, S L

    1985-01-01

    The Moloney murine sarcoma virus long terminal repeat (LTR) harbors two distinct positive activators of transcription, namely, a distal signal and an enhancer. In this report we demonstrate that infection by herpes simplex virus (HSV) can markedly affect the utilization of these two Moloney murine sarcoma virus transcription signals. We investigated the HSV-mediated trans-acting effects with two goals in mind: first, to gain insight into LTR function, and second, to probe the mechanisms used ...

  6. 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.

  7. 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.

  8. Ligand-binding properties of the carboxyl-terminal repeat domain of Streptococcus mutans glucan-binding protein A.

    Science.gov (United States)

    Haas, W; Banas, J A

    2000-02-01

    Streptococcus mutans glucan-binding protein A (GbpA) has sequence similarity in its carboxyl-terminal domain with glucosyltransferases (GTFs), the enzymes responsible for catalyzing the synthesis of the glucans to which GbpA and GTFs can bind and which promote S. mutans attachment to and accumulation on the tooth surface. It was predicted that this C-terminal region, comprised of what have been termed YG repeats, represents the GbpA glucan-binding domain (GBD). In an effort to test this hypothesis and to quantitate the ligand-binding specificities of the GbpA GBD, several fusion proteins were generated and tested by affinity electrophoresis or by precipitation of protein-ligand complexes, allowing the determination of binding constants. It was determined that the 16 YG repeats in GbpA comprise its GBD and that GbpA has a greater affinity for dextran (a water-soluble form of glucan) than for mutan (a water-insoluble form of glucan). Placement of the GBD at the carboxyl terminus was necessary for maximum glucan binding, and deletion of as few as two YG repeats from either end of the GBD reduced the affinity for dextran by over 10-fold. Interestingly, the binding constant of GbpA for dextran was 34-fold higher than that calculated for the GBDs of two S. mutans GTFs, one of which catalyzes the synthesis of water-soluble glucan and the other of which catalyzes the synthesis of water-insoluble glucan. PMID:10633107

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Inducible Polymerization and Two-Dimensional Assembly of the Repeats-in-Toxin (RTX) Domain from the Pseudomonas aeruginosa Alkaline Protease

    OpenAIRE

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

    2014-01-01

    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-phy...

  15. Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Wei [Department of Radiation Sciences, Oncology, Umea University, SE-90187 Umea (Sweden); Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 (China); Holmlund, Camilla; Nilsson, Jonas [Department of Radiation Sciences, Oncology, Umea University, SE-90187 Umea (Sweden); Inui, Shigeki [Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita-shi, Osaka, 565-0871 (Japan); Lei, Ting [Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030 (China); Itami, Satoshi [Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita-shi, Osaka, 565-0871 (Japan); Henriksson, Roger [Department of Radiation Sciences, Oncology, Umea University, SE-90187 Umea (Sweden); Hedman, Hakan, E-mail: hakan.hedman@onkologi.umu.se [Department of Radiation Sciences, Oncology, Umea University, SE-90187 Umea (Sweden)

    2011-02-15

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a recently discovered negative regulator of growth factor signaling. The LRIG1 integral membrane protein has been demonstrated to regulate various oncogenic receptor tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR), by cell-autonomous mechanisms. Here, we investigated whether LRIG1 ectodomains were shed, and if LRIG1 could regulate cell proliferation and EGF signaling in a paracrine manner. Cells constitutively shed LRIG1 ectodomains in vitro, and shedding was modulated by known regulators of metalloproteases, including the ADAM17 specific inhibitor TAPI-2. Furthermore, shedding was enhanced by ectopic expression of Adam17. LRIG1 ectodomains appeared to be shed in vivo, as well, as demonstrated by immunoblotting of mouse and human tissue lysates. Ectopic expression of LRIG1 in lymphocytes suppressed EGF signaling in co-cultured fibroblastoid cells, demonstrating that shed LRIG1 ectodomains can function in a paracrine fashion. Purified LRIG1 ectodomains suppressed EGF signaling without any apparent downregulation of EGFR levels. Taken together, the results show that the LRIG1 ectodomain can be proteolytically shed and can function as a non-cell-autonomous regulator of growth factor signaling. Thus, LRIG1 or its ectodomain could have therapeutic potential in the treatment of growth factor receptor-dependent cancers.

  16. 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

  17. Accumulation of multiple-repeat starch-binding domains (SBD2-SBD5) does not reduce amylose content of potato starch granules

    NARCIS (Netherlands)

    Nazarian, F.; Vincken, J.P.; Ji, Q.; Suurs, L.C.J.M.; Buléon, A.

    2007-01-01

    This study investigates whether it is possible to produce an amylose-free potato starch by displacing the amylose enzyme, granule-bound starch synthase I (GBSSI), from the starch granule by engineered, high-affinity, multiple-repeat family 20 starch-binding domains (SBD2, SBD3, SBD4, and SBD5). The

  18. 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.

  19. 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.

  20. 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

  1. Discovery of Small Molecule Inhibitors of the PH Domain Leucine-Rich Repeat Protein Phosphatase (PHLPP) by Chemical and Virtual Screening

    OpenAIRE

    Sierecki, Emma; Sinko, William; McCammon, J. Andrew; Newton, Alexandra C.

    2010-01-01

    PH domain Leucine-rich repeat protein phosphatase (PHLPP) directly dephosphorylates and inactivates Akt and protein kinase C, poising it as a prime target for pharmacological intervention of two major survival pathways. Here we report on the discovery of small molecule inhibitors of the phosphatase activity of PHLPP, a member of the PP2C family of phosphatases for which there are no general pharmacological inhibitors. First, the Diversity Set of the NCI was screened for inhibition of the puri...

  2. 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. PMID:25232897

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

    Directory of Open Access Journals (Sweden)

    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

  4. Effect of ADAMTS-2, a metalloproteinase containing a disintegrin domain and thrombospondin type I repeats, during angiogenesis in vitro and in vivo

    OpenAIRE

    Dubail, Johanne; Kesteloot, Frédéric; Motte, Patrick; Lambert, Vincent; Rakic, Jean-Marie; Lapière, Charles M.; Nusgens, Betty; Colige, Alain

    2004-01-01

    Formation of new blood vessels (angiogenesis) is a key step during the development of various pathologies, including cancer. Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They further contain specific domains, such as the ‘‘Thrombospondin type I’’ (TSP1) repeats, that are able to strongly repress angiogenesis, as described for thrombospondin-1 and -2, and for ADAMTS-1 and -8. The primary function of ADAMTS-2 is to process collagen type I, II and III precursors into matur...

  5. Difference in fibril core stability between two tau four-repeat domain proteins: a hydrogen-deuterium exchange coupled to mass spectrometry study.

    Science.gov (United States)

    Ramachandran, Gayathri; Udgaonkar, Jayant B

    2013-12-10

    One of the signatures of Alzheimer's disease and tauopathies is fibrillization of the microtubule-associated protein tau. The purpose of this study was to compare the high-resolution structure of fibrils formed by two different tau four-repeat domain constructs, tau4RD and tauK18, using hydrogen-deuterium exchange coupled to mass spectrometry as a tool. While the two fibrils are found to be constructed on similar structural principles, the tauK18 fibril has a slightly more stable core. This difference in fibril core stability appears to be reflective of the mechanistic differences in the aggregation pathways of the two proteins. PMID:24256615

  6. Automated Retinal Layer Segmentation Using Spectral Domain Optical Coherence Tomography: Evaluation of Inter-Session Repeatability and Agreement between Devices.

    Science.gov (United States)

    Terry, Louise; Cassels, Nicola; Lu, Kelly; Acton, Jennifer H; Margrain, Tom H; North, Rachel V; Fergusson, James; White, Nick; Wood, Ashley

    2016-01-01

    Retinal and intra-retinal layer thicknesses are routinely generated from optical coherence tomography (OCT) images, but on-board software capabilities and image scaling assumptions are not consistent across devices. This study evaluates the device-independent Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) for automated intra-retinal layer segmentation and image scaling for three OCT systems. Healthy participants (n = 25) underwent macular volume scans using a Cirrus HD-OCT (Zeiss), 3D-OCT 1000 (Topcon), and a non-commercial long-wavelength (1040nm) OCT on two occasions. Mean thickness of 10 intra-retinal layers was measured in three ETDRS subfields (fovea, inner ring and outer ring) using the Iowa Reference Algorithms. Where available, total retinal thicknesses were measured using on-board software. Measured axial eye length (AEL)-dependent scaling was used throughout, with a comparison made to the system-specific fixed-AEL scaling. Inter-session repeatability and agreement between OCT systems and segmentation methods was assessed. Inter-session coefficient of repeatability (CoR) for the foveal subfield total retinal thickness was 3.43μm, 4.76μm, and 5.98μm for the Zeiss, Topcon, and long-wavelength images respectively. For the commercial software, CoR was 4.63μm (Zeiss) and 7.63μm (Topcon). The Iowa Reference Algorithms demonstrated higher repeatability than the on-board software and, in addition, reliably segmented all 10 intra-retinal layers. With fixed-AEL scaling, the algorithm produced significantly different thickness values for the three OCT devices (Pimaged with these devices, however ocular biometry is required for accurate quantification of OCT images. PMID:27588683

  7. Ankyrin-B in lens architecture and biomechanics: Just not tethering but more.

    Science.gov (United States)

    Rao, Ponugoti Vasantha; Maddala, Rupalatha

    2016-01-01

    The ankyrins are a family of well-characterized metazoan adaptor proteins that play a key role in linking various membrane-spanning proteins to the underlying spectrin-actin cytoskeleton; a mechanistic understanding of their role in tissue architecture and mechanics, however, remains elusive. Here we comment on a recent study demonstrating a key role for ankyrin-B in maintaining the hexagonal shape and radial alignment of ocular lens fiber cells by regulating the membrane organization of periaxin, dystrophins/dystroglycan, NrCAM and spectrin-actin network of proteins, and revealing that ankyrin-B deficiency impairs fiber cell shape and mechanical properties of the ocular lens. These observations indicate that ankyrin-B plays an important role in maintaining tissue cytoarchitecture, cell shape and biomechanical properties via engaging in key protein: protein interactions required for membrane anchoring and organization of the spectrin-actin skeleton, scaffolding proteins and cell adhesive proteins. PMID:27044909

  8. Isoforms of Spectrin and Ankyrin Reflect the Functional Topography of the Mouse Kidney.

    Directory of Open Access Journals (Sweden)

    Michael C Stankewich

    Full Text Available The kidney displays specialized regions devoted to filtration, selective reabsorption, and electrolyte and metabolite trafficking. The polarized membrane pumps, channels, and transporters responsible for these functions have been exhaustively studied. Less examined are the contributions of spectrin and its adapter ankyrin to this exquisite functional topography, despite their established contributions in other tissues to cellular organization. We have examined in the rodent kidney the expression and distribution of all spectrins and ankyrins by qPCR, Western blotting, immunofluorescent and immuno electron microscopy. Four of the seven spectrins (αΙΙ, βΙ, βΙΙ, and βΙΙΙ are expressed in the kidney, as are two of the three ankyrins (G and B. The levels and distribution of these proteins vary widely over the nephron. αΙΙ/βΙΙ is the most abundant spectrin, found in glomerular endothelial cells; on the basolateral membrane and cytoplasmic vesicles in proximal tubule cells and in the thick ascending loop of Henle; and less so in the distal nephron. βΙΙΙ spectrin largely replaces βΙΙ spectrin in podocytes, Bowman's capsule, and throughout the distal tubule and collecting ducts. βΙ spectrin is only marginally expressed; its low abundance hinders a reliable determination of its distribution. Ankyrin G is the most abundant ankyrin, found in capillary endothelial cells and all tubular segments. Ankyrin B populates Bowman's capsule, podocytes, the ascending thick loop of Henle, and the distal convoluted tubule. Comparison to the distribution of renal protein 4.1 isoforms and various membrane proteins indicates a complex relationship between the spectrin scaffold, its adapters, and various membrane proteins. While some proteins (e.g. ankyrin B, βΙΙΙ spectrin, and aquaporin 2 tend to share a similar distribution, there is no simple mapping of different spectrins or ankyrins to most membrane proteins. The implications of this data

  9. Structural basis for the membrane association of ankyrinG via palmitoylation

    Science.gov (United States)

    Fujiwara, Yuichiro; Kondo, Hiroko X.; Shirota, Matsuyuki; Kobayashi, Megumi; Takeshita, Kohei; Nakagawa, Atsushi; Okamura, Yasushi; Kinoshita, Kengo

    2016-04-01

    By clustering various ion channels and transporters, ankyrin-G (AnkG) configures the membrane-excitation platforms in neurons and cardiomyocytes. AnkG itself localizes to specific areas on the plasma membrane via s-palmitoylation of Cys. However, the structural mechanism by which AnkG anchors to the membrane is not understood. In this study, we solved the crystal structures of the reduced and oxidized forms of the AnkG s-palmitoylation domain and used multiple long-term coarse-grained molecular dynamics simulations to analyze their membrane association. Here we report that the membrane anchoring of AnkG was facilitated by s-palmitoylation, defining a stable binding interface on the lipid membrane, and that AnkG without s-palmitoylation also preferred to stay near the membrane but did not have a unique binding interface. This suggests that AnkG in the juxtamembrane region is primed to accept lipid modification at Cys, and once that happens AnkG constitutes a rigid structural base upon which a membrane-excitation platform can be assembled.

  10. Interplay of positive and negative effectors in function of the C-terminal repeat domain of RNA polymerase II.

    OpenAIRE

    Li, Y.; Kornberg, R D

    1994-01-01

    RNA polymerase II lacking a C-terminal domain (CTD) was active in transcription with purified proteins from yeast but failed to support transcription in a yeast extract. CTD dependence could be reconstituted in the purified system by addition of two fractions from the extract. An inhibitory fraction abolished transcription by both wild-type and CTD-less RNA polymerases; a stimulatory fraction restored activity of the wild-type polymerase but had a much lesser effect on the CTD-less enzyme. Pa...

  11. Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB

    International Nuclear Information System (INIS)

    A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NFκB nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB. - Highlights: • Ectromelia virus encodes four Ank/F-box proteins, EVM002, EVM005, EVM154 and EVM165. • The Ank/F-box proteins inhibit NFκB nuclear translocation, dependent on the F-box. • The Ank/F-box proteins prevent IκBα degradation, suggesting they target the SCF. • Deletion of a single Ank/F-box gene from ECTV does not prevent viral NFκB inhibition. • This study identifies a new mechanism by which ectromelia virus inhibits NFκB

  12. Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB

    Energy Technology Data Exchange (ETDEWEB)

    Burles, Kristin, E-mail: burles@ualberta.ca; Buuren, Nicholas van; Barry, Michele

    2014-11-15

    A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NFκB nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB. - Highlights: • Ectromelia virus encodes four Ank/F-box proteins, EVM002, EVM005, EVM154 and EVM165. • The Ank/F-box proteins inhibit NFκB nuclear translocation, dependent on the F-box. • The Ank/F-box proteins prevent IκBα degradation, suggesting they target the SCF. • Deletion of a single Ank/F-box gene from ECTV does not prevent viral NFκB inhibition. • This study identifies a new mechanism by which ectromelia virus inhibits NFκB.

  13. 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

    2011-09-01

    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.

  14. 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

  15. 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.

  16. Activation of transient receptor potential ankyrin 1 by eugenol.

    Science.gov (United States)

    Chung, G; Im, S T; Kim, Y H; Jung, S J; Rhyu, M-R; Oh, S B

    2014-03-01

    Eugenol is a bioactive plant extract used as an analgesic agent in dentistry. The structural similarity of eugenol to cinnamaldehyde, an active ligand for transient receptor potential ankyrin 1 (TRPA1), suggests that eugenol might produce its effect via TRPA1, in addition to TRPV1 as we reported previously. In this study, we investigated the effect of eugenol on TRPA1, by fura-2-based calcium imaging and patch clamp recording in trigeminal ganglion neurons and in a heterologous expression system. As the result, eugenol induced robust calcium responses in rat trigeminal ganglion neurons that responded to a specific TRPA1 agonist, allyl isothiocyanate (AITC), and not to capsaicin. Capsazepine, a TRPV1 antagonist failed to inhibit eugenol-induced calcium responses in AITC-responding neurons. In addition, eugenol response was observed in trigeminal ganglion neurons from TRPV1 knockout mice and human embryonic kidney 293 cell lines that express human TRPA1, which was inhibited by TRPA1-specific antagonist HC-030031. Eugenol-evoked TRPA1 single channel activity and eugenol-induced TRPA1 currents were dose-dependent with EC50 of 261.5μM. In summary, these results demonstrate that the activation of TRPA1 might account for another molecular mechanism underlying the pharmacological action of eugenol.

  17. Unique nucleotide polymorphism of ankyrin gene cluster in Arabidopsis

    Indian Academy of Sciences (India)

    Jianchang Du; Xingna Wang; Mingsheng Zhang; Dacheng Tian; Yong-Hua Yang

    2007-01-01

    The ankyrin (ANK) gene cluster is a part of a multigene family encoding ANK transmembrane proteins in Arabidopsis thaliana, and plays an important role in protein–protein interactions and in signal pathways. In contrast to other regions of a genome, the ANK gene cluster exhibits an extremely high level of DNA polymorphism in an ∼5-kb region, without apparent decay. Phylogenetic analysis detects two clear, deeply differentiated haplotypes (dimorphism). The divergence between haplotypes of accession Col-0 and Ler-0 (Hap-C and Hap-L) is estimated to be 10.7%, approximately equal to the 10.5% average divergence between A. thaliana and A. lyrata. Sequence comparisons for the ANK gene cluster homologues in Col-0 indicate that the members evolve independently, and that the similarity among paralogues is lower than between alleles. Very little intralocus recombination or gene conversion is detected in ANK regions. All these characteristics of the ANK gene cluster are consistent with a tandem gene duplication and birth-and-death process. The possible mechanisms for and implications of this elevated nucleotide variation are also discussed, including the suggestion of balancing selection.

  18. 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

  19. 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.

  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. 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.

  2. Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood.

    Directory of Open Access Journals (Sweden)

    Lingquan Deng

    2014-12-01

    Full Text Available Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group

  3. Ankyrin and band 3 differentially affect expression of membrane glycoproteins but are not required for erythroblast enucleation.

    Science.gov (United States)

    Ji, Peng; Lodish, Harvey F

    2012-01-27

    During late stages of mammalian erythropoiesis the nucleus undergoes chromatin condensation, migration to the plasma membrane, and extrusion from the cytoplasm surrounded by a segment of plasma membrane. Since nuclear condensation occurs in all vertebrates, mammalian erythroid membrane and cytoskeleton proteins were implicated as playing important roles in mediating the movement and extrusion of the nucleus. Here we use erythroid ankyrin deficient and band 3 knockout mouse models to show that band 3, but not ankyrin, plays an important role in regulating the level of erythroid cell membrane proteins, as evidenced by decreased cell surface expression of glycophorin A in band 3 knockout mice. However, neither band 3 nor ankyrin are required for enucleation. These results demonstrate that mammalian erythroblast enucleation does not depend on the membrane integrity generated by the ankyrin-band 3 complex.

  4. Ankyrin and band 3 differentially affect expression of membrane glycoproteins but are not required for erythroblast enucleation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Peng, E-mail: peng-ji@fsm.northwestern.edu [Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (United States); Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (United States); Lodish, Harvey F. [Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (United States); Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Ankyrin and band 3 are not required for erythroblasts enucleation. Black-Right-Pointing-Pointer Loss of ankyrin does not affect erythroid membrane glycoprotein expression. Black-Right-Pointing-Pointer Loss of band 3 influences erythroid membrane glycoprotein expression. -- Abstract: During late stages of mammalian erythropoiesis the nucleus undergoes chromatin condensation, migration to the plasma membrane, and extrusion from the cytoplasm surrounded by a segment of plasma membrane. Since nuclear condensation occurs in all vertebrates, mammalian erythroid membrane and cytoskeleton proteins were implicated as playing important roles in mediating the movement and extrusion of the nucleus. Here we use erythroid ankyrin deficient and band 3 knockout mouse models to show that band 3, but not ankyrin, plays an important role in regulating the level of erythroid cell membrane proteins, as evidenced by decreased cell surface expression of glycophorin A in band 3 knockout mice. However, neither band 3 nor ankyrin are required for enucleation. These results demonstrate that mammalian erythroblast enucleation does not depend on the membrane integrity generated by the ankyrin-band 3 complex.

  5. ANKK1基因多态性与对纳洛酮治疗安眠药中毒疗效的影响%Clinic effect of Ankyrin repeat and kinase domain containing 1 gene of naloxone treatment on sleeping pills poisoning

    Institute of Scientific and Technical Information of China (English)

    孙涛; 朱桢

    2010-01-01

    目的 探讨锚蛋白重复和激酶域1(ANKK1)基因多态性与纳洛酮治疗安眠药中毒疗效的影响及临床意义.方法 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,对应用纳洛酮治疗安眠药中毒患者78例和78例正常人ANKK1基因的rs4938015、rs7118900、rs2734849、rs1800497多态性分型,并对ANKK1基因多态性与纳洛酮治疗安眠药中毒之间关系进行比较分析.结果 在纳洛酮治疗安眠药中毒后2h患者GCS评分的数值比较,rs2734849位点差异有统计学意义(F=5.89,P<0.05),且rs2734849位点中以纯合子T/T评分数值更高;各SNP位点与疗效的关系比较,rs2734849位点差异有统计学意义(χ2=8.72,P<0.05),其余各位点比较差异无统计学意义.结论 ANKK1基因与纳洛酮治疗安眠药中毒的疗效存在明显的相关性.

  6. 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.

  7. 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. PMID:25497915

  8. Repeated Miscarriage

    Science.gov (United States)

    f AQ FREQUENTLY ASKED QUESTIONS FAQ100 PREGNANCY Repeated Miscarriages • What is recurrent pregnancy loss? • What is the likelihood of having repeated miscarriages? • What is the most common cause of miscarriage? • ...

  9. Wound induced Beta vulgaris polygalacturonase-inhibiting protein genes encode a longer leucine-rich repeat domain and inhibit fungal polygalacturonases

    Science.gov (United States)

    Polygalacturonase-inhibiting proteins (PGIPs) are leucine-rich repeat (LRR) proteins involved in plant defense. Sugar beet (Beta vulgaris L.) PGIP genes, BvPGIP1, BvPGIP2 and BvPGIP3, were isolated from two breeding lines, F1016 and F1010. Full-length cDNA sequences of the three BvPGIP genes encod...

  10. Identification of a novel pentatricopeptide repeat subfamily with a C-terminal domain of bacterial origin acquired via ancient horizontal gene transfer

    OpenAIRE

    Manna, Sam; Barth, Christian

    2013-01-01

    Background Pentatricopeptide repeat (PPR) proteins are a large family of sequence-specific RNA binding proteins involved in organelle RNA metabolism. Very little is known about the origin and evolution of these proteins, particularly outside of plants. Here, we report the identification of a novel subfamily of PPR proteins not found in plants and explore their evolution. Results We identified a novel subfamily of PPR proteins, which all contain a C-terminal tRNA guanine methyltransferase (TGM...

  11. Activation of transient receptor potential ankyrin-1 (TRPA1) in lung cells by wood smoke particulate material.

    Science.gov (United States)

    Shapiro, Darien; Deering-Rice, Cassandra E; Romero, Erin G; Hughen, Ronald W; Light, Alan R; Veranth, John M; Reilly, Christopher A

    2013-05-20

    Cigarette smoke, diesel exhaust, and other combustion-derived particles activate the calcium channel transient receptor potential ankyrin-1 (TRPA1), causing irritation and inflammation in the respiratory tract. It was hypothesized that wood smoke particulate and select chemical constituents thereof would also activate TRPA1 in lung cells, potentially explaining the adverse effects of wood and other forms of biomass smoke on the respiratory system. TRPA1 activation was assessed using calcium imaging assays in TRPA1-overexpressing HEK-293 cells, mouse primary trigeminal neurons, and human adenocarcinoma (A549) lung cells. Particles from pine and mesquite smoke were less potent agonists of TRPA1 than an equivalent mass concentration of an ethanol extract of diesel exhaust particles; pine particles were comparable in potency to cigarette smoke condensate, and mesquite particles were the least potent. The fine particulate (PM particulate, 3,5-ditert-butylphenol, coniferaldehyde, formaldehyde, perinaphthenone, agathic acid, and isocupressic acid, were TRPA1 agonists. Pine particulate activated TRPA1 in mouse trigeminal neurons and A549 cells in a concentration-dependent manner, which was inhibited by the TRPA1 antagonist HC-030031. TRPA1 activation by wood smoke particles occurred through the electrophile/oxidant-sensing domain (i.e., C621/C641/C665/K710), based on the inhibition of cellular responses when the particles were pretreated with glutathione; a role for the menthol-binding site of TRPA1 (S873/T874) was demonstrated for 3,5-ditert-butylphenol. This study demonstrated that TRPA1 is a molecular sensor for wood smoke particulate and several chemical constituents thereof, in sensory neurons and A549 cells, suggesting that TRPA1 may mediate some of the adverse effects of wood smoke in humans.

  12. Transient Receptor Potential Ankyrin 1 (TRPA1) Channel and Neurogenic Inflammation in Pathogenesis of Asthma

    Science.gov (United States)

    Yang, Hang; Li, ShuZhuang

    2016-01-01

    Asthma is characterized by airway inflammation, airway obstruction, and airway hyperresponsiveness (AHR), and it affects 300 million people worldwide. However, our current understanding of the molecular mechanisms that underlie asthma remains limited. Recent studies have suggested that transient receptor potential ankyrin 1 (TRPA1), one of the transient receptor potential cation channels, may be involved in airway inflammation in asthma. The present review discusses the relationship between TRPA1 and neurogenic inflammation in asthma, hoping to enhance our understanding of the mechanisms of airway inflammation in asthma. PMID:27539812

  13. Regulation of Gap Junction Dynamics by UNC-44/ankyrin and UNC-33/CRMP through VAB-8 in C. elegans Neurons

    Science.gov (United States)

    Yan, Dong

    2016-01-01

    Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that UNC-44/ankyrin acts upstream of UNC-33/CRMP in regulation of a potential kinesin VAB-8 to control gap junction dynamics, and loss-of-function in the UNC-44/UNC-33/VAB-8 pathway suppresses the turnover of gap junction channels. Therefore, we first show a signal pathway including ankyrin, CRMP, and kinesin in regulating gap junctions. PMID:27015090

  14. Domain Modeling: NP_872414.2 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_872414.2 chr12 Crystal structure of a human Notch1 ankyrin domain mutant p2qc9b_ chr12/NP_872414.2.../NP_872414.2_apo_18-219.pdb p2he0a_ chr12/NP_872414.2/NP_872414.2_holo_18-219.pdb psi-blast 305L,306D,307H,308L,309V,340K EDO 1 ...

  15. 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.

  16. 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.

  17. 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.

  18. MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection

    OpenAIRE

    Gelfi Jacqueline; Blanié Sophie; Bertagnoli Stéphane; Camus-Bouclainville Christelle

    2010-01-01

    Abstract Myxoma virus (MYXV), a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor) and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has ...

  19. Bispecific designed ankyrin repeat proteins (DARPins) targeting epidermal growth factor receptor inhibit A431 cell proliferation and receptor recycling

    NARCIS (Netherlands)

    Boersma, Ykelien L; Chao, Ginger; Steiner, Daniel; Wittrup, K Dane; Plückthun, Andreas

    2011-01-01

    The EGF receptor (EGFR) has been implicated in the development and progression of many tumors. Although monoclonal antibodies directed against EGFR have been approved for the treatment of cancer in combination with chemotherapy, there are limitations in their clinical efficacy, necessitating the sea

  20. 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.

  1. 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.

  2. Plasmodium falciparum: an epitope within a highly conserved region of the 47-kDa amino-terminal domain of the serine repeat antigen is a target of parasite-inhibitory antibodies.

    Science.gov (United States)

    Fox, B A; Xing-Li, P; Suzue, K; Horii, T; Bzik, D J

    1997-02-01

    Previously, the Plasmodium falciparum serine repeat antigen has been shown to be protective in primate models of malaria immunity and also to be a target of in vitro parasite-inhibitory antibodies. To further define parasite-inhibitory epitopes a series of deletions from the amino-terminal 47-kDa domain of the serine repeat antigen (SERA) were constructed as glutathione-S-transferase fusion proteins. Several GST-SERA fusion proteins were used to vaccinate mice with Freund's adjuvant and the resulting immune sera were used to assay for the inhibition of P. falciparum invasion of erythrocytes in vitro. The minimal epitope shown to be the target of invasion-blocking antibodies was SERA amino acids 17-165. Additional GST-SERA deletion constructs of the 47-kDa domain were developed and evaluated for reactivity, by Western immunoblot analysis, with a parasite-inhibitory murine monoclonal antibody (mAb 43E5), a parasite-inhibitory pooled goat polyclonal sera, and a pooled human Nigerian immune serum. The parasite-inhibitory epitope defined by mAb 43E5 was mapped to SERA amino acids 17-110 and, at least, part of the epitope was defined to include amino acids in the region of amino acids 59-72. The parasite-inhibitory epitope recognized by mAb 43E5 appears to be well conserved between diverse geographical isolates of P. falciparum. The results have relevance for malaria vaccine development and suggest that an appropriately designed recombinant SERA antigen produced from a synthetic gene in Escherichia coli may be an effective component of a candidate malaria vaccine. PMID:9030663

  3. 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.

  4. Ankyrin-B directs membrane tethering of periaxin and is required for maintenance of lens fiber cell hexagonal shape and mechanics.

    Science.gov (United States)

    Maddala, Rupalatha; Walters, Mark; Brophy, Peter J; Bennett, Vann; Rao, Ponugoti V

    2016-01-15

    Periaxin (Prx), a PDZ domain protein expressed preferentially in myelinating Schwann cells and lens fibers, plays a key role in membrane scaffolding and cytoarchitecture. Little is known, however, about how Prx is anchored to the plasma membrane. Here we report that ankyrin-B (AnkB), a well-characterized adaptor protein involved in linking the spectrin-actin cytoskeleton to integral membrane proteins, is required for membrane association of Prx in lens fibers and colocalizes with Prx in hexagonal fiber cells. Under AnkB haploinsufficiency, Prx accumulates in the soluble fraction with a concomitant loss from the membrane-enriched fraction of mouse lenses. Moreover, AnkB haploinsufficiency induced age-dependent disruptions in fiber cell hexagonal geometry and radial alignment and decreased compressive stiffness in mouse lenses parallel to the changes observed in Prx null mouse lens. Both AnkB- and Prx-deficient mice exhibit disruptions in membrane organization of the spectrin-actin network and the dystrophin-glycoprotein complex in lens fiber cells. Taken together, these observations reveal that AnkB is required for Prx membrane anchoring and for maintenance of lens fiber cell hexagonal geometry, membrane skeleton organization, and biomechanics. PMID:26538089

  5. Regulatory polymorphisms in the bovine Ankyrin 1 gene promoter are associated with tenderness and intramuscular fat content

    Directory of Open Access Journals (Sweden)

    Sweeney Torres

    2010-12-01

    Full Text Available Abstract Background Recent QTL and gene expression studies have highlighted ankyrins as positional and functional candidate genes for meat quality. Our objective was to characterise the promoter region of the bovine ankyrin 1 gene and to test polymorphisms for association with sensory and technological meat quality measures. Results Seven novel promoter SNPs were identified in a 1.11 kb region of the ankyrin 1 promoter in Angus, Charolais and Limousin bulls (n = 15 per breed as well as 141 crossbred beef animals for which meat quality data was available. Eighteen haplotypes were inferred with significant breed variation in haplotype frequencies. The five most frequent SNPs and the four most frequent haplotypes were subsequently tested for association with sensory and technological measures of meat quality in the crossbred population. SNP1, SNP3 and SNP4 (which were subsequently designated regulatory SNPs and SNP5 were associated with traits that contribute to sensorial and technological measurements of tenderness and texture; Haplotype 1 and haplotype 4 were oppositely correlated with traits contributing to tenderness (P Conclusion The conclusion from this study is that alleles defining haplotypes 2 and 4 could usefully contribute to marker SNP panels used to select individuals with improved IMF/juiciness or tenderness in a genome-assisted selection framework.

  6. Regulatory polymorphisms in the bovine Ankyrin 1 gene promoter are associated with tenderness and intra-muscular fat content

    LENUS (Irish Health Repository)

    Aslan, Ozlem

    2010-12-15

    Abstract Background Recent QTL and gene expression studies have highlighted ankyrins as positional and functional candidate genes for meat quality. Our objective was to characterise the promoter region of the bovine ankyrin 1 gene and to test polymorphisms for association with sensory and technological meat quality measures. Results Seven novel promoter SNPs were identified in a 1.11 kb region of the ankyrin 1 promoter in Angus, Charolais and Limousin bulls (n = 15 per breed) as well as 141 crossbred beef animals for which meat quality data was available. Eighteen haplotypes were inferred with significant breed variation in haplotype frequencies. The five most frequent SNPs and the four most frequent haplotypes were subsequently tested for association with sensory and technological measures of meat quality in the crossbred population. SNP1, SNP3 and SNP4 (which were subsequently designated regulatory SNPs) and SNP5 were associated with traits that contribute to sensorial and technological measurements of tenderness and texture; Haplotype 1 and haplotype 4 were oppositely correlated with traits contributing to tenderness (P < 0.05). While no single SNP was associated with intramuscular fat (IMF), a clear association with increased IMF and juiciness was observed for haplotype 2. Conclusion The conclusion from this study is that alleles defining haplotypes 2 and 4 could usefully contribute to marker SNP panels used to select individuals with improved IMF\\/juiciness or tenderness in a genome-assisted selection framework.

  7. The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration.

    Science.gov (United States)

    Hall, A E; Lu, W-T; Godfrey, J D; Antonov, A V; Paicu, C; Moxon, S; Dalmay, T; Wilczynska, A; Muller, P A J; Bushell, M

    2016-01-01

    The integrity of the genome is maintained by a host of surveillance and repair mechanisms that are pivotal for cellular function. The tumour suppressor protein p53 is a major component of the DNA damage response pathway and plays a vital role in the maintenance of cell-cycle checkpoints. Here we show that a microRNA, miR-486, and its host gene ankyrin-1 (ANK1) are induced by p53 following DNA damage. Strikingly, the cytoskeleton adaptor protein ankyrin-1 was induced over 80-fold following DNA damage. ANK1 is upregulated in response to a variety of DNA damage agents in a range of cell types. We demonstrate that miR-486-5p is involved in controlling G1/S transition following DNA damage, whereas the induction of the ankyrin-1 protein alters the structure of the actin cytoskeleton and sustains limited cell migration during DNA damage. Importantly, we found that higher ANK1 expression correlates with decreased survival in cancer patients. Thus, these observations highlight ANK1 as an important effector downstream of the p53 pathway. PMID:27054339

  8. 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. PMID:26800847

  9. Novel SNPs in the Ankyrin 1 gene and their association with beef quality traits.

    Science.gov (United States)

    Horodyska, J; Sweeney, T; Ryan, M; Hamill, R M

    2015-10-01

    Single nucleotide polymorphisms (SNPs) in the promoter region of bovine Ankyrin 1 (ANK1) have been associated with tenderness and intramuscular fat level in beef. The objectives of this study were to characterise novel DNA variants in the coding region of bovine ANK1 and test for association with beef quality traits. A 3kb region of ANK1 cDNA was amplified and sequenced in 32 Charolais cattle using five sets of overlapping primers. Eighteen SNPs were identified and a predicted exon was confirmed. An in silico translation indicated that SNP4 and SNP16 were non-conservative. Three SNPs were genotyped in 158 crossbred cattle (n=158) with associated meat quality data. SNP6 was associated with texture scores while SNP17 was associated with juiciness. Haplotype (cHAP) 1 was associated with lightness, redness, ultimate pH, as well as sarcomere length. Alleles of the ANK1 gene could be potential targets for gene-assisted selection to improve a range of meat quality traits in beef. PMID:26051041

  10. Characterization of a ligand binding site in the human transient receptor potential ankyrin 1 pore.

    Science.gov (United States)

    Klement, Göran; Eisele, Lina; Malinowsky, David; Nolting, Andreas; Svensson, Mats; Terp, Gitte; Weigelt, Dirk; Dabrowski, Michael

    2013-02-19

    The pharmacology and regulation of Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel activity is intricate due to the physiological function as an integrator of multiple chemical, mechanical, and temperature stimuli as well as differences in species pharmacology. In this study, we describe and compare the current inhibition efficacy of human TRPA1 on three different TRPA1 antagonists. We used a homology model of TRPA1 based on Kv1.2 to select pore vestibule residues available for interaction with ligands entering the vestibule. Site-directed mutation constructs were expressed in Xenopus oocytes and their functionality and pharmacology assessed to support and improve our homology model. Based on the functional pharmacology results we propose an antagonist-binding site in the vestibule of the TRPA1 ion channel. We use the results to describe the proposed intravestibular ligand-binding site in TRPA1 in detail. Based on the single site substitutions, we designed a human TRPA1 receptor by substituting several residues in the vestibule and adjacent regions from the rat receptor to address and explain observed species pharmacology differences. In parallel, the lack of effect on HC-030031 inhibition by the vestibule substitutions suggests that this molecule interacts with TRPA1 via a binding site not situated in the vestibule.

  11. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.

    NARCIS (Netherlands)

    Auer-Grumbach, M.; Olschewski, A.; Papic, L.; Kremer, J.M.J.; McEntagart, M.E.; Uhrig, S.; Fischer, C.; Frohlich, E.; Balint, Z.; Tang, B.; Strohmaier, H.; Lochmuller, H.; Schlotter-Weigel, B.; Senderek, J.; Krebs, A.; Dick, K.J.; Petty, R.; Longman, C.; Anderson, N.E.; Padberg, G.W.A.M.; Schelhaas, H.J.; Ravenswaaij-Arts, C.M.A. van; Pieber, T.R.; Crosby, A.H.; Guelly, C.

    2010-01-01

    Spinal muscular atrophies (SMA, also known as hereditary motor neuropathies) and hereditary motor and sensory neuropathies (HMSN) are clinically and genetically heterogeneous disorders of the peripheral nervous system. Here we report that mutations in the TRPV4 gene cause congenital distal SMA, scap

  12. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C

    NARCIS (Netherlands)

    Auer-Grumbach, Michaela; Olschewski, Andrea; Papic, Lea; Kremer, Hannie; McEntagart, Meriel E.; Uhrig, Sabine; Fischer, Carina; Froehlich, Eleonore; Balint, Zoltan; Tang, Bi; Strohmaier, Heimo; Lochmueller, Hanns; Schlotter-Weigel, Beate; Senderek, Jan; Krebs, Angelika; Dick, Katherine J.; Petty, Richard; Longman, Cheryl; Anderson, Neil E.; Padberg, George W.; Schelhaas, Helenius J.; van Ravenswaaij-Arts, Conny M. A.; Pieber, Thomas R.; Crosby, Andrew H.; Guelly, Christian

    2010-01-01

    Spinal muscular atrophies (SMA, also known as hereditary motor neuropathies) and hereditary motor and sensory neuropathies (HMSN) are clinically and genetically heterogeneous disorders of the peripheral nervous system. Here we report that mutations in the TRPV4 gene cause congenital distal SMA, scap

  13. Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice

    Institute of Scientific and Technical Information of China (English)

    Tong Liu; Ru-Rong Ji

    2012-01-01

    Objective To investigate the role of oxidative stress in itch-indicative scratching behavior in mice,and furthermore,to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch.Methods Scratching behavior was induced by intradermal injection of the oxidants hydrogen peroxide (H2O2) or tert-butylhydroperoxide (tBHP) into the nape of the neck in mice.The mice were observed for 30 min.Results Intradermal H2O2 (0.03%-1%) or tBHP (1-30 μmol) elicited robust scratching behavior,displaying an inverted U-shaped dose-response curve.Naloxone,an opioid receptor antagonist,but not morphine,largely suppressed the oxidant-induced scratching.Chlorpheniramine,a histamine H 1 receptor antagonist,blocked histamine-but not oxidant-induced scratching,indicating the involvement of a histamine-independent mechanism in oxidant-evoked itch.Further,resiniferatoxin treatment abolished oxidant-induced scratching,suggesting an essential role of C-fibers.Notably,blockade of transient receptor potential subtype ankyrin 1 (TRPA1) with the selective TRPA1 antagonist HC-030031,or genetic deletion of Trpal but not Trpvl (subfamily V,member 1) resulted in a profound reduction in H2O2-evoked scratching.Finally,systemic administration of the antioxidant Nacety1-L-cysteine or trolox (a water-soluble vitamin E analog) attenuated scratching induced by the oxidants.Conclusion Oxidative stress by different oxidants induces profound scratching behavior,which is largely histamine-and TRPV1-independent but TRPA1-dependent.Antioxidants and TRPA1 antagonists may be used to treat human itch conditions associated with oxidative stress.

  14. Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice.

    Science.gov (United States)

    Cattaruzza, Fiore; Johnson, Cali; Leggit, Alan; Grady, Eileen; Schenk, A Katrin; Cevikbas, Ferda; Cedron, Wendy; Bondada, Sandhya; Kirkwood, Rebekah; Malone, Brian; Steinhoff, Martin; Bunnett, Nigel; Kirkwood, Kimberly S

    2013-06-01

    Chronic pancreatitis (CP) is a devastating disease characterized by persistent and uncontrolled abdominal pain. Our lack of understanding is partially due to the lack of experimental models that mimic the human disease and also to the lack of validated behavioral measures of visceral pain. The ligand-gated cation channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis and sustained pancreatic pain. We induced CP by injecting the chemical agent trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis, into the pancreatic duct of C57BL/6 trpa1(+/+) and trpa1(-/-) mice. Chronic inflammatory changes and pain behaviors were assessed after 2-3 wk. TNBS injection caused marked pancreatic fibrosis with increased collagen-staining intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic stellate cell activation, and these changes were reflected by increased histological damage scores. TNBS-injected animals showed mechanical hypersensitivity during von Frey filament probing of the abdomen, decreased daily voluntary wheel-running activity, and increased immobility scores during open-field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal to von Frey filament probing, suggesting central sensitization. Inflammatory changes and pain indexes were significantly reduced in trpa1(-/-) mice. In conclusion, we have characterized in mice a model of CP that resembles the human condition, with marked histological changes and behavioral measures of pain. We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain.

  15. The S-Domain Receptor Kinase Arabidopsis Receptor Kinase2 and the U Box/Armadillo Repeat-Containing E3 Ubiquitin Ligase9 Module Mediates Lateral Root Development under Phosphate Starvation in Arabidopsis.

    Science.gov (United States)

    Deb, Srijani; Sankaranarayanan, Subramanian; Wewala, Gayathri; Widdup, Ellen; Samuel, Marcus A

    2014-06-25

    When plants encounter nutrient-limiting conditions in the soil, the root architecture is redesigned to generate numerous lateral roots (LRs) that increase the surface area of roots, promoting efficient uptake of these deficient nutrients. Of the many essential nutrients, reduced availability of inorganic phosphate has a major impact on plant growth because of the requirement of inorganic phosphate for synthesis of organic molecules, such as nucleic acids, ATP, and phospholipids, that function in various crucial metabolic activities. In our screens to identify a potential role for the S-domain receptor kinase1-6 and its interacting downstream signaling partner, the Arabidopsis (Arabidopsis thaliana) plant U box/armadillo repeat-containing E3 ligase9 (AtPUB9), we identified a role for this module in regulating LR development under phosphate-starved conditions. Our results show that Arabidopsis double mutant plants lacking AtPUB9 and Arabidopsis Receptor Kinase2 (AtARK2; ark2-1/pub9-1) display severely reduced LRs when grown under phosphate-starved conditions. Under these starvation conditions, these plants accumulated very low to no auxin in their primary root and LR tips as observed through expression of the auxin reporter DR5::uidA transgene. Exogenous auxin was sufficient to rescue the LR developmental defects in the ark2-1/pub9-1 lines, indicating a requirement of auxin accumulation for this process. Our subcellular localization studies with tobacco (Nicotiana tabacum) suspension-cultured cells indicate that interaction between ARK2 and AtPUB9 results in accumulation of AtPUB9 in the autophagosomes. Inhibition of autophagy in wild-type plants resulted in reduction of LR development and auxin accumulation under phosphate-starved conditions, suggesting a role for autophagy in regulating LR development. Thus, our study has uncovered a previously unknown signaling module (ARK2-PUB9) that is required for auxin-mediated LR development under phosphate-starved conditions

  16. Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels

    DEFF Research Database (Denmark)

    Mitrovic, Martina; Shahbazian, Anaid; Bock, Elisabeth;

    2010-01-01

    Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modifi...

  17. Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liqing, E-mail: chenlq@uah.edu; Wang, Yujun [Laboratory for Structural Biology, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Department of Chemistry, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Graduate Program of Biotechnology, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Wells, David; Toh, Diana; Harold, Hunt [Laboratory for Structural Biology, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Zhou, Jing [Laboratory for Structural Biology, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Department of Chemistry, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Graduate Program of Biotechnology, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); DiGiammarino, Enrico [Laboratory for Structural Biology, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Meehan, Edward J. [Laboratory for Structural Biology, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Department of Chemistry, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States); Graduate Program of Biotechnology, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States)

    2006-09-01

    The crystal structure of the SH3 domain of human osteoclast-stimulating factor has been determined and refined to the ultrahigh resolution of 1.07 Å. The structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors. Osteoclast-stimulating factor (OSF) is an intracellular signaling protein, produced by osteoclasts themselves, that enhances osteoclast formation and bone resorption. It is thought to act via an Src-related signaling pathway and contains SH3 and ankyrin-repeat domains which are involved in protein–protein interactions. As part of a structure-based anti-bone-loss drug-design program, the atomic resolution X-ray structure of the recombinant human OSF SH3 domain (hOSF-SH3) has been determined. The domain, residues 12–72, yielded crystals that diffracted to the ultrahigh resolution of 1.07 Å. The overall structure shows a characteristic SH3 fold consisting of two perpendicular β-sheets that form a β-barrel. Structure-based sequence alignment reveals that the putative proline-rich peptide-binding site of hOSF-SH3 consists of (i) residues that are highly conserved in the SH3-domain family, including residues Tyr21, Phe23, Trp49, Pro62, Asn64 and Tyr65, and (ii) residues that are less conserved and/or even specific to hOSF, including Thr22, Arg26, Thr27, Glu30, Asp46, Thr47, Asn48 and Leu60, which might be key to designing specific inhibitors for hOSF to fight osteoporosis and related bone-loss diseases. There are a total of 13 well defined water molecules forming hydrogen bonds with the above residues in and around the peptide-binding pocket. Some of those water molecules might be important for drug-design approaches. The hOSF-SH3 structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors.

  18. 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....

  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. Dicty_cDB: Contig-U14519-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ankyrin domain... 47 0.002 A44269( A44269 ;A44268) ankyrin repeat acidic protein cactus...9_1( DQ000469 |pid:none) Wolbachia endosymbiont of Culex qu... 47 0.002 L03367_1( L03367 |pid:none) Drosophila melanogaster cactus

  1. In silico identification of carboxylate clamp type tetratricopeptide repeat proteins in Arabidopsis and rice as putative co-chaperones of Hsp90/Hsp70.

    Directory of Open Access Journals (Sweden)

    Bishun D Prasad

    Full Text Available The essential eukaryotic molecular chaperone Hsp90 operates with the help of different co-chaperones, which regulate its ATPase activity and serve as adaptors to recruit client proteins and other molecular chaperones, such as Hsp70, to the Hsp90 complex. Several Hsp90 and Hsp70 co-chaperones contain the tetratricopeptide repeat (TPR domain, which interacts with the highly conserved EEVD motif at the C-terminal ends of Hsp90 and Hsp70. The acidic side chains in EEVD interact with a subset of basic residues in the TPR binding pocket called a 'carboxylate clamp'. Since the carboxylate clamp residues are conserved in the TPR domains of known Hsp90/Hsp70 co-chaperones, we carried out an in silico search for TPR proteins in Arabidopsis and rice comprising of at least one three-motif TPR domain with conserved amino acid residues required for Hsp90/Hsp70 binding. This approach identified in Arabidopsis a total of 36 carboxylate clamp (CC-TPR proteins, including 24 novel proteins, with potential to interact with Hsp90/Hsp70. The newly identified CC-TPR proteins in Arabidopsis and rice contain additional protein domains such as ankyrin, SET, octicosapeptide/Phox/Bem1p (Phox/PB1, DnaJ-like, thioredoxin, FBD and F-box, and protein kinase and U-box, indicating varied functions for these proteins. To provide proof-of-concept of the newly identified CC-TPR proteins for interaction with Hsp90, we demonstrated interaction of AtTPR1 and AtTPR2 with AtHsp90 in yeast two-hybrid and in vitro pull down assays. These findings indicate that the in silico approach used here successfully identified in a genome-wide context CC-TPR proteins with potential to interact with Hsp90/Hsp70, and further suggest that the Hsp90/Hsp70 system relies on TPR co-chaperones more than it was previously realized.

  2. Inhibition of Ubiquitin Ligase F-box and WD Repeat Domain-containing 7α (Fbw7α) Causes Hepatosteatosis through Krüppel-like Factor 5 (KLF5)/Peroxisome Proliferator-activated Receptor γ2 (PPARγ2) Pathway but Not SREBP-1c Protein in Mice*

    OpenAIRE

    Kumadaki, Shin; Karasawa, Tadayoshi; Matsuzaka, Takashi; Ema, Masatsugu; Nakagawa, Yoshimi; Nakakuki, Masanori; Saito, Ryo; Yahagi, Naoya; Iwasaki, Hitoshi; Sone, Hirohito; Takekoshi, Kazuhiro; Yatoh, Shigeru; Kobayashi, Kazuto; Takahashi, Akimitsu; Suzuki, Hiroaki

    2011-01-01

    F-box and WD repeat domain-containing 7α (Fbw7α) is the substrate recognition component of a ubiquitin ligase that controls the degradation of factors involved in cellular growth, including c-Myc, cyclin E, and c-Jun. In addition, Fbw7α degrades the nuclear form of sterol regulatory element-binding protein (SREBP)-1a, a global regulator of lipid synthesis, particularly during mitosis in cultured cells. This study investigated the in vivo role of Fbw7α in hepatic lipid metabolism. siRNA knockd...

  3. Inhibition of Ubiquitin Ligase F-box and WD Repeat Domain-containing 7α (Fbw7α) Causes Hepatosteatosis through Krüppel-like Factor 5 (KLF5)/Peroxisome Proliferator-activated Receptor γ2 (PPARγ2) Pathway but Not SREBP-1c Protein in Mice

    OpenAIRE

    Kumadaki, Shin; Karasawa, Tadayoshi; Matsuzaka, Takashi; Ema, Masatsugu; Nakagawa, Yoshimi; Nakakuki, Masanori; Saito, Ryo; Yahagi, Naoya; Iwasaki, Hitoshi; Sone, Hirohito; Takekoshi, Kazuhiro; Yatoh, Shigeru; Kobayashi, Kazuto; Takahashi, Akimitsu; Suzuki, Hiroaki

    2011-01-01

    F-box and WD repeat domain-containing 7α (Fbw7α) is the substrate recognition component of a ubiquitin ligase that controls the degradation of factors involved in cellular growth, including c-Myc, cyclin E, and c-Jun. In addition, Fbw7α degrades the nuclear form of sterol regulatory element-binding protein (SREBP)-1a, a global regulator of lipid synthesis, particularly during mitosis in cultured cells. This study investigated the in vivo role of Fbw7α in hepatic lipid metabolism. siRNA knockd...

  4. Variable Glutamine-Rich Repeats Modulate Transcription Factor Activity

    OpenAIRE

    Gemayel, Rita; Chavali, Sreenivas; Pougach, Ksenia; Legendre, Matthieu; Zhu, Bo; Boeynaems, Steven; van der Zande, Elisa; Gevaert, Kris; Rousseau, Frederic; Schymkowitz, Joost; Babu, M Madan; Verstrepen, Kevin J.

    2015-01-01

    Summary Excessive expansions of glutamine (Q)-rich repeats in various human proteins are known to result in severe neurodegenerative disorders such as Huntington’s disease and several ataxias. However, the physiological role of these repeats and the consequences of more moderate repeat variation remain unknown. Here, we demonstrate that Q-rich domains are highly enriched in eukaryotic transcription factors where they act as functional modulators. Incremental changes in the number of repeats i...

  5. Production of small starch granules by expression of a tandem-repeat of a family 20 starch-binding domain (SBD3-SBD5) in an amylose-free potato genetic background

    NARCIS (Netherlands)

    Nazarian, F.; Trindade, L.M.; Visser, R.G.F.

    2012-01-01

    Starch exists typically as semicrystalline granules of varying size. Granule size plays an important role for many industrial starch applications. Microbial non-catalytic starch binding domains (SBD) exhibit an affinity for starch granules on their own. Three different constructs were introduced in

  6. Domains and domain loss

    DEFF Research Database (Denmark)

    Haberland, Hartmut

    2005-01-01

    politicians and in the media, especially in the discussion whether some languages undergo ‘domain loss’ vis-à-vis powerful international languages like English. An objection that has been raised here is that domains, as originally conceived, are parameters of language choice and not properties of languages...... theoretical constructs that can explain language choice which were supposed to be a more powerful explanatory tool than more obvious (and observable) parameters like topic, place (setting) and interlocutor. In the meantime, at least in Scandinavia, the term ‘domain’ has been taken up in the debate among...

  7. The expression of one ankyrin pk2 allele of the WO prophage is correlated with the Wolbachia feminizing effect in isopods

    Directory of Open Access Journals (Sweden)

    Pichon Samuel

    2012-04-01

    Full Text Available Abstract Background The maternally inherited α-Proteobacteria Wolbachia pipientis is an obligate endosymbiont of nematodes and arthropods, in which they induce a variety of reproductive alterations, including Cytoplasmic Incompatibility (CI and feminization. The genome of the feminizing wVulC Wolbachia strain harboured by the isopod Armadillidium vulgare has been sequenced and is now at the final assembly step. It contains an unusually high number of ankyrin motif-containing genes, two of which are homologous to the phage-related pk1 and pk2 genes thought to contribute to the CI phenotype in Culex pipiens. These genes encode putative bacterial effectors mediating Wolbachia-host protein-protein interactions via their ankyrin motifs. Results To test whether these Wolbachia homologs are potentially involved in altering terrestrial isopod reproduction, we determined the distribution and expression of both pk1 and pk2 genes in the 3 Wolbachia strains that induce CI and in 5 inducing feminization of their isopod hosts. Aside from the genes being highly conserved, we found a substantial copy number variation among strains, and that is linked to prophage diversity. Transcriptional analyses revealed expression of one pk2 allele (pk2b2 only in the feminizing Wolbachia strains of isopods. Conclusions These results reveal the need to investigate the functions of Wolbachia ankyrin gene products, in particular those of Pk2, and their host targets with respect to host sex manipulation.

  8. A novel ENU-mutation in ankyrin-1 disrupts malaria parasite maturation in red blood cells of mice.

    Directory of Open Access Journals (Sweden)

    Andreas Greth

    Full Text Available The blood stage of the plasmodium parasite life cycle is responsible for the clinical symptoms of malaria. Epidemiological studies have identified coincidental malarial endemicity and multiple red blood cell (RBC disorders. Many RBC disorders result from mutations in genes encoding cytoskeletal proteins and these are associated with increased protection against malarial infections. However the mechanisms underpinning these genetic, host responses remain obscure. We have performed an N-ethyl-N-nitrosourea (ENU mutagenesis screen and have identified a novel dominant (haploinsufficient mutation in the Ank-1 gene (Ank1(MRI23420 of mice displaying hereditary spherocytosis (HS. Female mice, heterozygous for the Ank-1 mutation showed increased survival to infection by Plasmodium chabaudi adami DS with a concomitant 30% decrease in parasitemia compared to wild-type, isogenic mice (wt. A comparative in vivo red cell invasion and parasite growth assay showed a RBC-autonomous effect characterised by decreased proportion of infected heterozygous RBCs. Within approximately 6-8 hours post-invasion, TUNEL staining of intraerythrocytic parasites, showed a significant increase in dead parasites in heterozygotes. This was especially notable at the ring and trophozoite stages in the blood of infected heterozygous mutant mice compared to wt (p<0.05. We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites.

  9. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.

    Science.gov (United States)

    Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Caceres, Ana I; Escalera, Jasmine; Jordt, Sven-Eric

    2009-04-01

    The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals. PMID:19036859

  10. 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.

  11. Suppression of hepcidin expression and iron overload mediate Salmonella susceptibility in ankyrin 1 ENU-induced mutant.

    Science.gov (United States)

    Yuki, Kyoko E; Eva, Megan M; Richer, Etienne; Chung, Dudley; Paquet, Marilène; Cellier, Mathieu; Canonne-Hergaux, François; Vaulont, Sophie; Vidal, Silvia M; Malo, Danielle

    2013-01-01

    Salmonella, a ubiquitous Gram-negative intracellular bacterium, is a food borne pathogen that infects a broad range of hosts. Infection with Salmonella Typhimurium in mice is a broadly recognized experimental model resembling typhoid fever in humans. Using a N-ethyl-N-nitrosurea (ENU) mutagenesis recessive screen, we report the identification of Ity16 (Immunity to Typhimurium locus 16), a locus responsible for increased susceptibility to infection. The position of Ity16 was refined on chromosome 8 and a nonsense mutation was identified in the ankyrin 1 (Ank1) gene. ANK1 plays an important role in the formation and stabilization of the red cell cytoskeleton. The Ank1(Ity16/Ity16) mutation causes severe hemolytic anemia in uninfected mice resulting in splenomegaly, hyperbilirubinemia, jaundice, extramedullary erythropoiesis and iron overload in liver and kidneys. Ank1(Ity16/Ity16) mutant mice demonstrated low levels of hepcidin (Hamp) expression and significant increases in the expression of the growth differentiation factor 15 (Gdf15), erythropoietin (Epo) and heme oxygenase 1 (Hmox1) exacerbating extramedullary erythropoiesis, tissue iron deposition and splenomegaly. As the infection progresses in Ank1(Ity16/Ity16), the anemia worsens and bacterial load were high in liver and kidneys compared to wild type mice. Heterozygous Ank1(+/Ity16) mice were also more susceptible to Salmonella infection although to a lesser extent than Ank1(Ity16/Ity16) and they did not inherently present anemia and splenomegaly. During infection, iron accumulated in the kidneys of Ank1(+/Ity16) mice where bacterial loads were high compared to littermate controls. The critical role of HAMP in the host response to Salmonella infection was validated by showing increased susceptibility to infection in Hamp-deficient mice and significant survival benefits in Ank1(+/Ity16) heterozygous mice treated with HAMP peptide. This study illustrates that the regulation of Hamp and iron balance are crucial

  12. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation.

    Directory of Open Access Journals (Sweden)

    Romina Nassini

    Full Text Available BACKGROUND: The transient receptor potential ankyrin 1 (TRPA1 channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1. METHODOLOGY/PRINCIPAL FINDINGS: By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1, a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists, or the neuropeptide substance P (SP, which is released from sensory nerve terminals by capsaicin, acrolein or CS, produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue in bronchoalveolar lavage (BAL fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves. CONCLUSIONS: Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1 activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests

  13. 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...

  14. Domain Engineering

    Science.gov (United States)

    Bjørner, Dines

    Before software can be designed we must know its requirements. Before requirements can be expressed we must understand the domain. So it follows, from our dogma, that we must first establish precise descriptions of domains; then, from such descriptions, “derive” at least domain and interface requirements; and from those and machine requirements design the software, or, more generally, the computing systems.

  15. Honesty through repeated interactions.

    Science.gov (United States)

    Rich, Patricia; Zollman, Kevin J S

    2016-04-21

    In the study of signaling, it is well known that the cost of deception is an essential element for stable honest signaling in nature. In this paper, we show how costs for deception can arise endogenously from repeated interactions between individuals. Utilizing the Sir Philip Sidney game as an illustrative case, we show that repeated interactions can sustain honesty with no observable signal costs, even when deception cannot be directly observed. We provide a number of potential experimental tests for this theory which distinguish it from the available alternatives. PMID:26869213

  16. 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.

  17. 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.

  18. 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.

  19. 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)

    2014-08-01

    The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage 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. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

  20. Repeat Customer Success in Extension

    Science.gov (United States)

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  1. Trusted Domain

    DEFF Research Database (Denmark)

    Hjorth, Theis Solberg; Torbensen, Rune

    2012-01-01

    In the digital age of home automation and with the proliferation of mobile Internet access, the intelligent home and its devices should be accessible at any time from anywhere. There are many challenges such as security, privacy, ease of configuration, incompatible legacy devices, a wealth...... of wireless standards, limited resources of embedded systems, etc. Taking these challenges into account, we present a Trusted Domain home automation platform, which dynamically and securely connects heterogeneous networks of Short-Range Wireless devices via simple non-expert user. interactions, and allows...... 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...

  2. 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

  3. Saturation of repeated quantum measurements

    Science.gov (United States)

    Haapasalo, Erkka; Heinosaari, Teiko; Kuramochi, Yui

    2016-08-01

    We study sequential measurement scenarios where the system is repeatedly subjected to the same measurement process. We first provide examples of such repeated measurements where further repetitions of the measurement do not increase our knowledge on the system after some finite number of measurement steps. We also prove, however, that repeating the Lüders measurement of an unsharp two-outcome observable never saturates in this sense, and we characterize the observable measured in the limit of infinitely many repetitions. Our result implies that a repeated measurement can be used to correct the inherent noise of an unsharp observable.

  4. 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)

  5. 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…

  6. Identifying Mutations of the Tetratricopeptide Repeat Domain 37 (TTC37) Gene in Infants With Intractable Diarrhea and a Comparison of Asian and Non-Asian Phenotype and Genotype: A Global Case-report Study of a Well-Defined Syndrome With Immunodeficiency.

    Science.gov (United States)

    Lee, Wen-I; Huang, Jing-Long; Chen, Chien-Chang; Lin, Ju-Li; Wu, Ren-Chin; Jaing, Tang-Her; Ou, Liang-Shiou

    2016-03-01

    Syndromic diarrhea/tricho-hepato-enteric syndrome (SD/THE) is a rare, autosomal recessive and severe bowel disorder mainly caused by mutations in the tetratricopeptide repeat domain 37 (TTC37) gene which act as heterotetrameric cofactors to enhance aberrant mRNAs decay. The phenotype and immune profiles of SD/THE overlap those of primary immunodeficiency diseases (PIDs). Neonates with intractable diarrhea underwent immunologic assessments including immunoglobulin levels, lymphocyte subsets, lymphocyte proliferation, superoxide production, and IL-10 signaling function. Candidate genes for PIDs predisposing to inflammatory bowel disease were sequencing in this study. Two neonates, born to nonconsanguineous parents, suffered from intractable diarrhea, recurrent infections, and massive hematemesis from esopharyngeal varices due to liver cirrhosis or accompanying Trichorrhexis nodosa that developed with age and thus guided the diagnosis of SD/THE compatible to TTC37 mutations (homozygous DelK1155H, Fs*2; heterozygous Y1169Ter and InsA1143, Fs*3). Their immunologic evaluation showed normal mitogen-stimulated lymphocyte proliferation, superoxide production, and IL-10 signaling, but low IgG levels, undetectable antibody to hepatitis B surface antigen and decreased antigen-stimulated lymphocyte proliferation. A PubMed search for bi-allelic TTC37 mutations and phenotypes were recorded in 14 Asian and 12 non-Asian cases. They had similar presentations of infantile onset refractory diarrhea, facial dysmorphism, hair anomalies, low IgG, low birth weight, and consanguinity. A higher incidence of heart anomalies (8/14 vs 2/12; P = 0.0344, Chi-square), nonsense mutations (19 in 28 alleles), and hot-spot mutations (W936Ter, 2779-2G>A, and Y1169Ter) were found in the Asian compared with the non-Asian patients. Despite immunoglobulin therapy in 20 of the patients, 4 died from liver cirrhosis and 1 died from sepsis. Patients of all ethnicities with SD/THE with the characteristic

  7. 78 FR 65594 - Vehicular Repeaters

    Science.gov (United States)

    2013-11-01

    ... Proceedings, 63 FR 24121 (May 1, 1998). Electronic Filers: Comments may be filed electronically using the... COMMISSION 47 CFR Part 90 Vehicular Repeaters AGENCY: Federal Communications Commission. ACTION: Proposed... the Commission's rules to allow the licensing and operation of vehicular repeater systems and...

  8. 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…

  9. Carbonyl stress-induced 5-hydroxytriptamine secretion from RIN-14B, rat pancreatic islet tumor cells, via the activation of transient receptor potential ankyrin 1.

    Science.gov (United States)

    Suzawa, Sayaka; Takahashi, Kenji; Shimada, Takahisa; Ohta, Toshio

    2016-07-01

    Methylglyoxal (MG), a highly reactive dicarbonyl substance, is known as an endogenous carbonyl stress-inducing substance related to various disease states. Irritable bowel syndrome (IBS) is one of the most frequently encountered gastrointestinal disorders and MG is considered to be its causal substance. An increased serum 5-hydroxytryptamine (5-HT) level is related to IBS symptoms and the majority of 5-HT originates from enterochromaffin (EC) cells in the intestine. Here we examine the mechanisms of MG-induced 5-HT secretion using RIN-14B cells derived from a rat pancreatic islet tumor since these cells are used as a model for EC cells. MG increased the intracellular Ca(2+) concentration ([Ca(2+)]i) and 5-HT secretion, both of which were inhibited by the removal of extracellular Ca(2+) and specific transient receptor potential ankyrin 1 (TRPA1) antagonists. MG elicited an inward current under voltage-clamped conditions. Prior application of MG evoked reciprocal suppression of subsequent [Ca(2+)]i responses to allylisothiocyanate, a TRPA1 agonist, and vice versa. Glyoxal, an analog of MG, also evoked [Ca(2+)]i and secretory responses but its potency was much lower than that of MG. The present results suggest that MG promotes 5-HT secretion through the activation of TRPA1 in RIN-14B cells. These results may indicate that TRPA1 is a promising target for the treatment of IBS and that the RIN-14B cell line is a useful model for investigation of IBS. PMID:27423812

  10. 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

  11. 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

  12. Thermal and Chemical Stability of Two Homologous POZ/BTB Domains of KCTD Proteins Characterized by a Different Oligomeric Organization

    Directory of Open Access Journals (Sweden)

    Luciano Pirone

    2013-01-01

    Full Text Available POZ/BTB domains are widespread modules detected in a variety of different biological contexts. Here, we report a biophysical characterization of the POZ/BTB of KCTD6, a protein that is involved in the turnover of the muscle small ankyrin-1 isoform 5 and, in combination with KCTD11, in the ubiquitination and degradation of HDAC1. The analyses show that the domain is a tetramer made up by subunits with the expected α/ structure. A detailed investigation of its stability, carried out in comparison with the homologous pentameric POZ/BTB domain isolated from KCTD5, highlights a number of interesting features, which are shared by the two domains despite their different organization. Their thermal/chemical denaturation curves are characterized by a single and sharp inflection point, suggesting that the denaturation of the two domains is a cooperative two-state process. Furthermore, both domains present a significant content of secondary structure in their denatured state and a reversible denaturation process. We suggest that the ability of these domains to fold and unfold reversibly, a property that is somewhat unexpected for these oligomeric assemblies, may have important implications for their biological function. Indeed, these properties likely favor the formation of heteromeric associations that may be essential for the intricate regulation of the processes in which these proteins are involved.

  13. 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…

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

    OpenAIRE

    Glass John I; Yooseph Shibu; Foecking Mark F; Röske Kerstin; Calcutt Michael J; Wise Kim S

    2010-01-01

    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 datab...

  15. Reversible Conformational Change in the Plasmodium falciparum Circumsporozoite Protein Masks Its Adhesion Domains

    OpenAIRE

    Herrera, Raul; Anderson, Charles; Kumar, Krishan; Molina-Cruz, Alvaro; Nguyen, Vu; Burkhardt, Martin; Reiter, Karine; Shimp, Richard; Howard, Randall F.; Srinivasan, Prakash; Nold, Michael J.; Ragheb, Daniel; Shi, Lirong; DeCotiis, Mark; Aebig, Joan

    2015-01-01

    The extended rod-like Plasmodium falciparum circumsporozoite protein (CSP) is comprised of three primary domains: a charged N terminus that binds heparan sulfate proteoglycans, a central NANP repeat domain, and a C terminus containing a thrombospondin-like type I repeat (TSR) domain. Only the last two domains are incorporated in RTS,S, the leading malaria vaccine in phase 3 trials that, to date, protects about 50% of vaccinated children against clinical disease. A seroepidemiological study in...

  16. 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

  17. 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.

  18. The different roles of aggrecan interaction domains

    DEFF Research Database (Denmark)

    Aspberg, Anders

    2012-01-01

    -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...

  19. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

    2012-11-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  20. Pentatricopeptide repeats: Modular blocks for building RNA-binding proteins

    OpenAIRE

    Filipovska, Aleksandra; Rackham, Oliver

    2013-01-01

    Pentatricopeptide repeat (PPR) proteins control diverse aspects of RNA metabolism across the eukaryotic domain. Recent computational and structural studies have provided new insights into how they recognize RNA, and show that the recognition is sequence-specific and modular. The modular code for RNA-binding by PPR proteins holds great promise for the engineering of new tools to target RNA and identifying RNAs bound by natural PPR proteins.

  1. 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.

  2. Sequencing Games with Repeated Players

    NARCIS (Netherlands)

    Estevez Fernandez, M.A.; Borm, P.E.M.; Calleja, P.; Hamers, H.J.M.

    2004-01-01

    Two classes of one machine sequencing situations are considered in which each job corresponds to exactly one player but a player may have more than one job to be processed, so called RP(repeated player) sequencing situations.In max-RP sequencing situations it is assumed that each player's cost funct

  3. A Semiparametric Bayesian Model for Repeatedly Repeated Binary Outcomes

    OpenAIRE

    Quintana, Fernando A.; Müller, Peter; Rosner, Gary L.; Mary V Relling

    2008-01-01

    We discuss the analysis of data from single nucleotide polymorphism (SNP) arrays comparing tumor and normal tissues. The data consist of sequences of indicators for loss of heterozygosity (LOH) and involve three nested levels of repetition: chromosomes for a given patient, regions within chromosomes, and SNPs nested within regions. We propose to analyze these data using a semiparametric model for multi-level repeated binary data. At the top level of the hierarchy we assume a sampling model fo...

  4. 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.

  5. 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.

  6. 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...

  7. 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.

  8. A repeating fast radio burst

    Science.gov (United States)

    Spitler, L. G.; Scholz, P.; 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.

    2016-03-01

    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 measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  9. 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

  10. Energy Landscapes of Dynamic Ensembles of Rolling Triplet Repeat Bulge Loops: Implications for DNA Expansion Associated with Disease States

    OpenAIRE

    Völker, Jens; Gindikin, Vera; Klump, Horst H.; Plum, G. Eric; Breslauer, Kenneth J.

    2012-01-01

    DNA repeat domains can form ensembles of canonical and noncanonical states, including stable and metastable DNA secondary structures. Such sequence-induced structural diversity creates complex conformational landscapes for DNA processing pathways, including those triplet expansion events that accompany replication, recombination, and/or repair. Here we demonstrate further levels of conformational complexity within repeat domains. Specifically, we show that bulge loop structures within an exte...

  11. 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.

  12. 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.

  13. Synthetic heterochromatin bypasses RNAi and centromeric repeats to establish functional centromeres

    OpenAIRE

    Kagansky, Alexander; Folco, Hernan Diego; Almeida, Ricardo; Pidoux, Alison L.; Boukaba, Abdelhalim; Simmer, Femke; Urano, Takeshi; Hamilton, Georgina L.; Allshire, Robin C.

    2009-01-01

    In the central domain of fission yeast centromeres, the kinetochore is assembled on CENP-A(Cnp1) nucleosomes. Normally, small interfering RNAs generated from flanking outer repeat transcripts direct histone H3 lysine 9 methyltransferase Clr4 to homologous loci to form heterochromatin. Outer repeats, RNA interference (RNAi), and centromeric heterochromatin are required to establish CENP-A(Cnp1) chromatin. We demonstrated that tethering Clr4 via DNA-binding sites at euchromatic loci induces het...

  14. 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.

  15. 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.

  16. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... MB] Read the MMWR Science Clips Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On ... live birth before age 20. Problem Too many teens, ages 15–19, have repeat births. Nearly 1 ...

  17. 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

  18. Essays in the theory of repeated games

    OpenAIRE

    Osório-Costa, António Miguel

    2010-01-01

    This thesis comprises three essays in economic theory. The first two are in the theory of repeated games. The third is also a theoretical contribution, which mixes con- cepts both from repeated games and the theory of incentives. The first chapter is a novel contribution to frequent monitoring in repeated games. The second one, studies for the first time, infinitely repeated games where the repetitions of the stage game are random. The last chapter, studies the provision of incentives in a pr...

  19. Lambda Exonuclease Digestion of CGG Trinucleotide Repeats

    OpenAIRE

    Conroy, R. S.; Koretsky, A P; Moreland, J.

    2009-01-01

    Fragile X syndrome and other triplet repeat diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. Using magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and na...

  20. 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.

  1. 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

  2. 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...

  3. 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...

  4. Topological characteristics of helical repeat proteins

    NARCIS (Netherlands)

    Groves, M R; Barford, D

    1999-01-01

    The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

  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. 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.

  7. 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.

  8. Expression, purification and preliminary crystallographic analysis of recombinant human small glutamine-rich tetratricopeptide-repeat protein

    International Nuclear Information System (INIS)

    The production and crystallization of the tetratricopeptide-repeat domain of human small glutamine-rich tetratricopeptide-repeat protein are reported. A 2.4 Å native diffraction data set has been obtained. Human small glutamine-rich tetratricopeptide-repeat protein (hSGT) is a 35 kDa protein implicated in a number of biological processes that include apoptosis, cell division and intracellular cell transport. The tetratricopeptide-repeat (TPR) domain of hSGT has been cloned and expressed in Escherichia coli and purified. Here, the crystallization and preliminary diffraction analysis of the TPR domain of hSGT is reported. X-ray diffraction data were processed to a resolution of 2.4 Å. Crystals belong to space group P21212, with unit-cell parameters a = 67.82, b = 81.93, c = 55.92 Å, α = β = γ = 90°

  9. 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.

  10. 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

  11. ProRepeat: an integrated repository for studying amino acid tandem repeats in proteins

    NARCIS (Netherlands)

    Luo, H.; Lin, K.; David, A.; Nijveen, H.; Leunissen, J.A.M.

    2012-01-01

    ProRepeat (http://prorepeat.bioinformatics.nl/) is an integrated curated repository and analysis platform for in-depth research on the biological characteristics of amino acid tandem repeats. ProRepeat collects repeats from all proteins included in the UniProt knowledgebase, together with 85 complet

  12. 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.

  13. 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

  14. Diamagnetic (Condon) domains

    International Nuclear Information System (INIS)

    This paper is the first systematic review of experimental research on diamagnetic (aka Condon) domains that form in nonmagnetic metals at low temperatures due to the development of Landau levels. A variety of methods were used to study the domains. Muon spectroscopy studies showed such domains to be present in all metals studied, pointing to the universal nature of the phenomenon. For silver, the domain structure size as measured by Hall microsensors turned out to be an order of magnitude larger than expected. In beryllium, it was found that domains do not come to the surface but rather remain in the bulk of the crystal. The magnetostriction of beryllium during domain formation is measured. It is shown that magnetization current in a domain wall is entirely caused by the charge density gradient in the wall, due to the lattice being deformed oppositely in neighboring domains. It is observed for the first time that the de Haas-van Alphen effect exhibits hysteresis at the transition to the domain state, and this fact was used for the experimental determination of the phase diagrams for the domain states of silver and beryllium. (reviews of topical problems)

  15. Polyomavirus large T antigen binds symmetrical repeats at the viral origin in an asymmetrical manner.

    Science.gov (United States)

    Harrison, Celia; Jiang, Tao; Banerjee, Pubali; Meinke, Gretchen; D'Abramo, Claudia M; Schaffhausen, Brian; Bohm, Andrew

    2013-12-01

    Polyomaviruses have repeating sequences at their origins of replication that bind the origin-binding domain of virus-encoded large T antigen. In murine polyomavirus, the central region of the origin contains four copies (P1 to P4) of the sequence G(A/G)GGC. They are arranged as a pair of inverted repeats with a 2-bp overlap between the repeats at the center. In contrast to simian virus 40 (SV40), where the repeats are nonoverlapping and all four repeats can be simultaneously occupied, the crystal structure of the four central murine polyomavirus sequence repeats in complex with the polyomavirus origin-binding domain reveals that only three of the four repeats (P1, P2, and P4) are occupied. Isothermal titration calorimetry confirms that the stoichiometry is the same in solution as in the crystal structure. Consistent with these results, mutation of the third repeat has little effect on DNA replication in vivo. Thus, the apparent 2-fold symmetry within the DNA repeats is not carried over to the protein-DNA complex. Flanking sequences, such as the AT-rich region, are known to be important for DNA replication. When the orientation of the central region was reversed with respect to these flanking regions, the origin was still able to replicate and the P3 sequence (now located at the P2 position with respect to the flanking regions) was again dispensable. This highlights the critical importance of the precise sequence of the region containing the pentamers in replication.

  16. 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

  17. Repeated Sprints: An Independent Not Dependent Variable.

    Science.gov (United States)

    Taylor, Jonathan M; Macpherson, Tom W; Spears, Iain R; Weston, Matthew

    2016-07-01

    The ability to repeatedly perform sprints has traditionally been viewed as a key performance measure in team sports, and the relationship between repeated-sprint ability (RSA) and performance has been explored extensively. However, when reviewing the repeated-sprint profile of team-sports match play it appears that the occurrence of repeated-sprint bouts is sparse, indicating that RSA is not as important to performance as commonly believed. Repeated sprints are, however, a potent and time-efficient training strategy, effective in developing acceleration, speed, explosive leg power, aerobic power, and high-intensity-running performance--all of which are crucial to team-sport performance. As such, we propose that repeated-sprint exercise in team sports should be viewed as an independent variable (eg, a means of developing fitness) as opposed to a dependent variable (eg, a means of assessing fitness/performance). PMID:27197118

  18. 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.

  19. 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.

  20. 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.

  1. Visualizing latent domain knowledge

    OpenAIRE

    Chen, C.; Kuljis, J; Paul, RJ

    2001-01-01

    Knowledge discovery and data mining commonly rely on finding salient patterns of association from a vast amount of data. Traditional citation analysis of scientific literature draws insights from strong citation patterns. Latent domain knowledge, in contrast to the mainstream domain knowledge, often consists of highly relevant but relatively infrequently cited scientific works. Visualizing latent domain knowledge presents a significant challenge to knowledge discovery and quantitative studies...

  2. 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.

  3. 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.

  4. 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

  5. Predicting detection performance with model observers: Fourier domain or spatial domain?

    Science.gov (United States)

    Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

    2016-03-01

    The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

  6. 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

  7. Positive association of the androgen receptor CAG repeat length polymorphism with the risk of prostate cancer.

    Science.gov (United States)

    Paz-Y-Miño, César; Robles, Paulo; Salazar, Carolina; Leone, Paola E; García-Cárdenas, Jennyfer M; Naranjo, Manuel; López-Cortés, Andrés

    2016-08-01

    Prostate cancer (PC) is the most frequently diagnosed cancer in Ecuador (15.6%). The androgen receptor gene codes for a protein that has an androgen‑binding domain, DNA‑binding domain and N‑terminal domain, which contains two polymorphic trinucleotide repeats (CAG and GGC). The aim of the present study was to determine whether variations in the number of repetitions of CAG and GGC are associated with the pathological features and the risk of developing PC. The polymorphic CAG and GGC repeat lengths in 108 mestizo patients with PC, 148 healthy mestizo individuals, and 78 healthy indigenous individuals were examined via a retrospective case‑control study. Genotypes were determined by genomic sequencing. The results demonstrated that patients with ≤21 CAG repeats have an increased risk of developing PC [odds ratio (OR)=2.99, 95% confidence interval (CI) =1.79‑5.01; P<0.001]. The presence of ≤21 CAG repeats was also associated with a tumor stage ≥T2c (OR=4.75; 95% CI=1.77‑12.72; P<0.005) and a Gleason score ≥7 (OR=2.9; 95% CI=1.1‑7.66; P=0.03). In addition, the combination of ≤21 CAG and ≥17 GGC repeats was associated with the risk of developing PC (OR=2.42; 95% CI=1.38‑4.25; P=0.002) and with tumor stage ≥T2c (OR=2.77; 95% CI=1.13‑6.79; P=0.02). In conclusion, the histopathological characteristics and PC risk in Ecuadorian indigenous and mestizo populations differs in association with the CAG repeats, and the combination of CAG and GGC repeats. PMID:27357524

  8. Detection of alpha-rod protein repeats using a neural network and application to huntingtin.

    Directory of Open Access Journals (Sweden)

    Gareth A Palidwor

    2009-03-01

    Full Text Available A growing number of solved protein structures display an elongated structural domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel alpha-helices. Alpha-rods are flexible and expose a large surface, which makes them suitable for protein interaction. Although most likely originating by tandem duplication of a two-helix unit, their detection using sequence similarity between repeats is poor. Here, we show that alpha-rod repeats can be detected using a neural network. The network detects more repeats than are identified by domain databases using multiple profiles, with a low level of false positives (<10%. We identify alpha-rod repeats in approximately 0.4% of proteins in eukaryotic genomes. We then investigate the results for all human proteins, identifying alpha-rod repeats for the first time in six protein families, including proteins STAG1-3, SERAC1, and PSMD1-2 & 5. We also characterize a short version of these repeats in eight protein families of Archaeal, Bacterial, and Fungal species. Finally, we demonstrate the utility of these predictions in directing experimental work to demarcate three alpha-rods in huntingtin, a protein mutated in Huntington's disease. Using yeast two hybrid analysis and an immunoprecipitation technique, we show that the huntingtin fragments containing alpha-rods associate with each other. This is the first definition of domains in huntingtin and the first validation of predicted interactions between fragments of huntingtin, which sets up directions toward functional characterization of this protein. An implementation of the repeat detection algorithm is available as a Web server with a simple graphical output: http://www.ogic.ca/projects/ard. This can be further visualized using BiasViz, a graphic tool for representation of multiple sequence alignments.

  9. Synthetic heterochromatin bypasses RNAi and centromeric repeats to establish functional centromeres.

    Science.gov (United States)

    Kagansky, Alexander; Folco, Hernan Diego; Almeida, Ricardo; Pidoux, Alison L; Boukaba, Abdelhalim; Simmer, Femke; Urano, Takeshi; Hamilton, Georgina L; Allshire, Robin C

    2009-06-26

    In the central domain of fission yeast centromeres, the kinetochore is assembled on CENP-A(Cnp1) nucleosomes. Normally, small interfering RNAs generated from flanking outer repeat transcripts direct histone H3 lysine 9 methyltransferase Clr4 to homologous loci to form heterochromatin. Outer repeats, RNA interference (RNAi), and centromeric heterochromatin are required to establish CENP-A(Cnp1) chromatin. We demonstrated that tethering Clr4 via DNA-binding sites at euchromatic loci induces heterochromatin assembly, with or without active RNAi. This synthetic heterochromatin completely substitutes for outer repeats on plasmid-based minichromosomes, promoting de novo CENP-A(Cnp1) and kinetochore assembly, to allow their mitotic segregation, even with RNAi inactive. Thus, the role of outer repeats in centromere establishment is simply the provision of RNAi substrates to direct heterochromatin formation; H3K9 methylation-dependent heterochromatin is alone sufficient to form functional centromeres. PMID:19556509

  10. Hybrid time/frequency domain modeling of nonlinear components

    DEFF Research Database (Denmark)

    Wiechowski, Wojciech Tomasz; Lykkegaard, Jan; Bak, Claus Leth;

    2007-01-01

    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...

  11. 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,

  12. 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

  13. 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

  14. 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.

  15. Topological Domain Theory

    OpenAIRE

    Battenfeld, Ingo

    2008-01-01

    This thesis presents Topological Domain Theory as a powerful and flexible framework for denotational semantics. Topological Domain Theory models a wide range of type constructions and can interpret many computational features. Furthermore, it has close connections to established frameworks for denotational semantics, as well as to well-studied mathematical theories, such as topology and computable analysis.

  16. Modeling Protein Domain Function

    Science.gov (United States)

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

    2007-01-01

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

  17. 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.

  18. Repeat prescribing: a role for community pharmacists in controlling and monitoring repeat prescriptions.

    OpenAIRE

    Bond, C.; Matheson, C.; Williams, S; Williams, P.; Donnan, P

    2000-01-01

    BACKGROUND: Traditional systems of managing repeat prescribing have been criticised for their lack of clinical and administrative controls. AIM: To compare a community pharmacist-managed repeat prescribing system with established methods of managing repeat prescribing. METHOD: A randomised controlled intervention study (19 general medical practices, 3074 patients, 62 community pharmacists). Patients on repeat medication were given sufficient three-monthly scripts, endorsed for monthly dispens...

  19. 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.

  20. Preservice science teachers' experiences with repeated, guided inquiry

    Science.gov (United States)

    Slack, Amy B.

    The purpose of this study was to examine preservice science teachers' experiences with repeated scientific inquiry (SI) activities. The National Science Education Standards (National Research Council, 1996) stress students should understand and possess the abilities to do SI. For students to meet these standards, science teachers must understand and be able to perform SI; however, previous research demonstrated that many teachers have naive understandings in this area. Teacher preparation programs provide an opportunity to facilitate the development of inquiry understandings and abilities. In this study, preservice science teachers had experiences with two inquiry activities that were repeated three times each. The research questions for this study were (a) How do preservice science teachers' describe their experiences with repeated, guided inquiry activities? (b) What are preservice science teachers' understandings and abilities of SI? This study was conducted at a large, urban university in the southeastern United States. The 5 participants had bachelor's degrees in science and were enrolled in a graduate science education methods course. The researcher was one of the course instructors but did not lead the activities. Case study methodology was used. Data was collected from a demographic survey, an open-ended questionnaire with follow-up interviews, the researcher's observations, participants' lab notes, personal interviews, and participants' journals. Data were coded and analyzed through chronological data matrices to identify patterns in participants' experiences. The five domains identified in this study were understandings of SI, abilities to conduct SI, personal feelings about the experience, science content knowledge, and classroom implications. Through analysis of themes identified within each domain, the four conclusions made about these preservice teachers' experiences with SI were that the experience increased their abilities to conduct inquiry

  1. Finding and Characterizing Repeats in Plant Genomes.

    Science.gov (United States)

    Nicolas, Jacques; Peterlongo, Pierre; Tempel, Sébastien

    2016-01-01

    Plant genomes contain a particularly high proportion of repeated structures of various types. This chapter proposes a guided tour of available software that can help biologists to look for these repeats and check some hypothetical models intended to characterize their structures. Since transposable elements are a major source of repeats in plants, many methods have been used or developed for this large class of sequences. They are representative of the range of tools available for other classes of repeats and we have provided a whole section on this topic as well as a selection of the main existing software. In order to better understand how they work and how repeats may be efficiently found in genomes, it is necessary to look at the technical issues involved in the large-scale search of these structures. Indeed, it may be hard to keep up with the profusion of proposals in this dynamic field and the rest of the chapter is devoted to the foundations of the search for repeats and more complex patterns. The second section introduces the key concepts that are useful for understanding the current state of the art in playing with words, applied to genomic sequences. This can be seen as the first stage of a very general approach called linguistic analysis that is interested in the analysis of natural or artificial texts. Words, the lexical level, correspond to simple repeated entities in texts or strings. In fact, biologists need to represent more complex entities where a repeat family is built on more abstract structures, including direct or inverted small repeats, motifs, composition constraints as well as ordering and distance constraints between these elementary blocks. In terms of linguistics, this corresponds to the syntactic level of a language. The last section introduces concepts and practical tools that can be used to reach this syntactic level in biological sequence analysis. PMID:26519414

  2. A conserved BURP domain defines a novel group of plant proteins with unusual primary structures.

    Science.gov (United States)

    Hattori, J; Boutilier, K A; van Lookeren Campagne, M M; Miki, B L

    1998-09-01

    We have identified a new class of plant proteins containing a common C-terminal region, which we have termed the BURP domain. These proteins are defined not only by the BURP domain, but also by the overall similarity in their modular construction. The BURP domain proteins consist of either three or four modules: (i) an N-terminal hydrophobic domain -- a presumptive transit peptide, joined to (ii) a short conserved segment or other short segment, (iii) an optional segment consisting of repeated units which is unique to each member, and (iv) the C-terminal BURP domain. These individual modules appear to be combined to form two main classes of BURP domain proteins. The BURP domain proteins, despite the similarities in their primary structural features, show no obvious similarities in the tissues or conditions under which they are expressed. The presence of the conserved BURP domain in diverse plant proteins suggests an important and fundamental functional role for this domain. PMID:9790599

  3. Multiplexed Memory-Insensitive Quantum Repeaters

    CERN Document Server

    Collins, O A; Kennedy, T A B; Kuzmich, A

    2006-01-01

    Long-distance quantum communication via distant pairs of entangled quantum bits (qubits) is the first step towards technologies such as perfectly secure message transmission and distributed quantum computing. To date, the most promising proposals require quantum repeaters to mitigate the exponential decrease in communication rate due to optical fiber losses. However, quantum repeaters are exquisitely sensitive to the lifetimes of the memory elements they use. We propose a new approach based on a real-time hardware reconfiguration of multiplexed quantum nodes. This scheme should enable the construction of multiplexed quantum repeater networks that are largely insensitive to the coherence times of the quantum memory elements.

  4. 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.

  5. 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...

  6. Structure and biochemical function of a prototypical Arabidopsis U-box domain

    DEFF Research Database (Denmark)

    Andersen, Pernille; Kragelund, Birthe B; Olsen, Addie N;

    2004-01-01

    U-box proteins, as well as other proteins involved in regulated protein degradation, are apparently over-represented in Arabidopsis compared with other model eukaryotes. The Arabidopsis protein AtPUB14 contains a typical U-box domain followed by an Armadillo repeat region, a domain organization...

  7. 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.

  8. 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)

  9. 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.

  10. The multiple roles of epidermal growth factor repeat O-glycans in animal development.

    Science.gov (United States)

    Haltom, Amanda R; Jafar-Nejad, Hamed

    2015-10-01

    The epidermal growth factor (EGF)-like repeat is a common, evolutionarily conserved motif found in secreted proteins and the extracellular domain of transmembrane proteins. EGF repeats harbor six cysteine residues which form three disulfide bonds and help generate the three-dimensional structure of the EGF repeat. A subset of EGF repeats harbor consensus sequences for the addition of one or more specific O-glycans, which are initiated by O-glucose, O-fucose or O-N-acetylglucosamine. These glycans are relatively rare compared to mucin-type O-glycans. However, genetic experiments in model organisms and cell-based assays indicate that at least some of the glycosyltransferases involved in the addition of O-glycans to EGF repeats play important roles in animal development. These studies, combined with state-of-the-art biochemical and structural biology experiments have started to provide an in-depth picture of how these glycans regulate the function of the proteins to which they are linked. In this review, we will discuss the biological roles assigned to EGF repeat O-glycans and the corresponding glycosyltransferases. Since Notch receptors are the best studied proteins with biologically-relevant O-glycans on EGF repeats, a significant part of this review is devoted to the role of these glycans in the regulation of the Notch signaling pathway. We also discuss recently identified proteins other than Notch which depend on EGF repeat glycans to function properly. Several glycosyltransferases involved in the addition or elongation of O-glycans on EGF repeats are mutated in human diseases. Therefore, mechanistic understanding of the functional roles of these carbohydrate modifications is of interest from both basic science and translational perspectives. PMID:26175457

  11. 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...

  12. Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects.

    Science.gov (United States)

    Reichen, Christian; Madhurantakam, Chaithanya; Hansen, Simon; Grütter, Markus G; Plückthun, Andreas; Mittl, Peer R E

    2016-01-01

    The armadillo repeat serves as a scaffold for the development of modular peptide-recognition modules. In order to develop such a system, three crystal structures of designed armadillo-repeat proteins with third-generation N-caps (YIII-type), four or five internal repeats (M-type) and second-generation C-caps (AII-type) were determined at 1.8 Å (His-YIIIM4AII), 2.0 Å (His-YIIIM5AII) and 1.95 Å (YIIIM5AII) resolution and compared with those of variants with third-generation C-caps. All constructs are full consensus designs in which the internal repeats have exactly the same sequence, and hence identical conformations of the internal repeats are expected. The N-cap and internal repeats M1 to M3 are indeed extremely similar, but the comparison reveals structural differences in internal repeats M4 and M5 and the C-cap. These differences are caused by long-range effects of the C-cap, contacting molecules in the crystal, and the intrinsic design of the repeat. Unfortunately, the rigid-body movement of the C-terminal part impairs the regular arrangement of internal repeats that forms the putative peptide-binding site. The second-generation C-cap improves the packing of buried residues and thereby the stability of the protein. These considerations are useful for future improvements of an armadillo-repeat-based peptide-recognition system. PMID:26894544

  13. The WD40 domain is required for LRRK2 neurotoxicity.

    Directory of Open Access Journals (Sweden)

    Nathan D Jorgensen

    Full Text Available BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2 are the most common genetic cause of Parkinson disease (PD. LRRK2 contains an "enzymatic core" composed of GTPase and kinase domains that is flanked by leucine-rich repeat (LRR and WD40 protein-protein interaction domains. While kinase activity and GTP-binding have both been implicated in LRRK2 neurotoxicity, the potential role of other LRRK2 domains has not been as extensively explored. PRINCIPAL FINDINGS: We demonstrate that LRRK2 normally exists in a dimeric complex, and that removing the WD40 domain prevents complex formation and autophosphorylation. Moreover, loss of the WD40 domain completely blocks the neurotoxicity of multiple LRRK2 PD mutations. CONCLUSION: These findings suggest that LRRK2 dimerization and autophosphorylation may be required for the neurotoxicity of LRRK2 PD mutations and highlight a potential role for the WD40 domain in the mechanism of LRRK2-mediated cell death.

  14. 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

  15. NCBI nr-aa BLAST: CBRC-ACAR-01-0651 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available subfamily A member 1 (Ankyrin-like with transmembrane domains protein 1) (Transformation sensitive protein p120) emb|CAA71610.1| ankyrin-like protein [Homo sapiens] O75762 0.46 27% ...

  16. Improved Computational Target Site Prediction for Pentatricopeptide Repeat RNA Editing Factors

    OpenAIRE

    TAKENAKA, MIZUKI; Zehrmann, Anja; Brennicke, Axel; Graichen, Knut

    2013-01-01

    Pentatricopeptide repeat (PPR) proteins with an E domain have been identified as specific factors for C to U RNA editing in plant organelles. These PPR proteins bind to a unique sequence motif 5′ of their target editing sites. Recently, involvement of a combinatorial amino acid code in the P (normal length) and S type (short) PPR domains in sequence specific RNA binding was reported. PPR proteins involved in RNA editing, however, contain not only P and S motifs but also their long variants L ...

  17. 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.

  18. Domain Theory for Concurrency

    DEFF Research Database (Denmark)

    Nygaard, Mikkel

    Concurrent computation can be given an abstract mathematical treatment very similar to that provided for sequential computation by domain theory and denotational semantics of Scott and Strachey. A simple domain theory for concurrency is presented. Based on a categorical model of linear logic...... of affine-linear logic. This language adds to HOPLA an interesting tensor operation at the price of linearity constraints on the occurrences of variables. The tensor can be understood as a juxtaposition of independent processes, and allows Affine HOPLA to encode processes of the kind found in treatments...... of nondeterministic dataflow. The domain theory can be generalised to presheaf models, providing a more refined treatment of nondeterministic branching and supporting notions of bisimulation. The operational semantics for HOPLA is guided by the idea that derivations of transitions in the operational semantics should...

  19. Reasoning in incomplete domains

    Energy Technology Data Exchange (ETDEWEB)

    Rosenberg, S.

    1979-01-01

    Most real-world domains differ from the micro-worlds traditionally used in A.I. in that they have an incomplete factual data base which changes over time. Understanding in these domains can be thought of as the gneration of plausible infoerences which are able to use the facts available, and respond to changes in them. A traditional rule interpreter such as Planner can be extended to construct plausible inferences in these domains by allowing assumptions to be made in applying rules, resultsing in simplifications of rules which can be used in an incomplete data base; monitoring the antecedents and consequents of a rule so that inferences can be maintained over a changing data base.

  20. 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.

  1. High-resolution CW lidar altimetry using repeating intensity-modulated waveforms and Fourier transform reordering.

    Science.gov (United States)

    Campbell, Joel F; Lin, Bing; Nehrir, Amin R; Harrison, F Wallace; Obland, Michael D

    2014-10-15

    An interpolation method is described for range measurements of high precision and altimetry using repeating intensity-modulated continuous wave (IM-CW) lidar waveforms, where the range is determined by means of a cross-correlation between the digital form of the transmitted signal and the digitized return signal collected by the lidar receiver. This method uses reordering of the array elements in the frequency domain to convert a repeating synthetic pulse signal to single highly interpolated pulse. The computation of this processing is marginally greater than the correlation itself, as it only involves reordering of the correlation in the frequency domain, which makes it possible to implement this in a real time application. It is shown through theoretical arguments and flight-testing that this is a viable method for high-speed interpolated range measurements. Standard deviation is 0.75 m over water with only 350 mw of transmitted power at 2600 m. PMID:25361160

  2. Structure of filamin A immunoglobulin-like repeat 10 from Homo sapiens

    International Nuclear Information System (INIS)

    The structure of immunoglobulin-like repeat 10 from human filamin A solved at 2.44 Å resolution suggests the potential effects of mutations correlated with otopalatodigital syndrome spectrum disorders. Filamin A (FlnA) plays a critical role in cytoskeletal organization, cell motility and cellular signaling. FlnA utilizes different binding sites on a series of 24 immunoglobulin-like domains (Ig repeats) to interact with diverse cytosolic proteins and with cytoplasmic portions of membrane proteins. Mutations in a specific domain, Ig10 (FlnA-Ig10), are correlated with two severe forms of the otopalatodigital syndrome spectrum disorders Melnick–Needles syndrome and frontometaphyseal dysplasia. The crystal structure of FlnA-Ig10 determined at 2.44 Å resolution provides insight into the perturbations caused by these mutations

  3. Quantum key distribution over probabilistic quantum repeaters

    Science.gov (United States)

    Amirloo, Jeyran; Razavi, Mohsen; Majedi, A. Hamed

    2010-09-01

    A feasible route toward 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 (London)NATUAS0028-083610.1038/35106500 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 with and without a repeater node. We find the crossover distance beyond which the repeater system outperforms the nonrepeater one. That provides us with the optimum internode distancing in quantum repeater systems. We also find the optimal excitation probability at which the QKD rate peaks. Such an optimum probability, in most regimes of interest, is insensitive to the total distance.

  4. 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.

  5. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    International Nuclear Information System (INIS)

    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.

  6. 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.

  7. Deoxynivalenol (Vomitoxin)-Induced Cholecystokinin and Glucagon-Like Peptide-1 Release in the STC-1 Enteroendocrine Cell Model Is Mediated by Calcium-Sensing Receptor and Transient Receptor Potential Ankyrin-1 Channel.

    Science.gov (United States)

    Zhou, Hui-Ren; Pestka, James J

    2015-06-01

    Food refusal is a hallmark of exposure of experimental animals to the trichothecene mycotoxin deoxynivalenol (DON), a common foodborne contaminant. Although studies in the mouse suggest that DON suppresses food intake by aberrantly inducing the release of satiety hormones from enteroendocrine cells (EECs) found in the gut epithelium, the underlying mechanisms for this effect are not understood. To address this gap, we employed the murine neuroendocrine tumor STC-1 cell line, a widely used EEC model, to test the hypothesis that DON-induced hormone exocytosis is mediated by G protein-coupled receptor (GPCR)-mediated Ca(2+) signaling. The results indicate for the first time that DON elicits Ca(2)-dependent secretion of cholecystokinin (CCK) and glucagon-like peptide-1(7-36) amide (GLP-1), hormones that regulate food intake and energy homeostasis and that are products of 2 critical EEC populations--I cells of the small intestine and L cells of the large intestine, respectively. Furthermore, these effects were mediated by the GPCR Ca(2+)-sensing receptor (CaSR) and involved the following serial events: (1)PLC-mediated activation of the IP3 receptor and mobilization of intracellular Ca(2+) stores, (2) activation of transient receptor potential melastatin-5 ion channel and resultant L-type voltage-sensitive Ca(2+) channel-facilitated extracellular Ca(2+) entry, (3) amplification of extracellular Ca(2+) entry by transient receptor potential ankyrin-1 channel activation, and finally (4) Ca(2+)-driven CCK and GLP-1 excytosis. These in vitro findings provide a foundation for future investigation of mechanisms by which DON and other trichothecenes modulate EEC function in ex vivo and in vivo models. PMID:25787141

  8. Transient Receptor Potential Ankyrin 1 Channel in Neuropathic Pain (review)%瞬时受体电位A1通道在神经病理性疼痛中的研究进展

    Institute of Scientific and Technical Information of China (English)

    张林净; 刘若卓; 于生元

    2016-01-01

    Transient receptor potential ankyrin 1 (TRPA1) is a family member of the transient receptor potential (TRPs). It is primarily localized to a subpopulation of primary sensory neurons, such as trigeminus, vagus and dorsal root ganglia. Neuropathic pain is often caused by peripheral nerve injury, diabetes and chemotherapeutics. A large of oxidative/nitrative stress products are produced during neuropathic pain, which cause acute nociception, allodynia, and hyperalgesia. TRPA1 antagonists may be beneficial in the treatment of neuropathic pain. Here, the role of TRPA1 in neuropathic pain is summarized.%瞬时受体电位A1(TRPA1)是瞬时受体电位大家族中的一员,主要分布在初级感觉神经元上,如三叉神经节、迷走神经节及背根神经节。神经病理性疼痛最常见的原因是周围神经损伤、糖尿病以及化疗药物所致。神经病理性疼痛过程中产生的大量氧化、硝化应激产物作用于TRPA1,产生急性伤害感受刺激、异常感觉痛以及多种刺激超敏状态。TRPA1特异性拮抗剂有望用于神经病理性疼痛的治疗。本文总结了TRPA1在神经病理性疼痛中的研究进展。

  9. Repeat surgery after failed midurethral slings

    DEFF Research Database (Denmark)

    Hansen, Margrethe Foss; 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...... they had undergone their primary synthetic MUS. CONCLUSION: In this nationwide cohort study of synthetic MUS a repeat synthetic MUS was the first choice and urethral injection therapy a frequent second choice. The majority of reoperations (82 %) took place in the same department as the primary operation....

  10. Repeating pneumatic pellet injector in JAERI

    International Nuclear Information System (INIS)

    A repeating pneumatic pellet injector has been developed and constructed at Japan Atomic Energy Research Institute. This injector can provide repetitive pellet injection to fuel tokamak plasmas for an extended period of time, aiming at the improvement of plasma performance. The pellets with nearly identical speed and mass can be repeatedly injected with a repetition rate of 2-3.3 Hz and a speed of up to 1.7 km/s by controlling the temperature of the cryogenic system, the piston speed and the pressure of the propellant gas. (author)

  11. Genome-wide Analysis of Kelch Repeat-containing F-box Family

    Institute of Scientific and Technical Information of China (English)

    Yujin Sun; Xiaofan Zhou; Hong Ma

    2007-01-01

    The ubiquitin-dependent protein degradation pathway plays diverse roles in eukaryotes. Previous studies indicate that both F-box and Kelch motifs are common in a variety of organisms. F-box proteins are subunits of E3 ubiquitin ligase complexes called SCFs (SKP1, Cullinl, F-box protein, and Rbx1); they have an N-terminal F-box motif that binds to SKP1 (S-phase kinase associated protein), and often have C-terminal protein-protein interaction domains, which specify the protein substrates for degradation via the ubiquitin pathway. One of the most frequently found protein interaction domains in F-box proteins is the Kelch repeat domain. Although both the F-box and Kelch repeats are ancient motifs, Kelch repeats-containing F-box proteins (KFB) have only been reported for human and Arabidopsis previously. The recent sequencing of the rice genome and other plant genomes provides an opportunity to examine the possible evolution history of KFB. We carried out extensive BLAST searches to identify putative KFBs in selected organisms, and analyzed their relationships phylogenetically. We also carried out the analysis of both gene duplication and gene expression of the KFBs in rice and Arabidopsis. Our study indicates that the origin of KFBs occurs before the divergence of animals and plants, and plant KFBs underwent rapid gene duplications.

  12. Atomic Pseudo-Valuation Domains

    CERN Document Server

    Stines, Elijah

    2012-01-01

    Pseudo-valuation domains have been studied since their introduction in 1978 by Hedstrom and Houston. Related objects, boundary valuation domains, were introduced by Maney in 2004. Here, it is shown that the class of atomic pseudo-valuation domains coincides with the class of boundary valuation domains. It is also shown that power series rings and generalized power series rings give examples of pseudo-valuation domains whose congruence lattices can be characterized. The paper also introduces, and makes use of, a sufficient condition on the group of divisibility of a domain to guarantee that it is a pseudo-valuation domain.

  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. 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.

  15. Cellulose binding domain proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc (Davis, CA); Doi, Roy (Davis, CA)

    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.

  16. Skyrmions and domain walls

    OpenAIRE

    Piette, B.; Zakrzewski, W. J.

    1997-01-01

    We study the 3+1 dimensional Skyrme model with a mass term different from the usual one. We show that this new model possesses domain walls solutions. We describe how, in the equivalent 2+1 dimensional model, the Skyrmion is absorbed by the wall.

  17. 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.

  18. Fuzzy Bases of Fuzzy Domains

    OpenAIRE

    Sanping Rao; Qingguo Li

    2013-01-01

    This paper is an attempt to develop quantitative domain theory over frames. Firstly, we propose the notion of a fuzzy basis, and several equivalent characterizations of fuzzy bases are obtained. Furthermore, the concept of a fuzzy algebraic domain is introduced, and a relationship between fuzzy algebraic domains and fuzzy domains is discussed from the viewpoint of fuzzy basis. We finally give an application of fuzzy bases, where the image of a fuzzy domain can be preserved under some special ...

  19. Atomic Pseudo-Valuation Domains

    OpenAIRE

    Stines, Elijah

    2012-01-01

    Pseudo-valuation domains have been studied since their introduction in 1978 by Hedstrom and Houston. Related objects, boundary valuation domains, were introduced by Maney in 2004. Here, it is shown that the class of atomic pseudo-valuation domains coincides with the class of boundary valuation domains. It is also shown that power series rings and generalized power series rings give examples of pseudo-valuation domains whose congruence lattices can be characterized. The paper also introduces, ...

  20. Sequence-specific DNA binding of individual cut repeats of the human CCAAT displacement/cut homeodomain protein.

    Science.gov (United States)

    Aufiero, B; Neufeld, E J; Orkin, S H

    1994-08-01

    CCAAT displacement protein (CDP), a nuclear protein of 180-190 kDa, contains a triplicated motif, the cut domain, similar (80-90% conserved) to three repeats of 60-65 amino acids first identified in Drosophila cut, a homeo-domain protein involved in cell-fate decisions in development. Cut repeats bind DNA and exhibit subtle differences in target-site recognition. DNA sequences specifically bound by cut repeats were isolated by PCR-mediated DNA target-site selection. Sequences selected for cut repeat 2 and 3 (CR2 and CR3) binding are A+T-rich and favor an ATA motif with similar, but not identical, flanking base preferences. CR2 and CR3 discriminate among similar target sequences. CR1, which is more divergent from CR2 and CR3, displays the most restricted pattern of DNA sequence recognition. Methylation interference analysis demonstrates different protein-DNA contacts for CR1 and CR3 binding to a target sequence. Thus, CDP/cut is a complex protein whose DNA-binding properties reflect the combinatorial interaction of four domains (three cut repeats and one homeodomain) with target DNA sequences. PMID:7914370

  1. 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 ...

  2. 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…

  3. 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…

  4. 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...

  5. 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.

  6. 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)

  7. 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…

  8. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P;

    1991-01-01

    that the psychological climate of the home may be more important than the rupture of early home life. It is noteworthy that the group of repeaters, as against the first-evers, could be characterized by personality disorders and abuse, especially of alcohol: disorders known to be precipitated by a discordant childhood...

  9. 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.

  10. Structural basis for triplet repeat disorders

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves;

    1999-01-01

    that approximately 150 bp is a general threshold length far repeat instability Since this is about the length of DNA wrapped up in a single nucleosome care particle, we speculate that chromatin structure may play an important role in the expansion mechanism. We furthermore suggest that expansion afa dodecamer repent...

  11. 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...

  12. Testing Multiple Outcomes in Repeated Measures Designs

    Science.gov (United States)

    Lix, Lisa M.; Sajobi, Tolulope

    2010-01-01

    This study investigates procedures for controlling the familywise error rate (FWR) when testing hypotheses about multiple, correlated outcome variables in repeated measures (RM) designs. A content analysis of RM research articles published in 4 psychology journals revealed that 3 quarters of studies tested hypotheses about 2 or more outcome…

  13. 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.

  14. 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.

  15. 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

  16. Interacting domains of the HN and F Proteins of paramyxovirus

    Institute of Scientific and Technical Information of China (English)

    WANG Xiaojia; ZHANG Guozhong; ZHAO Jixun; WANG Ming

    2005-01-01

    Binding sialates to hemagglutinin-neuramini- dase (HN) activates (triggers) the fusion protein (F) to start the membrane fusion process of paramyxovirus, but the mechanism by which the HN and F associate with each other to induce membrane fusion is still unclear. It is noteworthy to study the interaction domains of HN and F of paramyxovirus. To screen interacting domains of the HN and F proteins of Avian parainfluenza virus-2 (APIV-2) and identify the structure of binding proteins, the GST pull-down assay and mass spectroscopy (MS) and circular dichroism (CD) experiments were performed in this study. The study revealed that the globular head region of HN protein tends to form a complex with either the heptad repeat 1 (HR1) or the heptad repeat 2 (HR2) of F protein respectively. This paper discusses the novel fusion mechanism induced by paramyxovirus HN and F proteins.

  17. Accuracy of velocities from repeated GPS measurements

    Science.gov (United States)

    Akarsu, V.; Sanli, D. U.; Arslan, E.

    2015-04-01

    Today repeated GPS measurements are still in use, because we cannot always employ GPS permanent stations due to a variety of limitations. One area of study that uses velocities/deformation rates from repeated GPS measurements is the monitoring of crustal motion. This paper discusses the quality of the velocities derived using repeated GPS measurements for the aim of monitoring crustal motion. From a global network of International GNSS Service (IGS) stations, we processed GPS measurements repeated monthly and annually spanning nearly 15 years and estimated GPS velocities for GPS baseline components latitude, longitude and ellipsoidal height. We used web-based GIPSY for the processing. Assuming true deformation rates can only be determined from the solutions of 24 h observation sessions, we evaluated the accuracy of the deformation rates from 8 and 12 h sessions. We used statistical hypothesis testing to assess the velocities derived from short observation sessions. In addition, as an alternative control method we checked the accuracy of GPS solutions from short observation sessions against those of 24 h sessions referring to statistical criteria that measure the accuracy of regression models. Results indicate that the velocities of the vertical component are completely affected when repeated GPS measurements are used. The results also reveal that only about 30% of the 8 h solutions and about 40% of 12 h solutions for the horizontal coordinates are acceptable for velocity estimation. The situation is much worse for the vertical component in which none of the solutions from campaign measurements are acceptable for obtaining reliable deformation rates.

  18. 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.

  19. Domain-specific languages

    OpenAIRE

    Jasný, Vojtěch

    2009-01-01

    The topic of the thesis are domain-specific languages (DSL) and their use in software development. The target audience are developers interested in learning more about this progressive area of software development. It starts with a necessary theoretical introduction to programming languages. Then, a classification of DSLs is given and software development methodologies based on DSLs are described, notably Language Oriented Programming and Intentional Programming. Another important piece in co...

  20. Implementing maritime domain awareness

    OpenAIRE

    Watts, Robert B.

    2006-01-01

    CHDS State/Local As an attempt to gain understanding of everything in the global maritime environment that can impact the security of the United States, the Maritime Domain Awareness initiative is one of the most ambitious projects ever undertaken by the U.S. government. Information that falls under the prevue of MDA is tremendously diverse and complex, having application in the regulatory, law enforcement, and military arenas. As such, MDA is a multi-agency effort that encompasses 16 resp...

  1. 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...

  2. On Free Z-domains%自由Z-domain

    Institute of Scientific and Technical Information of China (English)

    姚丽娟; 徐晓泉

    2011-01-01

    给出由偏序集生成的自由Z-domain,讨论自由Z-domain和偏序集的Dedekind-MacNeille完备化的一些性质.%The free Z-domains generated by posets are given.Some properties of tte free Z-domains and the Dedekind-MacNeille completions of posets are investigated.

  3. Designed armadillo repeat proteins as general peptide-binding scaffolds: consensus design and computational optimization of the hydrophobic core

    DEFF Research Database (Denmark)

    Parmeggiani, Fabio; Pellarin, Riccardo; Larsen, Anders Peter;

    2007-01-01

    Armadillo repeat proteins are abundant eukaryotic proteins involved in several cellular processes, including signaling, transport, and cytoskeletal regulation. They are characterized by an armadillo domain, composed of tandem armadillo repeats of approximately 42 amino acids, which mediates...... interactions with peptides or parts of proteins in extended conformation. The conserved binding mode of the peptide in extended form, observed for different targets, makes armadillo repeat proteins attractive candidates for the generation of modular peptide-binding scaffolds. Taking advantage of the large...... number of repeat sequences available, a consensus-based approach combined with a force field-based optimization of the hydrophobic core was used to derive soluble, highly expressed, stable, monomeric designed proteins with improved characteristics compared to natural armadillo proteins. These sequences...

  4. 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

  5. Origin and evolution of glutamyl-prolyl tRNA synthetase WHEP domains reveal evolutionary relationships within Holozoa.

    Directory of Open Access Journals (Sweden)

    Partho Sarothi Ray

    Full Text Available Repeated domains in proteins that have undergone duplication or loss, and sequence divergence, are especially informative about phylogenetic relationships. We have exploited divergent repeats of the highly structured, 50-amino acid WHEP domains that join the catalytic subunits of bifunctional glutamyl-prolyl tRNA synthetase (EPRS as a sequence-informed repeat (SIR to trace the origin and evolution of EPRS in holozoa. EPRS is the only fused tRNA synthetase, with two distinct aminoacylation activities, and a non-canonical translation regulatory function mediated by the WHEP domains in the linker. Investigating the duplications, deletions and divergence of WHEP domains, we traced the bifunctional EPRS to choanozoans and identified the fusion event leading to its origin at the divergence of ichthyosporea and emergence of filozoa nearly a billion years ago. Distribution of WHEP domains from a single species in two or more distinct clades suggested common descent, allowing the identification of linking organisms. The discrete assortment of choanoflagellate WHEP domains with choanozoan domains as well as with those in metazoans supported the phylogenetic position of choanoflagellates as the closest sister group to metazoans. Analysis of clustering and assortment of WHEP domains provided unexpected insights into phylogenetic relationships amongst holozoan taxa. Furthermore, observed gaps in the transition between WHEP domain groupings in distant taxa allowed the prediction of undiscovered or extinct evolutionary intermediates. Analysis based on SIR domains can provide a phylogenetic counterpart to palaentological approaches of discovering "missing links" in the tree of life.

  6. 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.

  7. 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.

  8. Repeated interactions in open quantum systems

    International Nuclear Information System (INIS)

    Analyzing the dynamics of open quantum systems has a long history in mathematics and physics. Depending on the system at hand, basic physical phenomena that one would like to explain are, for example, convergence to equilibrium, the dynamics of quantum coherences (decoherence) and quantum correlations (entanglement), or the emergence of heat and particle fluxes in non-equilibrium situations. From the mathematical physics perspective, one of the main challenges is to derive the irreversible dynamics of the open system, starting from a unitary dynamics of the system and its environment. The repeated interactions systems considered in these notes are models of non-equilibrium quantum statistical mechanics. They are relevant in quantum optics, and more generally, serve as a relatively well treatable approximation of a more difficult quantum dynamics. In particular, the repeated interaction models allow to determine the large time (stationary) asymptotics of quantum systems out of equilibrium

  9. Repeated interactions in open quantum systems

    Energy Technology Data Exchange (ETDEWEB)

    Bruneau, Laurent, E-mail: laurent.bruneau@u-cergy.fr [Laboratoire AGM, Université de Cergy-Pontoise, Site Saint-Martin, BP 222, 95302 Cergy-Pontoise (France); Joye, Alain, E-mail: Alain.Joye@ujf-grenoble.fr [Institut Fourier, UMR 5582, CNRS-Université Grenoble I, BP 74, 38402 Saint-Martin d’Hères (France); Merkli, Marco, E-mail: merkli@mun.ca [Department of Mathematics and Statistics Memorial University of Newfoundland, St. John' s, NL Canada A1C 5S7 (Canada)

    2014-07-15

    Analyzing the dynamics of open quantum systems has a long history in mathematics and physics. Depending on the system at hand, basic physical phenomena that one would like to explain are, for example, convergence to equilibrium, the dynamics of quantum coherences (decoherence) and quantum correlations (entanglement), or the emergence of heat and particle fluxes in non-equilibrium situations. From the mathematical physics perspective, one of the main challenges is to derive the irreversible dynamics of the open system, starting from a unitary dynamics of the system and its environment. The repeated interactions systems considered in these notes are models of non-equilibrium quantum statistical mechanics. They are relevant in quantum optics, and more generally, serve as a relatively well treatable approximation of a more difficult quantum dynamics. In particular, the repeated interaction models allow to determine the large time (stationary) asymptotics of quantum systems out of equilibrium.

  10. 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.

  11. 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....

  12. 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

  13. 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...

  14. Aging and Repeated Thought Suppression Success

    OpenAIRE

    Ann E Lambert; Smyth, Frederick L.; Jessica R Beadel; Teachman, Bethany A.

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differe...

  15. Repeat Gamma Knife surgery for vestibular schwannomas

    OpenAIRE

    Sarah Lonneville; Carine Delbrouck; Cécile Renier; Daniel Devriendt; Nicolas Massager

    2015-01-01

    Background: Gamma Knife (GK) surgery is a recognized treatment option for the management of small to medium-sized vestibular schwannoma (VS) associated with high-tumor control and low morbidity. When a radiosurgical treatment fails to stop tumor growth, repeat GK surgery can be proposed in selected cases. Methods : A series of 27 GK retreatments was performed in 25 patients with VS; 2 patients underwent three procedures. The median time interval between GK treatments was 45 months. The me...

  16. 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.

  17. Capacities of repeater-assisted quantum communications

    OpenAIRE

    Pirandola, Stefano

    2016-01-01

    We establish the ultimate rates for transmitting quantum information, distilling entanglement, and distributing secret keys in repeater-assisted quantum communications, under the most fundamental decoherence models for both discrete and continuous variable systems, including lossy channels, quantum-limited amplifiers, dephasing and erasure channels. These capacities are derived considering the most general adaptive protocols for quantum and private communication between the two end-points of ...

  18. Repeated Optional Gambles and Risk Aversion

    OpenAIRE

    Christian Gollier

    1996-01-01

    We analyze in this paper the effect of age on the optimal dynamic strategy toward repeated independent gambles. When deciding to accept or to reject a lottery that is offered today, the gambler knows how many lotteries can yet be played in the future. We first characterize the optimal dynamic strategy when future lotteries are identically distributed. We show that the existence of future lotteries always increases the willingness to gamble today. When the sequence of lotteries is independent ...

  19. Quantum Key Distribution over Probabilistic Quantum Repeaters

    OpenAIRE

    Amirloo, Jeyran; Razavi, Mohsen; 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 a...

  20. Homophilic interactions mediated by receptor tyrosine phosphatases mu and kappa. A critical role for the novel extracellular MAM domain

    DEFF Research Database (Denmark)

    Zondag, G C; Koningstein, G M; Jiang, Y P;

    1995-01-01

    The receptor-like protein tyrosine phosphatases (RPTP) mu and RPTP kappa have a modular ectodomain consisting of four fibronectin type III-like repeats, a single Ig-like domain, and a newly identified N-terminal MAM domain. The function of the latter module, which comprises about 160 amino acids...

  1. Multiplexing schemes for quantum repeater networks

    Science.gov (United States)

    Aparicio, Luciano; Van Meter, Rodney

    2011-08-01

    When built, quantum repeaters will allow the distribution of entangled quantum states across large distances, playing a vital part in many proposed quantum technologies. Enabling multiple users to connect through the same network will be key to their real-world deployment. Previous work on repeater technologies has focussed only on simple entanglment production, without considering the issues of resource scarcity and competition that necessarily arise in a network setting. In this paper we simulated a thirteen-node network with up to five flows sharing different parts of the network, measuring the total throughput and fairness for each case. Our results suggest that the Internet-like approach of statistical multiplexing use of a congested link gives the highest aggregate throughput. Time division multiplexing and buffer space multiplexing were slightly less effective, but all three schemes allow the sum of multiple flows to substantially exceed that of any one flow, improving over circuit switching by taking advantage of resources that are forced to remain idle in circuit switching. All three schemes proved to have excellent fairness. The high performance, fairness and simplicity of implementation support a recommendation of statistical multiplexing for shared quantum repeater networks.

  2. Domain Engineering: An Empirical Study

    OpenAIRE

    Harris, Charles; Frakes, William B.

    2006-01-01

    This paper presents a summary and analysis of data gathered from thirteen domain engineering projects, participant surveys, and demographic information. Taking a failure modes approach, project data is compared to an ideal model of the DARE methodology, revealing valuable insights into points of failure in the domain engineering process. This study suggests that success is a function of the domain analyst’s command of a specific set of domain engineering concepts and skills, the time invested...

  3. A Convenient Category of Domains

    OpenAIRE

    Battenfeld, Ingo; Schröder, Matthias; Simpson, Alexander

    2007-01-01

    We motivate and define a category of topological domains, whose objects are certain topological spaces, generalising the usual ω-continuous dcppos of domain theory. Our category supports all the standard constructions of domain theory, including the solution of recursive domain equations. It also supports the construction of free algebras for (in)equational theories, can be used as the basis for a theory of computability, and provides a model of parametric polymorphism.

  4. A convenient category of domains

    OpenAIRE

    Battenfeld, Ingo; Schröder, Matthias; Simpson, Alex

    2007-01-01

    We motivate and define a category of "topological domains", whose objects are certain topological spaces, generalising the usual $omega$-continuous dcppos of domain theory. Our category supports all the standard constructions of domain theory, including the solution of recursive domain equations. It also supports the construction of free algebras for (in)equational theories, provides a model of parametric polymorphism, and can be used as the basis for a theory of computab...

  5. Myb-domain protein Teb1 controls histone levels and centromere assembly in fission yeast

    OpenAIRE

    Valente, Luis P.; Dehé, Pierre-Marie; Klutstein, Michael; Aligianni, Sofia; Watt, Stephen; Bähler, Jürg; Promisel Cooper, Julia

    2013-01-01

    The TTAGGG motif is common to two seemingly unrelated dimensions of chromatin function—the vertebrate telomere repeat and the promoter regions of many Schizosaccharomyces pombe genes, including all of those encoding canonical histones. The essential S. pombe protein Teb1 contains two Myb-like DNA binding domains related to those found in telomere proteins and binds the human telomere repeat sequence TTAGGG. Here, we analyse Teb1 binding throughout the genome and the consequences of reduced Te...

  6. The Domain Structure of Centromeres Is Conserved from Fission Yeast to Humans

    OpenAIRE

    Kniola, Barbara; O'Toole, Eileen; McIntosh, J. Richard; Mellone, Barbara; Allshire, Robin; Mengarelli, Silwa; Hultenby, Kjell; Ekwall, Karl

    2001-01-01

    The centromeric DNA of fission yeast is arranged with a central core flanked by repeated sequences. The centromere-associated proteins, Mis6p and Cnp1p (SpCENP-A), associate exclusively with central core DNA, whereas the Swi6 protein binds the surrounding repeats. Here, electron microscopy and immunofluorescence light microscopy reveal that the central core and flanking regions occupy distinct positions within a heterochromatic domain. An “anchor” structure containing ...

  7. Conservation of the Human Integrin-Type Beta-Propeller Domain in Bacteria

    Science.gov (United States)

    Chouhan, Bhanupratap; Denesyuk, Alexander; Heino, Jyrki; Johnson, Mark S.; Denessiouk, Konstantin

    2011-01-01

    Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and sometimes two tandem

  8. Conservation of the human integrin-type beta-propeller domain in bacteria.

    Directory of Open Access Journals (Sweden)

    Bhanupratap Chouhan

    Full Text Available Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca(2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca(2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and

  9. Domain Bridging Associations Support Creativity

    OpenAIRE

    Kötter, Tobias; Thiel, Kilian; Berthold, Michael R

    2010-01-01

    This paper proposes a new approach to support creativity through assisting the discovery of unexpected associations across different domains. This is achieved by integrating information from heterogeneous domains into a single network, enabling the interactive discovery of links across the corresponding information resources. We discuss three different pattern of domain crossing associations in this context.

  10. A novel 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime compound is a potent Transient Receptor Potential Ankyrin 1 and Vanilloid 1 (TRPA1 and V1) receptor antagonist.

    Science.gov (United States)

    Payrits, M; Sághy, É; Mátyus, P; Czompa, A; Ludmerczki, R; Deme, R; Sándor, Z; Helyes, Zs; Szőke, É

    2016-06-01

    Transient Receptor Potential Ankyrin 1 and Vanilloid 1 (TRPA1, TRPV1) ion channels expressed on nociceptive primary sensory neurons are important regulators of pain and inflammation. TRPA1 is activated by several inflammatory mediators including formaldehyde and methylglyoxal that are products of the semicarbazide-sensitive amine-oxidase enzyme (SSAO). SZV-1287 is a new 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime SSAO inhibitor, its chemical structure is similar to other oxime derivatives described as TRPA1 antagonists. Therefore, we investigated its effects on TRPA1 and TRPV1 receptor activation on the cell bodies and peripheral terminals of primary sensory neurons and TRPA1 or TRPV1 receptor-expressing cell lines. Calcium influx in response to the TRPA1 agonist allyl-isothiocyanate (AITC) (200μM) and the TRPV1 stimulator capsaicin (330nM) in rat trigeminal neurons or TRPA1 and TRPV1 receptor-expressing cell lines was measured by microfluorimetry or radioactive (45)Ca(2+) uptake experiments. Calcitonin gene-related peptide (CGRP) release as the indicator of 100μM AITC - or 100nM capsaicin-induced peripheral sensory nerve terminal activation was measured by radioimmunoassay. SZV-1287 (100, 500 and 1000nM) exerted a concentration-dependent significant inhibition on both AITC- and capsaicin-evoked calcium influx in trigeminal neurons and TRPA1 or TRPV1 receptor-expressing cell lines. It also significantly inhibited the TRPA1, but not the TRPV1 activation-induced CGRP release from the peripheral sensory nerve endings in a concentration-dependent manner. In contrast, the reference SSAO inhibitor LJP 1207 with a different structure had no effect on TRPA1 or TRPV1 activation in either model system. This is the first evidence that our novel oxime compound SZV-1287 originally developed as a SSAO inhibitor has a potent dual antagonistic action on TRPA1 and TRPV1 ion channels on primary sensory neurons. PMID:26930003

  11. 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.

  12. A Complete and Accurate Ab Initio Repeat Finding Algorithm.

    Science.gov (United States)

    Lian, Shuaibin; Chen, Xinwu; Wang, Peng; Zhang, Xiaoli; Dai, Xianhua

    2016-03-01

    It has become clear that repetitive sequences have played multiple roles in eukaryotic genome evolution including increasing genetic diversity through mutation, changes in gene expression and facilitating generation of novel genes. However, identification of repetitive elements can be difficult in the ab initio manner. Currently, some classical ab initio tools of finding repeats have already presented and compared. The completeness and accuracy of detecting repeats of them are little pool. To this end, we proposed a new ab initio repeat finding tool, named HashRepeatFinder, which is based on hash index and word counting. Furthermore, we assessed the performances of HashRepeatFinder with other two famous tools, such as RepeatScout and Repeatfinder, in human genome data hg19. The results indicated the following three conclusions: (1) The completeness of HashRepeatFinder is the best one among these three compared tools in almost all chromosomes, especially in chr9 (8 times of RepeatScout, 10 times of Repeatfinder); (2) in terms of detecting large repeats, HashRepeatFinder also performed best in all chromosomes, especially in chr3 (24 times of RepeatScout and 250 times of Repeatfinder) and chr19 (12 times of RepeatScout and 60 times of Repeatfinder); (3) in terms of accuracy, HashRepeatFinder can merge the abundant repeats with high accuracy. PMID:26272474

  13. 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.

  14. 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...

  15. ACTN1 rod domain mutation associated with congenital macrothrombocytopenia.

    Science.gov (United States)

    Yasutomi, Motoko; Kunishima, Shinji; Okazaki, Shintaro; Tanizawa, Akihiko; Tsuchida, Shinya; Ohshima, Yusei

    2016-01-01

    Mutations in ACTN1, the gene encoding the actin-crosslinking protein α-actinin-1, cause autosomal dominant macrothrombocytopenia. α-Actinin-1 exists as antiparallel dimers, composed of an N-terminal actin-binding domain (ABD), four spectrin-like repeats (SLRs), which form the spacer rod, and a C-terminal calmodulin-like (CaM) domain. All of the previously reported ACTN1 mutations associated with macrothrombocytopenia reside within the ABD and the CaM domain and not within the SLR domain. In this report, we describe a mutation in SLR2 of α-actinin-1 (p.Leu395Gln) associated with familial macrothrombocytopenia. A 3-year-old boy and his mother both had this mutation. They showed a mild form of thrombocytopenia without severe bleeding, accompanied by an elevated mean platelet volume. Consistent with the previous reports of mutations that reside in the ABD or the CaM domain, immunofluorescence examination revealed disorganization of the actin cytoskeleton in Gln395 mutant-transduced Chinese hamster ovary cells. Our findings suggest a novel mechanism for the pathogenesis of ACTN1-related macrothrombocytopenia that does not involve functional domain mutations. PMID:26453073

  16. The phosphoCTD-interacting domain of Topoisomerase I

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jianhong; Phatnani, Hemali P.; Hsieh, Tao-Shih [Department of Biochemistry, Duke University Medical Center, Durham, NC 27710 (United States); Greenleaf, Arno L., E-mail: arno.greenleaf@duke.edu [Department of Biochemistry, Duke University Medical Center, Durham, NC 27710 (United States)

    2010-06-18

    The N-terminal domain (NTD) of Drosophila melanogaster (Dm) Topoisomerase I has been shown to bind to RNA polymerase II, but the domain of RNAPII with which it interacts is not known. Using bacterially-expressed fusion proteins carrying all or half of the NTDs of Dm and human (Homo sapiens, Hs) Topo I, we demonstrate that the N-terminal half of each NTD binds directly to the hyperphosphorylated C-terminal repeat domain (phosphoCTD) of the largest RNAPII subunit, Rpb1. Thus, the amino terminal segment of metazoan Topo I (1-157 for Dm and 1-114 for Hs) contains a novel phosphoCTD-interacting domain that we designate the Topo I-Rpb1 interacting (TRI) domain. The long-known in vivo association of Topo I with active genes presumably can be attributed, wholly or in part, to the TRI domain-mediated binding of Topo I to the phosphoCTD of transcribing RNAPII.

  17. The phosphoCTD-interacting domain of Topoisomerase I

    International Nuclear Information System (INIS)

    The N-terminal domain (NTD) of Drosophila melanogaster (Dm) Topoisomerase I has been shown to bind to RNA polymerase II, but the domain of RNAPII with which it interacts is not known. Using bacterially-expressed fusion proteins carrying all or half of the NTDs of Dm and human (Homo sapiens, Hs) Topo I, we demonstrate that the N-terminal half of each NTD binds directly to the hyperphosphorylated C-terminal repeat domain (phosphoCTD) of the largest RNAPII subunit, Rpb1. Thus, the amino terminal segment of metazoan Topo I (1-157 for Dm and 1-114 for Hs) contains a novel phosphoCTD-interacting domain that we designate the Topo I-Rpb1 interacting (TRI) domain. The long-known in vivo association of Topo I with active genes presumably can be attributed, wholly or in part, to the TRI domain-mediated binding of Topo I to the phosphoCTD of transcribing RNAPII.

  18. Versatile TPR domains accommodate different modes of target protein recognition and function.

    Science.gov (United States)

    Allan, Rudi Kenneth; Ratajczak, Thomas

    2011-07-01

    The tetratricopeptide repeat (TPR) motif is one of many repeat motifs that form structural domains in proteins that can act as interaction scaffolds in the formation of multi-protein complexes involved in numerous cellular processes such as transcription, the cell cycle, protein translocation, protein degradation and host defence against invading pathogens. The crystal structures of many TPR domain-containing proteins have been determined, showing TPR motifs as two anti-parallel α-helices packed in tandem arrays to form a structure with an amphipathic groove which can bind a target peptide. This is however not the only mode of target recognition by TPR domains, with short amino acid insertions and alternative TPR motif conformations also shown to contribute to protein interactions, highlighting diversity in TPR domains and the versatility of this structure in mediating biological events.

  19. Domain structures and magnetization reversal in Co/Pd and CoFeB/Pd multilayers

    Energy Technology Data Exchange (ETDEWEB)

    Sbiaa, R., E-mail: rachid@squ.edu.om [Department of Physics, Sultan Qaboos University, P.O. Box 36, PC 123 (Oman); Ranjbar, M. [Physics Department, University of Gothenburg, 412 96 Gothenburg (Sweden); Åkerman, J. [Physics Department, University of Gothenburg, 412 96 Gothenburg (Sweden); Materials Physics, School of ICT, Royal Institute of Technology (KTH), 164 40 Kista (Sweden)

    2015-05-07

    Domain structures and magnetization reversal of (Co/Pd) and (CoFeB/Pd) multilayers with 7 and 14 repeats were investigated. The Co-based multilayers show much larger coercivities, a better squareness, and a sharper magnetization switching than CoFeB-based multilayers. From magnetic force microscopy observations, both structures show strong reduction in domains size as the number of repeats increases but the magnetic domains for Co-based multilayers are more than one order of magnitude larger than for CoFeB-based multilayers. By imaging domains at different times, breaks in the (CoFeB/Pd) multilayer stripes were observed within only few hours, while no change could be seen for (Co/Pd) multilayers. Although CoFeB single layers are suitable for magnetoresistive devices due to their large spin polarization and low damping constants, their lamination with Pd suffers mainly from thermal instability.

  20. The framing of scientific domains

    DEFF Research Database (Denmark)

    Dam Christensen, Hans

    2014-01-01

    Purpose: By using the UNISIST models this article argues for the necessity of domain analysis in order to qualify scientific information seeking. The models better understanding of communication processes in a scientific domain and embraces the point that domains are always both unstable over time...... and changeable according to the specific perspective. This understanding is even more important today as numerous digitally generated information tools as well as collaborative and interdisciplinary research are blurring the domain borders. Nevertheless, researchers navigate “intuitively” in “their” specific...... as according to the agents that are charting them. As such, power in a Foucauldian sense is unavoidable in outlining a domain. Originality/value 1. The UNISIST models are applied to the domain of art history; and 2. the article discusses the instability of a scientific domain as well as, at the same time...

  1. An efficient repeating signal detector to investigate earthquake swarms

    Science.gov (United States)

    Skoumal, Robert J.; Brudzinski, Michael R.; Currie, Brian S.

    2016-08-01

    Repetitive earthquake swarms have been recognized as key signatures in fluid injection induced seismicity, precursors to volcanic eruptions, and slow slip events preceding megathrust earthquakes. We investigate earthquake swarms by developing a Repeating Signal Detector (RSD), a computationally efficient algorithm utilizing agglomerative clustering to identify similar waveforms buried in years of seismic recordings using a single seismometer. Instead of relying on existing earthquake catalogs of larger earthquakes, RSD identifies characteristic repetitive waveforms by rapidly identifying signals of interest above a low signal-to-noise ratio and then grouping based on spectral and time domain characteristics, resulting in dramatically shorter processing time than more exhaustive autocorrelation approaches. We investigate seismicity in four regions using RSD: (1) volcanic seismicity at Mammoth Mountain, California, (2) subduction-related seismicity in Oaxaca, Mexico, (3) induced seismicity in Central Alberta, Canada, and (4) induced seismicity in Harrison County, Ohio. In each case, RSD detects a similar or larger number of earthquakes than existing catalogs created using more time intensive methods. In Harrison County, RSD identifies 18 seismic sequences that correlate temporally and spatially to separate hydraulic fracturing operations, 15 of which were previously unreported. RSD utilizes a single seismometer for earthquake detection which enables seismicity to be quickly identified in poorly instrumented regions at the expense of relying on another method to locate the new detections. Due to the smaller computation overhead and success at distances up to ~50 km, RSD is well suited for real-time detection of low-magnitude earthquake swarms with permanent regional networks.

  2. Telomeric Repeat Containing RNA (TERRA): Aging and Cancer.

    Science.gov (United States)

    Sinha, Sonam; Shukla, Samriddhi; Khan, Sajid; Farhan, Mohammad; Kamal, Mohammad Amjad; Meeran, Syed Musthapa

    2015-01-01

    Telomeric repeat containing RNAs (TERRA) are small RNA molecules synthesized from telomeric regions which were previously considered as silent genomic domains. In normal cells, these RNAs are transcribed in a direction from subtelomeric region towards the chromosome ends, but in case of cancer cells, their expression remains limited or absent. Telomerase is a rate limiting enzyme for cellular senescence, cancer and aging. Most of the studies deal with the manipulation of telomerase enzyme in cancer and aging either by synthetic oligonucleotide or by natural phytochemicals. Here, we collected evidences and discussed intensely about the bio-molecular structure of TERRA, naturally occurring ligands of telomerase, and their genetic and epigenetic regulations in aging associated diseases. Due to their capability to act as naturally occurring ligands of telomerase, these RNAs can overcome the limitations possessed by synthetic oligonucleotides, which are aimed against telomerase. Drugs specifically targeting TERRA molecules could modulate telomerase-mediated telomere lengthening. Thus, targeting TERRA-mediated regulation of telomerase would be a promising therapeutic strategy against cancer and age-associated diseases.

  3. Hydroxychloroquine binding to cytoplasmic domain of Band 3 in human erythrocytes: Novel mechanistic insights into drug structure, efficacy and toxicity.

    Science.gov (United States)

    Nakagawa, Mizuki; Sugawara, Kotomi; Goto, Tatsufumi; Wakui, Hideki; Nunomura, Wataru

    2016-05-13

    Hydroxychloroquine (HCQ) is a widely used drug in the treatment of autoimmune diseases, such as arthritis and systemic lupus erythematosus. It has also been prescribed for the treatment of malaria owing to its lower toxicity compared to its closely related compound chloroquine (CQ). However, the mechanisms of action of HCQ in erythrocytes (which bind preferentially this drug) have not been documented and the reasons underlying the lower side effects of HCQ compared to CQ remain unclear. Here we show that, although the activity of erythrocyte lactate dehydrogenase (LDH), but not GAPDH, was inhibited by both HCQ and CQ in vitro, LDH activity in erythrocytes incubated with 20 mM HCQ was not significantly reduced within 5 h in contrast to CQ did. Using HCQ coupled Sepharose chromatography (HCQ-Sepharose), we identified Band 3, spectrin, ankyrin, protein 4.1R and protein 4.2 as HCQ binding proteins in human erythrocyte plasma membrane. Recombinant cytoplasmic N-terminal 43 kDa domain of Band 3 bound to HCQ-Sepharose and was eluted with 40 mM (but not 20 mM) HCQ. Band 3 transport activity was reduced by only 23% in the presence of 20 mM HCQ. Taken together, these data demonstrate that HCQ binds to the cytoplasmic N-terminal domain of Band 3 in human erythrocytes but does not inhibit dramatically its transport activity. We hypothesize that the trapping of HCQ on Band 3 contributes to the lower side effects of the drug on energy production in erythrocytes. PMID:27049308

  4. Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin.

    Science.gov (United States)

    Bhutoria, Savita; Kalpana, Ganjam V; Acharya, Seetharama A

    2016-09-01

    The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein-protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV-1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c-MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. PMID:27261671

  5. Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin.

    Science.gov (United States)

    Bhutoria, Savita; Kalpana, Ganjam V; Acharya, Seetharama A

    2016-09-01

    The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein-protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV-1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c-MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1.

  6. Repeated vitrification/warming of human sperm gives better results than repeated slow programmable freezing

    Institute of Scientific and Technical Information of China (English)

    Teraporn Vutyavanich; Worashorn Lattiwongsakorn; Waraporn Piromlertamorn; Sudarat Samchimchom

    2012-01-01

    In this study,we compared the effects of repeated freezing/thawing of human sperm by our in-house method of rapid freezing with slow programmable freezing.Sperm samples from 11 normozoospermic subjects were processed through density gradients and divided into three aliquots:non-frozen,rapid freezing and slow programmable freezing.Sperm in the rapid freezing group had better motility and viability than those in the slow freezing group (P<O.01) after the first,second and third cycles of freezing/thawing,but there was no difference in morphology.In the second experiment,rapid freezing was repeated three times in 20 subjects.The samples from each thawing cycle were evaluated for DNA fragmentation using the alkaline comet assay.DNA fragmentation began to increase considerably after the second cycle of freezing/thawing,but to a level that was not clinically important.In the third experiment,rapid freezing was done repeatedly in 10 subjects,until no motile sperm were observed after thawing.The median number of repeated freezing/thawing that yielded no motile sperm was seven (range:5-8,mean:6.8).In conclusion,we demonstrated that repeated freezing/thawing of processed semen using our rapid freezing method gave better results than standard slow programmable freezing.This method can help maximize the usage of precious cryopreserved sperm samples in assisted reproduction technology.

  7. A tandem repeat gene in a picornavirus.

    OpenAIRE

    Forss, S; Schaller, H

    1982-01-01

    Three closely related genes for the small genome-linked protein (VPg) of picornaviruses have been identified by sequence analysis as a tandem repeat in the genome of Foot and Mouth Disease Virus (FMDV), strain O1K. This unusual structure was also found in the genome of strain C1O, belonging to a different FMDV serotype. Predicted biochemical properties of the three VPg gene products are in excellent agreement with the data from protein analysis of a heterogeneous VPg population from a third F...

  8. Source coding model for repeated snapshot imaging

    CERN Document Server

    Li, Junhui; Yang, Dongyue; wu, Guohua; Yin, Longfei; Guo, Hong

    2016-01-01

    Imaging based on successive repeated snapshot measurement is modeled as a source coding process in information theory. The necessary number of measurement to maintain a certain level of error rate is depicted as the rate-distortion function of the source coding. Quantitative formula of the error rate versus measurement number relation is derived, based on the information capacity of imaging system. Second order fluctuation correlation imaging (SFCI) experiment with pseudo-thermal light verifies this formula, which paves the way for introducing information theory into the study of ghost imaging (GI), both conventional and computational.

  9. Mechanical processes with repeated attenuated impacts

    CERN Document Server

    Nagaev, R F

    1999-01-01

    This book is devoted to considering in the general case - using typical concrete examples - the motion of machines and mechanisms of impact and vibro-impact action accompanied by a peculiar phenomenon called "impact collapse". This phenomenon is that after the initial collision, a sequence of repeated gradually quickening collisions of decreasing-to-zero intensity occurs, with the final establishment of protracted contact between the interacting bodies. The initiation conditions of the impact collapse are determined and calculation techniques for the quantitative characteristics of the corresp

  10. Platelet peripheral benzodiazepine receptors in repeated stress

    Energy Technology Data Exchange (ETDEWEB)

    Dar, D.E.; Bidder, M.; Gavish, M. (Technion-Israel Institute of Technology, Haifa (Israel)); Weizman, A.; Karp, L.; Tyano, S. (Tel Aviv Univ. (Israel)); Grinshpoon, A.; Bleich, A.

    1991-01-01

    ({sup 3}H)PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.

  11. Protein domain organisation: adding order

    Directory of Open Access Journals (Sweden)

    Kummerfeld Sarah K

    2009-01-01

    Full Text Available Abstract Background Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. Results We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Conclusion Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected

  12. Repetitive sequences in the crocodilian mitochondrial control region: poly-A sequences and heteroplasmic tandem repeats.

    Science.gov (United States)

    Ray, David A; Densmore, Llewellyn D

    2003-06-01

    Heteroplasmic tandem repeats in the mitochondrial control region have been documented in a wide variety of vertebrate species. We have examined the control region from 11 species in the family Crocodylidae and identified two different types of heteroplasmic repetitive sequences in the conserved sequence block (CSB) domain-an extensive poly-A tract that appears to be involved in the formation of secondary structure and a series of tandem repeats located downstream ranging from approximately 50 to approximately 80 bp in length. We describe this portion of the crocodylian control region in detail and focus on members of the family Crocodylidae. We then address the origins of the tandemly repeated sequences in this family and suggest hypotheses to explain possible mechanisms of expansion/contraction of the sequences. We have also examined control region sequences from Alligator and Caiman and offer hypotheses for the origin of tandem repeats found in those taxa. Finally, we present a brief analysis of intraindividual and interindividual haplotype variation by examining representatives of Morelet's crocodile (Crocodylus moreletii). PMID:12716979

  13. Starch‐binding domains in the CBM45 family – low‐affinity domains from glucan, water dikinase and α‐amylase involved in plastidial starch metabolism

    DEFF Research Database (Denmark)

    Glaring, Mikkel Andreas; Baumann, Martin; Abou Hachem, Maher;

    2011-01-01

    Starch‐binding domains are noncatalytic carbohydrate‐binding modules that mediate binding to granular starch. The starch‐binding domains from the carbohydrate‐binding module family 45 (CBM45, ) are found as N‐terminal tandem repeats in a small number of enzymes, primarily from photosynthesizing...... amylolytic enzymes. This suggests that low‐affinity starch‐binding domains are a recurring feature in plastidial starch metabolism, and supports the hypothesis that reversible binding, effectuated through low‐affinity interaction with starch granules, facilitates dynamic regulation of enzyme activities and...... organisms. Isolated domains from representatives of each of the two classes of enzyme carrying CBM45‐type domains, the Solanum tuberosumα‐glucan, water dikinase and the Arabidopsis thaliana plastidial α‐amylase 3, were expressed as recombinant proteins and characterized. Differential scanning calorimetry...

  14. Automated Planning in Repeated Adversarial Games

    CERN Document Server

    de Cote, Enrique Munoz; Sykulski, Adam M; Jennings, Nicholas R

    2012-01-01

    Game theory's prescriptive power typically relies on full rationality and/or self-play interactions. In contrast, this work sets aside these fundamental premises and focuses instead on heterogeneous autonomous interactions between two or more agents. Specifically, we introduce a new and concise representation for repeated adversarial (constant-sum) games that highlight the necessary features that enable an automated planing agent to reason about how to score above the game's Nash equilibrium, when facing heterogeneous adversaries. To this end, we present TeamUP, a model-based RL algorithm designed for learning and planning such an abstraction. In essence, it is somewhat similar to R-max with a cleverly engineered reward shaping that treats exploration as an adversarial optimization problem. In practice, it attempts to find an ally with which to tacitly collude (in more than two-player games) and then collaborates on a joint plan of actions that can consistently score a high utility in adversarial repeated gam...

  15. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  16. Repeated proton beam therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A

  17. Extending Teach and Repeat to Pivoting Wheelchairs

    Directory of Open Access Journals (Sweden)

    Guillermo Del Castillo

    2003-02-01

    Full Text Available The paper extends the teach-and-repeat paradigm that has been successful for the control of holonomic robots to nonholonomic wheelchairs which may undergo pivoting action over the course of their taught movement. Due to the nonholonomic nature of the vehicle kinematics, estimation is required -- in the example given herein, based upon video detection of wall-mounted cues -- both in the teaching and the tracking events. In order to accommodate motion that approaches pivoting action as well as motion that approaches straight-line action, the estimation equations of the Extended Kalman Filter and the control equations are formulated using two different definitions of a nontemporal independent variable. The paper motivates the need for pivoting action in real-life settings by reporting extensively on the abilities and limitations of estimation-based teach-and-repeat action where pivoting and near-pivoting action is disallowed. Following formulation of the equations in the near-pivot mode, the paper reports upon experiments where taught trajectories which entail a seamless mix of near-straight and near-pivot action are tracked.

  18. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty;

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  19. Molecular basis for TPR domain-mediated regulation of protein phosphatase 5.

    Science.gov (United States)

    Yang, Jing; Roe, S Mark; Cliff, Matthew J; Williams, Mark A; Ladbury, John E; Cohen, Patricia T W; Barford, David

    2005-01-12

    Protein phosphatase 5 (Ppp5) is a serine/threonine protein phosphatase comprising a regulatory tetratricopeptide repeat (TPR) domain N-terminal to its phosphatase domain. Ppp5 functions in signalling pathways that control cellular responses to stress, glucocorticoids and DNA damage. Its phosphatase activity is suppressed by an autoinhibited conformation maintained by the TPR domain and a C-terminal subdomain. By interacting with the TPR domain, heat shock protein 90 (Hsp90) and fatty acids including arachidonic acid stimulate phosphatase activity. Here, we describe the structure of the autoinhibited state of Ppp5, revealing mechanisms of TPR-mediated phosphatase inhibition and Hsp90- and arachidonic acid-induced stimulation of phosphatase activity. The TPR domain engages with the catalytic channel of the phosphatase domain, restricting access to the catalytic site. This autoinhibited conformation of Ppp5 is stabilised by the C-terminal alphaJ helix that contacts a region of the Hsp90-binding groove on the TPR domain. Hsp90 activates Ppp5 by disrupting TPR-phosphatase domain interactions, permitting substrate access to the constitutively active phosphatase domain, whereas arachidonic acid prompts an alternate conformation of the TPR domain, destabilising the TPR-phosphatase domain interface.

  20. Domain combination of the vertebrate-like TLR gene family: implications for their origin and evolution

    Indian Academy of Sciences (India)

    Baojun Wu; Tianxiao Huan; Jing Gong; Pin Zhou; Zengliang Bai

    2011-12-01

    Domain shuffling, which is an important mechanism in the evolution of multi-domain proteins, has shaped the evolutionary development of the immune system in animals. Toll and Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate and adaptive immune systems. Draft genome sequences provide the opportunity to compare the Toll/TLR gene repertoire among representative metazoans. In this study, we investigated the combination of Toll/interleukin-1 receptor (TIR) and leucine-rich repeat (LRR) domains of metazoan Toll/TLRs. Before Toll with both domains occurred in Cnidaria (sea anemone, Nematostella vectensis), through domain combinations, TIR-only and LRR-only proteins had already appeared in sponges (Amphimedon queenslandica). Although vertebrate-like TIR (V-TIR) domain already appeared in Cnidaria, the vertebrate-like TLR (V-TLR) with both domains appeared much later. The first combination between V-TIR domain and vertebrate-like LRR (V-LRR) domain for V-TLR may have occurred after the divergence of Cnidaria and bilateria. Then, another combination for V-TLR, a recombination of both domains, possibly occurred before or during the evolution of primitive vertebrates. Taken together, two rounds of domain combinations may thus have co-shaped the vertebrate TLRs.

  1. Quantum repeaters free of polarization disturbance and phase noise

    OpenAIRE

    Yin, Zhen-Qiang; Zhao, Yi-bo; Yong YANG; Han, Zheng-Fu; Guo, Guang-Can

    2009-01-01

    Original quantum repeater protocols based on single-photon interference suffer from phase noise of the channel, which makes the long-distance quantum communication infeasible. Fortunately, two-photon interference type quantum repeaters can be immune to phase noise of the channel. However, this type quantum repeaters may still suffer from polarization disturbance of the channel. Here we propose a quantum repeaters protocol which is free of polarization disturbance of the channel based on the i...

  2. Erroneous Memories Arising from Repeated Attempts to Remember

    Science.gov (United States)

    Henkel, Linda A.

    2004-01-01

    The impact of repeated and prolonged attempts at remembering on false memory rates was assessed in three experiments. Participants saw and imagined pictures and then made repeated recall attempts before taking a source memory test. Although the number of items recalled increased with repeated tests, the net gains were associated with more source…

  3. 47 CFR 90.247 - Mobile repeater stations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Mobile repeater stations. 90.247 Section 90.247... MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.247 Mobile repeater stations. A... repeater to extend the communications range of hand-carried units subject to the following: (a)...

  4. Dynamical domain wall and localization

    Directory of Open Access Journals (Sweden)

    Yuta Toyozato

    2016-03-01

    Full Text Available Based on the previous works (Toyozato et al., 2013 [24]; Higuchi and Nojiri, 2014 [25], we investigate the localization of the fields on the dynamical domain wall, where the four-dimensional FRW universe is realized on the domain wall in the five-dimensional space–time. Especially we show that the chiral spinor can localize on the domain wall, which has not been succeeded in the past works as the seminal work in George et al. (2009 [23].

  5. Domain imaging in FINEMET ribbons

    Energy Technology Data Exchange (ETDEWEB)

    Silveyra, J.M., E-mail: jsilveyra@fi.uba.a [Laboratorio de Solidos Amorfos, INTECIN, Facultad de Ingenieria, UBA-CONICET, Paseo Colon 850, (C1063ACV) Buenos Aires (Argentina); Vlasak, G.; Svec, P.; Janickovic, D. [Institute of Physics, Slovak Academy of Sciences, Dubravska cesta 9, 845 11 Bratislava (Slovakia); Cremaschi, V.J., E-mail: vcremas@gmail.co [Laboratorio de Solidos Amorfos, INTECIN, Facultad de Ingenieria, UBA-CONICET, Paseo Colon 850, (C1063ACV) Buenos Aires (Argentina); Member of Carrera del Investigador, CONICET (Argentina)

    2010-09-15

    The magnetization behaviour of a ferromagnetic material depends on its domain structure, which in turn is largely determined by magnetic anisotropies. In this work, domain patterns were observed by a quite forgotten but still the simplest and the cheapest technique: the Bitter method. A systematic study of the evolution of the domain structure in FINEMET ribbons after thermal annealing is presented, correlating the results with the crystalline structure, magnetostriction and coercivity measurements.

  6. Who Repeats Algebra, and How Does Initial Performance Relate to Improvement When the Course Is Repeated?

    Science.gov (United States)

    Fong, Anthony; Jaquet, Karina; Finkelstein, Neal

    2016-01-01

    The information provided in this report shows how students perform when they repeat algebra I and how the level of improvement varies depending on initial course performance and the academic measure (course grades or CST scores). This information can help inform decisions and policies regarding whether and under what circumstances students should…

  7. Repeat Testing Effects on Credentialing Exams: Are Repeaters Misinformed or Uninformed?

    Science.gov (United States)

    Feinberg, Richard A.; Raymond, Mark R.; Haist, Steven A.

    2015-01-01

    To mitigate security concerns and unfair score gains, credentialing programs routinely administer new test material to examinees retesting after an initial failing attempt. Counterintuitively, a small but growing body of recent research suggests that repeating the identical form does not create an unfair advantage. This study builds upon and…

  8. Mapping the Moral Domain

    Science.gov (United States)

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

    2010-01-01

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

  9. De-coding and re-coding RNA recognition by PUF and PPR repeat proteins.

    Science.gov (United States)

    Hall, Traci M Tanaka

    2016-02-01

    PUF and PPR proteins are two families of α-helical repeat proteins that recognize single-stranded RNA sequences. Both protein families hold promise as scaffolds for designed RNA-binding domains. A modular protein RNA recognition code was apparent from the first crystal structures of a PUF protein in complex with RNA, and recent studies continue to advance our understanding of natural PUF protein recognition (de-coding) and our ability to engineer specificity (re-coding). Degenerate recognition motifs make de-coding specificity of individual PPR proteins challenging. Nevertheless, re-coding PPR protein specificity using a consensus recognition code has been successful. PMID:26874972

  10. Design principles for efficient, repeated jumpgliding

    International Nuclear Information System (INIS)

    Combined jumping and gliding locomotion, or ‘jumpgliding’, can be an efficient way for small robots or animals to travel over cluttered terrain. This paper presents functional requirements and models for a simple jumpglider which formalize the benefits and limitations of using aerodynamic surfaces to augment jumping ability. Analysis of the model gives insight into design choices and control strategies for higher performance and to accommodate special conditions such as a slippery launching surface. The model informs the design of a robotic platform that can perform repeated jumps using a carbon fiber spring and a pivoting wing. Experiments with two different versions of the platform agree with predictions from the model and demonstrate a significantly greater range, and lower cost-of-transport, than a comparable ballistic jumper. (papers)

  11. Trochlear Nerve Schwannoma With Repeated Intratumoral Hemorrhage.

    Science.gov (United States)

    Liu, Pengfei; Bao, Yuhai; Zhang, Wenchuan

    2016-09-01

    Trochlear nerve schwannoma is extremely rare, with only 35 pathologically confirmed patients being reported in the literature. Here, the authors report a patient of trochlear nerve schwannoma in the prepontine cistern manifesting as facial pain and double vision and presenting the image characteristics of repeated intratumoral hemorrhage, which has never been reported in the literature. Total tumor along with a portion of the trochlear nerve was removed by using a retrosigmoid approach. Facial pain disappeared after operation, and the diplopia remained. Follow-up studies have shown no tumor recurrence for 2 years and the simultaneous alleviation of diplopia. Information regarding the clinical presentation, radiological features and surgical outcomes of trochlear nerve schwannoma are discussed and reviewed in the paper. PMID:27607129

  12. Aging and repeated thought suppression success.

    Directory of Open Access Journals (Sweden)

    Ann E Lambert

    Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

  13. Aging and repeated thought suppression success.

    Science.gov (United States)

    Lambert, Ann E; Smyth, Frederick L; Beadel, Jessica R; Teachman, Bethany A

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility. PMID:23776442

  14. Statistical Properties of repeating FRB 121102

    CERN Document Server

    Wang, F Y

    2016-01-01

    Fast radio bursts (FRBs) are millisecond-duration radio signals possibly occurring at cosmological distances. However the physical model of FRBs is mystery, many models have been proposed. Here we study the frequency distributions of peak flux, fluence, duration and waiting time for repeating FRB 121102. The cumulative distributions of peak flux, fluence and duration show power-law forms. The waiting time distribution also shows power-law distribution, and is consistent with a non-stationary Poisson process. We also use the statistical results to test the proposed models for FRBs. Comparing with the model predications, we find that the theoretical models proposed by Dai et al. (2016) and Katz (2016) are favored. These distributions are consistent with the predications from avalanche models of driven systems.

  15. Hybrid quantum repeater using bright coherent light.

    Science.gov (United States)

    van Loock, P; Ladd, T D; Sanaka, K; Yamaguchi, F; Nemoto, Kae; Munro, W J; Yamamoto, Y

    2006-06-23

    We describe a quantum repeater protocol for long-distance quantum communication. In this scheme, entanglement is created between qubits at intermediate stations of the channel by using a weak dispersive light-matter interaction and distributing the outgoing bright coherent-light pulses among the stations. Noisy entangled pairs of electronic spin are then prepared with high success probability via homodyne detection and postselection. The local gates for entanglement purification and swapping are deterministic and measurement-free, based upon the same coherent-light resources and weak interactions as for the initial entanglement distribution. Finally, the entanglement is stored in a nuclear-spin-based quantum memory. With our system, qubit-communication rates approaching 100 Hz over 1280 km with fidelities near 99% are possible for reasonable local gate errors.

  16. Simple sequence repeats in mycobacterial genomes

    Indian Academy of Sciences (India)

    Vattipally B Sreenu; Pankaj Kumar; Javaregowda Nagaraju; Hampapathalu A Nagarajaram

    2007-01-01

    Simple sequence repeats (SSRs) or microsatellites are the repetitive nucleotide sequences of motifs of length 1–6 bp. They are scattered throughout the genomes of all the known organisms ranging from viruses to eukaryotes. Microsatellites undergo mutations in the form of insertions and deletions (INDELS) of their repeat units with some bias towards insertions that lead to microsatellite tract expansion. Although prokaryotic genomes derive some plasticity due to microsatellite mutations they have in-built mechanisms to arrest undue expansions of microsatellites and one such mechanism is constituted by post-replicative DNA repair enzymes MutL, MutH and MutS. The mycobacterial genomes lack these enzymes and as a null hypothesis one could expect these genomes to harbour many long tracts. It is therefore interesting to analyse the mycobacterial genomes for distribution and abundance of microsatellites tracts and to look for potentially polymorphic microsatellites. Available mycobacterial genomes, Mycobacterium avium, M. leprae, M. bovis and the two strains of M. tuberculosis (CDC1551 and H37Rv) were analysed for frequencies and abundance of SSRs. Our analysis revealed that the SSRs are distributed throughout the mycobacterial genomes at an average of 220–230 SSR tracts per kb. All the mycobacterial genomes contain few regions that are conspicuously denser or poorer in microsatellites compared to their expected genome averages. The genomes distinctly show scarcity of long microsatellites despite the absence of a post-replicative DNA repair system. Such severe scarcity of long microsatellites could arise as a result of strong selection pressures operating against long and unstable sequences although influence of GC-content and role of point mutations in arresting microsatellite expansions can not be ruled out. Nonetheless, the long tracts occasionally found in coding as well as non-coding regions may account for limited genome plasticity in these genomes.

  17. PPR8522 encodes a chloroplast-targeted pentatricopeptide repeat protein necessary for maize embryogenesis and vegetative development

    OpenAIRE

    Sosso, Davide; Canut, Matthieu; Gendrot, Ghislaine; Dedieu, Annick; Chambrier, Pierre; Barkan, Alice; Consonni, Gabriella; M. Rogowsky, Peter

    2012-01-01

    The pentatricopeptide repeat (PPR) domain is an RNA binding domain allowing members of the PPR superfamily to participate in post-transcriptional processing of organellar RNA. Loss of PPR8522 from maize (Zea mays) confers an embryo-specific (emb) phenotype. The emb8522 mutation was isolated in an active Mutator (Mu) population and co-segregation analysis revealed that it was tightly linked to a MuDR insertion in the first exon of PPR8522. Independent evidence that disruption of PPR8522 caused...

  18. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten;

    2013-01-01

    on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency...

  19. Hydrophobic compounds reshape membrane domains.

    Directory of Open Access Journals (Sweden)

    Jonathan Barnoud

    2014-10-01

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

  20. Comparison of the backbone dynamics of a natural and a consensus designed 3-TPR domain.

    Science.gov (United States)

    Jarymowycz, Virginia A; Cortajarena, Aitziber L; Regan, Lynne; Stone, Martin J

    2008-07-01

    The tetratricopeptide repeat (TPR) is a 34-amino acid helix-turn-helix motif that occurs in tandem arrays in numerous proteins. Here we compare the backbone dynamics of a natural 3-repeat TPR domain, from the protein UBP, with the behavior of a designed protein CTPR3, which consists of three identical consensus TPR units. Although the three tandem TPR repeats in both CTPR3 and UBP behave as a single unit, with no evidence of independent repeat motions, the data indicate that certain positions in UBP are significantly more flexible than are the corresponding positions in CTPR3. Most of the dynamical changes occur at or adjacent to positions that are involved in intra-repeat packing interactions. These observations lead us to suggest that the three-TPR domain of UBP does not incorporate optimized packing, compared to that seen in the idealized CTPR. The natural TPR domain is not only less stable overall than CTPR3, but also presents increased local flexibility at the positions where the sequences differs from the conserved consensus.

  1. The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Behrendt, N; Ploug, M; Patthy, L;

    1991-01-01

    with the internal repeats of u-PAR constitute the extracellular part of Ly-6 antigens and of the squid glycoprotein Sgp-2. Like u-PAR, these proteins are attached to the membrane by a glycosyl-phosphatidylinositol anchor. The hydrophilic, ligand-binding u-PAR domain identified in the present study has potential...

  2. The Plant Leucine-Rich Repeat Receptor-Like Kinase PSY1R from Head to Toe

    DEFF Research Database (Denmark)

    Oehlenschlæger, Christian Berg

    PSY1R belongs to the family of plant leucine-rich repeat receptor-like kinases that play important roles in processes such as growth regulation and plant immunity response. PSY1R was proposed to be the receptor of the plant peptide hormone PSY1 which promotes cell expansion. PSY1R was furthermore...... activated. This work provides the first study of the direct interaction between PSY1R and the peptide ligand PSY1. The binding was evaluated both for full length PSY1R expressed in plants and for the isolated extracellular domain expressed in insect cells. PSY1 binds to the extracellular domain of PSY1R...... Thr963. Thr959 and Thr963 are conserved among related plant leucine-rich repeat receptor-like kinases whereas Ser951 is unique for PSY1R which suggests that it may serve a specialized function in regulation of PSY1R kinase activity....

  3. Role of DNA Polymerases in Repeat-Mediated Genome Instability

    Directory of Open Access Journals (Sweden)

    Kartik A. Shah

    2012-11-01

    Full Text Available Expansions of simple DNA repeats cause numerous hereditary diseases in humans. We analyzed the role of DNA polymerases in the instability of Friedreich’s ataxia (GAAn repeats in a yeast experimental system. The elementary step of expansion corresponded to ∼160 bp in the wild-type strain, matching the size of Okazaki fragments in yeast. This step increased when DNA polymerase α was mutated, suggesting a link between the scale of expansions and Okazaki fragment size. Expandable repeats strongly elevated the rate of mutations at substantial distances around them, a phenomenon we call repeat-induced mutagenesis (RIM. Notably, defects in the replicative DNA polymerases δ and ∊ strongly increased rates for both repeat expansions and RIM. The increases in repeat-mediated instability observed in DNA polymerase δ mutants depended on translesion DNA polymerases. We conclude that repeat expansions and RIM are two sides of the same replicative mechanism.

  4. Deletion of intragenic tandem repeats in unit C of FLO1 of Saccharomyces cerevisiae increases the conformational stability of flocculin under acidic and alkaline conditions.

    Directory of Open Access Journals (Sweden)

    Ee Li

    Full Text Available Flocculation is an attractive property for Saccaromyces cerevisiae, which plays important roles in fermentation industry and environmental remediation. The process of flocculation is mediated by a family of cell surface flocculins. As one member of flocculins, Flo1 is characterized by four families of repeats (designated as repeat units A, B, C and D in the central domain. It is generally accepted that variation of repeat unit A in length in Flo1 influences the degree of flocculation or specificity for sugar recognization. However, no reports were observed for other repeat units. Here, we compared the flocculation ability and its sensitivity to environmental factors between yeast strain YSF1 carrying the intact FLO1 gene and yeast strains carrying the derived forms of FLO1 with partial or complete deletion of repeats in unit C. No obvious differences in flocculation ability and specificity of carbohydrate recognition were observed among these yeast strains, which indicates the truncated flocculins can stride across the cell wall and cluster the N-terminal domain on the surface of yeast cells as the intact Flo1 thereby improving intercellular binding. However, yeast strains with the truncated flocculins required more mannose to inhibit completely the flocculation, displayed broad tolerance of flocculation to pH fluctuation, and the fewer the repeats in unit C, the stronger adaptability of flocculation to pH change, which was not relevant to the position of deletion. This suggests that more stable active conformation is obtained for flocculin by deletion the repeat unit C in the central domain of Flo1, which was validated further by the higher hydrophobicity on the surface of cells of YSF1c with complete deletion of unit C under neutral and alkaline conditions and the stabilization of GFP conformation by fusion with flocculin with complete deletion of unit C in the central domain.

  5. On Probability Domains

    Science.gov (United States)

    Frič, Roman; Papčo, Martin

    2010-12-01

    Motivated by IF-probability theory (intuitionistic fuzzy), we study n-component probability domains in which each event represents a body of competing components and the range of a state represents a simplex S n of n-tuples of possible rewards-the sum of the rewards is a number from [0,1]. For n=1 we get fuzzy events, for example a bold algebra, and the corresponding fuzzy probability theory can be developed within the category ID of D-posets (equivalently effect algebras) of fuzzy sets and sequentially continuous D-homomorphisms. For n=2 we get IF-events, i.e., pairs ( μ, ν) of fuzzy sets μ, ν∈[0,1] X such that μ( x)+ ν( x)≤1 for all x∈ X, but we order our pairs (events) coordinatewise. Hence the structure of IF-events (where ( μ 1, ν 1)≤( μ 2, ν 2) whenever μ 1≤ μ 2 and ν 2≤ ν 1) is different and, consequently, the resulting IF-probability theory models a different principle. The category ID is cogenerated by I=[0,1] (objects of ID are subobjects of powers I X ), has nice properties and basic probabilistic notions and constructions are categorical. For example, states are morphisms. We introduce the category S n D cogenerated by Sn=\\{(x1,x2,ldots ,xn)in In;sum_{i=1}nxi≤ 1\\} carrying the coordinatewise partial order, difference, and sequential convergence and we show how basic probability notions can be defined within S n D.

  6. Texture of lipid bilayer domains

    DEFF Research Database (Denmark)

    Jensen, Uffe Bernchou; Brewer, Jonathan R.; Midtiby, Henrik Skov;

    2009-01-01

    We investigate the texture of gel (g) domains in binary lipid membranes composed of the phospholipids DPPC and DOPC. Lateral organization of lipid bilayer membranes is a topic of fundamental and biological importance. Whereas questions related to size and composition of fluid membrane domain...

  7. Taxonomies of Educational Objective Domain

    Directory of Open Access Journals (Sweden)

    Eman Ghanem Nayef

    2013-09-01

    Full Text Available This paper highlights an effort to study the educational objective domain taxonomies including Bloom’s taxonomy, Lorin Anderson’s taxonomy, and Wilson’s taxonomy. In this study a comparison among these three taxonomies have been done. Results show that Bloom’s taxonomy is more suitable as an analysis tool to Educational Objective domain.

  8. Taxonomies of Educational Objective Domain

    OpenAIRE

    Eman Ghanem Nayef; Nik Rosila Nik Yaacob; Hairul Nizam Ismail

    2013-01-01

    This paper highlights an effort to study the educational objective domain taxonomies including Bloom’s taxonomy, Lorin Anderson’s taxonomy, and Wilson’s taxonomy. In this study a comparison among these three taxonomies have been done. Results show that Bloom’s taxonomy is more suitable as an analysis tool to Educational Objective domain.

  9. Hydrophobic compounds reshape membrane domains

    NARCIS (Netherlands)

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

    2014-01-01

    Cell membranes have a complex lateral organization featuring domains with distinct composition, also known as rafts, which play an essential role in cellular processes such as signal transduction and protein trafficking. In vivo, perturbations of membrane domains (e.g., by drugs or lipophilic compou

  10. Learning processes across knowledge domains

    DEFF Research Database (Denmark)

    Hall-Andersen, Lene Bjerg; Broberg, Ole

    2014-01-01

    organization, it remained discrete in 'pockets' of learning; mainly at an individual level, at project level or as domain-specific learning. Learning processes were intertwined with elements of domain-specific interests, power, managerial support, structural conditions, material and epistemic differences...

  11. Domain wall description of superconductivity

    CERN Document Server

    Brito, F A; Silva, J C M

    2012-01-01

    In the present work we shall address the issue of electrical conductivity in superconductors in the perspective of superconducting domain wall solutions in the realm of field theory. We take our set up made out of a dynamical complex scalar field coupled to gauge field to be responsible for superconductivity and an extra scalar real field that plays the role of superconducting domain walls. The temperature of the system is interpreted as the parameter to move type I to type II domain walls. Alternatively, this means that the domain wall surface is suffering an acceleration as one goes from one type to another. On the other hand, changing from type I to type II state means a formation of a condensate what is in perfect sense of lowering the temperature around the superconductor. One can think of this scenario as an analog of holographic scenarios where this set up is replaced by a black hole near the domain wall.

  12. Structure and evolution of the magnetochrome domains: no longer alone

    Directory of Open Access Journals (Sweden)

    Pascal eArnoux

    2014-03-01

    Full Text Available Magnetotactic bacteria (MTB can swim along Earth’s magnetic field lines, thanks to the alignment of dedicated cytoplasmic organelles. These organelles, termed magnetosomes, are proteolipidic vesicles filled by a 35-120 nm crystal of either magnetite or greigite. The formation and alignment of magnetosomes are mediated by a group of specific genes, the mam genes, encoding the magnetosome-associated proteins. The whole process of magnetosome biogenesis can be divided into four sequential steps; (i cytoplasmic membrane invagination, (ii magnetosomes alignment, (iii iron crystal nucleation and (iv species-dependent mineral size and shape control. Since both magnetite and greigite are a mix of iron(III and iron(II, iron redox state management within the magnetosome vesicle is a key issue. Recently, studies have started pointing out the importance of a MTB-specific c-type cytochrome domain found in several magnetosome-associated proteins (MamE, P, T and X. This magnetochrome (MCR domain is almost always found in tandem, and this tandem is either found alone (MamT, in combination with a PDZ domain (MamP, a domain of unknown function (MamX or with a trypsin combined to one or two PDZ domains (MamE. By taking advantage of new genomic data available on MTB and a recent structural study of MamP, which helped define the MCR domain boundaries, we attempt to retrace the evolutionary history within and between the different MCR-containing proteins. We propose that the observed tandem repeat of MCR is the result of a convergent evolution and attempt to explain why this domain is rarely found alone.

  13. Structure and evolution of the magnetochrome domains: no longer alone.

    Science.gov (United States)

    Arnoux, Pascal; Siponen, Marina I; Lefèvre, Christopher T; Ginet, Nicolas; Pignol, David

    2014-01-01

    Magnetotactic bacteria (MTB) can swim along Earth's magnetic field lines, thanks to the alignment of dedicated cytoplasmic organelles. These organelles, termed magnetosomes, are proteolipidic vesicles filled by a 35-120 nm crystal of either magnetite or greigite. The formation and alignment of magnetosomes are mediated by a group of specific genes, the mam genes, encoding the magnetosome-associated proteins. The whole process of magnetosome biogenesis can be divided into four sequential steps; (i) cytoplasmic membrane invagination, (ii) magnetosomes alignment, (iii) iron crystal nucleation and (iv) species-dependent mineral size and shape control. Since both magnetite and greigite are a mix of iron (III) and iron (II), iron redox state management within the magnetosome vesicle is a key issue. Recently, studies have started pointing out the importance of a MTB-specific c-type cytochrome domain found in several magnetosome-associated proteins (MamE, P, T, and X). This magnetochrome (MCR) domain is almost always found in tandem, and this tandem is either found alone (MamT), in combination with a PDZ domain (MamP), a domain of unknown function (MamX) or with a trypsin combined to one or two PDZ domains (MamE). By taking advantage of new genomic data available on MTB and a recent structural study of MamP, which helped define the MCR domain boundaries, we attempt to retrace the evolutionary history within and between the different MCR-containing proteins. We propose that the observed tandem repeat of MCR is the result of a convergent evolution and attempt to explain why this domain is rarely found alone. PMID:24723915

  14. Molecular mechanics of the alpha-actinin rod domain: bending, torsional, and extensional behavior.

    Directory of Open Access Journals (Sweden)

    Javad Golji

    2009-05-01

    Full Text Available alpha-Actinin is an actin crosslinking molecule that can serve as a scaffold and maintain dynamic actin filament networks. As a crosslinker in the stressed cytoskeleton, alpha-actinin can retain conformation, function, and strength. alpha-Actinin has an actin binding domain and a calmodulin homology domain separated by a long rod domain. Using molecular dynamics and normal mode analysis, we suggest that the alpha-actinin rod domain has flexible terminal regions which can twist and extend under mechanical stress, yet has a highly rigid interior region stabilized by aromatic packing within each spectrin repeat, by electrostatic interactions between the spectrin repeats, and by strong salt bridges between its two anti-parallel monomers. By exploring the natural vibrations of the alpha-actinin rod domain and by conducting bending molecular dynamics simulations we also predict that bending of the rod domain is possible with minimal force. We introduce computational methods for analyzing the torsional strain of molecules using rotating constraints. Molecular dynamics extension of the alpha-actinin rod is also performed, demonstrating transduction of the unfolding forces across salt bridges to the associated monomer of the alpha-actinin rod domain.

  15. Control of magnetic domains and domain walls by themal gradients

    OpenAIRE

    Stärk, Martin

    2015-01-01

    The aim of this work is to study heat effects in thin magnetic films to verify the theoretical prediction of domain wall motion towards a heat source. In the theory, a domain wall moves from a cold region towards the hotter part due to energy minimization processes. It is shown that no electron transport is necessary for this effect as it has been observed in insulators. An analytical model describes the effective field that acts on a domain wall as an external applied magnetic field. This is pr...

  16. Genus-specific protein binding to the large clusters of DNA repeats (short regularly spaced repeats) present in Sulfolobus genomes

    DEFF Research Database (Denmark)

    Peng, Xu; Brügger, Kim; Shen, Biao;

    2003-01-01

    Short regularly spaced repeats (SRSRs) occur in multiple large clusters in archaeal chromosomes and as smaller clusters in some archaeal conjugative plasmids and bacterial chromosomes. The sequence, size, and spacing of the repeats are generally constant within a cluster but vary between clusters....... For the crenarchaeon Sulfolobus solfataricus P2, the repeats in the genome fall mainly into two closely related sequence families that are arranged in seven clusters containing a total of 441 repeats which constitute ca. 1% of the genome. The Sulfolobus conjugative plasmid pNOB8 contains a small cluster of six repeats...... that are identical in sequence to one of the repeat variants in the S. solfataricus chromosome. Repeats from the pNOB8 cluster were amplified and tested for protein binding with cell extracts from S. solfataricus. A 17.5-kDa SRSR-binding protein was purified from the cell extracts and sequenced. The protein is N...

  17. WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family

    Directory of Open Access Journals (Sweden)

    Paoletti Mathieu

    2010-05-01

    Full Text Available Abstract Background Genes involved in non-self recognition and host defence are typically capable of rapid diversification and exploit specialized genetic mechanism to that end. Fungi display a non-self recognition phenomenon termed heterokaryon incompatibility that operates when cells of unlike genotype fuse and leads to the cell death of the fusion cell. In the fungus Podospora anserina, three genes controlling this allorecognition process het-d, het-e and het-r are paralogs belonging to the same hnwd gene family. HNWD proteins are STAND proteins (signal transduction NTPase with multiple domains that display a WD-repeat domain controlling recognition specificity. Based on genomic sequence analysis of different P. anserina isolates, it was established that repeat regions of all members of the gene family are extremely polymorphic and undergoing concerted evolution arguing for frequent recombination within and between family members. Results Herein, we directly analyzed the genetic instability and diversification of this allorecognition gene family. We have constituted a collection of 143 spontaneous mutants of the het-R (HNWD2 and het-E (hnwd5 genes with altered recognition specificities. The vast majority of the mutants present rearrangements in the repeat arrays with deletions, duplications and other modifications as well as creation of novel repeat unit variants. Conclusions We investigate the extreme genetic instability of these genes and provide a direct illustration of the diversification strategy of this eukaryotic allorecognition gene family.

  18. Modelling repeatedly flaring delta-sunspots

    CERN Document Server

    Chatterjee, Piyali; Carlsson, Mats

    2016-01-01

    Active regions (AR) appearing on the surface of the Sun are classified into $\\alpha$, $\\beta$, $\\gamma$, and $\\delta$ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the $\\delta$-sunspots are known to be super-active and produce the most X-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin sub-photospheric magnetic sheet breaks into multiple flux-tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic $\\delta$-sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  19. The pneumococcal serine-rich repeat protein is an intra-species bacterial adhesin that promotes bacterial aggregation in vivo and in biofilms.

    Directory of Open Access Journals (Sweden)

    Carlos J Sanchez

    Full Text Available The Pneumococcal serine-rich repeat protein (PsrP is a pathogenicity island encoded adhesin that has been positively correlated with the ability of Streptococcus pneumoniae to cause invasive disease. Previous studies have shown that PsrP mediates bacterial attachment to Keratin 10 (K10 on the surface of lung cells through amino acids 273-341 located in the Basic Region (BR domain. In this study we determined that the BR domain of PsrP also mediates an intra-species interaction that promotes the formation of large bacterial aggregates in the nasopharynx and lungs of infected mice as well as in continuous flow-through models of mature biofilms. Using numerous methods, including complementation of mutants with BR domain deficient constructs, fluorescent microscopy with Cy3-labeled recombinant (rBR, Far Western blotting of bacterial lysates, co-immunoprecipitation with rBR, and growth of biofilms in the presence of antibodies and competitive peptides, we determined that the BR domain, in particular amino acids 122-166 of PsrP, promoted bacterial aggregation and that antibodies against the BR domain were neutralizing. Using similar methodologies, we also determined that SraP and GspB, the Serine-rich repeat proteins (SRRPs of Staphylococcus aureus and Streptococcus gordonii, respectively, also promoted bacterial aggregation and that their Non-repeat domains bound to their respective SRRPs. This is the first report to show the presence of biofilm-like structures in the lungs of animals infected with S. pneumoniae and show that SRRPs have dual roles as host and bacterial adhesins. These studies suggest that recombinant Non-repeat domains of SRRPs (i.e. BR for S. pneumoniae may be useful as vaccine antigens to protect against Gram-positive bacteria that cause infection.

  20. Domain Modeling: NP_071371.3 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_071371.3 chr20 Solution structure of three tandem repeats of zf-C2H2 domains fro...m human Kruppel-like factor 5 p2ebta_ chr20/NP_071371.3/NP_071371.3_holo_107-199.pdb blast 117G,119K,126C,128K,139H,143H,151C,154C,167H,170I,171H,179C,181I,182C,195H,196L,199H _ZN 0 ...

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

    Directory of Open Access Journals (Sweden)

    Liao Li

    2010-10-01

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

  2. Wavefield extrapolation in pseudodepth domain

    KAUST Repository

    Ma, Xuxin

    2013-02-01

    Wavefields are commonly computed in the Cartesian coordinate frame. Its efficiency is inherently limited due to spatial oversampling in deep layers, where the velocity is high and wavelengths are long. To alleviate this computational waste due to uneven wavelength sampling, we convert the vertical axis of the conventional domain from depth to vertical time or pseudodepth. This creates a nonorthognal Riemannian coordinate system. Isotropic and anisotropic wavefields can be extrapolated in the new coordinate frame with improved efficiency and good consistency with Cartesian domain extrapolation results. Prestack depth migrations are also evaluated based on the wavefield extrapolation in the pseudodepth domain.© 2013 Society of Exploration Geophysicists. All rights reserved.

  3. Partial domain wall partition functions

    OpenAIRE

    Foda, O.; Wheeler, M.

    2012-01-01

    We consider six-vertex model configurations on an n-by-N lattice, n =< N, that satisfy a variation on domain wall boundary conditions that we define and call "partial domain wall boundary conditions". We obtain two expressions for the corresponding "partial domain wall partition function", as an (N-by-N)-determinant and as an (n-by-n)-determinant. The latter was first obtained by I Kostov. We show that the two determinants are equal, as expected from the fact that they are partition functions...

  4. Segmented Domain Decomposition Multigrid For 3-D Turbomachinery Flows

    Science.gov (United States)

    Celestina, M. L.; Adamczyk, J. J.; Rubin, S. G.

    2001-01-01

    A Segmented Domain Decomposition Multigrid (SDDMG) procedure was developed for three-dimensional viscous flow problems as they apply to turbomachinery flows. The procedure divides the computational domain into a coarse mesh comprised of uniformly spaced cells. To resolve smaller length scales such as the viscous layer near a surface, segments of the coarse mesh are subdivided into a finer mesh. This is repeated until adequate resolution of the smallest relevant length scale is obtained. Multigrid is used to communicate information between the different grid levels. To test the procedure, simulation results will be presented for a compressor and turbine cascade. These simulations are intended to show the ability of the present method to generate grid independent solutions. Comparisons with data will also be presented. These comparisons will further demonstrate the usefulness of the present work for they allow an estimate of the accuracy of the flow modeling equations independent of error attributed to numerical discretization.

  5. Abundant intergenic TAACTGA direct repeats and putative alternate RNA polymerase β´ subunits in marine Beggiatoaceae genomes: possible regulatory roles and origins

    Directory of Open Access Journals (Sweden)

    Barbara J. MacGregor

    2015-12-01

    Full Text Available The genome sequences of several giant marine sulfur-oxidizing bacteria present evidence of a possible post-transcriptional regulatory network that may have been transmitted to or from two distantly related bacteria lineages. The draft genome of a Cand. Maribeggiatoa filament from the Guaymas Basin (Gulf of California, Mexico seafloor contains 169 sets of TAACTGA direct repeats and one indirect repeat, with two to six copies per set. Related heptamers are rarely or never found as direct repeats. TAACTGA direct repeats are also found in some other Beggiatoaceae, Thiocystis violascens, a range of Cyanobacteria, and five Bacteroidetes. This phylogenetic distribution suggests they may have been transmitted horizontally, but no mechanism is evident. There is no correlation between total TAACTGA occurrences and repeats per genome. In most species the repeat units are relatively short, but longer arrays of up to 43 copies are found in several Bacteroidetes and Cyanobacteria. The majority of TAACTGA repeats in the Cand. Maribeggiatoa Orange Guaymas (BOGUAY genome are within several nucleotides upstream of a putative start codon, suggesting they may be binding sites for a post-transcriptional regulator. Candidates include members of the ribosomal protein S1, Csp (cold shock protein, and Csr (carbon storage regulator families. No pattern was evident in the predicted functions of the open reading frames (ORFs downstream of repeats, but some encode presumably essential products such as ribosomal proteins. Among these is an ORF encoding a possible alternate or modified RNA polymerase beta prime subunit, predicted to have the expected subunit interaction domains but lacking most catalytic residues. A similar ORF was found in the Thioploca ingrica draft genome, but in no others. In both species they are immediately upstream of putative sensor kinase genes with nearly identical domain structures. In the marine Beggiatoaceae, a role for the TAACTGA repeats in

  6. Abundant Intergenic TAACTGA Direct Repeats and Putative Alternate RNA Polymerase β' Subunits in Marine Beggiatoaceae Genomes: Possible Regulatory Roles and Origins.

    Science.gov (United States)

    MacGregor, Barbara J

    2015-01-01

    The genome sequences of several giant marine sulfur-oxidizing bacteria present evidence of a possible post-transcriptional regulatory network that may have been transmitted to or from two distantly related bacteria lineages. The draft genome of a Cand. "Maribeggiatoa" filament from the Guaymas Basin (Gulf of California, Mexico) seafloor contains 169 sets of TAACTGA direct repeats and one indirect repeat, with two to six copies per set. Related heptamers are rarely or never found as direct repeats. TAACTGA direct repeats are also found in some other Beggiatoaceae, Thiocystis violascens, a range of Cyanobacteria, and five Bacteroidetes. This phylogenetic distribution suggests they may have been transmitted horizontally, but no mechanism is evident. There is no correlation between total TAACTGA occurrences and repeats per genome. In most species the repeat units are relatively short, but longer arrays of up to 43 copies are found in several Bacteroidetes and Cyanobacteria. The majority of TAACTGA repeats in the Cand. "Maribeggiatoa" Orange Guaymas (BOGUAY) genome are within several nucleotides upstream of a putative start codon, suggesting they may be binding sites for a post-transcriptional regulator. Candidates include members of the ribosomal protein S1, Csp (cold shock protein), and Csr (carbon storage regulator) families. No pattern was evident in the predicted functions of the open reading frames (ORFs) downstream of repeats, but some encode presumably essential products such as ribosomal proteins. Among these is an ORF encoding a possible alternate or modified RNA polymerase beta prime subunit, predicted to have the expected subunit interaction domains but lacking most catalytic residues. A similar ORF was found in the Thioploca ingrica draft genome, but in no others. In both species they are immediately upstream of putative sensor kinase genes with nearly identical domain structures. In the marine Beggiatoaceae, a role for the TAACTGA repeats in translational

  7. Survey of simple sequence repeats in woodland strawberry (Fragaria vesca).

    Science.gov (United States)

    Guan, L; Huang, J F; Feng, G Q; Wang, X W; Wang, Y; Chen, B Y; Qiao, Y S

    2013-07-30

    The use of simple sequence repeats (SSRs), or microsatellites, as genetic markers has become popular due to their abundance and variation in length among individuals. In this study, we investigated linkage groups (LGs) in the woodland strawberry (Fragaria vesca) and demonstrated variation in the abundances, densities, and relative densities of mononucleotide, dinucleotide, and trinucleotide repeats. Mononucleotide, dinucleotide, and trinucleotide repeats were more common than longer repeats in all LGs examined. Perfect SSRs were the predominant SSR type found and their abundance was extremely stable among LGs and chloroplasts. Abundances of mononucleotide, dinucleotide, and trinucleotide repeats were positively correlated with LG size, whereas those of tetranucleotide and hexanucleotide SSRs were not. Generally, in each LG, the abundance, relative abundance, relative density, and the proportion of each unique SSR all declined rapidly as the repeated unit increased. Furthermore, the lengths and frequencies of SSRs varied among different LGs.

  8. Quasimonomorphic Mononucleotide Repeats for High-Level Microsatellite Instability Analysis

    Directory of Open Access Journals (Sweden)

    Olivier Buhard

    2004-01-01

    Full Text Available Microsatellite instability (MSI analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability.

  9. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting.

    Science.gov (United States)

    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F; Ignatova, Zoya

    2016-08-26

    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5' end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1. PMID:27382061

  10. Toward a theory of repeat purchase drivers for consumer services

    OpenAIRE

    Paul, M; Hennig-Thurau, T.; Gremler, D.D.; Gwinner, K. P.; Wiertz, C.

    2009-01-01

    The marketing discipline’s knowledge about the drivers of service customers’ repeat purchase behavior is highly fragmented. This research attempts to overcome that fragmented state of knowledge by making major advances toward a theory of repeat purchase drivers for consumer services. Drawing on means–end theory, the authors develop a hierarchical classification scheme that organizes repeat purchase drivers into an integrative and comprehensive framework. They then identify drivers on the basi...

  11. Assembly of Repeat Content Using Next Generation Sequencing Data

    Energy Technology Data Exchange (ETDEWEB)

    labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex

    2014-03-17

    Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

  12. Triplet repeat length bias and variation in the human transcriptome

    OpenAIRE

    Molla, Michael; Delcher, Arthur; Sunyaev, Shamil; Cantor, Charles; Kasif, Simon

    2009-01-01

    Length variation in short tandem repeats (STRs) is an important family of DNA polymorphisms with numerous applications in genetics, medicine, forensics, and evolutionary analysis. Several major diseases have been associated with length variation of trinucleotide (triplet) repeats including Huntington's disease, hereditary ataxias and spinobulbar muscular atrophy. Using the reference human genome, we have catalogued all triplet repeats in genic regions. This data revealed a bias in noncoding D...

  13. Repeatability of nest morphology in African weaver birds

    OpenAIRE

    Walsh, Patrick T.; Hansell, Mike; Borello, Wendy D.; Healy, Susan D.

    2009-01-01

    It is generally assumed that birds build nests according to a genetic 'template', little influenced by learning or memory. One way to confirm the role of genetics in nest building is to assess the repeatability of nest morphology with repeated nest attempts. Solitary weaver birds, which build multiple nests in a single breeding season, are a useful group with which to do this. Here we show that repeatability of nest morphology was low, but significant, in male Southern Masked weaver birds and...

  14. Physiological Consequences of Repeated Exposures to Conditioned Fear

    OpenAIRE

    Thompson, Robert S.; Strong, Paul V; Monika Fleshner

    2012-01-01

    Activation of the stress response evokes a cascade of physiological reactions that may be detrimental when repeated or chronic, and when triggered after exposure to psychological/emotional stressors. Investigation of the physiological mechanisms responsible for the health damaging effects requires animal paradigms that repeatedly evoke a response to psychological/emotional stressors. To this end, adult male Sprague Dawley rats were repeatedly exposed (2X per day for 20 days) to a context that...

  15. Structural and functional dissection of Toxoplasma gondii armadillo repeats only protein.

    Science.gov (United States)

    Mueller, Christina; Samoo, Atta; Hammoudi, Pierre-Mehdi; Klages, Natacha; Kallio, Juha Pekka; Kursula, Inari; Soldati-Favre, Dominique

    2016-03-01

    Rhoptries are club-shaped, regulated secretory organelles that cluster at the apical pole of apicomplexan parasites. Their discharge is essential for invasion and the establishment of an intracellular lifestyle. Little is known about rhoptry biogenesis and recycling during parasite division. In Toxoplasma gondii, positioning of rhoptries involves the armadillo repeats only protein (ARO) and myosin F (MyoF). Here, we show that two ARO partners, ARO-interacting protein (AIP) and adenylate cyclase β (ACβ) localize to a rhoptry subcompartment. In absence of AIP, ACβ disappears from the rhoptries. By assessing the contribution of each ARO armadillo (ARM) repeat, we provide evidence that ARO is multifunctional, participating not only in positioning but also in clustering of rhoptries. Structural analyses show that ARO resembles the myosin-binding domain of the Caenorhabditis elegans myosin chaperone UNC-45. A conserved patch of aromatic and acidic residues denotes the putative MyoF-binding site, and the overall arrangement of the ARM repeats explains the dramatic consequences of deleting each of them. Finally, Plasmodium falciparum ARO functionally complements ARO depletion and interacts with the same partners, highlighting the conservation of rhoptry biogenesis in Apicomplexa. PMID:26769898

  16. Repeated epitope in the recombinant epitope-peptide could enhance ELDKWA-epitope-specific antibody response

    Institute of Scientific and Technical Information of China (English)

    LIU Zuqiang; WANG Zuguang; CHEN Yinghua

    2005-01-01

    Based on the hypothesis suggested by us that epitope-vaccine may be a new strategy against HIV mutation, we have studied several neutralizing epitopes on HIV envelope proteins. However we do not know whether a repeated epitope in a recombinant epitope-peptide can enhance epitope-specific antibody response or not. ELDKWA-epitope (aa669-674) on the C-domain of HIV-1 gp41 is a neutralizing epitope defined by the monoclonal antibody (mAb) 2F5 with broad neutralizing activity. In this study, we designed and prepared a series of the recombinant epitope-peptides bearing 1, 4 and 8 copies of ELDKWA-epitope respectively. In the comparison of the antisera induced by the three recombinant antigens, an obviously increased titre of ELDKWA-epitope-specific antibody was observed in the case of four and eight repeated epitopes. In flow cytometry analysis, the epitope-specific antibodies in both antisera showed stronger activity to bind the transfected CHO-WT cells that stably express HIV-1 envelope glycoprotein on the cell surfaces. These experimental results indicated that repeated epitope in the recombinant epitope-peptide could enhance ELDKWA-epitope-specific antibody response, which could contribute to designing an effective recombinant epitope-vaccine.

  17. Concept Convergence in Empirical Domains

    Science.gov (United States)

    Ontañón, Santiago; Plaza, Enric

    How to achieve shared meaning is a significant issue when more than one intelligent agent is involved in the same domain. We define the task of concept convergence, by which intelligent agents can achieve a shared, agreed-upon meaning of a concept (restricted to empirical domains). For this purpose we present a framework that, integrating computational argumentation and inductive concept learning, allows a pair of agents to (1) learn a concept in an empirical domain, (2) argue about the concept's meaning, and (3) reach a shared agreed-upon concept definition. We apply this framework to marine sponges, a biological domain where the actual definitions of concepts such as orders, families and species are currently open to discussion. An experimental evaluation on marine sponges shows that concept convergence is achieved, within a reasonable number of interchanged arguments, and reaching short and accurate definitions (with respect to precision and recall).

  18. Intragenic tandem repeat variation between Legionella pneumophila strains

    Directory of Open Access Journals (Sweden)

    Jarraud Sophie

    2008-12-01

    Full Text Available Abstract Background Bacterial genomes harbour a large number of tandem repeats, yet the possible phenotypic effects of those found within the coding region of genes are only beginning to be examined. Evidence exists from other organisms that these repeats can be involved in the evolution of new genes, gene regulation, adaptation, resistance to environmental stresses, and avoidance of the immune system. Results In this study, we have investigated the presence and variability in copy number of intragenic tandemly repeated sequences in the genome of Legionella pneumophila, the etiological agent of a severe pneumonia known as Legionnaires' disease. Within the genome of the Philadelphia strain, we have identified 26 intragenic tandem repeat sequences using conservative selection criteria. Of these, seven were "polymorphic" in terms of repeat copy number between a large number of L. pneumophila serogroup 1 strains. These strains were collected from a wide variety of environments and patients in several geographical regions. Within this panel of strains, all but one of these seven genes exhibited statistically different patterns in repeat copy number between samples from different origins (environmental, clinical, and hot springs. Conclusion These results support the hypothesis that intragenic tandem repeats could play a role in virulence and adaptation to different environments. While tandem repeats are an increasingly popular focus of molecular typing studies in prokaryotes, including in L. pneumophila, this study is the first examining the difference in tandem repeat distribution as a function of clinical or environmental origin.

  19. Coexistence of 3G repeaters with LTE base stations.

    Science.gov (United States)

    Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

    2013-01-01

    Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

  20. Integration of decoy domains derived from protein targets of pathogen effectors into plant immune receptors is widespread.

    Science.gov (United States)

    Kroj, Thomas; Chanclud, Emilie; Michel-Romiti, Corinne; Grand, Xavier; Morel, Jean-Benoit

    2016-04-01

    Plant immune receptors of the class of nucleotide-binding and leucine-rich repeat domain (NLR) proteins can contain additional domains besides canonical NB-ARC (nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC)) and leucine-rich repeat (LRR) domains. Recent research suggests that these additional domains act as integrated decoys recognizing effectors from pathogens. Proteins homologous to integrated decoys are suspected to be effector targets and involved in disease or resistance. Here, we scrutinized 31 entire plant genomes to identify putative integrated decoy domains in NLR proteins using the Interpro search. The involvement of the Zinc Finger-BED type (ZBED) protein containing a putative decoy domain, called BED, in rice (Oryza sativa) resistance was investigated by evaluating susceptibility to the blast fungus Magnaporthe oryzae in rice over-expression and knock-out mutants. This analysis showed that all plants tested had integrated various atypical protein domains into their NLR proteins (on average 3.5% of all NLR proteins). We also demonstrated that modifying the expression of the ZBED gene modified disease susceptibility. This study suggests that integration of decoy domains in NLR immune receptors is widespread and frequent in plants. The integrated decoy model is therefore a powerful concept to identify new proteins involved in disease resistance. Further in-depth examination of additional domains in NLR proteins promises to unravel many new proteins of the plant immune system. PMID:26848538

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-10-14

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

  2. Functional analysis of helicase and three tandem HRDC domains of RecQ in Deinococcus radiodurans

    Institute of Scientific and Technical Information of China (English)

    HUANG Li-fen; HUA Xiao-ting; LU Hui-ming; GAO Guan-jun; TIAN Bing; SHEN Bing-hui; HUA Yue-jin

    2006-01-01

    RecQ is a highly conserved helicase necessary for maintaining genome stability in all organisms. Genome comparison showed that a homologue of RecQ in Deinococcus radiodurans designated as DR1289 is a member of RecQ family with unusual domain arrangement: a helicase domain, an RecQ C-terminal domain, and surprisingly three HRDC domain repeats, whose function, however, remains obscure currently. Using an insertion deletion, we discovered that the DRRecQ mutation causes an increase in gamma radiation, hydroxyurea and mitomycine C and UV sensitivity. Using the shuttle plasmid pRADK, we complemented various domains of the D. Radiodurans RecQ (DRRecQ) to the mutant in vivo. Results suggested that both the helicase and helicase-and-Rnase-D-C-terminal (HRDC) domains are essential for complementing several phenotypes. The complementation and biochemical function of DRRecQ variants with different domains truncated in vitro suggested that both the helicase and three HRDC domains are necessary for RecQ functions in D. Radiodurans, while three HRDC domains have a synergistic effect on the whole function. Our finding leads to the hypothesis that the RecF recombination pathway is likely a primary path of double strand break repair in this well-known radioresistant organism.

  3. Engineered CH2 domains (nanoantibodies).

    Science.gov (United States)

    Dimitrov, Dimiter S

    2009-01-01

    Currently, almost all FDA approved therapeutic antibodies (except ReoPro, Lucentis and Cimzia which are Fabs), and the vast majority of those in clinical trials are full-size antibodies mostly in IgG1 format of about 150 kDa size. A fundamental problem for such large molecules is their poor penetration into tissues (e.g., solid tumors) and poor or absent binding to regions on the surface of some molecules (e.g., on the HIV envelope glycoprotein) which are fully accessible only by molecules of smaller size. Therefore, much work especially during the last decade has been aimed at developing novel scaffolds of much smaller size and high stability. Here I briefly describe a proposition to use the immunoglobulin (Ig) constant CH2 domain (CH3 for IgE and IgM) as a scaffold. CH2 is critical for the Ig effector functions. Isolated CH2 is stable monomer in contrast to all other constant domains and most of the variable domains. CH2 and engineered CH2 domains with improved stability can be used as scaffolds for construction of libraries containing diverse binders to various antigens. Such binders based on a CH2 scaffold could also confer some effector functions. Because the CH2 domains are the smallest independently folded antibody domains that can be engineered to contain simultaneously antigen-binding sites and binding sites mediating effector and stability functions, and to distinguish them from domain antibodies which are used to denote engineered VH or VL domains or nanobodies which are used to denote camelid VHH, I termed them nanoantibodies (nAbs). PMID:20046570

  4. Engineered bacterial hydrophobic oligopeptide repeats in a synthetic yeast prion, [REP-PSI+

    Directory of Open Access Journals (Sweden)

    Fátima eGasset-Rosa

    2015-04-01

    Full Text Available The yeast translation termination factor Sup35p, by aggregating as the [PSI+] prion, enables ribosomes to read-through stop codons, thus expanding the diversity of the Saccharomyces cerevisiae proteome. Yeast prions are functional amyloids that replicate by templating their conformation on native protein molecules, then assembling as large aggregates and fibers. Prions propagate epigenetically from mother to daughter cells by fragmentation of such assemblies. In the N-terminal prion-forming domain, Sup35p has glutamine/asparagine-rich oligopeptide repeats (OPRs, which enable propagation through chaperone-elicited shearing. We have engineered chimeras by replacing the polar OPRs in Sup35p by up to five repeats of a hydrophobic amyloidogenic sequence from the synthetic bacterial prionoid RepA-WH1. The resulting hybrid, [REP-PSI+], i was functional in a stop codon read-through assay in S. cerevisiae; ii generates weak phenotypic variants upon both its expression or transformation into [psi-] cells; iii these variants correlated with high molecular weight aggregates resistant to SDS during electrophoresis; and iv according to fluorescence microscopy, the fusion of the prion domains from the engineered chimeras to the reporter protein mCherry generated perivacuolar aggregate foci in yeast cells. All these are signatures of bona fide yeast prions. As assessed through biophysical approaches, the chimeras assembled as oligomers rather than as the fibers characteristic of [PSI+]. These results suggest that it is the balance between polar and hydrophobic residues in OPRs what determines prion conformational dynamics. In addition, our findings illustrate the feasibility of enabling new propagation traits in yeast prions by engineering OPRs with heterologous amyloidogenic sequence repeats.

  5. Seismicity along the Main Marmara Fault, Turkey: from space-time distribution to repeating events

    Science.gov (United States)

    Schmittbuhl, Jean; Karabulut, Hayrullah; Lengliné, Olivier; Bouchon, Michel

    2016-04-01

    The North Anatolian Fault (NAF) poses a significant hazard for the large cities surrounding the Marmara Sea region particularly the megalopolis of Istanbul. Indeed, the NAF is presently hosting a long unruptured segment below the Sea of Marmara. This seismic gap is approximately 150 km long and corresponds to the Main Marmara Fault (MMF). The seismicity along the Main Marmara Fault (MMF) below the Marmara Sea is analyzed here during the 2007-2012 period to provide insights on the recent evolution of this important regional seismic gap. High precision locations show that seismicity is strongly varying along strike and depth providing fine details of the fault behavior that are inaccessible from geodetic inversions. The activity strongly clusters at the regions of transition between basins. The Central basin shows significant seismicity located below the shallow locking depth inferred from GPS measurements. Its b-value is low and the average seismic slip is high. Interestingly we found also several long term repeating earthquakes in this domain. Using a template matching technique, we evidenced two new families of repeaters: a first family that typically belongs to aftershock sequences and a second family of long lasting repeaters with a multi-month recurrence period. All observations are consistent with a deep creep of this segment. On the contrary, the Kumburgaz basin at the center of the fault shows sparse seismicity with the hallmarks of a locked segment. In the eastern Marmara Sea, the seismicity distribution along the Princes Island segment in the Cinarcik basin, is consistent with the geodetic locking depth of 10km and a low contribution to the regional seismic energy release. The assessment of the locked segment areas provide an estimate of the magnitude of the main forthcoming event to be about 7.3 assuming that the rupture will not enter significantly within creeping domains.

  6. Kinetochore and heterochromatin domains of the fission yeast centromere.

    Science.gov (United States)

    Pidoux, Alison L; Allshire, Robin C

    2004-01-01

    Fission yeast centromeres are composed of two distinctive chromatin domains. The central domain nucleosomes contain the histone H3-like protein CENP-A(Cnp1). In contrast, the flanking repeats are coated with silent chromatin in which Swi6 (HP1) binds histone H3 methylated on lysine 9 that is induced by the action of the RNA interference pathway on non-coding centromeric transcripts. The overall structure is similar to that of metazoan centromeres where the kinetochore is embedded in surrounding heterochromatin. Kinetochore specific proteins associate with the central domain and affect silencing in that region. The flanking heterochromatin is required to recruit cohesin and mediate tight physical cohesion between sister centromeres. The loss of silencing that accompanies defects in heterochromatin has been invaluable as a tool in the investigation of centromere function. Both the heterochromatin and kinetochore regions are required for the de novo assembly of a functional centromere on DNA constructs, suggesting that heterochromatin may provide an environment that promotes kinetochore assembly within the central domain. The process is clearly epigenetically regulated. Fission yeast kinetochores associate with 2-4 microtubules, and flanking heterochromatin may be required to promote the orientation of multiple microtubule binding sites on one kinetochore towards the same pole and thus prevent merotelic orientation. PMID:15289660

  7. Geometric characterization of the Arjuna orbital domain

    CERN Document Server

    Marcos, C de la Fuente

    2014-01-01

    Arjuna-type orbits are characterized by being Earth-like, having both low-eccentricity and low-inclination. Objects following these trajectories experience repeated trappings in the 1:1 commensurability with the Earth and can become temporary Trojans, horseshoe librators, quasi-satellites, and even transient natural satellites. Here, we review what we know about this peculiar dynamical group and use a Monte Carlo simulation to characterize geometrically the Arjuna orbital domain, studying its visibility both from the ground and with the European Space Agency Gaia spacecraft. The visibility analysis from the ground together with the discovery circumstances of known objects are used as proxies to estimate the current size of this population. The impact cross-section of the Earth for minor bodies in this resonant group is also investigated. We find that, for ground-based observations, the solar elongation at perigee of nearly half of these objects is less than 90 degrees. They are best observed by space-borne te...

  8. Global Repeat Map Method for Higher Order Repeat Alpha Satellites in Human and Chimpanzee Genomes (Build 37.2 Assembly)

    OpenAIRE

    Glunčić, Matko; Rosandić, Marija; Jelovina, Denis; Dekanić, Krešimir; Vlahović, Ines; Paar, Vladimir

    2012-01-01

    Alpha satellites are tandemly repeated sequences found in all human centromeres. In addition to the functional and structural role within centromere they are also a suitable model for evolutionary stud-ies, because of being subject to concerted evolution. The Global Repeat Map (GRM) algorithm is a convenient computational tool to determine consensus repeat units and their exact size within a given genomic sequence, both of monomeric and higher-order (HOR) type. Using GRM, we identify in Build...

  9. The energy landscapes of repeat-containing proteins: topology, cooperativity, and the folding funnels of one-dimensional architectures.

    Directory of Open Access Journals (Sweden)

    Diego U Ferreiro

    2008-05-01

    Full Text Available Repeat-proteins are made up of near repetitions of 20- to 40-amino acid stretches. These polypeptides usually fold up into non-globular, elongated architectures that are stabilized by the interactions within each repeat and those between adjacent repeats, but that lack contacts between residues distant in sequence. The inherent symmetries both in primary sequence and three-dimensional structure are reflected in a folding landscape that may be analyzed as a quasi-one-dimensional problem. We present a general description of repeat-protein energy landscapes based on a formal Ising-like treatment of the elementary interaction energetics in and between foldons, whose collective ensemble are treated as spin variables. The overall folding properties of a complete "domain" (the stability and cooperativity of the repeating array can be derived from this microscopic description. The one-dimensional nature of the model implies there are simple relations for the experimental observables: folding free-energy (DeltaG(water and the cooperativity of denaturation (m-value, which do not ordinarily apply for globular proteins. We show how the parameters for the "coarse-grained" description in terms of foldon spin variables can be extracted from more detailed folding simulations on perfectly funneled landscapes. To illustrate the ideas, we present a case-study of a family of tetratricopeptide (TPR repeat proteins and quantitatively relate the results to the experimentally observed folding transitions. Based on the dramatic effect that single point mutations exert on the experimentally observed folding behavior, we speculate that natural repeat proteins are "poised" at particular ratios of inter- and intra-element interaction energetics that allow them to readily undergo structural transitions in physiologically relevant conditions, which may be intrinsically related to their biological functions.

  10. Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms.

    Science.gov (United States)

    Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R

    2015-01-01

    Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called "repeat-swap modeling" to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport also

  11. Reversible Conformational Change in the Plasmodium falciparum Circumsporozoite Protein Masks Its Adhesion Domains.

    Science.gov (United States)

    Herrera, Raul; Anderson, Charles; Kumar, Krishan; Molina-Cruz, Alvaro; Nguyen, Vu; Burkhardt, Martin; Reiter, Karine; Shimp, Richard; Howard, Randall F; Srinivasan, Prakash; Nold, Michael J; Ragheb, Daniel; Shi, Lirong; DeCotiis, Mark; Aebig, Joan; Lambert, Lynn; Rausch, Kelly M; Muratova, Olga; Jin, Albert; Reed, Steven G; Sinnis, Photini; Barillas-Mury, Carolina; Duffy, Patrick E; MacDonald, Nicholas J; Narum, David L

    2015-10-01

    The extended rod-like Plasmodium falciparum circumsporozoite protein (CSP) is comprised of three primary domains: a charged N terminus that binds heparan sulfate proteoglycans, a central NANP repeat domain, and a C terminus containing a thrombospondin-like type I repeat (TSR) domain. Only the last two domains are incorporated in RTS,S, the leading malaria vaccine in phase 3 trials that, to date, protects about 50% of vaccinated children against clinical disease. A seroepidemiological study indicated that the N-terminal domain might improve the efficacy of a new CSP vaccine. Using a panel of CSP-specific monoclonal antibodies, well-characterized recombinant CSPs, label-free quantitative proteomics, and in vitro inhibition of sporozoite invasion, we show that native CSP is N-terminally processed in the mosquito host and undergoes a reversible conformational change to mask some epitopes in the N- and C-terminal domains until the sporozoite interacts with the liver hepatocyte. Our findings show the importance of understanding processing and the biophysical change in conformation, possibly due to a mechanical or molecular signal, and may aid in the development of a new CSP vaccine. PMID:26169272

  12. Reversible Conformational Change in the Plasmodium falciparum Circumsporozoite Protein Masks Its Adhesion Domains

    Science.gov (United States)

    Herrera, Raul; Anderson, Charles; Kumar, Krishan; Molina-Cruz, Alvaro; Nguyen, Vu; Burkhardt, Martin; Reiter, Karine; Shimp, Richard; Howard, Randall F.; Srinivasan, Prakash; Nold, Michael J.; Ragheb, Daniel; Shi, Lirong; DeCotiis, Mark; Aebig, Joan; Lambert, Lynn; Rausch, Kelly M.; Muratova, Olga; Jin, Albert; Reed, Steven G.; Sinnis, Photini; Barillas-Mury, Carolina; Duffy, Patrick E.; MacDonald, Nicholas J.

    2015-01-01

    The extended rod-like Plasmodium falciparum circumsporozoite protein (CSP) is comprised of three primary domains: a charged N terminus that binds heparan sulfate proteoglycans, a central NANP repeat domain, and a C terminus containing a thrombospondin-like type I repeat (TSR) domain. Only the last two domains are incorporated in RTS,S, the leading malaria vaccine in phase 3 trials that, to date, protects about 50% of vaccinated children against clinical disease. A seroepidemiological study indicated that the N-terminal domain might improve the efficacy of a new CSP vaccine. Using a panel of CSP-specific monoclonal antibodies, well-characterized recombinant CSPs, label-free quantitative proteomics, and in vitro inhibition of sporozoite invasion, we show that native CSP is N-terminally processed in the mosquito host and undergoes a reversible conformational change to mask some epitopes in the N- and C-terminal domains until the sporozoite interacts with the liver hepatocyte. Our findings show the importance of understanding processing and the biophysical change in conformation, possibly due to a mechanical or molecular signal, and may aid in the development of a new CSP vaccine. PMID:26169272

  13. Anti-candidal activity of genetically engineered histatin variants with multiple functional domains.

    Directory of Open Access Journals (Sweden)

    Frank G Oppenheim

    Full Text Available The human bodily defense system includes a wide variety of innate antimicrobial proteins. Histatins are small molecular weight proteins produced by the human salivary glands that exhibit antifungal and antibacterial activities. While evolutionarily old salivary proteins such as mucins and proline-rich proteins contain large regions of tandem repeats, relatively young proteins like histatins do not contain such repeated domains. Anticipating that domain duplications have a functional advantage, we genetically engineered variants of histatin 3 with one, two, three, or four copies of the functional domain by PCR and splice overlap. The resulting proteins, designated reHst3 1-mer, reHist3 2-mer, reHis3 3-mer and reHist3 4-mer, exhibited molecular weights of 4,062, 5,919, 7,777, and 9,634 Da, respectively. The biological activities of these constructs were evaluated in fungicidal assays toward Candida albicans blastoconidia and germinated cells. The antifungal activities per mole of protein increased concomitantly with the number of functional domains present. This increase, however, was higher than could be anticipated from the molar concentration of functional domains present in the constructs. The demonstrated increase in antifungal activity may provide an evolutionary explanation why such domain multiplication is a frequent event in human salivary proteins.

  14. Domain movement within a gene: a novel evolutionary mechanism for protein diversification.

    Directory of Open Access Journals (Sweden)

    Yoshikazu Furuta

    Full Text Available A protein function is carried out by a specific domain localized at a specific position. In the present study, we report that, within a gene, a specific amino acid sequence can move between a certain position and another position. This was discovered when the sequences of restriction-modification systems within the bacterial species Helicobacter pylori were compared. In the specificity subunit of Type I restriction-modification systems, DNA sequence recognition is mediated by target recognition domain 1 (TRD1 and TRD2. To our surprise, several sequences are shared by TRD1 and TRD2 of genes (alleles at the same locus (chromosomal location; these domains appear to have moved between the two positions. The gene/protein organization can be represented as x-(TRD1-y-x-(TRD2-y, where x and y represent repeat sequences. Movement probably occurs by recombination at these flanking DNA repeats. In accordance with this hypothesis, recombination at these repeats also appears to decrease two TRDs into one TRD or increase these two TRDs to three TRDs (TRD1-TRD2-TRD2 and to allow TRD movement between genes even at different loci. Similar movement of domains between TRD1 and TRD2 was observed for the specificity subunit of a Type IIG restriction enzyme. Similar movement of domain between TRD1 and TRD2 was observed for Type I restriction-modification enzyme specificity genes in two more eubacterial species, Streptococcus pyogenes and Mycoplasma agalactiae. Lateral domain movements within a protein, which we have designated DOMO (domain movement, represent novel routes for the diversification of proteins.

  15. Anks3 alters the sub-cellular localization of the Nek7 kinase

    Energy Technology Data Exchange (ETDEWEB)

    Ramachandran, Haribaskar; Engel, Christina; Müller, Barbara [Renal Division, Department of Medicine, University Freiburg Medical Center, Hugstetter Str. 55, 79106 Freiburg (Germany); Dengjel, Jörn [Department of Dermatology, University Freiburg Medical Center and Center of Biological Systems Analysis, Habsburgerstr. 49, 79104 Freiburg (Germany); Walz, Gerd [Renal Division, Department of Medicine, University Freiburg Medical Center, Hugstetter Str. 55, 79106 Freiburg (Germany); Center for Biological Signaling Studies (BIOSS), Albertstr. 19, 79104 Freiburg (Germany); Yakulov, Toma A., E-mail: toma.antonov.yakulov@uniklinik-freiburg.de [Renal Division, Department of Medicine, University Freiburg Medical Center, Hugstetter Str. 55, 79106 Freiburg (Germany)

    2015-08-28

    Nephronophthisis (NPH) is an autosomal recessive cystic kidney disease, and a frequent cause of end-stage renal failure in children. To date, 17 NPH-associated gene products (NPHPs) have been identified. Most NPHPs participate in large multi-protein complexes that localize to the cilium and/or basal body; however, the precise composition of these complexes and their biological function remain largely unknown. We recently observed that the ankyrin repeat protein Anks3 interacts with the NPH family member Anks6. Both Anks3 and Anks6 form complexes with multiple other NPHPs, suggesting that both proteins function in similar or overlapping signaling pathways. Here, we show that Anks3, but not Anks6 interacted with the NIMA-related kinase Nek7, and was heavily modified in the presence of Nek7, resulting in an approximately 20 kD increase in molecular weight. Although mass spectrometry revealed increased serine and threonine phosphorylation of Anks3 primarily within the N-terminal ankyrin repeats also required for Nek7 interaction, the molecular weight increase occurred even in the presence of a kinase-dead Nek7 mutant, indicating that this modification was not caused by Nek7-dependent Anks3 phosphorylation. Furthermore, the Anks3 modification was specific for Nek7, and did not occur in the presence of Nek8. Importantly, Anks3 retained Nek7 in the cytoplasm, suggesting that, Nek7 triggers the modification of Anks3, which in turn prevents the nuclear localization of Nek7. - Highlights: • Anks3 interacted with Nek7 kinase, and was heavily modified in the presence of Nek7. • Anks3 N-terminal ankyrin repeats, but not SAM domain required for Nek7 interaction. • Nek7 increased Ser/Thr phosphorylation of Anks3 primarily within ankyrin domain. • Interaction with Anks3 led to cytoplasmic retention and nuclear exclusion of Nek7.

  16. Domain Decomposition Solvers for Frequency-Domain Finite Element Equations

    KAUST Repository

    Copeland, Dylan

    2010-10-05

    The paper is devoted to fast iterative solvers for frequency-domain finite element equations approximating linear and nonlinear parabolic initial boundary value problems with time-harmonic excitations. Switching from the time domain to the frequency domain allows us to replace the expensive time-integration procedure by the solution of a simple linear elliptic system for the amplitudes belonging to the sine- and to the cosine-excitation or a large nonlinear elliptic system for the Fourier coefficients in the linear and nonlinear case, respectively. The fast solution of the corresponding linear and nonlinear system of finite element equations is crucial for the competitiveness of this method. © 2011 Springer-Verlag Berlin Heidelberg.

  17. Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Ji-Hye [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Won Kyung [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Heeyoun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Eunhee; Cheong, Chaejoon [Magnetic Resonance Team, Korea Basic Science Institute (KBSI), Ochang, Chungbuk 363-883 (Korea, Republic of); Cho, Myeon Haeng [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2014-09-26

    Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminal Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2{sub 1–64}) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2{sub 1–64} and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences.

  18. Vocabulary Learning through Assisted and Unassisted Repeated Reading

    Science.gov (United States)

    Webb, Stuart; Chang, Anna C-S.

    2012-01-01

    Previous research investigating the effects of unassisted and assisted repeated reading has primarily focused on how each approach may contribute to improvement in reading comprehension and fluency. Incidental learning of the form and meaning of unknown or partially known words encountered through assisted and unassisted repeated reading has yet…

  19. Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

    Directory of Open Access Journals (Sweden)

    Shanshan Huang

    2015-10-01

    Full Text Available In polyglutamine (polyQ diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17, we found that a large polyQ (105 glutamines in the TATA-box-binding protein (TBP preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.

  20. Hybrid quantum repeater protocol with fast local processing

    DEFF Research Database (Denmark)

    Borregaard, Johannes; Brask, Jonatan Bohr; Sørensen, Anders Søndberg

    2012-01-01

    We propose a hybrid quantum repeater protocol combining the advantages of continuous and discrete variables. The repeater is based on the previous work of Brask et al. [ Phys. Rev. Lett. 105 160501 (2010)] but we present two ways of improving this protocol. In the previous protocol entangled single...

  1. Impact of Inclusion or Exclusion of Repeaters on Test Equating

    Science.gov (United States)

    Puhan, Gautam

    2011-01-01

    This study examined the effect of including or excluding repeaters on the equating process and results. New forms of two tests were equated to their respective old forms using either all examinees or only the first timer examinees in the new form sample. Results showed that for both tests used in this study, including or excluding repeaters in the…

  2. Secret key rates for an encoded quantum repeater

    Science.gov (United States)

    Bratzik, Sylvia; Kampermann, Hermann; Bruß, Dagmar

    2014-03-01

    We investigate secret key rates for the quantum repeater using encoding [L. Jiang et al., Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325] and compare them to the standard repeater scheme by Briegel, Dür, Cirac, and Zoller. The former scheme has the advantage of a minimal consumption of classical communication. We analyze the trade-off in the secret key rate between the communication time and the required resources. For this purpose we introduce an error model for the repeater using encoding which allows for input Bell states with a fidelity smaller than one, in contrast to the model given by L. Jiang et al. [Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325]. We show that one can correct additional errors in the encoded connection procedure of this repeater and develop a suitable decoding algorithm. Furthermore, we derive the rate of producing entangled pairs for the quantum repeater using encoding and give the minimal parameter values (gate quality and initial fidelity) for establishing a nonzero secret key. We find that the generic quantum repeater is optimal regarding the secret key rate per memory per second and show that the encoded quantum repeater using the simple three-qubit repetition code can even have an advantage with respect to the resources compared to other recent quantum repeater schemes with encoding.

  3. Development of Repeated Sprint Ability in Talented Youth Basketball Players

    NARCIS (Netherlands)

    te Wierike, Sanne C. M.; de Jong, Mark C.; Tromp, Eveline J. Y.; Vuijk, Pieter J.; Lemmink, Koen A. P. M.; Malina, Robert M.; Elferink-Gemser, Marije T.; Visscher, Chris

    2014-01-01

    te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated i

  4. Repeatable mechanochemical activation of dynamic covalent bonds in thermoplastic elastomers.

    Science.gov (United States)

    Imato, Keiichi; Kanehara, Takeshi; Nojima, Shiki; Ohishi, Tomoyuki; Higaki, Yuji; Takahara, Atsushi; Otsuka, Hideyuki

    2016-08-18

    Repeated mechanical scission and recombination of dynamic covalent bonds incorporated in segmented polyurethane elastomers are demonstrated by utilizing a diarylbibenzofuranone-based mechanophore and by the design of the segmented polymer structures. The repeated mechanochemical reactions can accompany clear colouration and simultaneous fading. PMID:27424868

  5. Turkish population data on the short tandem repeat locus TPOX

    DEFF Research Database (Denmark)

    Vural, B; Poda, M; Atlioglu, E;

    1998-01-01

    Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals.......Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals....

  6. Short-sequence DNA repeats in prokaryotic genomes

    NARCIS (Netherlands)

    A.F. van Belkum (Alex); S. Scherer; L. van Alphen (Loek); H.A. Verbrugh (Henri)

    1998-01-01

    textabstractShort-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many prokaryotic genomes. These loci harbor short or long stretches of repeated nucleotide sequence motifs. DNA sequence motifs in a single locus can be identical and/or heterogeneo

  7. Sequence-structure-function relations of the mosquito leucine-rich repeat immune proteins

    Directory of Open Access Journals (Sweden)

    Povelones Michael

    2010-09-01

    Full Text Available Abstract Background The discovery and characterisation of factors governing innate immune responses in insects has driven the elucidation of many immune system components in mammals and other organisms. Focusing on the immune system responses of the malaria mosquito, Anopheles gambiae, has uncovered an array of components and mechanisms involved in defence against pathogen infections. Two of these immune factors are LRIM1 and APL1C, which are leucine-rich repeat (LRR containing proteins that activate complement-like defence responses against malaria parasites. In addition to their LRR domains, these leucine-rich repeat immune (LRIM proteins share several structural features including signal peptides, patterns of cysteine residues, and coiled-coil domains. Results The identification and characterisation of genes related to LRIM1 and APL1C revealed putatively novel innate immune factors and furthered the understanding of their likely molecular functions. Genomic scans using the shared features of LRIM1 and APL1C identified more than 20 LRIM-like genes exhibiting all or most of their sequence features in each of three disease-vector mosquitoes with sequenced genomes: An. gambiae, Aedes aegypti, and Culex quinquefasciatus. Comparative sequence analyses revealed that this family of mosquito LRIM-like genes is characterised by a variable number of 6 to 14 LRRs of different lengths. The "Long" LRIM subfamily, with 10 or more LRRs, and the "Short" LRIMs, with 6 or 7 LRRs, also share the signal peptide, cysteine residue patterning, and coiled-coil sequence features of LRIM1 and APL1C. The "TM" LRIMs have a predicted C-terminal transmembrane region, and the "Coil-less" LRIMs exhibit the characteristic LRIM sequence signatures but lack the C-terminal coiled-coil domains. Conclusions The evolutionary plasticity of the LRIM LRR domains may provide templates for diverse recognition properties, while their coiled-coil domains could be involved in the formation

  8. Effects of 3-repeat tau on taxol mobility through microtubules

    Science.gov (United States)

    Park, Hyunjoo; Fygenson, Deborah; Kim, Mahn Won

    2005-03-01

    Both the anti-cancer drug taxol and the microtubule-associated protein tau suppress dynamics of microtubules (MT). We have observed taxol mobility with full-length 3-repeat tau, one of six tau isoforms, using fluorescence recovery after photobleaching (FRAP) on MTs and compare with earlier results on recombinant full-length adult 4-repeat tau. Taxol mobility becomes highly sensitive to taxol concentration in the presence of 3-repeat tau (up to 1:1 molar ratio) as it does in the presence of 4-repeat tau, but is 2 to 3 times faster at low taxol concentrations. Fitting to a mean-field binding reaction model [J.L. Ross et.al, PNAS 101:12910-5 (2004)] suggests that the presence of 3-repeat tau enhances taxol movement through pores in the MT walls.

  9. Trimeric Autotransporters of Haemophilus parasuis: Generation of an Extensive Passenger Domain Repertoire Specific for Pathogenic Strains▿ †

    OpenAIRE

    Pina, Sonia; Olvera, Alex; Barceló, Anna; Bensaid, Albert

    2008-01-01

    Haemophilus parasuis is the agent responsible for causing Glässer's disease, but little is known about the pathogenic determinants of this major pig disease. Here we describe, for the pathogenic strain Nagasaki, the molecular characterization of 13 trimeric autotransporters as assessed by the presence of YadA C-terminal translocator domains which were classified into three groups. All passenger domains possess motifs and repeats characteristic of adhesins, hemagglutinins, and invasins with va...

  10. Invertebrate and vertebrate class III myosins interact with MORN repeat-containing adaptor proteins.

    Directory of Open Access Journals (Sweden)

    Kirk L Mecklenburg

    Full Text Available In Drosophila photoreceptors, the NINAC-encoded myosin III is found in a complex with a small, MORN-repeat containing, protein Retinophilin (RTP. Expression of these two proteins in other cell types showed NINAC myosin III behavior is altered by RTP. NINAC deletion constructs were used to map the RTP binding site within the proximal tail domain of NINAC. In vertebrates, the RTP ortholog is MORN4. Co-precipitation experiments demonstrated that human MORN4 binds to human myosin IIIA (MYO3A. In COS7 cells, MORN4 and MYO3A, but not MORN4 and MYO3B, co-localize to actin rich filopodia extensions. Deletion analysis mapped the MORN4 binding to the proximal region of the MYO3A tail domain. MYO3A dependent MORN4 tip localization suggests that MYO3A functions as a motor that transports MORN4 to the filopodia tips and MORN4 may enhance MYO3A tip localization by tethering it to the plasma membrane at the protrusion tips. These results establish conserved features of the RTP/MORN4 family: they bind within the tail domain of myosin IIIs to control their behavior.

  11. Consistency of Repeated Naming in Aphasia

    Directory of Open Access Journals (Sweden)

    Elizabeth E. Galletta

    2015-09-01

    Full Text Available Background People with mild aphasia and healthy elderly often exhibit similar impairments on language tests of word retrieval. However, variable practice effects in object naming by three individuals with aphasia compared to young and elderly adults have been reported (Wingfield et al. 2006. Wingfield et al. (2006 found that naming of the same pictures of objects over five trials demonstrated decreasing response latencies over repeated trials for both older and younger adults, but not for individuals with aphasia. In fact, among their three participants with aphasia, response latencies in the consecutive trials differed considerably. The authors suggested that different underlying processes may be involved in word retrieval for people with aphasia compared to adults without brain injuries. In our study we aimed to further consider the effect of practice on both object and action naming in individuals with mild aphasia. Method One woman with anomic aphasia (age 38 years; WAB Aphasia Quotient = 88 and one healthy woman (age 25 years participated. Both were native English speakers and reported 18 years of formal education. Participants were tested individually, with a set of 27 object pictures and a set of 27 action pictures presented one at a time on a computer screen. The participants were instructed to name each picture as quickly as possible as soon as each picture appeared on the screen. There were 10 trials of each set of pictures, with different random orders for each trial. The order of presentation of the object and action picture sets alternated across participants. Naming responses were recorded to computer sound files for later measurements of response latencies. A brief tone was presented simultaneous with the picture onset, allowing later measurement of response latencies from the onset of picture presentation to the onset of the participant’s correct response. Results Our findings resembled those reported in Wingfield et al. (2006

  12. Gradient Domain Guided Image Filtering.

    Science.gov (United States)

    Kou, Fei; Chen, Weihai; Wen, Changyun; Li, Zhengguo

    2015-11-01

    Guided image filter (GIF) is a well-known local filter for its edge-preserving property and low computational complexity. Unfortunately, the GIF may suffer from halo artifacts, because the local linear model used in the GIF cannot represent the image well near some edges. In this paper, a gradient domain GIF is proposed by incorporating an explicit first-order edge-aware constraint. The edge-aware constraint makes edges be preserved better. To illustrate the efficiency of the proposed filter, the proposed gradient domain GIF is applied for single-image detail enhancement, tone mapping of high dynamic range images and image saliency detection. Both theoretical analysis and experimental results prove that the proposed gradient domain GIF can produce better resultant images, especially near the edges, where halos appear in the original GIF. PMID:26285153

  13. Strategy When Faced with Failure: Persistence and Degree Attainment of Course Repeaters versus Non-Repeaters. AIR 2002 Forum Paper.

    Science.gov (United States)

    Fenton, Kathleen S.

    Graduation and persistence rates were compared for 184 students, 92 of whom had repeated multiple courses or at least 1 course 3 times. A control group of 92 nonrepeating students was drawn from the remaining 303 students of the entire 1996 cohort. There was no difference between the graduation rate of repeaters and nonrepeaters. The persistence…

  14. Domain wall description of superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Brito, F.A. [Departamento de Física, Universidade Federal de Campina Grande, Caixa Postal 10071, 58109-970 Campina Grande, Paraíba (Brazil); Freire, M.L.F. [Departamento de Física, Universidade Estadual da Paraíba, 58109-753 Campina Grande, Paraíba (Brazil); Mota-Silva, J.C. [Departamento de Física, Universidade Federal de Campina Grande, Caixa Postal 10071, 58109-970 Campina Grande, Paraíba (Brazil); Departamento de Física, Universidade Federal da Paraíba, Caixa Postal 5008, 58051-970 João Pessoa, Paraíba (Brazil)

    2014-01-20

    In the present work we shall address the issue of electrical conductivity in superconductors in the perspective of superconducting domain wall solutions in the realm of field theory. We take our set up made out of a dynamical complex scalar field coupled to gauge field to be responsible for superconductivity and an extra scalar real field that plays the role of superconducting domain walls. The temperature of the system is interpreted through the fact that the soliton following accelerating orbits is a Rindler observer experiencing a thermal bath.

  15. Domain wall description of superconductivity

    International Nuclear Information System (INIS)

    In the present work we shall address the issue of electrical conductivity in superconductors in the perspective of superconducting domain wall solutions in the realm of field theory. We take our set up made out of a dynamical complex scalar field coupled to gauge field to be responsible for superconductivity and an extra scalar real field that plays the role of superconducting domain walls. The temperature of the system is interpreted through the fact that the soliton following accelerating orbits is a Rindler observer experiencing a thermal bath

  16. Repeating and not so Repeating Large Earthquakes in the Mexican Subduction Zone

    Science.gov (United States)

    Hjorleifsdottir, V.; Singh, S.; Iglesias, A.; Perez-Campos, X.

    2013-12-01

    The rupture area and recurrence interval of large earthquakes in the mexican subduction zone are relatively small and almost the entire length of the zone has experienced a large (Mw≥7.0) earthquake in the last 100 years (Singh et al., 1981). Several segments have experienced multiple large earthquakes in this time period. However, as the rupture areas of events prior to 1973 are only approximately known, the recurrence periods are uncertain. Large earthquakes occurred in the Ometepec, Guerrero, segment in 1937, 1950, 1982 and 2012 (Singh et al., 1981). In 1982, two earthquakes (Ms 6.9 and Ms 7.0) occurred about 4 hours apart, one apparently downdip from the other (Astiz & Kanamori, 1984; Beroza et al. 1984). The 2012 earthquake on the other hand had a magnitude of Mw 7.5 (globalcmt.org), breaking approximately the same area as the 1982 doublet, but with a total scalar moment about three times larger than the 1982 doublet combined. It therefore seems that 'repeat earthquakes' in the Ometepec segment are not necessarily very similar one to another. The Central Oaxaca segment broke in large earthquakes in 1928 (Mw7.7) and 1978 (Mw7.7) . Seismograms for the two events, recorded at the Wiechert seismograph in Uppsala, show remarkable similarity, suggesting that in this area, large earthquakes can repeat. The extent to which the near-trench part of the fault plane participates in the ruptures is not well understood. In the Ometepec segment, the updip portion of the plate interface broke during the 25 Feb 1996 earthquake (Mw7.1), which was a slow earthquake and produced anomalously low PGAs (Iglesias et al., 2003). Historical records indicate that a great tsunamigenic earthquake, M~8.6, occurred in the Oaxaca region in 1787, breaking the Central Oaxaca segment together with several adjacent segments (Suarez & Albini 2009). Whether the updip portion of the fault broke in this event remains speculative, although plausible based on the large tsunami. Evidence from the

  17. The L3MBTL3 Methyl-Lysine Reader Domain Functions As a Dimer.

    Science.gov (United States)

    Baughman, Brandi M; Pattenden, Samantha G; Norris, Jacqueline L; James, Lindsey I; Frye, Stephen V

    2016-03-18

    L3MBTL3 recognizes mono- and dimethylated lysine residues on histone tails. The recently reported X-ray cocrystal structures of the chemical probe UNC1215 and inhibitor UNC2533 bound to the methyl-lysine reading MBT domains of L3MBTL3 demonstrate a unique and flexible 2:2 dimer mode of recognition. In this study, we describe our in vitro analysis of L3MBTL3 dimerization via its MBT domains and additionally show that this dimerization occurs within a cellular context in the absence of small molecule ligands. Furthermore, mutations to the first and second MBT domains abrogated L3MBTL3 dimerization both in vitro and in cells. These observations are consistent with the hypothesis that L3MBTL3 engages methylated histone tails as a dimer while carrying out its normal function and provides an explanation for the presence of repeated MBT domains within L3MBTL3. PMID:26317848

  18. Repeating earthquakes recorded by Liaoning Regional Seismograph Network

    Institute of Scientific and Technical Information of China (English)

    LI Yu-tong; WU Zhong-liang; JIANG Chang-sheng; LI Guang-ping

    2008-01-01

    In the list of 'repeating pairs' or 'doublets' of earthquakes in China identified by Schaff and Richards using tele-seismic waveform cross-correlation, there were 23 repeating pairs located in Liaoning Province. In this study the waveforms of these events were cross-correlated using records from Liaoning Regional Seismograph Network (LRSN), and the 'repeating events' in the sense of regional waveform cross-correlation were obtained. The result was compared with that of Schaff and Richards and was used for the assessment of the seismic phase picking and event location practice of LRSN. The result shows that 'repeating events' in the sense of teleseismic waveform cross-correlation and those in the sense of regional waveform cross-correlation have significant difference, al-though with some overlap. However, the overall assessment of the location accuracy and the phase pick errors of LRSN by using these two sets of 'repeating events', respectively, provides similar results, while 'repeating events' in the sense of regional waveform cross-correlation seem to be better performing in such an assessment. With the assumption that the separation between the 'repeaters' be less than 1 km, the uncertainty in routine earthquake location of LRSN is estimated to be below 5 km, with the average of 2 km. In the observational bulletins of LRSN the time error in phase picking is estimated to be within±Is for 94% Pg readings and for 88% Sg readings.

  19. Exploring the repeat protein universe through computational protein design.

    Science.gov (United States)

    Brunette, T J; Parmeggiani, Fabio; Huang, Po-Ssu; Bhabha, Gira; Ekiert, Damian C; Tsutakawa, Susan E; Hura, Greg L; Tainer, John A; Baker, David

    2015-12-24

    A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.

  20. A De Novo Genome Assembly Algorithm for Repeats and Nonrepeats

    Directory of Open Access Journals (Sweden)

    Shuaibin Lian

    2014-01-01

    Full Text Available Background. Next generation sequencing platforms can generate shorter reads, deeper coverage, and higher throughput than those of the Sanger sequencing. These short reads may be assembled de novo before some specific genome analyses. Up to now, the performances of assembling repeats of these current assemblers are very poor. Results. To improve this problem, we proposed a new genome assembly algorithm, named SWA, which has four properties: (1 assembling repeats and nonrepeats; (2 adopting a new overlapping extension strategy to extend each seed; (3 adopting sliding window to filter out the sequencing bias; and (4 proposing a compensational mechanism for low coverage datasets. SWA was evaluated and validated in both simulations and real sequencing datasets. The accuracy of assembling repeats and estimating the copy numbers is up to 99% and 100%, respectively. Finally, the extensive comparisons with other eight leading assemblers show that SWA outperformed others in terms of completeness and correctness of assembling repeats and nonrepeats. Conclusions. This paper proposed a new de novo genome assembly method for resolving complex repeats. SWA not only can detect where repeats or nonrepeats are but also can assemble them completely from NGS data, especially for assembling repeats. This is the advantage over other assemblers.

  1. Automorphism group of exceptional symmetric domains RVI

    Institute of Scientific and Technical Information of China (English)

    许以超

    2000-01-01

    Here we give the definition of the exceptional symmetric Siegel domain RVI (27) in (?)27, and compute the exceptional symmetric domain .RvI(27) = r(RVI(27)), where τ is the Bergman mapping of the Siegel domain RVI(27). Moreover, we present the holomorphical automorphism group Aut(.RVI|(27)) of the exceptional symmetric domain .

  2. Computations of Bergman Kernels on Hua Domains

    Institute of Scientific and Technical Information of China (English)

    殷慰萍; 王安; 赵振刚; 赵晓霞; 管冰辛

    2001-01-01

    @@The Bergman kernel function plays an important ro1e in several complex variables.There exists the Bergman kernel function on any bounded domain in Cn. But we can get the Bergman kernel functions in explicit formulas for a few types of domains only,for example:the bounded homogeneous domains and the egg domain in some cases.

  3. Analysis of repeated outcome measures from longitudinal studies

    Institute of Scientific and Technical Information of China (English)

    Yuanjia WANG; Naihua DUAN

    2011-01-01

    @@ In many clinical studies repeated measurements of an outcome are collected over time.For example,in an 8-week study of treatment for obsessive compulsive disorder,the severity of the disorder may be measured weekly using the Yale-Brown-Obsessive-Compulsive-Disorder-Scale (YBOCS).For each study participant who completes the study,there will be nine repeated measures of YBOCS (a baseline assessment plus eight assessments during the course of treatment).Such a study in which participants are followed and measured repeatedly over time is called a longitudinal study and the resulting data are called longitudinal data.

  4. Frequency Bandwidth of Half-Wave Impedance Repeater

    Directory of Open Access Journals (Sweden)

    Marek Dvorsky

    2012-01-01

    Full Text Available This article brings in the second part general information about half-wave impedance repeater. The third part describes the basic functional principles of the half-wave impedance repeater using Smith chart. The main attention is focused in part four on the derivation of repeater frequency bandwidth depending on characteristics and load impedance of unknown feeder line. Derived dependences are based on the elementary features of the feeder lines with specific length. The described functionality is proved in part 4.3 by measurement of transformed impedance using vector several unbalanced feeder lines and network analyzer VNWA3+.

  5. Secure quantum network coding for controlled repeater networks

    Science.gov (United States)

    Shang, Tao; Li, Jiao; Liu, Jian-wei

    2016-07-01

    To realize efficient quantum communication based on quantum repeater, we propose a secure quantum network coding scheme for controlled repeater networks, which adds a controller as a trusted party and is able to control the process of EPR-pair distribution. As the key operations of quantum repeater, local operations and quantum communication are designed to adopt quantum one-time pad to enhance the function of identity authentication instead of local operations and classical communication. Scheme analysis shows that the proposed scheme can defend against active attacks for quantum communication and realize long-distance quantum communication with minimal resource consumption.

  6. Superconductivity in domains with corners

    DEFF Research Database (Denmark)

    Bonnaillie-Noel, Virginie; Fournais, Søren

    2007-01-01

    We study the two-dimensional Ginzburg-Landau functional in a domain with corners for exterior magnetic field strengths near the critical field where the transition from the superconducting to the normal state occurs. We discuss and clarify the definition of this field and obtain a complete...

  7. Overlap/Domain-wall reweighting

    CERN Document Server

    Fukaya, H; Cossu, G; Hashimoto, S; Kaneko, T; Noaki, J

    2013-01-01

    We investigate the eigenvalues of nearly chiral lattice Dirac operators constructed with five-dimensional implementations. Allowing small violation of the Ginsparg-Wilson relation, the HMC simulation is made much faster while the eigenvalues are not significantly affected. We discuss the possibility of reweighting the gauge configurations generated with domain-wall fermions to those of exactly chiral lattice fermions.

  8. Domain specific MT in use

    DEFF Research Database (Denmark)

    Offersgaard, Lene; Povlsen, Claus; Almsten, Lisbeth Kjeldgaard;

    2008-01-01

    The paper focuses on domain specific use of MT with a special focus on SMT in the workflow of a Language Service Provider (LSP). We report on the feedback of post-editors using fluency/adequacy evaluation and the evaluation metric ’Usability’, understood in this context as where users on a three ...

  9. Cellulose binding domain fusion proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    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.

  10. Nonlinear Evolution of Ferroelectric Domains

    Institute of Scientific and Technical Information of China (English)

    WeiLU; Dai-NingFANG; 等

    1997-01-01

    The nonlinear evolution of ferroelectric domains is investigated in the paper and amodel is proposed which can be applied to numerical computation.Numerical results show that the model can accurately predict some nonlinear behavior and consist with those experimental results.

  11. Ubiquitin domain proteins in disease

    DEFF Research Database (Denmark)

    Klausen, Louise Kjær; Schulze, Andrea; Seeger, Michael;

    2007-01-01

    The human genome encodes several ubiquitin-like (UBL) domain proteins (UDPs). Members of this protein family are involved in a variety of cellular functions and many are connected to the ubiquitin proteasome system, an essential pathway for protein degradation in eukaryotic cells. Despite...... and cancer. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com)....

  12. Modules over discrete valuation domains

    CERN Document Server

    Tuganbaev, Askar A

    2008-01-01

    This book provides the first systematic treatment of modules over discrete valuation domains which plays an important role in various areas of algebra, especially in commutative algebra. Many important results representing the state of the art are presented in the text which is supplemented by exercises and interesting open problems. An important contribution to commutative algebra.

  13. Partial domain wall partition functions

    CERN Document Server

    Foda, O

    2012-01-01

    We consider six-vertex model configurations on a rectangular lattice with n (N) horizontal (vertical) lines, and "partial domain wall boundary conditions" defined as 1. all 2n arrows on the left and right boundaries point inwards, 2. n_u (n_l) arrows on the upper (lower) boundary, such that n_u + n_l = N - n, also point inwards, 3. all remaining n+N arrows on the upper and lower boundaries point outwards, and 4. all spin configurations on the upper and lower boundaries are summed over. To generate (n-by-N) "partial domain wall configurations", one can start from A. (N-by-N) configurations with domain wall boundary conditions and delete n_u (n_l) upper (lower) horizontal lines, or B. (2n-by-N) configurations that represent the scalar product of an n-magnon Bethe eigenstate and an n-magnon generic state on an N-site spin-1/2 chain, and delete the n lines that represent the Bethe eigenstate. The corresponding "partial domain wall partition function" is computed in construction {A} ({B}) as an N-by-N (n-by-n) det...

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

    NARCIS (Netherlands)

    van Rossum, AGSH; Schuuring-Scholtes, E; Seggelen, VV; Kluin, PM; Schuuring, E

    2005-01-01

    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 (Arp)2/3 mediated actin polymerization. It shares a high amino acid seque

  15. Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency

    NARCIS (Netherlands)

    Lemoine, Roxane; Pachlopnik-Schmid, Jana; Farin, Henner F; Bigorgne, Amélie; Debré, Marianne; Sepulveda, Fernando; Héritier, Sébastien; Lemale, Julie; Talbotec, Cécile; Rieux-Laucat, Frédéric; Ruemmele, Frank; Morali, Alain; Cathebras, Pascal; Nitschke, Patrick; Bole-Feysot, Christine; Blanche, Stéphane; Brousse, Nicole; Picard, Capucine; Clevers, Hans; Fischer, Alain; de Saint Basile, Geneviève

    2014-01-01

    BACKGROUND: Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases, but the underlying molecular mechanisms remain largely unknown. Studies of monogenic diseases can provide insight into the pathogenesis of IBD. OBJECTIVE: We thought to determine the underlying

  16. Screening multicomponent reactions for X-linked inhibitor of apoptosis-baculoviral inhibitor of apoptosis protein repeats domain binder

    NARCIS (Netherlands)

    Monfardini, Ilaria; Huang, Jui-Wen; Beck, Barbara; Cellitti, Jason F; Pellecchia, Maurizio; Dömling, Alexander

    2011-01-01

    We report a second example of a general reaction screening approach to discover low molecular weight inhibitors of protein protein interactions. On the basis of the known pharmacophore model of SMAC mimetics, we predicted several inhibitors based on four different multicomponent reactions. The predi

  17. CATHEDRAL: a fast and effective algorithm to predict folds and domain boundaries from multidomain protein structures.

    Directory of Open Access Journals (Sweden)

    Oliver C Redfern

    2007-11-01

    Full Text Available We present CATHEDRAL, an iterative protocol for determining the location of previously observed protein folds in novel multidomain protein structures. CATHEDRAL builds on the features of a fast secondary-structure-based method (using graph theory to locate known folds within a multidomain context and a residue-based, double-dynamic programming algorithm, which is used to align members of the target fold groups against the query protein structure to identify the closest relative and assign domain boundaries. To increase the fidelity of the assignments, a support vector machine is used to provide an optimal scoring scheme. Once a domain is verified, it is excised, and the search protocol is repeated in an iterative fashion until all recognisable domains have been identified. We have performed an initial benchmark of CATHEDRAL against other publicly available structure comparison methods using a consensus dataset of domains derived from the CATH and SCOP domain classifications. CATHEDRAL shows superior performance in fold recognition and alignment accuracy when compared with many equivalent methods. If a novel multidomain structure contains a known fold, CATHEDRAL will locate it in 90% of cases, with <1% false positives. For nearly 80% of assigned domains in a manually validated test set, the boundaries were correctly delineated within a tolerance of ten residues. For the remaining cases, previously classified domains were very remotely related to the query chain so that embellishments to the core of the fold caused significant differences in domain sizes and manual refinement of the boundaries was necessary. To put this performance in context, a well-established sequence method based on hidden Markov models was only able to detect 65% of domains, with 33% of the subsequent boundaries assigned within ten residues. Since, on average, 50% of newly determined protein structures contain more than one domain unit, and typically 90% or more of these

  18. Weakly distributive domains(Ⅱ)

    Institute of Scientific and Technical Information of China (English)

    JIANG Ying; ZHANG Guo-Qiang

    2007-01-01

    In our previous work(Inform.and Comput.,2005,202:87-103),we have shown that for any ω-algebraic meet-cpo D,if all higher-order stable function spaces built from D are ω-algebraic,then D is finitary.This accomplishes the first of a possible,two-step process in solving the problem raised(LNCS,1991,530:16-33;Domainsand lambda-calculi,Cambridge Univ.Press,1998)whetherthe category of stable bifinite domains of Amadio-Droste-G(o)bel(LNCS,1991,530:16-33;Theor.Comput.Sci.,1993,111:89-101)is the largest cartesian closed full subcategory within the category of ω-algebraic meet-cpos with stable functions.This paper presents the results of the second step,which is to show that for any ω-algebraic meet-cpo D satisfying axioms M and I to be contained in a cartesian closed full sub-category using ω-algebraic meet-cpos with stable functions,it must not violate M I∞.We introduce a new class of domains called weakly distributive domains and show that for these domains to be in a cartesian closed category using ω-algebraic meet-cpos,property M I must not be violated.Further,we demonstrate that principally distributive domains(those for which each principle ideal is distributive)form a proper subclass of weakly distributive domains,and Birkhoff's M3 and N5(Introduction to Lattices and order,Cambridge Univ.Press,2002)are weakly distributive(but non-distributive).Then,we establish characterization results for weakly distributive domains.We also introduce the notion of meet-generators in constructing stable functions and show that if an ω-algebraic meet-cpo D contains an infinite number of meet-generators,then[D→D]fails I.However,the original problem of Amadio and Curien remains open.

  19. Compiling Dictionaries Using Semantic Domains*

    Directory of Open Access Journals (Sweden)

    Ronald Moe

    2011-10-01

    Full Text Available

    Abstract: The task of providing dictionaries for all the world's languages is prodigious, re-quiring efficient techniques. The text corpus method cannot be used for minority languages lacking texts. To meet the need, the author has constructed a list of 1 600 semantic domains, which he has successfully used to collect words. In a workshop setting, a group of speakers can collect as many as 17 000 words in ten days. This method results in a classified word list that can be efficiently expanded into a full dictionary. The method works because the mental lexicon is a giant web or-ganized around key concepts. A semantic domain can be defined as an important concept together with the words directly related to it by lexical relations. A person can utilize the mental web to quickly jump from word to word within a domain. The author is developing a template for each domain to aid in collecting words and in de-scribing their semantics. Investigating semantics within the context of a domain yields many in-sights. The method permits the production of both alphabetically and semantically organized dic-tionaries. The list of domains is intended to be universal in scope and applicability. Perhaps due to universals of human experience and universals of linguistic competence, there are striking simi-larities in various lists of semantic domains developed for languages around the world. Using a standardized list of domains to classify multiple dictionaries opens up possibilities for cross-lin-guistic research into semantic and lexical universals.

    Keywords: SEMANTIC DOMAINS, SEMANTIC FIELDS, SEMANTIC CATEGORIES, LEX-ICAL RELATIONS, SEMANTIC PRIMITIVES, DOMAIN TEMPLATES, MENTAL LEXICON, SEMANTIC UNIVERSALS, MINORITY LANGUAGES, LEXICOGRAPHY

    Opsomming: Samestelling van woordeboeke deur gebruikmaking van se-mantiese domeine. Die taak van die voorsiening van woordeboeke aan al die tale van die wêreld is geweldig en vereis doeltreffende tegnieke. Die

  20. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura

    Science.gov (United States)

    Zheng, X. Long; Wu, Haifeng M.; Shang, Dezhi; Falls, Erica; Skipwith, Christopher G.; Cataland, Spero R.; Bennett, Charles L.; Kwaan, Hau C.

    2010-01-01

    Background Type G immunoglobulins against ADAMTS13 are the primary cause of acquired (idiopathic) thrombotic thrombocytopenic purpura. However, the domains of ADAMTS13 which the type G anti-ADAMT13 immunoglobulins target have not been investigated in a large cohort of patients with thrombotic thrombocytopenic purpura. Design and Methods Sixty-seven patients with acquired idiopathic thrombotic thrombocytopenic purpura were prospectively collected from three major U.S. centers. An enzyme-linked immunosorbent assay determined plasma concentrations of anti-ADAMTS13 type G immunoglobulins, whereas immunoprecipitation plus western blotting determined the binding domains of these type G immunoglobulins. Results Plasma anti-ADAMTS13 type G immunoglobulins from 67 patients all bound full-length ADAMTS13 and a variant truncated after the eighth TSP1 repeat (delCUB). Approximately 97% (65/67) of patients harbored type G immunoglobulins targeted against a variant truncated after the spacer domain (MDTCS). However, only 12% of patients’ samples reacted with a variant lacking the Cys-rich and spacer domains (MDT). In addition, approximately 37%, 31%, and 46% of patients’ type G immunoglobulins interacted with the ADAMTS13 fragment containing TSP1 2-8 repeats (T2-8), CUB domains, and TSP1 5-8 repeats plus CUB domains (T5-8CUB), respectively. The presence of type G immunoglobulins targeted against the T2-8 and/or CUB domains was inversely correlated with the patients’ platelet counts on admission. Conclusions This multicenter study further demonstrated that the multiple domains of ADAMTS13, particularly the Cys-rich and spacer domains, are frequently targeted by anti-ADAMTS13 type G immunoglobulins in patients with acquired (idiopathic) thrombotic thrombocytopenic purpura. Our data shed more light on the pathogenesis of acquired thrombotic thrombocytopenic purpura and provide further rationales for adjunctive immunotherapy. PMID:20378566

  1. High-resolution long-reach distributed Brillouin sensing based on combined time-domain and correlation-domain analysis.

    Science.gov (United States)

    Elooz, David; Antman, Yair; Levanon, Nadav; Zadok, Avi

    2014-03-24

    A new scheme for distributed Brillouin sensing of strain and temperature in optical fibers is proposed, analyzed and demonstrated experimentally. The technique combines between time-domain and correlation-domain analysis. Both Brillouin pump and signal waves are repeatedly co-modulated by a relatively short, high-rate phase sequence, which introduces Brillouin interactions in a large number of discrete correlation peaks. In addition, the pump wave is also modulated by a single amplitude pulse, which leads to a temporal separation between the generation of different peaks. The Brillouin amplification of the signal wave at individual peak locations is resolved in the time domain. The technique provides the high spatial resolution and long range of unambiguous measurement offered by correlation-domain Brillouin analysis, together with reduced acquisition time through the simultaneous interrogation of a large number of resolution points. In addition, perfect Golomb codes are used in the phase modulation of the two waves instead of random sequences, in order to reduce noise due to residual, off-peak Brillouin interactions. The principle of the method is supported by extensive numerical simulations. Using the proposed scheme, the Brillouin gain spectrum is mapped experimentally along a 400 m-long fiber under test with a spatial resolution of 2 cm, or 20,000 resolution points, with only 127 scans per choice of frequency offset between pump and signal. Compared with corresponding phase-coded, Brillouin correlation domain analysis schemes with equal range and resolution, the acquisition time is reduced by a factor of over 150. A 5 cm-long hot spot, located towards the output end of the pump wave, is properly identified in the measurements. The method represents a significant advance towards practical high-resolution and long range Brillouin sensing systems.

  2. Decomposition and Removability Properties of John Domains

    Indian Academy of Sciences (India)

    M Huang; S Ponnusamy; X Wang

    2008-08-01

    In this paper we characterize John domains in terms of John domain decomposition property. In addition, we also show that a domain in $\\mathbb{R}^n$ is a John domain if and only if $D\\backslash P$ is a John domain, where is a subset of containing finitely many points of . The best possibility and an application of the second result are also discussed.

  3. Structure of the calcium-rich signature domain of human thrombospondin-2

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, C. Britt; Bernstein, Douglas A.; Annis, Douglas S.; Misenheimer, Tina M. (UW)

    2010-07-13

    Thrombospondins (THBSs) are secreted glycoproteins that have key roles in interactions between cells and the extracellular matrix. Here, we describe the 2.6-{angstrom}-resolution crystal structure of the glycosylated signature domain of human THBS2, which includes three epidermal growth factor-like modules, 13 aspartate-rich repeats and a lectin-like module. These elements interact extensively to form three structural regions termed the stalk, wire and globe. The THBS2 signature domain is stabilized by these interactions and by a network of 30 bound Ca{sup 2+} ions and 18 disulfide bonds. The structure suggests how genetic alterations of THBSs result in disease.

  4. The effects of multi-domain versus single-domain cognitive training in non-demented older people: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Cheng Yan

    2012-03-01

    Full Text Available Abstract Background Whether healthy older people can benefit from cognitive training (CogTr remains controversial. This study explored the benefits of CogTr in community dwelling, healthy, older adults and compared the effects of single-domain with multi-domain CogTr interventions. Methods A randomized, controlled, 3-month trial of CogTr with double-blind assessments at baseline and immediate, 6-month and 12-month follow-up after training completion was conducted. A total of 270 healthy Chinese older people, 65 to 75 years old, were recruited from the Ganquan-area community in Shanghai. Participants were randomly assigned to three groups: multi-domain CogTr, single-domain CogTr, and a wait-list control group. Twenty-four sessions of CogTr were administrated to the intervention groups over a three-month period. Six months later, three booster training sessions were offered to 60% of the initial training participants. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Form A, the Color Word Stroop test (CWST, the Visual Reasoning test and the Trail Making test (TMT were used to assess cognitive function. Results Multi-domain CogTr produced statistically significant training effects on RBANS, visual reasoning, and immediate and delayed memory, while single-domain CogTr showed training effects on RBANS, visual reasoning, word interference, and visuospatial/constructional score (all P Conclusions Cognitive training can improve memory, visual reasoning, visuospatial construction, attention and neuropsychological status in community-living older people and can help maintain their functioning over time. Multi-domain CogTr enhanced memory proficiency, while single-domain CogTr augmented visuospatial/constructional and attention abilities. Multi-domain CogTr had more advantages in training effect maintenance. Clinical Trial Registration Chinese Clinical Trial Registry. Registration number: ChiCTR-TRC-09000732.

  5. Analysis of Simple Sequence Repeats in Genomes of Rhizobia

    Institute of Scientific and Technical Information of China (English)

    GAO Ya-mei; HAN Yi-qiang; TANG Hui; SUN Dong-mei; WANG Yan-jie; WANG Wei-dong

    2008-01-01

    Simple sequence repeats (SSRs) or microsatellites, as genetic markers, are ubiquitous in genomes of various organisms. The analysis of SSR in rhizobia genome provides useful information for a variety of applications in population genetics of rhizobia. We analyzed the occurrences, relative abundance, and relative density of SSRs, the most common in Bradyrhizobium japonicum, Mesorhizobium loti, and Sinorhizobium meliloti genomes se-quenced in the microorganisms tandem repeats database, and SSRs in the three species genomes were compared with each other. The result showed that there were 1 410, 859, and 638 SSRs in B. japonicum, M. loti, and 5. meliloti genomes, respectively. In the genomes of B. japonicum, M. loti, and 5. meliloti, tetranucleotide, pentanucleotide, and hexanucleotide repeats were more abundant and indicated higher mutation rates in these species. The least abundance was mononucleotide repeat. The SSRs type and distribution were similar among these species.

  6. Quantitation of Leishmania lipophosphoglycan repeat units by capillary electrophoresis.

    Science.gov (United States)

    Barron, Tamara L; Turco, Salvatore J

    2006-04-01

    The glycosylphosphatidylinositol (GPI)-anchored lipophosphoglycan (LPG) of Leishmania is the dominant cell surface glycoconjugate of these pathogenic parasites. LPG is structurally characterized by a series of phosphoglycan repeat units. Determining the number of repeat units per LPG molecule has proven difficult using current technologies, such as mass spectrometry. As an alternative method to quantitate the number of repeat units in LPG, a procedure based on capillary electrophoretic analysis of the proportion of mannose to 2,5-anhydromannose (derived from the nonacetylated glucosamine of the GPI anchor of LPG) was developed. The CE-based technique is sensitive and relatively rapid compared to GC-MS-based protocols. Its application was demonstrated in quantitating the number of LPG repeat units from several species of Leishmania as well as from two life-cycle stages of these organisms. PMID:16310310

  7. Correct use of repeated measures analysis of variance.

    Science.gov (United States)

    Park, Eunsik; Cho, Meehye; Ki, Chang-Seok

    2009-02-01

    In biomedical research, researchers frequently use statistical procedures such as the t-test, standard analysis of variance (ANOVA), or the repeated measures ANOVA to compare means between the groups of interest. There are frequently some misuses in applying these procedures since the conditions of the experiments or statistical assumptions necessary to apply these procedures are not fully taken into consideration. In this paper, we demonstrate the correct use of repeated measures ANOVA to prevent or minimize ethical or scientific problems due to its misuse. We also describe the appropriate use of multiple comparison tests for follow-up analysis in repeated measures ANOVA. Finally, we demonstrate the use of repeated measures ANOVA by using real data and the statistical software package SPSS (SPSS Inc., USA).

  8. Repeated morphine treatment influences operant and spatial learning differentially

    Institute of Scientific and Technical Information of China (English)

    Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

    2006-01-01

    Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

  9. Discriminant analysis for repeated measures data: a review

    Directory of Open Access Journals (Sweden)

    Lisa Lix

    2010-09-01

    Full Text Available Discriminant analysis (DA encompasses procedures for classifying observations into groups (i.e., predictive discriminative analysis and describing the relative importance of variables for distinguishing amongst groups (i.e., descriptive discriminative analysis. In recent years, a number of developments have occurred in DA procedures for the analysis of data from repeated measures designs. Specifically, DA procedures have been developed for repeated measures data characterized by missing observations and/or unbalanced measurement occasions, as well as high-dimensional data in which measurements are collected repeatedly on two or more variables. This paper reviews the literature on DA procedures for univariate and multivariate repeated measures data, focusing on covariance pattern and linear mixed-effects models. A numeric example illustrates their implementation using SAS software.

  10. Reduction of starch granule size by expression of an engineered tandem starch-binding domain in potato plants

    NARCIS (Netherlands)

    Ji, Q.; Oomen, R.J.F.J.; Vincken, J.P.; Bolam, D.N.; Gilbert, H.J.; Suurs, L.C.J.M.; Visser, R.G.F.

    2004-01-01

    Granule size is an important parameter when using starch in industrial applications. An artificial tandem repeat of a family 20 starch-binding domain (SBD2) was engineered by two copies of the SBD derived from Bacillus circulans cyclodextrin glycosyltransferase via the Pro-Thr-rich linker peptice fr

  11. Rapid Brownian Motion Primes Ultrafast Reconstruction of Intrinsically Disordered Phe-Gly Repeats Inside the Nuclear Pore Complex

    Science.gov (United States)

    Moussavi-Baygi, R.; Mofrad, M. R. K.

    2016-01-01

    Conformational behavior of intrinsically disordered proteins, such as Phe-Gly repeat domains, alters drastically when they are confined in, and tethered to, nan channels. This has challenged our understanding of how they serve to selectively facilitate translocation of nuclear transport receptor (NTR)-bearing macromolecules. Heterogeneous FG-repeats, tethered to the NPC interior, nonuniformly fill the channel in a diameter-dependent manner and adopt a rapid Brownian motion, thereby forming a porous and highly dynamic polymeric meshwork that percolates in radial and axial directions and features two distinguishable zones: a dense hydrophobic rod-like zone located in the center, and a peripheral low-density shell-like zone. The FG-meshwork is locally disrupted upon interacting with NTR-bearing macromolecules, but immediately reconstructs itself between 0.44 μs and 7.0 μs, depending on cargo size and shape. This confers a perpetually-sealed state to the NPC, and is solely due to rapid Brownian motion of FG-repeats, not FG-repeat hydrophobic bonds. Elongated-shaped macromolecules, both in the presence and absence of NTRs, penetrate more readily into the FG-meshwork compared to their globular counterparts of identical volume and surface chemistry, highlighting the importance of the shape effects in nucleocytoplasmic transport. These results can help our understanding of geometrical effects in, and the design of, intelligent and responsive biopolymer-based materials in nanofiltration and artificial nanopores. PMID:27470900

  12. Reversible and Irreversible Aggregation of Proteins from the FET Family: Influence of Repeats in Protein Chain on Its Aggregation Capacity.

    Science.gov (United States)

    Galzitskaya, Oxana V

    2016-01-01

    The discovery of protein chain regions responsible for protein aggregation is an important result of studying of the molecular mechanisms of prion diseases and different proteinopathies associated with the formation of pathological aggregations through the prion mechanism. The ability to control aggregation of proteins could be an important tool in the arsenal of the drug development. Here we demonstrate, on an example of RNA-binding proteins of the FET family from six animal species (human, gorilla, pig, mouse, chicken, zebra fish), the possible role of repeats within the disordered regions. For these proteins, different repeats are revealed in the prion-like (N-terminal disordered) domains, and in the C-terminal disordered regions, predicted using bioinformatics methods. Moreover, we have found that in more complex organisms the number of repeats is increased. It can be hypothesized that the presence of a large number of repeats in the disordered regions in the proteins of the FET-family could both modulate and accelerate the formation of a dynamic cross-beta structure, and pathological aggregates. PMID:26100283

  13. Rapid Brownian Motion Primes Ultrafast Reconstruction of Intrinsically Disordered Phe-Gly Repeats Inside the Nuclear Pore Complex.

    Science.gov (United States)

    Moussavi-Baygi, R; Mofrad, M R K

    2016-01-01

    Conformational behavior of intrinsically disordered proteins, such as Phe-Gly repeat domains, alters drastically when they are confined in, and tethered to, nan channels. This has challenged our understanding of how they serve to selectively facilitate translocation of nuclear transport receptor (NTR)-bearing macromolecules. Heterogeneous FG-repeats, tethered to the NPC interior, nonuniformly fill the channel in a diameter-dependent manner and adopt a rapid Brownian motion, thereby forming a porous and highly dynamic polymeric meshwork that percolates in radial and axial directions and features two distinguishable zones: a dense hydrophobic rod-like zone located in the center, and a peripheral low-density shell-like zone. The FG-meshwork is locally disrupted upon interacting with NTR-bearing macromolecules, but immediately reconstructs itself between 0.44 μs and 7.0 μs, depending on cargo size and shape. This confers a perpetually-sealed state to the NPC, and is solely due to rapid Brownian motion of FG-repeats, not FG-repeat hydrophobic bonds. Elongated-shaped macromolecules, both in the presence and absence of NTRs, penetrate more readily into the FG-meshwork compared to their globular counterparts of identical volume and surface chemistry, highlighting the importance of the shape effects in nucleocytoplasmic transport. These results can help our understanding of geometrical effects in, and the design of, intelligent and responsive biopolymer-based materials in nanofiltration and artificial nanopores. PMID:27470900

  14. The Dynamics of Repeat Migration: A Markov Chain Analysis

    OpenAIRE

    Zimmermann, Klaus F.; Amelie F. Constant

    2003-01-01

    While the literature has established that there is substantial and highly selective return migration, the growing importance of repeat migration has been largely ignored. Using Markov chain analysis, this paper provides a modeling framework for repeated moves of migrants between the host and home countries. The Markov transition matrix between the states in two consecutive periods is parameterized and estimated using a logit specification and a large panel data with 14 waves. The analysis for...

  15. Allele-selective inhibition of trinucleotide repeat genes

    OpenAIRE

    Matsui, Masayuki; Corey, David R.

    2012-01-01

    Expanded trinucleotide repeats cause Huntington’s disease (HD) and many other neurodegenerative disorders. There are no cures for these devastating illnesses and treatments are urgently needed. Each trinucleotide repeat disorder is the result of the mutation of just one gene, and agents that block expression of the mutant gene offer a promising option for treatment. Therapies that block expression of both mutant and wild-type alleles can have adverse effects, challenging researchers to develo...

  16. Are major repeater patients addicted to suicidal behavior?

    Science.gov (United States)

    Blasco-Fontecilla, Hilario; Artieda-Urrutia, Paula; Berenguer-Elias, Nuria; Garcia-Vega, Juan Manuel; Fernandez-Rodriguez, Monica; Rodriguez-Lomas, Cesar; Gonzalez-Villalobos, Isabel; Iruela-Cuadrado, Luis; de Leon, José

    2014-01-01

    The literature provides support for the hypothesis that some major repeaters (individuals with >=5 lifetime suicide attempts) are addicted to suicidal behavior (SB). This study explores whether major repeaters are addicted to SB or not using 7 criteria: tolerance (Criterion 1), withdrawal (Criterion 2), loss of control (Criterion 3), problems in quitting/cutting down (Criterion 4), much time spent using (Criterion 5), substantial reduction in activities (Criterion 6), and adverse physiological/physical consequences (Criterion 7). Total dependence on SB was indicated by the presence of 3 or more of the 7 criteria in the last 12 months. This cross-sectional study at Puerta de Hierro University Hospital (Madrid, Spain) recruited 118 suicide attempters including 8 major repeaters (7%, 8/118), who were all females. The association between each SB addiction criterion, physiological dependence and total dependence with major repeater status was tested for significance and for effect size with odds ratios (ORs) and their 95% confidence intervals. As hypothesized, major repeaters met significantly higher frequency of criteria for total dependence on SB, OR=62.9 (6.4-615). A backward stepwise logistic regression model was used to provide an OR between major repeater status and total dependence status corrected by confounding variables. Age, panic disorder without agoraphobia, borderline personality disorder, history of psychiatric inpatient admission, and total dependence on SB were introduced as independent variables with major repeater status as the dependent variable. The model selected total dependence and age as the remaining significant variables in the last step. Accordingly, major repeaters appear to be addicted to SB. PMID:25580865

  17. Gene conversion homogenizes the CMT1A paralogous repeats

    OpenAIRE

    Hurles Matthew E

    2001-01-01

    Abstract Background Non-allelic homologous recombination between paralogous repeats is increasingly being recognized as a major mechanism causing both pathogenic microdeletions and duplications, and structural polymorphism in the human genome. It has recently been shown empirically that gene conversion can homogenize such repeats, resulting in longer stretches of absolute identity that may increase the rate of non-allelic homologous recombination. Results Here, a statistical test to detect ge...

  18. Failure Characteristic of Laser Cladding Samples on Repeated Impact

    Institute of Scientific and Technical Information of China (English)

    SHI Shi-hong; ZHENG Qi-guang; FU Ge-yan; ZHANG Jin-ping

    2004-01-01

    Using self-made impact fatigue test instruments and related analytic devices,the mechanical components with laser cladding layer have been attempted.It is found that,on repeated impact force,several failure modes of the components include the surface cracks,surface plastic deformation,corrosive pitting and coat collapse,etc.The paper reported the test method and initial analysis conclusions about the unique failure characteristics of the mechanical components on repeated impact load.

  19. Fully integrated, fully automated generation of short tandem repeat profiles

    OpenAIRE

    Tan, Eugene; Rosemary S. Turingan; Hogan, Catherine; Vasantgadkar, Sameer; Palombo, Luke; Schumm, James W.; Richard F Selden

    2013-01-01

    Background The generation of short tandem repeat profiles, also referred to as ‘DNA typing,’ is not currently performed outside the laboratory because the process requires highly skilled technical operators and a controlled laboratory environment and infrastructure with several specialized instruments. The goal of this work was to develop a fully integrated system for the automated generation of short tandem repeat profiles from buccal swab samples, to improve forensic laboratory process flow...

  20. Memory-based quantum repeater in quantum information communication

    Institute of Scientific and Technical Information of China (English)

    Wu Xiang-Sheng

    2004-01-01

    This paper studies the quantum repeater in quantum information communication. We propose to introduce the photon buffer mechanism for storing photons, which uses fibre delay loops as photon memories and a programmable 1 × N switcher for distributing photon delay time. Meanwhile, we also consider entanglement purification and entanglement swapping restoration at an entanglement purification or entanglement swapping failure and introduce a protection link mechanism that allows the photonic quantum repeater of a broken connection to initiate a connection restoration process.