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Sample records for au-rich signature motif

  1. An AU-Rich Sequence Element (UUUN[A/U]U) Downstream of the Edited C in Apolipoprotein B mRNA Is a High-Affinity Binding Site for Apobec-1: Binding of Apobec-1 to This Motif in the 3′ Untranslated Region of c-myc Increases mRNA Stability

    PubMed Central

    Anant, Shrikant; Davidson, Nicholas O.

    2000-01-01

    Apobec-1, the catalytic subunit of the mammalian apolipoprotein B (apoB) mRNA-editing enzyme, is a cytidine deaminase with RNA binding activity for AU-rich sequences. This RNA binding activity is required for Apobec-1 to mediate C-to-U RNA editing. Filter binding assays, using immobilized Apobec-1, demonstrate saturable binding to a 105-nt apoB RNA with a Kd of ∼435 nM. A series of AU-rich templates was used to identify a high-affinity (∼50 nM) binding site of consensus sequence UUUN[A/U]U, with multiple copies of this sequence constituting the high-affinity binding site. In order to determine whether this consensus site could be functionally demonstrated from within an apoB RNA, circular-permutation analysis was performed, revealing one major (UUUGAU) and one minor (UU) site located 3 and 16 nucleotides, respectively, downstream of the edited base. Secondary-structure predictions reveal a stem-loop flanking the edited base with Apobec-1 binding to the consensus site(s) at an open loop. A similar consensus (AUUUA) is present in the 3′ untranslated regions of several mRNAs, including that of c-myc, that are known to undergo rapid degradation. In this context, it is presumed that the consensus motif acts as a destabilizing element. As an independent test of the ability of Apobec-1 to bind to this sequence, F442A cells were transfected with Apobec-1 and the half-life of c-myc mRNA was determined following actinomycin D treatment. These studies demonstrated an increase in the half-life of c-myc mRNA from 90 to 240 min in control versus Apobec-1-expressing cells. Apobec-1 expression mutants, in which RNA binding activity is eliminated, failed to alter c-myc mRNA turnover. Taken together, the data establish a consensus binding site for Apobec-1 embedded in proximity to the edited base in apoB RNA. Binding to this site in other target RNAs raises the possibility that Apobec-1 may be involved in other aspects of RNA metabolism, independent of its role as an apoB RNA

  2. A type of nucleotide motif that distinguishes tobamovirus species more efficiently than nucleotide signatures.

    PubMed

    Gibbs, A J; Armstrong, J S; Gibbs, M J

    2004-10-01

    The complete genomic sequences of forty-eight tobamoviruses were classified and found to form at least twelve species clusters. Individual species were not conveniently defined by 'nucleotide signatures' (i.e. strings of one or more nucleotides unique to a taxon) as these were scattered sparsely throughout the genomes and were mostly single nucleotides. By contrast all the species were concisely and uniquely distinguished by short nucleotide motifs consisting of conserved genus-specific sites intercalated with variable sites that provided species-specific combinations of nucleotides (nucleotide combination motifs; NC-motifs). We describe the procedure for finding NC-motifs in a convenient and phylogenetically conserved region of the tobamovirus RNA polymerase gene, the '4404-50 motif'. NC-motifs have been found in other sets of homologous sequences, and are convenient for use in published taxonomic descriptions.

  3. Spectroscopic Signatures and Structural Motifs of Dopamine: a Computational Study

    NASA Astrophysics Data System (ADS)

    Srivastava, Santosh Kumar; Singh, Vipin Bahadur

    2016-06-01

    Dopamine (DA) is an essential neurotransmitter in the central nervous system and it plays integral role in numerous brain functions including behaviour, cognition, emotion, working memory and associated learning. In the present work the conformational landscapes of neutral and protonated dopamine have been investigated in the gas phase and in aqueous solution by MP2 and DFT (M06-2X, ωB97X-D, B3LYP and B3LYP-D3) methods. Twenty lowest energy structures of neutral DA were subjected to geometry optimization and the gauche conformer, GIa, was found to be the lowest gas phase structure at the each level of theory in agreement with the experimental rotational spectroscopy. All folded gauche conformers (GI) where lone electron pair of the NH2 group is directed towards the π system of the aromatic ring ( 'non up' ) are found more stable in the gas phase. While in aqueous solution, all those gauche conformers (GII) where lone electron pair of the NH2 group is directed opposite from the π system of the aromatic ring ('up' structures) are stabilized significantly.Nine lowest energy structures, protonated at the amino group, are optimized at the same MP2/aug-cc-pVDZ level of theory. In the most stable gauche structures, g-1 and g+1, mainly electrostatic cation - π interaction is further stabilized by significant dispersion forces as predicted by the substantial differences between the DFT and dispersion corrected DFT-D3 calculations. In aqueous environment the intra-molecular cation- π distance in g-1 and g+1 isomers, slightly increases compared to the gas phase and the magnitude of the cation- π interaction is reduced relative to the gas phase, because solvation of the cation decreases its interaction energy with the π face of aromatic system. The IR intensity of the bound N-H+ stretching mode provides characteristic 'IR spectroscopic signatures' which can reflect the strength of cation- π interaction energy. The CC2 lowest lying S1 ( 1ππ* ) excited state of neutral

  4. Structural Relationships in the Lysozyme Superfamily: Significant Evidence for Glycoside Hydrolase Signature Motifs

    PubMed Central

    Wohlkönig, Alexandre; Huet, Joëlle; Looze, Yvan; Wintjens, René

    2010-01-01

    Background Chitin is a polysaccharide that forms the hard, outer shell of arthropods and the cell walls of fungi and some algae. Peptidoglycan is a polymer of sugars and amino acids constituting the cell walls of most bacteria. Enzymes that are able to hydrolyze these cell membrane polymers generally play important roles for protecting plants and animals against infection with insects and pathogens. A particular group of such glycoside hydrolase enzymes share some common features in their three-dimensional structure and in their molecular mechanism, forming the lysozyme superfamily. Results Besides having a similar fold, all known catalytic domains of glycoside hydrolase proteins of lysozyme superfamily (families and subfamilies GH19, GH22, GH23, GH24 and GH46) share in common two structural elements: the central helix of the all-α domain, which invariably contains the catalytic glutamate residue acting as general-acid catalyst, and a β-hairpin pointed towards the substrate binding cleft. The invariant β-hairpin structure is interestingly found to display the highest amino acid conservation in aligned sequences of a given family, thereby allowing to define signature motifs for each GH family. Most of such signature motifs are found to have promising performances for searching sequence databases. Our structural analysis further indicates that the GH motifs participate in enzymatic catalysis essentially by containing the catalytic water positioning residue of inverting mechanism. Conclusions The seven families and subfamilies of the lysozyme superfamily all have in common a β-hairpin structure which displays a family-specific sequence motif. These GH β-hairpin motifs contain potentially important residues for the catalytic activity, thereby suggesting the participation of the GH motif to catalysis and also revealing a common catalytic scheme utilized by enzymes of the lysozyme superfamily. PMID:21085702

  5. Hallmarks of cancer and AU-rich elements.

    PubMed

    Khabar, Khalid S A

    2017-01-01

    Post-transcriptional control of gene expression is aberrant in cancer cells. Sustained stabilization and enhanced translation of specific mRNAs are features of tumor cells. AU-rich elements (AREs), cis-acting mRNA decay determinants, play a major role in the posttranscriptional regulation of many genes involved in cancer processes. This review discusses the role of aberrant ARE-mediated posttranscriptional processes in each of the hallmarks of cancer, including sustained cellular growth, resistance to apoptosis, angiogenesis, invasion, and metastasis. WIREs RNA 2017, 8:e1368. doi: 10.1002/wrna.1368 For further resources related to this article, please visit the WIREs website.

  6. Evolution of the Ferric Reductase Domain (FRD) Superfamily: Modularity, Functional Diversification, and Signature Motifs

    PubMed Central

    Zhang, Xuezhi; Krause, Karl-Heinz; Xenarios, Ioannis; Soldati, Thierry; Boeckmann, Brigitte

    2013-01-01

    A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria. PMID:23505460

  7. Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR.

    PubMed

    Kim, Henry S; Kuwano, Yuki; Zhan, Ming; Pullmann, Rudolf; Mazan-Mamczarz, Krystyna; Li, Huai; Kedersha, Nancy; Anderson, Paul; Wilce, Matthew C J; Gorospe, Myriam; Wilce, Jacqueline A

    2007-10-01

    The RNA-binding protein TIAR (related to TIA-1 [T-cell-restricted intracellular antigen 1]) was shown to associate with subsets of mRNAs bearing U-rich sequences in their 3' untranslated regions. TIAR can function as a translational repressor, particularly in response to cytotoxic agents. Using unstressed colon cancer cells, collections of mRNAs associated with TIAR were isolated by immunoprecipitation (IP) of (TIAR-RNA) ribonucleoprotein (RNP) complexes, identified by microarray analysis, and used to elucidate a common signature motif present among TIAR target transcripts. The predicted TIAR motif was an unexpectedly cytosine-rich, 28- to 32-nucleotide-long element forming a stem and a loop of variable size with an additional side loop. The ability of TIAR to bind an RNA oligonucleotide with a representative C-rich TIAR motif sequence was verified in vitro using surface plasmon resonance. By this analysis, TIAR containing two or three RNA recognition domains (TIAR12 and TIAR123) showed low but significant binding to the C-rich sequence. In vivo, insertion of the C-rich motif into a heterologous reporter strongly suppressed its translation in cultured cells. Using this signature motif, an additional approximately 2,209 UniGene targets were identified (2.0% of the total UniGene database). A subset of specific mRNAs were validated by RNP IP analysis. Interestingly, in response to treatment with short-wavelength UV light (UVC), a stress agent causing DNA damage, each of these target mRNAs bearing C-rich motifs dissociated from TIAR. In turn, expression of the encoded proteins was elevated in a TIAR-dependent manner. In sum, we report the identification of a C-rich signature motif present in TIAR target mRNAs whose association with TIAR decreases following exposure to a stress-causing agent.

  8. Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA

    NASA Astrophysics Data System (ADS)

    Schmidt, Thomas P.; Perna, Anna M.; Fugmann, Tim; Böhm, Manja; Jan Hiss; Haller, Sarah; Götz, Camilla; Tegtmeyer, Nicole; Hoy, Benjamin; Rau, Tilman T.; Neri, Dario; Backert, Steffen; Schneider, Gisbert; Wessler, Silja

    2016-03-01

    The cell adhesion protein and tumour suppressor E-cadherin exhibits important functions in the prevention of gastric cancer. As a class-I carcinogen, Helicobacter pylori (H. pylori) has developed a unique strategy to interfere with E-cadherin functions. In previous studies, we have demonstrated that H. pylori secretes the protease high temperature requirement A (HtrA) which cleaves off the E-cadherin ectodomain (NTF) on epithelial cells. This opens cell-to-cell junctions, allowing bacterial transmigration across the polarised epithelium. Here, we investigated the molecular mechanism of the HtrA-E-cadherin interaction and identified E-cadherin cleavage sites for HtrA. Mass-spectrometry-based proteomics and Edman degradation revealed three signature motifs containing the [VITA]-[VITA]-x-x-D-[DN] sequence pattern, which were preferentially cleaved by HtrA. Based on these sites, we developed a substrate-derived peptide inhibitor that selectively bound and inhibited HtrA, thereby blocking transmigration of H. pylori. The discovery of HtrA-targeted signature sites might further explain why we detected a stable 90 kDa NTF fragment during H. pylori infection, but also additional E-cadherin fragments ranging from 105 kDa to 48 kDa in in vitro cleavage experiments. In conclusion, HtrA targets E-cadherin signature sites that are accessible in in vitro reactions, but might be partially masked on epithelial cells through functional homophilic E-cadherin interactions.

  9. A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity

    PubMed Central

    Xu, Xiaojie; Fan, Zhongyi; Liang, Chaoyang; Li, Ling; Wang, Lili; Liang, Yingchun; Wu, Jun; Chang, Shaohong; Yan, Zhifeng; Lv, Zhaohui; Fu, Jing; Liu, Yang; Jin, Shuai; Wang, Tao; Hong, Tian; Dong, Yishan; Ding, Lihua; Cheng, Long; Liu, Rui; Fu, Shenbo; Jiao, Shunchang; Ye, Qinong

    2017-01-01

    Tumour radiotherapy resistance involves the cell cycle pathway. CDC25 phosphatases are key cell cycle regulators. However, how CDC25 activity is precisely controlled remains largely unknown. Here, we show that LIM domain-containing proteins, such as FHL1, increase inhibitory CDC25 phosphorylation by forming a complex with CHK2 and CDC25, and sequester CDC25 in the cytoplasm by forming another complex with 14-3-3 and CDC25, resulting in increased radioresistance in cancer cells. FHL1 expression, induced by ionizing irradiation in a SP1- and MLL1-dependent manner, positively correlates with radioresistance in cancer patients. We identify a cell-penetrating 11 amino-acid motif within LIM domains (eLIM) that is sufficient for binding CHK2 and CDC25, reducing the CHK2–CDC25 and CDC25–14-3-3 interaction and enhancing CDC25 activity and cancer radiosensitivity accompanied by mitotic catastrophe and apoptosis. Our results provide novel insight into molecular mechanisms underlying CDC25 activity regulation. LIM protein inhibition or use of eLIM may be new strategies for improving tumour radiosensitivity. PMID:28094252

  10. Signature motifs identify an Acinetobacter Cif virulence factor with epoxide hydrolase activity.

    PubMed

    Bahl, Christopher D; Hvorecny, Kelli L; Bridges, Andrew A; Ballok, Alicia E; Bomberger, Jennifer M; Cady, Kyle C; O'Toole, George A; Madden, Dean R

    2014-03-14

    Endocytic recycling of the cystic fibrosis transmembrane conductance regulator (CFTR) is blocked by the CFTR inhibitory factor (Cif). Originally discovered in Pseudomonas aeruginosa, Cif is a secreted epoxide hydrolase that is transcriptionally regulated by CifR, an epoxide-sensitive repressor. In this report, we investigate a homologous protein found in strains of the emerging nosocomial pathogens Acinetobacter nosocomialis and Acinetobacter baumannii ("aCif"). Like Cif, aCif is an epoxide hydrolase that carries an N-terminal secretion signal and can be purified from culture supernatants. When applied directly to polarized airway epithelial cells, mature aCif triggers a reduction in CFTR abundance at the apical membrane. Biochemical and crystallographic studies reveal a dimeric assembly with a stereochemically conserved active site, confirming our motif-based identification of candidate Cif-like pathogenic EH sequences. Furthermore, cif expression is transcriptionally repressed by a CifR homolog ("aCifR") and is induced in the presence of epoxides. Overall, this Acinetobacter protein recapitulates the essential attributes of the Pseudomonas Cif system and thus may facilitate airway colonization in nosocomial lung infections.

  11. SPECIFIC PROTEIN DOMAINS MEDIATE COOPERATIVE ASSEMBLY OF HuR OLIGOMERS ON AU-RICH mRNA-DESTABILIZING SEQUENCES*

    PubMed Central

    Fialcowitz-White, Elizabeth J.; Brewer, Brandy Y.; Ballin, Jeff D.; Willis, Chris D.; Toth, Eric A.; Wilson, Gerald M.

    2007-01-01

    The RNA-binding factor HuR is a ubiquitously expressed member of the Hu protein family that binds and stabilizes mRNAs containing AU-rich elements (AREs). Hu proteins share a common domain organization of two tandemly arrayed RNA Recognition Motifs (RRMs) near the N-terminus followed by a basic hinge domain and a third RRM near the C-terminus. In this study we have engineered recombinant wild type and mutant HuR proteins lacking affinity tags to characterize their ARE-binding properties. Using combinations of electrophoretic mobility shift and fluorescence anisotropy-based binding assays, we show that HuR can bind ARE substrates as small as 13 nucleotides with low nanomolar affinity, but forms cooperative, oligomeric protein complexes on ARE substrates of at least 18 nucleotides in length. Analyses of deletion mutant proteins indicate that RRM3 does not contribute to high affinity recognition of ARE substrates, but is required for cooperative assembly of HuR oligomers on RNA. Finally, the hinge domain between RRMs 2 and 3 contributes significant binding energy to HuR:ARE complex formation in an ARE length-dependent manner. The hinge does not enhance RNA-binding activity by increased ion pair formation despite extensive positive charge within this region, nor does it thermodynamically stabilize protein folding. Together, these studies define distinct roles for the HuR hinge and RRM3 domains in formation of cooperative HuR:ARE complexes in solution. PMID:17517897

  12. In Vivo Addition of Poly(A) Tail and AU-Rich Sequences to the 3′ Terminus of the Sindbis Virus RNA Genome: a Novel 3′-End Repair Pathway

    PubMed Central

    Raju, Ramaswamy; Hajjou, Mustapha; Hill, Kristie R.; Botta, Vandana; Botta, Sisir

    1999-01-01

    Alphaviruses are mosquito-transmitted RNA viruses that cause important diseases in both humans and livestock. Sindbis virus (SIN), the type species of the alphavirus genus, carries a 11.7-kb positive-sense RNA genome which is capped at its 5′ end and polyadenylated at its 3′ end. The 3′ nontranslated region (3′NTR) of the SIN genome carries many AU-rich motifs, including a 19-nucleotide (nt) conserved element (3′CSE) and a poly(A) tail. This 3′CSE and the adjoining poly(A) tail are believed to regulate the synthesis of negative-sense RNA and genome replication in vivo. We have recently demonstrated that the SIN genome lacking the poly(A) tail was infectious and that de novo polyadenylation could occur in vivo (K. R. Hill, M. Hajjou, J. Hu, and R. Raju, J. Virol. 71:2693–2704, 1997). Here, we demonstrate that the 3′-terminal 29-nt region of the SIN genome carries a signal for possible cytoplasmic polyadenylation. To further investigate the polyadenylation signals within the 3′NTR, we generated a battery of mutant genomes with mutations in the 3′NTR and tested their ability to generate infectious virus and undergo 3′ polyadenylation in vivo. Engineered SIN genomes with terminal deletions within the 19-nt 3′CSE were infectious and regained their poly(A) tail. Also, a SIN genome carrying the poly(A) tail but lacking a part or the entire 19-nt 3′CSE was also infectious. Sequence analysis of viruses generated from these engineered SIN genomes demonstrated the addition of a variety of AU-rich sequence motifs just adjacent to the poly(A) tail. The addition of AU-rich motifs to the mutant SIN genomes appears to require the presence of a significant portion of the 3′NTR. These results indicate the ability of alphavirus RNAs to undergo 3′ repair and the existence of a pathway for the addition of AU-rich sequences and a poly(A) tail to their 3′ end in the infected host cell. Most importantly, these results indicate the ability of alphavirus

  13. Identification of novel proteins binding the AU-rich element of α-prothymosin mRNA through the selection of open reading frames (RIDome).

    PubMed

    Patrucco, Laura; Peano, Clelia; Chiesa, Andrea; Guida, Filomena; Luisi, Imma; Boria, Ilenia; Mignone, Flavio; De Bellis, Gianluca; Zucchelli, Silvia; Gustincich, Stefano; Santoro, Claudio; Sblattero, Daniele; Cotella, Diego

    2015-01-01

    We describe here a platform for high-throughput protein expression and interaction analysis aimed at identifying the RNA-interacting domainome. This approach combines the selection of a phage library displaying "filtered" open reading frames with next-generation DNA sequencing. The method was validated using an RNA bait corresponding to the AU-rich element of α-prothymosin, an RNA motif that promotes mRNA stability and translation through its interaction with the RNA-binding protein ELAVL1. With this strategy, we not only confirmed known RNA-binding proteins that specifically interact with the target RNA (such as ELAVL1/HuR and RBM38) but also identified proteins not previously known to be ARE-binding (R3HDM2 and RALY). We propose this technology as a novel approach for studying the RNA-binding proteome.

  14. A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors

    PubMed Central

    Chan, Chun Ming; Fulton, Joel; Montiel-Duarte, Cristina; Collins, Hilary M.; Bharti, Neetu; Wadelin, Frances R.; Moran, Paula M.; Mongan, Nigel P.; Heery, David M.

    2013-01-01

    Despite their physiological importance, selective interactions between nuclear receptors (NRs) and their cofactors are poorly understood. Here, we describe a novel signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that facilitates its selective interaction with members of the NR2E/F subfamily. Two copies of this motif (named here as RID1 and RID2) permit BCL11A to bind COUP-TFs (NR2F1;NR2F2;NR2F6) and Tailless/TLX (NR2E1), whereas RID1, but not RID2, binds PNR (NR2E3). We confirmed the existence of endogenous BCL11A/TLX complexes in mouse cortex tissue. No interactions of RID1 and RID2 with 20 other ligand-binding domains from different NR subtypes were observed. We show that RID1 and RID2 are required for BCL11A-mediated repression of endogenous γ-globin gene and the regulatory non-coding transcript Bgl3, and we identify COUP-TFII binding sites within the Bgl3 locus. In addition to their importance for BCL11A function, we show that F/YSXXLXXL/Y motifs are conserved in other NR cofactors. A single FSXXLXXL motif in the NR-binding SET domain protein NSD1 facilitates its interactions with the NR2E/F subfamily. However, the NSD1 motif incorporates features of both LXXLL and FSXXLXXL motifs, giving it a distinct NR-binding pattern in contrast to other cofactors. In summary, our results provide new insights into the selectivity of NR/cofactor complex formation. PMID:23975195

  15. Post-Transcriptional Regulation of Cytokine Signaling by AU-Rich and GU-Rich Elements

    PubMed Central

    Bohjanen, Paul R.

    2014-01-01

    Cytokines are necessary for cell communication to enable responses to external stimuli that are imperative for the survival and maintenance of homeostasis. Dysfunction of the cytokine network has detrimental effects on intra- and extracellular environments. Thus, it is critical that the expression of cytokines and the signals transmitted by cytokines to target cells are tightly regulated at numerous levels, including transcriptional and post-transcriptional levels. Here, we briefly summarize the role of AU-rich elements (AREs) in the regulation of cytokine gene expression at the post-transcriptional level and describe a role for GU-rich elements (GREs) in coordinating the regulation of cytokine signaling. GREs function as post-transcriptional regulators of proteins that control cellular activation, growth, and apoptosis. GREs and AREs work in concert to coordinate cytokine signal transduction pathways. The precise regulation of cytokine signaling is particularly important, because its dysregulation can lead to human diseases. PMID:24697201

  16. Comparative Analysis of P450 Signature Motifs EXXR and CXG in the Large and Diverse Kingdom of Fungi: Identification of Evolutionarily Conserved Amino Acid Patterns Characteristic of P450 Family

    PubMed Central

    Syed, Khajamohiddin; Mashele, Samson Sitheni

    2014-01-01

    Cytochrome P450 monooxygenases (P450s) are heme-thiolate proteins distributed across the biological kingdoms. P450s are catalytically versatile and play key roles in organisms primary and secondary metabolism. Identification of P450s across the biological kingdoms depends largely on the identification of two P450 signature motifs, EXXR and CXG, in the protein sequence. Once a putative protein has been identified as P450, it will be assigned to a family and subfamily based on the criteria that P450s within a family share more than 40% homology and members of subfamilies share more than 55% homology. However, to date, no evidence has been presented that can distinguish members of a P450 family. Here, for the first time we report the identification of EXXR- and CXG-motifs-based amino acid patterns that are characteristic of the P450 family. Analysis of P450 signature motifs in the under-explored fungal P450s from four different phyla, ascomycota, basidiomycota, zygomycota and chytridiomycota, indicated that the EXXR motif is highly variable and the CXG motif is somewhat variable. The amino acids threonine and leucine are preferred as second and third amino acids in the EXXR motif and proline and glycine are preferred as second and third amino acids in the CXG motif in fungal P450s. Analysis of 67 P450 families from biological kingdoms such as plants, animals, bacteria and fungi showed conservation of a set of amino acid patterns characteristic of a particular P450 family in EXXR and CXG motifs. This suggests that during the divergence of P450 families from a common ancestor these amino acids patterns evolve and are retained in each P450 family as a signature of that family. The role of amino acid patterns characteristic of a P450 family in the structural and/or functional aspects of members of the P450 family is a topic for future research. PMID:24743800

  17. Evolution of the Twist Subfamily Vertebrate Proteins: Discovery of a Signature Motif and Origin of the Twist1 Glycine-Rich Motifs in the Amino-Terminus Disordered Domain

    PubMed Central

    Rodriguez, Yacidzohara; Gonzalez-Mendez, Ricardo R.

    2016-01-01

    Twist proteins belong to the basic helix-loop-helix (bHLH) family of multifunctional transcriptional factors. These factors are known to use domains other than the common bHLH in protein-protein interactions. There has been much work characterizing the bHLH domain and the C-terminus in protein-protein interactions but despite a few attempts more focus is needed at the N-terminus. Since the region of highest diversity in Twist proteins is the N-terminus, we analyzed the conservation of this region in different vertebrate Twist proteins and study the sequence differences between Twist1 and Twist2 with emphasis on the glycine-rich regions found in Twist1. We found a highly conserved sequence motif in all Twist1 (SSSPVSPADDSLSNSEEE) and Twist2 (SSSPVSPVDSLGTSEEE) mammalian species with unknown function. Through sequence comparison we demonstrate that the Twist protein family ancestor was “Twist2-like” and the two glycine-rich regions found in Twist1 sequences were acquired late in evolution, apparently not at the same time. The second glycine-rich region started developing first in the fish vertebrate group, while the first glycine region arose afterwards within the reptiles. Disordered domain and secondary structure predictions showed that the amino acid sequence and disorder feature found at the N-terminus is highly evolutionary conserved and could be a functional site that interacts with other proteins. Detailed examination of the glycine-rich regions in the N-terminus of Twist1 demonstrate that the first region is completely aliphatic while the second region contains some polar residues that could be subject to post-translational modification. Phylogenetic and sequence space analysis showed that the Twist1 subfamily is the result of a gene duplication during Twist2 vertebrate fish evolution, and has undergone more evolutionary drift than Twist2. We identified a new signature motif that is characteristic of each Twist paralog and identified important residues

  18. Translational regulation of human beta interferon mRNA: association of the 3' AU-rich sequence with the poly(A) tail reduces translation efficiency in vitro.

    PubMed Central

    Grafi, G; Sela, I; Galili, G

    1993-01-01

    The 3' AU-rich region of human beta-1 interferon (hu-IFN beta) mRNA was found to act as a translational inhibitory element. The translational regulation of this 3' AU-rich sequence and the effect of its association with the poly(A) tail were studied in cell-free rabbit reticulocyte lysate. A poly(A)-rich hu-IFN beta mRNA (110 A residues) served as an inefficient template for protein synthesis. However, translational efficiency was considerably improved when the poly(A) tract was shortened (11 A residues) or when the 3' AU-rich sequence was deleted, indicating that interaction between these two regions was responsible for the reduced translation of the poly(A)-rich hu-IFN beta mRNA. Differences in translational efficiency of the various hu-IFN beta mRNAs correlated well with their polysomal distribution. The poly(A)-rich hu-IFN beta mRNA failed to form large polysomes, while its counterpart bearing a short poly(A) tail was recruited more efficiently into large polysomes. The AU-rich sequence-binding activity was reduced when the RNA probe contained both the 3' AU-rich sequence and long poly(A) tail, supporting a physical association between these two regions. Further evidence for this interaction was achieved by RNase H protection assay. We suggest that the 3' AU-rich sequence may regulate the translation of hu-IFN beta mRNA by interacting with the poly(A) tail. Images PMID:7684500

  19. AU-Rich-Element-Dependent Translation Repression Requires the Cooperation of Tristetraprolin and RCK/P54

    PubMed Central

    Qi, Mei-Yan; Wang, Zhi-Zhang; Zhang, Zhuo; Shao, Qin; Zeng, An; Li, Xiang-Qi; Li, Wen-Qing; Wang, Chen; Tian, Fu-Ju; Li, Qing; Zou, Jun; Qin, Yong-Wen; Brewer, Gary; Huang, Shuang

    2012-01-01

    AU-rich elements (AREs), residing in the 3′ untranslated region (UTR) of many labile mRNAs, are important cis-acting elements that modulate the stability of these mRNAs by collaborating with trans-acting factors such as tristetraprolin (TTP). AREs also regulate translation, but the underlying mechanism is not fully understood. Here we examined the function and mechanism of TTP in ARE-mRNA translation. Through a luciferase-based reporter system, we used knockdown, overexpression, and tethering assays in 293T cells to demonstrate that TTP represses ARE reporter mRNA translation. Polyribosome fractionation experiments showed that TTP shifts target mRNAs to lighter fractions. In murine RAW264.7 macrophages, knocking down TTP produces significantly more tumor necrosis factor alpha (TNF-α) than the control, while the corresponding mRNA level has a marginal change. Furthermore, knockdown of TTP increases the rate of biosynthesis of TNF-α, suggesting that TTP can exert effects at translational levels. Finally, we demonstrate that the general translational repressor RCK may cooperate with TTP to regulate ARE-mRNA translation. Collectively, our studies reveal a novel function of TTP in repressing ARE-mRNA translation and that RCK is a functional partner of TTP in promoting TTP-mediated translational repression. PMID:22203041

  20. IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice

    PubMed Central

    Hodge, Deborah L.; Berthet, Cyril; Coppola, Vincenzo; Kastenmüller, Wolfgang; Buschman, Matthew D.; Schaughency, Paul M.; Shirota, Hidekazu; Scarzello, Anthony J.; Subleski, Jeff J.; Anver, Miriam R.; Ortaldo, John R.; Lin, Fanching; Reynolds, Della A.; Sanford, Michael E.; Kaldis, Philipp; Tessarollo, Lino; Klinman, Dennis M.; Young, Howard A.

    2014-01-01

    We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in the 3′ untranslated region (3′UTR) of the interferon-gamma (IFN-γ) gene that results in chronic circulating serum IFN-γ levels. Mice homozygous for the ARE deletion (ARE-Del) −/− present both serologic and cellular abnormalities typical of patients with systemic lupus erythematosus (SLE). ARE-Del−/− mice display increased numbers of pDCs in bone marrow and spleen. Addition of IFN-γ to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2-fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone B (MZB) cells and marginal zone macrophages (MZMs) are absent in ARE-Del−/− mice. ARE-Del+/− mice retain both MZB cells and MZMs and develop no or mild autoimmunity. However, low dose clodronate treatment in ARE-Del+/− mice specifically eliminates MZMs and promotes anti-DNA antibody development and glomerulonephritis. Our findings demonstrate the consequences of a chronic IFN-γ milieu on B220+ cell types and in particular the impact of MZB cell loss on MZM function in autoimmunity. Furthermore, similarities between disease states in ARE-Del−/− mice and SLE patients suggest that IFN-γ may not only be a product of SLE but may be critical for disease onset and progression. PMID:24583068

  1. IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice.

    PubMed

    Hodge, Deborah L; Berthet, Cyril; Coppola, Vincenzo; Kastenmüller, Wolfgang; Buschman, Matthew D; Schaughency, Paul M; Shirota, Hidekazu; Scarzello, Anthony J; Subleski, Jeff J; Anver, Miriam R; Ortaldo, John R; Lin, Fanching; Reynolds, Della A; Sanford, Michael E; Kaldis, Philipp; Tessarollo, Lino; Klinman, Dennis M; Young, Howard A

    2014-09-01

    We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in the 3' untranslated region (3'UTR) of the interferon-gamma (IFN-γ) gene that results in chronic circulating serum IFN-γ levels. Mice homozygous for the ARE deletion (ARE-Del) (-/-) present both serologic and cellular abnormalities typical of patients with systemic lupus erythematosus (SLE). ARE-Del(-/-) mice display increased numbers of pDCs in bone marrow and spleen. Addition of IFN-γ to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2-fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone B (MZB) cells and marginal zone macrophages (MZMs) are absent in ARE-Del(-/-) mice. ARE-Del(+/-) mice retain both MZB cells and MZMs and develop no or mild autoimmunity. However, low dose clodronate treatment in ARE-Del(+/-) mice specifically eliminates MZMs and promotes anti-DNA antibody development and glomerulonephritis. Our findings demonstrate the consequences of a chronic IFN-γ milieu on B220(+) cell types and in particular the impact of MZB cell loss on MZM function in autoimmunity. Furthermore, similarities between disease states in ARE-Del(-/-) mice and SLE patients suggest that IFN-γ may not only be a product of SLE but may be critical for disease onset and progression.

  2. RNA Helicase Associated with AU-rich Element (RHAU/DHX36) Interacts with the 3′-Tail of the Long Non-coding RNA BC200 (BCYRN1)*

    PubMed Central

    Booy, Evan P.; McRae, Ewan K. S.; Howard, Ryan; Deo, Soumya R.; Ariyo, Emmanuel O.; Dzananovic, Edis; Meier, Markus; Stetefeld, Jörg; McKenna, Sean A.

    2016-01-01

    RNA helicase associated with AU-rich element (RHAU) is an ATP-dependent RNA helicase that demonstrates high affinity for quadruplex structures in DNA and RNA. To elucidate the significance of these quadruplex-RHAU interactions, we have performed RNA co-immunoprecipitation screens to identify novel RNAs bound to RHAU and characterize their function. In the course of this study, we have identified the non-coding RNA BC200 (BCYRN1) as specifically enriched upon RHAU immunoprecipitation. Although BC200 does not adopt a quadruplex structure and does not bind the quadruplex-interacting motif of RHAU, it has direct affinity for RHAU in vitro. Specifically designed BC200 truncations and RNase footprinting assays demonstrate that RHAU binds to an adenosine-rich region near the 3′-end of the RNA. RHAU truncations support binding that is dependent upon a region within the C terminus and is specific to RHAU isoform 1. Tests performed to assess whether BC200 interferes with RHAU helicase activity have demonstrated the ability of BC200 to act as an acceptor of unwound quadruplexes via a cytosine-rich region near the 3′-end of the RNA. Furthermore, an interaction between BC200 and the quadruplex-containing telomerase RNA was confirmed by pull-down assays of the endogenous RNAs. This leads to the possibility that RHAU may direct BC200 to bind and exert regulatory functions at quadruplex-containing RNA or DNA sequences. PMID:26740632

  3. AU-rich element-mediated translational control: complexity and multiple activities of trans-activating factors.

    PubMed

    Zhang, T; Kruys, V; Huez, G; Gueydan, C

    2002-11-01

    Tumour necrosis factor (TNF)-alpha mRNA contains an AU-rich element (ARE) in its 3' untranslated region (3'UTR), which determines its half-life and translational efficiency. In unstimulated macrophages, TNF-alpha mRNA is repressed translationally, and becomes efficiently translated upon cell activation. Gel retardation experiments and screening of a macrophage cDNA expression library with the TNF-alpha ARE allowed the identification of TIA-1-related protein (TIAR), T-cell intracellular antigen-1 (TIA-1) and tristetraprolin (TTP) as TNF-alpha ARE-binding proteins. Whereas TIAR and TIA-1 bind the TNF-alpha ARE independently of the activation state of macrophages, the TTP-ARE complex is detectable upon stimulation with lipopolysaccharide (LPS). Moreover, treatment of LPS-induced macrophage extracts with phosphatase significantly abrogates TTP binding to the TNF-alpha ARE, indicating that TTP phosphorylation is required for ARE binding. Carballo, Lai and Blackshear [(1998) Science 281, 1001-1005] showed that TTP was a TNF-alpha mRNA destabilizer. In contrast, TIA-1, and most probably TIAR, acts as a TNF-alpha mRNA translational silencer. A two-hybrid screening with TIAR and TIA-1 revealed the capacity of these proteins to interact with other RNA-binding proteins. Interestingly, TIAR and TIA-1 are not engaged in the same interaction, indicating for the first time that TIAR and TIA-1 can be functionally distinct. These findings also suggest that ARE-binding proteins interact with RNA as multimeric complexes, which might define their function and their sequence specificity.

  4. Endothelin-1 expression is strongly repressed by AU-rich elements in the 3'-untranslated region of the gene.

    PubMed

    Reimunde, Francisco M; Castañares, Cristina; Redondo-Horcajo, Mariano; Lamas, Santiago; Rodríguez-Pascual, Fernando

    2005-05-01

    The regulation of the synthesis of the endothelial-derived vasoconstrictor ET-1 (endothelin-1) is a complex process that occurs mainly at the mRNA level. Transcription of the gene accounts for an important part of the regulation of expression, as already described for different modulators such as the cytokine TGF-beta (transforming growth factor-beta). However, very little is known about mechanisms governing ET-1 expression at the post-transcriptional level. The aim of the present study was to investigate the regulation of the ET-1 expression at this level. Since the 3'-UTR (3'-untranslated region) of mRNAs commonly contains genetic determinants for the post-transcriptional control of gene expression, we focused on the potential role of the 3'-UTR of ET-1 mRNA. Experiments performed with luciferase reporter constructs containing the 3'-UTR showed that this region exerts a potent destabilizing effect. Deletional analyses allowed us to locate this activity within a region at positions 924-1127. Some (but not all) of the AREs (AU-rich elements) present in this region were found to be essential for this mRNA-destabilizing activity. We also present evidence that cytosolic proteins from endothelial cells interact specifically with these RNA elements, and that a close correlation exists between the ability of the AREs to destabilize ET-1 mRNA and the binding of proteins to these elements. Our results are compatible with the existence of a strong repressional control of ET-1 expression mediated by destabilization of the mRNA exerted through the interaction of specific cytosolic proteins with AREs present in the 3'-UTR of the gene.

  5. Permuting the PGF Signature Motif Blocks both Archaeosortase-Dependent C-Terminal Cleavage and Prenyl Lipid Attachment for the Haloferax volcanii S-Layer Glycoprotein

    PubMed Central

    Abdul Halim, Mohd Farid; Karch, Kelly R.; Zhou, Yitian; Haft, Daniel H.; Garcia, Benjamin A.

    2015-01-01

    ABSTRACT For years, the S-layer glycoprotein (SLG), the sole component of many archaeal cell walls, was thought to be anchored to the cell surface by a C-terminal transmembrane segment. Recently, however, we demonstrated that the Haloferax volcanii SLG C terminus is removed by an archaeosortase (ArtA), a novel peptidase. SLG, which was previously shown to be lipid modified, contains a C-terminal tripartite structure, including a highly conserved proline-glycine-phenylalanine (PGF) motif. Here, we demonstrate that ArtA does not process an SLG variant where the PGF motif is replaced with a PFG motif (slgG796F,F797G). Furthermore, using radiolabeling, we show that SLG lipid modification requires the PGF motif and is ArtA dependent, lending confirmation to the use of a novel C-terminal lipid-mediated protein-anchoring mechanism by prokaryotes. Similar to the case for the ΔartA strain, the growth, cellular morphology, and cell wall of the slgG796F,F797G strain, in which modifications of additional H. volcanii ArtA substrates should not be altered, are adversely affected, demonstrating the importance of these posttranslational SLG modifications. Our data suggest that ArtA is either directly or indirectly involved in a novel proteolysis-coupled, covalent lipid-mediated anchoring mechanism. Given that archaeosortase homologs are encoded by a broad range of prokaryotes, it is likely that this anchoring mechanism is widely conserved. IMPORTANCE Prokaryotic proteins bound to cell surfaces through intercalation, covalent attachment, or protein-protein interactions play critical roles in essential cellular processes. Unfortunately, the molecular mechanisms that anchor proteins to archaeal cell surfaces remain poorly characterized. Here, using the archaeon H. volcanii as a model system, we report the first in vivo studies of a novel protein-anchoring pathway involving lipid modification of a peptidase-processed C terminus. Our findings not only yield important insights into

  6. Structural modelling and phylogenetic analyses of PgeIF4A2 (Eukaryotic translation initiation factor) from Pennisetum glaucum reveal signature motifs with a role in stress tolerance and development

    PubMed Central

    Agarwal, Aakrati; Mudgil, Yashwanti; Pandey, Saurabh; Fartyal, Dhirendra; Reddy, Malireddy K

    2016-01-01

    Eukaryotic translation initiation factor 4A (eIF4A) is an indispensable component of the translation machinery and also play a role in developmental processes and stress alleviation in plants and animals. Different eIF4A isoforms are present in the cytosol of the cell, namely, eIF4A1, eIF4A2, and eIF4A3 and their expression is tightly regulated in cap-dependent translation. We revealed the structural model of PgeIF4A2 protein using the crystal structure of Homo sapiens eIF4A3 (PDB ID: 2J0S) as template by Modeller 9.12. The resultant PgeIF4A2 model structure was refined by PROCHECK, ProSA, Verify3D and RMSD that showed the model structure is reliable with 77 % amino acid sequence identity with template. Investigation revealed two conserved signatures for ATP-dependent RNA Helicase DEAD-box conserved site (VLDEADEML) and RNA helicase DEAD-box type, Q-motif in sheet-turn-helix and α-helical region respectively. All these conserved motifs are responsible for response during developmental stages and stress tolerance in plants. PMID:28358146

  7. p38 Mitogen-Activated Protein Kinase-Dependent and -Independent Signaling of mRNA Stability of AU-Rich Element-Containing Transcripts

    PubMed Central

    Frevel, Mathias A. E.; Bakheet, Tala; Silva, Aristobolo M.; Hissong, John G.; Khabar, Khalid S. A.; Williams, Bryan R. G.

    2003-01-01

    Adenylate/uridylate-rich element (ARE)-mediated mRNA turnover is an important regulatory component of gene expression for innate and specific immunity, in the hematopoietic system, in cellular growth regulation, and for many other cellular processes. This diversity is reflected in the distribution of AREs in the human genome, which we have established as a database of more than 900 ARE-containing genes that may utilize AREs as a means of controlling cellular mRNA levels. The p38 mitogen-activated protein kinase (MAP kinase) pathway has been implicated in regulating the stability of nine ARE-containing transcripts. Here we explored the entire spectrum of ARE-containing genes for p38-dependent regulation of ARE-mediated mRNA turnover with a custom cDNA array containing probes for 950 ARE mRNAs. The human monocytic cell line THP-1 treated with lipopolysaccharide (LPS) was used as a reproducible cellular model system that allowed us to precisely control the conditions of mRNA induction and decay in the absence and presence of the p38 inhibitor SB203580. This approach allowed us to establish an LPS-induced ARE mRNA expression profile in human monocytes and determine the half-lives of 470 AU-rich mRNAs. Most importantly, we identified 42 AU-rich genes, previously unrecognized, that show p38-dependent mRNA stabilization. In addition to a number of cytokines, several interesting novel AU-rich transcripts likely to play a role in macrophage activation by LPS exhibited p38-dependent transcript stabilization, including macrophage-specific colony-stimulating factor 1, carbonic anhydrase 2, Bcl2, Bcl2-like 2, and nuclear factor erythroid 2-like 2. Finally, the identification of the p38-dependent upstream activator MAP kinase kinase 6 as a member of this group identifies a positive feedback loop regulating macrophage signaling via p38 MAP kinase-dependent transcript stabilization. PMID:12509443

  8. Signature motifs of GDP polyribonucleotidyltransferase, a non-segmented negative strand RNA viral mRNA capping enzyme, domain in the L protein are required for covalent enzyme-pRNA intermediate formation.

    PubMed

    Neubauer, Julie; Ogino, Minako; Green, Todd J; Ogino, Tomoaki

    2016-01-08

    The unconventional mRNA capping enzyme (GDP polyribonucleotidyltransferase, PRNTase; block V) domain in RNA polymerase L proteins of non-segmented negative strand (NNS) RNA viruses (e.g. rabies, measles, Ebola) contains five collinear sequence elements, Rx(3)Wx(3-8)ΦxGxζx(P/A) (motif A; Φ, hydrophobic; ζ, hydrophilic), (Y/W)ΦGSxT (motif B), W (motif C), HR (motif D) and ζxxΦx(F/Y)QxxΦ (motif E). We performed site-directed mutagenesis of the L protein of vesicular stomatitis virus (VSV, a prototypic NNS RNA virus) to examine participation of these motifs in mRNA capping. Similar to the catalytic residues in motif D, G1100 in motif A, T1157 in motif B, W1188 in motif C, and F1269 and Q1270 in motif E were found to be essential or important for the PRNTase activity in the step of the covalent L-pRNA intermediate formation, but not for the GTPase activity that generates GDP (pRNA acceptor). Cap defective mutations in these residues induced termination of mRNA synthesis at position +40 followed by aberrant stop-start transcription, and abolished virus gene expression in host cells. These results suggest that the conserved motifs constitute the active site of the PRNTase domain and the L-pRNA intermediate formation followed by the cap formation is essential for successful synthesis of full-length mRNAs.

  9. Signature motifs of GDP polyribonucleotidyltransferase, a non-segmented negative strand RNA viral mRNA capping enzyme, domain in the L protein are required for covalent enzyme–pRNA intermediate formation

    PubMed Central

    Neubauer, Julie; Ogino, Minako; Green, Todd J.; Ogino, Tomoaki

    2016-01-01

    The unconventional mRNA capping enzyme (GDP polyribonucleotidyltransferase, PRNTase; block V) domain in RNA polymerase L proteins of non-segmented negative strand (NNS) RNA viruses (e.g. rabies, measles, Ebola) contains five collinear sequence elements, Rx(3)Wx(3–8)ΦxGxζx(P/A) (motif A; Φ, hydrophobic; ζ, hydrophilic), (Y/W)ΦGSxT (motif B), W (motif C), HR (motif D) and ζxxΦx(F/Y)QxxΦ (motif E). We performed site-directed mutagenesis of the L protein of vesicular stomatitis virus (VSV, a prototypic NNS RNA virus) to examine participation of these motifs in mRNA capping. Similar to the catalytic residues in motif D, G1100 in motif A, T1157 in motif B, W1188 in motif C, and F1269 and Q1270 in motif E were found to be essential or important for the PRNTase activity in the step of the covalent L-pRNA intermediate formation, but not for the GTPase activity that generates GDP (pRNA acceptor). Cap defective mutations in these residues induced termination of mRNA synthesis at position +40 followed by aberrant stop–start transcription, and abolished virus gene expression in host cells. These results suggest that the conserved motifs constitute the active site of the PRNTase domain and the L-pRNA intermediate formation followed by the cap formation is essential for successful synthesis of full-length mRNAs. PMID:26602696

  10. Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies.

    PubMed

    Kontoyiannis, D; Pasparakis, M; Pizarro, T T; Cominelli, F; Kollias, G

    1999-03-01

    We addressed the impact of deleting TNF AU-rich elements (ARE) from the mouse genome on the regulation of TNF biosynthesis and the physiology of the host. Absence of the ARE affected mechanisms responsible for TNF mRNA destabilization and translational repression in hemopoietic and stromal cells. In stimulated conditions, TNF ARE were required both for the alleviation and reinforcement of message destabilization and translational silencing. Moreover, the mutant mRNA was no longer responsive to translational modulation by the p38 and JNK kinases, demonstrating that TNF ARE are targets for these signals. Development of two specific pathologies in mutant mice, i.e., chronic inflammatory arthritis and Crohn's-like inflammatory bowel disease, suggests that defective function of ARE may be etiopathogenic for the development of analogous human pathologies.

  11. Murine Spam1 mRNA: involvement of AU-rich elements in the 3'UTR and antisense RNA in its tight post-transcriptional regulation in spermatids.

    PubMed

    Zhang, Hong; Barnoski, Barry L; Sol-Church, Katia; Stabley, Deborah L; Martin-Deleon, Patricia A

    2006-02-01

    Sperm adhesion molecule1 (SPAM1), the best characterized hyaluronidase gene, is abundantly expressed in the testis. We attempted to overexpress mouse Spam1 via transgenesis using either the endogenous promoter in a BAC or a heterologous Protamine1 promoter for a Spam1 cDNA transgene. Although transgene-copy numbers ranged from 2 to 15 and transgenic transcripts were expressed, there was a general failure of overexpression of the RNA and protein in the testis of all seven founders. Also, three transgenic lines showed a modest downregulation or co-suppression of the RNA for Spam1 and Hyal5, present on the BAC. We provide evidence for the potential involvement of two co-ordinating post-transcriptional regulatory processes in the failure of overexpression: abundant endogenous antisense RNA and adenosine-uridine (AU)-rich element-mediated regulation of RNA turnover. We demonstrate that AU-rich elements (AREs) in the 3'UTR of mRNAs, well-known to interact with trans-acting proteins to target the RNA for (in)stability, are present in Spam1 RNA and specifically bind to six testicular cytoplasmic proteins. These AU-binding proteins (AUBPs) were virtually absent from the kidney where transcripts are rare, and were shown to interact with the cytoskeleton, which modulates mRNA turnover. In addition to a role in the RNAi pathway, antisense RNA can also modulate ARE-mediated regulation of mRNA by hybridizing to the AREs and specifically silencing their function. This potentially links the two processes in the regulation of Spam1 expression. We hypothesize that testicular Spam1 RNA is regulated post-transcriptionally by cis-acting ARE(s) in the 3'UTR which recognize AUBPs and which are modulated by antisense transcripts.

  12. A Dimer Interface Mutation in Glyceraldehyde-3-Phosphate Dehydrogenase Regulates Its Binding to AU-rich RNA*

    PubMed Central

    White, Michael R.; Khan, Mohd M.; Deredge, Daniel; Ross, Christina R.; Quintyn, Royston; Zucconi, Beth E.; Wysocki, Vicki H.; Wintrode, Patrick L.; Wilson, Gerald M.; Garcin, Elsa D.

    2015-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an enzyme best known for its role in glycolysis. However, extra-glycolytic functions of GAPDH have been described, including regulation of protein expression via RNA binding. GAPDH binds to numerous adenine-uridine rich elements (AREs) from various mRNA 3′-untranslated regions in vitro and in vivo despite its lack of a canonical RNA binding motif. How GAPDH binds to these AREs is still unknown. Here we discovered that GAPDH binds with high affinity to the core ARE from tumor necrosis factor-α mRNA via a two-step binding mechanism. We demonstrate that a mutation at the GAPDH dimer interface impairs formation of the second RNA-GAPDH complex and leads to changes in the RNA structure. We investigated the effect of this interfacial mutation on GAPDH oligomerization by crystallography, small-angle x-ray scattering, nano-electrospray ionization native mass spectrometry, and hydrogen-deuterium exchange mass spectrometry. We show that the mutation does not significantly affect GAPDH tetramerization as previously proposed. Instead, the mutation promotes short-range and long-range dynamic changes in regions located at the dimer and tetramer interface and in the NAD+ binding site. These dynamic changes are localized along the P axis of the GAPDH tetramer, suggesting that this region is important for RNA binding. Based on our results, we propose a model for sequential GAPDH binding to RNA via residues located at the dimer and tetramer interfaces. PMID:25451934

  13. LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation.

    PubMed

    Küspert, Maritta; Murakawa, Yasuhiro; Schäffler, Katrin; Vanselow, Jens T; Wolf, Elmar; Juranek, Stefan; Schlosser, Andreas; Landthaler, Markus; Fischer, Utz

    2015-07-01

    mRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting "mRNP code" determines the fate of any given mRNA and thus controlling gene expression at the post-transcriptional level. The La-related protein 4B (LARP4B) belongs to an evolutionarily conserved family of RNA-binding proteins characterized by the presence of a La-module implicated in direct RNA binding. Biochemical experiments have shown previously direct interactions of LARP4B with factors of the translation machinery. This finding along with the observation of an association with actively translating ribosomes suggested that LARP4B is a factor contributing to the mRNP code. To gain insight into the function of LARP4B in vivo we tested its mRNA association at the transcriptome level and its impact on the proteome. PAR-CLIP analyses allowed us to identify the in vivo RNA targets of LARP4B. We show that LARP4B binds to a distinct set of cellular mRNAs by contacting their 3' UTRs. Biocomputational analysis combined with in vitro binding assays identified the LARP4B-binding motif on mRNA targets. The reduction of cellular LARP4B levels leads to a marked destabilization of its mRNA targets and consequently their reduced translation. Our data identify LARP4B as a component of the mRNP code that influences the expression of its mRNA targets by affecting their stability.

  14. Deletion of AU-Rich Elements within the Bcl2 3′UTR Reduces Protein Expression and B Cell Survival In Vivo

    PubMed Central

    Díaz-Muñoz, Manuel D.; Bell, Sarah E.; Turner, Martin

    2015-01-01

    Post-transcriptional mRNA regulation by RNA binding proteins (RBPs) associated with AU-rich elements (AREs) present in the 3′ untranslated region (3’UTR) of specific mRNAs modulates transcript stability and translation in eukaryotic cells. Here we have functionally characterised the importance of the AREs present within the Bcl2 3’UTR in order to maintain Bcl2 expression. Gene targeting deletion of 300 nucleotides of the Bcl2 3’UTR rich in AREs diminishes Bcl2 mRNA stability and protein levels in primary B cells, decreasing cell lifespan. Generation of chimeric mice indicates that Bcl2-ARE∆/∆ B cells have an intrinsic competitive disadvantage compared to wild type cells. Biochemical assays and predictions using a bioinformatics approach show that several RBPs bind to the Bcl2 AREs, including AUF1 and HuR proteins. Altogether, association of RBPs to Bcl2 AREs contributes to Bcl2 protein expression by stabilizing Bcl2 mRNA and promotes B cell maintenance. PMID:25680182

  15. Identification of TIAR as a protein binding to the translational regulatory AU-rich element of tumor necrosis factor alpha mRNA.

    PubMed

    Gueydan, C; Droogmans, L; Chalon, P; Huez, G; Caput, D; Kruys, V

    1999-01-22

    In monocyte/macrophages, the translation of tumor necrosis factor alpha (TNF-alpha) mRNA is tightly regulated. In unstimulated cells, translation of TNF-alpha mRNA is blocked. Upon stimulation with lipopolysaccharides, this repression is overcome, and the mRNA becomes efficiently translated. The key element in this regulation is the AU-rich element (ARE). We have previously reported the binding of two cytosolic protein complexes to the TNF-alpha mRNA ARE. One of these complexes (complex 1) forms with extracts of both unstimulated and lipopolysaccharide-stimulated macrophages and requires a large fragment of the ARE containing clustered AUUUA pentamers. The other complex (complex 2) is only detected after cell activation, binds to a minimal UUAUUUAUU nonamer, and is composed of a 55-kDa protein. Here, we report the identification of the RNA-binding protein TIAR as a protein involved in complex 1. The RNA sequence bound by TIAR and the cytoplasmic localization of this protein in macrophages argue for an involvement of TIAR in TNF mRNA posttranscriptional regulation.

  16. Binding of G-quadruplexes to the N-terminal Recognition Domain of the RNA Helicase Associated with AU-rich Element (RHAU)*

    PubMed Central

    Meier, Markus; Patel, Trushar R.; Booy, Evan P.; Marushchak, Oksana; Okun, Natalie; Deo, Soumya; Howard, Ryan; McEleney, Kevin; Harding, Stephen E.; Stetefeld, Jörg; McKenna, Sean A.

    2013-01-01

    Polynucleotides containing consecutive tracts of guanines can adopt an intramolecular G-quadruplex structure where multiple planar tetrads of hydrogen-bound guanines stack on top of each other. Remodeling of G-quadruplexes impacts numerous aspects of nucleotide biology including transcriptional and translational control. RNA helicase associated with AU-rich element (RHAU), a member of the ATP-dependent DEX(H/D) family of RNA helicases, has been established as a major cellular quadruplex resolvase. RHAU contains a core helicase domain responsible for ATP binding/hydrolysis/helicase activity and is flanked on either side by N- and C-terminal extensions. The N-terminal extension is required for quadruplex recognition, and we have previously demonstrated complex formation between this domain and a quadruplex from human telomerase RNA. Here we used an integrated approach that includes small angle x-ray scattering, nuclear magnetic resonance spectroscopy, circular dichroism, and dynamic light scattering methods to demonstrate the recognition of G-quadruplexes by the N-terminal domain of RHAU. Based on our results, we conclude that (i) quadruplex from the human telomerase RNA and its DNA analog both adopt a disc shape in solution, (ii) RHAU53–105 adopts a defined and extended conformation in solution, and (iii) the N-terminal domain mediates an interaction with a guanine tetrad face of quadruplexes. Together, these data form the foundation for understanding the recognition of quadruplexes by the N-terminal domain of RHAU. PMID:24151078

  17. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene.

    PubMed

    Rouvier, E; Luciani, M F; Mattéi, M G; Denizot, F; Golstein, P

    1993-06-15

    To detect novel molecules involved in immune functions, a subtracted cDNA library between closely related murine lymphoid cells was prepared using improved technology. Differential screening of this library yielded several clones with a very restricted tissue specificity, including one that we named CTLA-8. CTLA-8 transcripts could be detected only in T cell hybridoma clones related to the one used to prepare the library. Southern blots showed that the CTLA-8 gene was single copy in mice, rats, and humans. By radioactive in situ hybridization, the CTLA-8 gene was mapped at a single site on mouse chromosome 1A and human chromosome 2q31, in a known interspecific syntenic region. The CTLA-8 cDNA sequence indicated the presence, in the 3'-untranslated region of the mRNA, of AU-rich repeats previously found in the mRNA of various cytokines, growth factors, and oncogenes. The CTLA-8 cDNA contained an open reading frame encoding a putative protein of 150 amino acids. This protein was 57% homologous to the putative protein encoded by the ORF13 gene of herpesvirus Saimiri, a T lymphotropic virus. These findings are discussed in the context of other genes of this herpesvirus homologous to known immunologically active molecules. More generally, CTLA-8 may belong to the growing set of virus-captured functionally important cellular genes related to the immune system or to cell death and cell survival.

  18. Post-transcriptional regulation of cytokine genes in fish: A role for conserved AU-rich elements located in the 3'-untranslated region of their mRNAs.

    PubMed

    Roca, Francisco J; Cayuela, María L; Secombes, Chris J; Meseguer, José; Mulero, Victoriano

    2007-01-01

    The overproduction of cytokines, such us interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha), contributes to the pathological complications observed in many inflammatory diseases caused by bacterial endotoxins. The synthesis of these cytokines is tightly regulated at both transcriptional and post-transcriptional levels. Post-transcriptional regulation of gene expression depends on specific cis-acting sequences and trans-acting factors. Thus, the presence of adenylate- and uridylate-rich (AU-rich) elements (AREs) has been described in the 3'-untranslated regions (UTRs) of many unstable mammalian mRNAs. Although, it represents the most widespread, phylogenetically conserved and efficient determinant of mRNA stability among those so far characterized in mammalian cells, no studies are available on the functional relevance of this sequence in non-mammalian vertebrates. In this contribution, we study the enzymatic activity of various luciferase reporter constructs, containing or lacking the 3'UTR of IL-1beta and TNFalpha from different fish species, and report the finding that bony fish AREs are able to decrease luciferase activity but are less potent than their mammalian counterparts. Surprisingly, the 3'UTR of the IL-1beta from the cartilaginous fish small spotted catshark had the greatest ability to decrease luciferase activity. Lastly, the functional significance of the above was confirmed by measuring the half-life of IL-1beta and TNFalpha mRNAs in gilthead seabream leukocytes by blocking transcription with actinomycin D. Both cytokine mRNAs were unstable with an estimated half-life of about 45 min in control and activated cells.

  19. The 3'-untranslated region length and AU-rich RNA location modulate RNA-protein interaction and translational control of β2-adrenergic receptor mRNA.

    PubMed

    Subramaniam, Kothandharaman; Kandasamy, Karthikeyan; Joseph, Kusumam; Spicer, Eleanor K; Tholanikunnel, Baby G

    2011-06-01

    Posttranscriptional controls play a major role in β(2)-adrenergic receptor (β(2)-AR) expression. We recently reported that β(2)-AR mRNA translation is suppressed by elements in its 3'-untranslated region (UTR). We also identified T-cell-restricted intracellular antigen-related protein (TIAR) and HuR as prominent AU-rich (ARE) RNA-binding proteins that associate with β(2)-AR mRNA 3'-UTR. In this study, we identified a poly(U) region at the distal end of the 3'-UTR as critical for TIAR binding to β(2)-AR mRNA and for translational suppression. Here, we also report that the locations of the poly(U) and ARE sequences within the 3'-UTR are important determinants that control the translation of β(2)-AR mRNA. Consistent with this finding, a 20-nucleotide ARE RNA from the proximal 3'-UTR that did not inhibit mRNA translation in its native position was able to suppress translation when re-located to the distal 3'-UTR of the receptor mRNA. Immunoprecipitation and polysome profile analysis demonstrated the importance of 3'-UTR length and the ARE RNA location within the 3'-UTR, as key determinants of RNA/protein interactions and translational control of β(2)-AR mRNA. Further, the importance of 3'-UTR length and ARE location in TIAR and HuR association with mRNA and translational suppression was demonstrated using a chimeric luciferase reporter gene.

  20. Characteristics of the interaction of a synthetic human tristetraprolin tandem zinc finger peptide with AU-rich element-containing RNA substrates.

    PubMed

    Blackshear, Perry J; Lai, Wi S; Kennington, Elizabeth A; Brewer, Gary; Wilson, Gerald M; Guan, Xiaoju; Zhou, Pei

    2003-05-30

    Tristetraprolin (TTP) and its two known mammalian family members are tandem CCCH zinc finger proteins that can bind to AU-rich elements (AREs) in cellular mRNAs and destabilize those transcripts, apparently by initiating their deadenylation. Previous studies have shown that the approximately 70-amino acid tandem zinc finger domain of TTP is required and sufficient for RNA binding, and that the integrity of both zinc fingers is also required. However, little is known about the kinetics or structure of the peptide-RNA interaction, in part because of difficulties in obtaining soluble recombinant protein or peptides. We characterized the binding of a synthetic 73-amino acid peptide from human TTP to the tumor necrosis factor (TNF) ARE by gel mobility shift analyses and fluorescence anisotropy experiments. Both types of studies yielded a peptide-RNA dissociation constant of approximately 10 nM. Surprisingly, we found that the "footprint" from the TNF ARE required for peptide binding was only approximately 9 bases and that two molecules of peptide could bind to probes containing as little as 19 bases. An identical recombinant peptide exhibited gel shift characteristics similar to those of the synthetic peptide. NMR analysis of the 15N-labeled recombinant peptide suggested that its first zinc finger was structured in solution but that the second was not. The titration of oligonucleotides representing 17, 13, and even 9 bases of the TNF ARE caused an essentially identical, dramatic shift of existing resonances, and the appearance of new resonances in the peptide spectra, so that all amino acids could be assigned. These data suggest that this TTP peptide-RNA complex is structured in solution and might be amenable to NMR structure determination.

  1. Saturated fatty acids induce post-transcriptional regulation of HAMP mRNA via AU-rich element-binding protein, human antigen R (HuR).

    PubMed

    Lu, Sizhao; Mott, Justin L; Harrison-Findik, Duygu Dee

    2015-10-02

    Iron is implicated in fatty liver disease pathogenesis. The human hepcidin gene, HAMP, is the master switch of iron metabolism. The aim of this study is to investigate the regulation of HAMP expression by fatty acids in HepG2 cells. For these studies, both saturated fatty acids (palmitic acid (PA) and stearic acid (SA)) and unsaturated fatty acid (oleic acid (OA)) were used. PA and, to a lesser extent, SA, but not OA, up-regulated HAMP mRNA levels, as determined by real-time PCR. To understand whether PA regulates HAMP mRNA at the transcriptional or post-transcriptional level, the transcription inhibitor actinomycin D was employed. PA-mediated induction of HAMP mRNA expression was not blocked by actinomycin D. Furthermore, PA activated HAMP 3'-UTR, but not promoter, activity, as shown by reporter assays. HAMP 3'-UTR harbors a single AU-rich element (ARE). Mutation of this ARE abolished the effect of PA, suggesting the involvement of ARE-binding proteins. The ARE-binding protein human antigen R (HuR) stabilizes mRNA through direct interaction with AREs on 3'-UTR. HuR is regulated by phosphorylation-mediated nucleo-cytoplasmic shuttling. PA activated this process. The binding of HuR to HAMP mRNA was also induced by PA in HepG2 cells. Silencing of HuR by siRNA abolished PA-mediated up-regulation of HAMP mRNA levels. PKC is known to phosphorylate HuR. Staurosporine, a broad-spectrum PKC inhibitor, inhibited both PA-mediated translocation of HuR and induction of HAMP expression. Similarly, rottlerin, a novel class PKC inhibitor, abrogated PA-mediated up-regulation of HAMP expression. In conclusion, lipids mediate post-transcriptional regulation of HAMP throughPKC- and HuR-dependent mechanisms.

  2. Endothelin-1 expression is strongly repressed by AU-rich elements in the 3′-untranslated region of the gene

    PubMed Central

    2004-01-01

    The regulation of the synthesis of the endothelial-derived vasoconstrictor ET-1 (endothelin-1) is a complex process that occurs mainly at the mRNA level. Transcription of the gene accounts for an important part of the regulation of expression, as already described for different modulators such as the cytokine TGF-β (transforming growth factor-β). However, very little is known about mechanisms governing ET-1 expression at the post-transcriptional level. The aim of the present study was to investigate the regulation of the ET-1 expression at this level. Since the 3′-UTR (3′-untranslated region) of mRNAs commonly contains genetic determinants for the post-transcriptional control of gene expression, we focused on the potential role of the 3′-UTR of ET-1 mRNA. Experiments performed with luciferase reporter constructs containing the 3′-UTR showed that this region exerts a potent destabilizing effect. Deletional analyses allowed us to locate this activity within a region at positions 924–1127. Some (but not all) of the AREs (AU-rich elements) present in this region were found to be essential for this mRNA-destabilizing activity. We also present evidence that cytosolic proteins from endothelial cells interact specifically with these RNA elements, and that a close correlation exists between the ability of the AREs to destabilize ET-1 mRNA and the binding of proteins to these elements. Our results are compatible with the existence of a strong repressional control of ET-1 expression mediated by destabilization of the mRNA exerted through the interaction of specific cytosolic proteins with AREs present in the 3′-UTR of the gene. PMID:15595926

  3. A HuD-ZBP1 ribonucleoprotein complex localizes GAP-43 mRNA into axons through its 3' untranslated region AU-rich regulatory element.

    PubMed

    Yoo, Soonmoon; Kim, Hak H; Kim, Paul; Donnelly, Christopher J; Kalinski, Ashley L; Vuppalanchi, Deepika; Park, Michael; Lee, Seung J; Merianda, Tanuja T; Perrone-Bizzozero, Nora I; Twiss, Jeffery L

    2013-09-01

    Localized translation of axonal mRNAs contributes to developmental and regenerative axon growth. Although untranslated regions (UTRs) of many different axonal mRNAs appear to drive their localization, there has been no consensus RNA structure responsible for this localization. We recently showed that limited expression of ZBP1 protein restricts axonal localization of both β-actin and GAP-43 mRNAs. β-actin 3'UTR has a defined element for interaction with ZBP1, but GAP-43 mRNA shows no homology to this RNA sequence. Here, we show that an AU-rich regulatory element (ARE) in GAP-43's 3'UTR is necessary and sufficient for its axonal localization. Axonal GAP-43 mRNA levels increase after in vivo injury, and GAP-43 mRNA shows an increased half-life in regenerating axons. GAP-43 mRNA interacts with both HuD and ZBP1, and HuD and ZBP1 co-immunoprecipitate in an RNA-dependent fashion. Reporter mRNA with the GAP-43 ARE competes with endogenous β-actin mRNA for axonal localization and decreases axon length and branching similar to the β-actin 3'UTR competing with endogenous GAP-43 mRNA. Conversely, over-expressing GAP-43 coding sequence with its 3'UTR ARE increases axonal elongation and this effect is lost when just the ARE is deleted from GAP-43's 3'UTR. We have recently found that over-expression of GAP-43 using an axonally targeted construct with the 3'UTRs of GAP-43 promoted elongating growth of axons, while restricting the mRNA to the cell body with the 3'UTR of γ-actin had minimal effect on axon length. In this study, we show that the ARE in GAP-43's 3'UTR is responsible for localization of GAP-43 mRNA into axons and is sufficient for GAP-43 protein's role in elongating axonal growth.

  4. Protospacer recognition motifs

    PubMed Central

    Shah, Shiraz A.; Erdmann, Susanne; Mojica, Francisco J.M.; Garrett, Roger A.

    2013-01-01

    Protospacer adjacent motifs (PAMs) were originally characterized for CRISPR-Cas systems that were classified on the basis of their CRISPR repeat sequences. A few short 2–5 bp sequences were identified adjacent to one end of the protospacers. Experimental and bioinformatical results linked the motif to the excision of protospacers and their insertion into CRISPR loci. Subsequently, evidence accumulated from different virus- and plasmid-targeting assays, suggesting that these motifs were also recognized during DNA interference, at least for the recently classified type I and type II CRISPR-based systems. The two processes, spacer acquisition and protospacer interference, employ different molecular mechanisms, and there is increasing evidence to suggest that the sequence motifs that are recognized, while overlapping, are unlikely to be identical. In this article, we consider the properties of PAM sequences and summarize the evidence for their dual functional roles. It is proposed to use the terms protospacer associated motif (PAM) for the conserved DNA sequence and to employ spacer acqusition motif (SAM) and target interference motif (TIM), respectively, for acquisition and interference recognition sites. PMID:23403393

  5. Motif enrichment tool.

    PubMed

    Blatti, Charles; Sinha, Saurabh

    2014-07-01

    The Motif Enrichment Tool (MET) provides an online interface that enables users to find major transcriptional regulators of their gene sets of interest. MET searches the appropriate regulatory region around each gene and identifies which transcription factor DNA-binding specificities (motifs) are statistically overrepresented. Motif enrichment analysis is currently available for many metazoan species including human, mouse, fruit fly, planaria and flowering plants. MET also leverages high-throughput experimental data such as ChIP-seq and DNase-seq from ENCODE and ModENCODE to identify the regulatory targets of a transcription factor with greater precision. The results from MET are produced in real time and are linked to a genome browser for easy follow-up analysis. Use of the web tool is free and open to all, and there is no login requirement. ADDRESS: http://veda.cs.uiuc.edu/MET/.

  6. [Personal motif in art].

    PubMed

    Gerevich, József

    2015-01-01

    One of the basic questions of the art psychology is whether a personal motif is to be found behind works of art and if so, how openly or indirectly it appears in the work itself. Analysis of examples and documents from the fine arts and literature allow us to conclude that the personal motif that can be identified by the viewer through symbols, at times easily at others with more difficulty, gives an emotional plus to the artistic product. The personal motif may be found in traumatic experiences, in communication to the model or with other emotionally important persons (mourning, disappointment, revenge, hatred, rivalry, revolt etc.), in self-searching, or self-analysis. The emotions are expressed in artistic activity either directly or indirectly. The intention nourished by the artist's identity (Kunstwollen) may stand in the way of spontaneous self-expression, channelling it into hidden paths. Under the influence of certain circumstances, the artist may arouse in the viewer, consciously or unconsciously, an illusionary, misleading image of himself. An examination of the personal motif is one of the important research areas of art therapy.

  7. Signature control

    NASA Astrophysics Data System (ADS)

    Pyati, Vittal P.

    The reduction of vehicle radar signature is accomplished by means of vehicle shaping, the use of microwave frequencies-absorbent materials, and either passive or active cancellation techniques; such techniques are also useful in the reduction of propulsion system-associated IR emissions. In some anticipated scenarios, the objective is not signature-reduction but signature control, for deception, via decoy vehicles that mimic the signature characteristics of actual weapons systems. As the stealthiness of airframes and missiles increases, their propulsion systems' exhaust plumes assume a more important role in detection by an adversary.

  8. The Rev protein of human immunodeficiency virus type 1 counteracts the effect of an AU-rich negative element in the human papillomavirus type 1 late 3' untranslated region.

    PubMed Central

    Tan, W; Schwartz, S

    1995-01-01

    We have identified a sequence in the late 3' untranslated region of human papillomavirus type 1 mRNAs that acts posttranscriptionally to repress gene expression. Deletion analysis localized the inhibitory element to an AU-rich sequence between nucleotides 6958 and 6984 on the human papillomavirus type 1 genome. This sequence inhibits gene expression in an orientation-dependent manner. Upon transfection of eucaryotic cells with plasmids containing this sequence, approximately 4-fold-lower cytoplasmic mRNA levels and 64- to 128-fold-lower protein levels were produced compared with those produced by plasmids lacking the inhibitory sequence. Interestingly, providing the constitutive transport element of simian retrovirus type 1 in sense orientation counteracted inhibition exerted by the human papillomavirus type 1 sequence. Inhibition could also be overcome by the presence of human immunodeficiency virus type 1 Rev protein in trans and its target sequence, the Rev-responsive element, in cis. Rev is a nuclear protein and acts by promoting nuclear export of human immunodeficiency virus type 1 mRNAs encoding structural proteins. Our results are consistent with a model for human papillomavirus type 1 late-gene expression in which mRNAs containing human papillomavirus type 1 inhibitory sequences enter a nonproductive route in the nucleus, resulting in inefficient mRNA utilization. Rev directs mRNA containing inhibitory sequences to a productive route by interacting with the Rev-responsive element. PMID:7707519

  9. 3'UTR AU-Rich Elements (AREs) and the RNA-Binding Protein Tristetraprolin (TTP) Are Not Required for the LPS-Mediated Destabilization of Phospholipase-Cβ-2 mRNA in Murine Macrophages.

    PubMed

    Shukla, Smita; Elson, Genie; Blackshear, Perry J; Lutz, Carol S; Leibovich, S Joseph

    2017-04-01

    We have shown previously that bacterial lipopolysaccharide (LPS)-mediated suppression of phospholipase-Cβ-2 (PLCβ-2) expression is involved in M1 (inflammatory) to M2-like (wound healing) phenotypic switching of macrophages triggered by adenosine. This suppression is mediated post-transcriptionally by destabilization of PLCβ-2 mRNA (messenger ribonucleic acid). To investigate the mechanism of this LPS-mediated destabilization, we examined the roles of RNA-binding agents including microRNAs and RNA-binding proteins that are involved in regulating stability of mRNAs encoding growth factors, inflammatory mediators, and proto-oncogenes. Adenylate and uridylate (AU)-rich elements (AREs) in 3'UTRs are specific recognition sites for RNA-binding proteins including tristetraprolin (TTP), HuR, and AUF1 and for microRNAs that are involved in regulating mRNA stability. In this study, we investigated the role of TTP and AREs in regulating PLCβ-2 mRNA stability. The 3'UTR of the PLCβ-2 gene was inserted into the pLightswitch luciferase reporter plasmid and transfected into RAW264.7 cells. LPS suppressed luciferase expression from this reporter. Luciferase expression from mutant 3'UTR constructs lacking AREs was similarly downregulated, suggesting that these regions are not required for LPS-mediated suppression of PLCβ-2. TTP was rapidly upregulated in both primary murine macrophages and RAW264.7 cells in response to LPS. Suppression of PLCβ-2 by LPS was examined using macrophages from mice lacking TTP (TTP(-/-)). LPS suppressed PLCβ-2 expression to the same extent in wild type (WT) and TTP(-/-) macrophages. Also, the rate of decay of PLCβ-2 mRNA in LPS-treated macrophages following transcriptional blockade was similar in WT and TTP(-/-) macrophages, clearly indicating that TTP is not involved in LPS-mediated destabilization of PLCβ-2 mRNA in macrophages.

  10. Motif types, motif locations and base composition patterns around the RNA polyadenylation site in microorganisms, plants and animals

    PubMed Central

    2014-01-01

    Background The polyadenylation of RNA is critical for gene functioning, but the conserved sequence motifs (often called signal or signature motifs), motif locations and abundances, and base composition patterns around mRNA polyadenylation [poly(A)] sites are still uncharacterized in most species. The evolutionary tendency for poly(A) site selection is still largely unknown. Results We analyzed the poly(A) site regions of 31 species or phyla. Different groups of species showed different poly(A) signal motifs: UUACUU at the poly(A) site in the parasite Trypanosoma cruzi; UGUAAC (approximately 13 bases upstream of the site) in the alga Chlamydomonas reinhardtii; UGUUUG (or UGUUUGUU) at mainly the fourth base downstream of the poly(A) site in the parasite Blastocystis hominis; and AAUAAA at approximately 16 bases and approximately 19 bases upstream of the poly(A) site in animals and plants, respectively. Polyadenylation signal motifs are usually several hundred times more abundant around poly(A) sites than in whole genomes. These predominant motifs usually had very specific locations, whether upstream of, at, or downstream of poly(A) sites, depending on the species or phylum. The poly(A) site was usually an adenosine (A) in all analyzed species except for B. hominis, and there was weak A predominance in C. reinhardtii. Fungi, animals, plants, and the protist Phytophthora infestans shared a general base abundance pattern (or base composition pattern) of “U-rich—A-rich—U-rich—Poly(A) site—U-rich regions”, or U-A-U-A-U for short, with some variation for each kingdom or subkingdom. Conclusion This study identified the poly(A) signal motifs, motif locations, and base composition patterns around mRNA poly(A) sites in protists, fungi, plants, and animals and provided insight into poly(A) site evolution. PMID:25052519

  11. Small yet effective: the ethylene responsive element binding factor-associated amphiphilic repression (EAR) motif.

    PubMed

    Kagale, Sateesh; Rozwadowski, Kevin

    2010-06-01

    The Ethylene-responsive element binding factor-associated Amphiphilic Repression (EAR) motif is a small yet distinct regulatory motif that is conserved in many plant transcriptional regulator (TR) proteins associated with diverse biological functions. We have previously established a list of high-confidence Arabidopsis EAR repressors, the EAR repressome, comprising 219 TRs belonging to 21 different TR families. This class of proteins and the sequence context of the EAR motif exhibited a high degree of conservation across evolutionarily diverse plant species. Our comprehensive genome-wide analysis enabled refining EAR motifs as comprising either LxLxL or DLNxxP. Comparing the representation of these sequence signatures in TRs to that of other repressor motifs we show that the EAR motif is the one most frequently represented, detected in 10 to 25% of the TRs from diverse plant species. The mechanisms involved in regulation of EAR motif function and the cellular fates of EAR repressors are currently not well understood. Our earlier analysis had implicated amino acid residues flanking the EAR motifs in regulation of their functionality. Here, we present additional evidence supporting possible regulation of EAR motif function by phosphorylation of integral or adjacent Ser and/or Thr residues. Additionally, we discuss potential novel roles of EAR motifs in plant-pathogen interaction and processes other than transcriptional repression.

  12. Herpes simplex virus 1 induces cytoplasmic accumulation of TIA-1/TIAR and both synthesis and cytoplasmic accumulation of tristetraprolin, two cellular proteins that bind and destabilize AU-rich RNAs.

    PubMed

    Esclatine, Audrey; Taddeo, Brunella; Roizman, Bernard

    2004-08-01

    Herpes simplex virus 1 causes a shutoff of cellular protein synthesis through the degradation of RNA that is mediated by the virion host shutoff (Vhs) protein encoded by the U(L)41 gene. We reported elsewhere that the Vhs-dependent degradation of RNA is selective, and we identified RNAs containing AU-rich elements (AREs) that were upregulated after infection but degraded by deadenylation and progressive 3'-to-5' degradation. We also identified upregulated RNAs that were not subject to Vhs-dependent degradation (A. Esclatine, B. Taddeo, L. Evans, and B. Roizman, Proc. Natl. Acad. Sci. USA 101:3603-3608, 2004). Among the latter was the RNA encoding tristetraprolin, a protein that binds AREs and is known to be associated with the degradation of RNAs containing AREs. Prompted by this observation, we examined the status of the ARE binding proteins tristetraprolin and TIA-1/TIAR in infected cells. We report that tristetraprolin was made and accumulated in the cytoplasm of wild-type virus-infected human foreskin fibroblasts as early as 2 h and in HEp-2 cells as early as 6 h after infection. The amounts of tristetraprolin that accumulated in the cytoplasm of cells infected with a mutant virus lacking U(L)41 were significantly lower than those in wild-type virus-infected cells. The localization of tristetraprolin was not modified in cells infected with a mutant lacking the gene encoding infected cell protein 4 (ICP4). TIA-1 and TIAR are two other proteins that are associated with the regulation of ARE-containing RNAs and that normally reside in nuclei. In infected cells, they started to accumulate in the cytoplasm after 6 h of infection. In cells infected with the mutant virus lacking U(L)41, TIA-1/TIAR accumulated in the cytoplasm in granular structures reminiscent of stress granules in a significant percentage of the cells. In addition, an antibody to tristetraprolin coprecipitated the Vhs protein from lysates of cells late in infection. The results indicate that the Vhs

  13. An AU-rich element in the 3{prime} untranslated region of the spinach chloroplast petD gene participates in sequence-specific RNA-protein complex formation

    SciTech Connect

    Chen, Qiuyun; Adams, C.C.; Usack, L.

    1995-04-01

    In chloroplasts, the 3{prime} untranslated regions of most mRNAs contain a stem-loop-forming inverted repeat (IR) sequence that is required for mRNA stability and correct 3{prime}-end formation. The IR regions of several mRNAs are also known to bind chloroplast proteins, as judged from in vitro gel mobility shift and UV cross-linking assays, and these RNA-protein interactions may be involved in the regulation of chloroplast mRNA processing and/or stability. Here we describe in detail the RNA and protein components that are involved in 3{prime} IR-containing RNA (3{prime} IR-RNA)-protein complex formation for the spinach chloroplast petD gene, which encodes subunit IV of the cytochrome b{sub 6}/f complex. We show that the complex contains 55-, 41-, and 29-kDa RNA-binding proteins (ribonucleoproteins [RNPs]). These proteins together protect a 90-nucleotide segment of RNA from RNase T{sub 1} digestion; this RNA contains the IR and downstream flanking sequences. Competition experiments using 3{prime} IR-RNAs from the psbA or rbcL gene demonstrate that the RNPs have a strong specificity for the petD sequence. Site-directed mutagenesis was carried out to define the RNA sequence elements required for complex formation. These studies identified an 8-nucleotide AU-rich sequence downstream of the IR; mutations within this sequence had moderate to severe effects on RNA-protein complex formation. Although other similar sequences are present in the petD 3{prime} untranslated region, only a single copy, which we have termed box II, appears to be essential for in vivo protein binding. In addition, the IR itself is necessary for optimal complex formation. These two sequence elements together with an RNP complex may direct correct 3{prime}-end processing and/or influence the stability of petD mRNA in chloroplasts. 48 refs., 9 figs., 2 tabs.

  14. Motif Yggdrasil: sampling sequence motifs from a tree mixture model.

    PubMed

    Andersson, Samuel A; Lagergren, Jens

    2007-06-01

    In phylogenetic foot-printing, putative regulatory elements are found in upstream regions of orthologous genes by searching for common motifs. Motifs in different upstream sequences are subject to mutations along the edges of the corresponding phylogenetic tree, consequently taking advantage of the tree in the motif search is an appealing idea. We describe the Motif Yggdrasil sampler; the first Gibbs sampler based on a general tree that uses unaligned sequences. Previous tree-based Gibbs samplers have assumed a star-shaped tree or partially aligned upstream regions. We give a probabilistic model (MY model) describing upstream sequences with regulatory elements and build a Gibbs sampler with respect to this model. The model allows toggling, i.e., the restriction of a position to a subset of nucleotides, but does not require aligned sequences nor edge lengths, which may be difficult to come by. We apply the collapsing technique to eliminate the need to sample nuisance parameters, and give a derivation of the predictive update formula. We show that the MY model improves the modeling of difficult motif instances and that the use of the tree achieves a substantial increase in nucleotide level correlation coefficient both for synthetic data and 37 bacterial lexA genes. We investigate the sensitivity to errors in the tree and show that using random trees MY sampler still has a performance similar to the original version.

  15. [Prediction of Promoter Motifs in Virophages].

    PubMed

    Gong, Chaowen; Zhou, Xuewen; Pan, Yingjie; Wang, Yongjie

    2015-07-01

    Virophages have crucial roles in ecosystems and are the transport vectors of genetic materials. To shed light on regulation and control mechanisms in virophage--host systems as well as evolution between virophages and their hosts, the promoter motifs of virophages were predicted on the upstream regions of start codons using an analytical tool for prediction of promoter motifs: Multiple EM for Motif Elicitation. Seventeen potential promoter motifs were identified based on the E-value, location, number and length of promoters in genomes. Sputnik and zamilon motif 2 with AT-rich regions were distributed widely on genomes, suggesting that these motifs may be associated with regulation of the expression of various genes. Motifs containing the TCTA box were predicted to be late promoter motif in mavirus; motifs containing the ATCT box were the potential late promoter motif in the Ace Lake mavirus . AT-rich regions were identified on motif 2 in the Organic Lake virophage, motif 3 in Yellowstone Lake virophage (YSLV)1 and 2, motif 1 in YSLV3, and motif 1 and 2 in YSLV4, respectively. AT-rich regions were distributed widely on the genomes of virophages. All of these motifs may be promoter motifs of virophages. Our results provide insights into further exploration of temporal expression of genes in virophages as well as associations between virophages and giant viruses.

  16. Knowledge discovery of multilevel protein motifs

    SciTech Connect

    Conklin, D.; Glasgow, J.; Fortier, S.

    1994-12-31

    A new category of protein motif is introduced. This type of motif captures, in addition to global structure, the nested structure of its component parts. A dataset of four proteins is represented using this scheme. A structured machine discovery procedure is used to discover recurrent amino acid motifs and this knowledge is utilized for the expression of subsequent protein motif discoveries. Examples of discovered multilevel motifs are presented.

  17. Sequential visibility-graph motifs

    NASA Astrophysics Data System (ADS)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-04-01

    Visibility algorithms transform time series into graphs and encode dynamical information in their topology, paving the way for graph-theoretical time series analysis as well as building a bridge between nonlinear dynamics and network science. In this work we introduce and study the concept of sequential visibility-graph motifs, smaller substructures of n consecutive nodes that appear with characteristic frequencies. We develop a theory to compute in an exact way the motif profiles associated with general classes of deterministic and stochastic dynamics. We find that this simple property is indeed a highly informative and computationally efficient feature capable of distinguishing among different dynamics and robust against noise contamination. We finally confirm that it can be used in practice to perform unsupervised learning, by extracting motif profiles from experimental heart-rate series and being able, accordingly, to disentangle meditative from other relaxation states. Applications of this general theory include the automatic classification and description of physical, biological, and financial time series.

  18. Artefacts in statistical analyses of network motifs: general framework and application to metabolic networks.

    PubMed

    Beber, Moritz Emanuel; Fretter, Christoph; Jain, Shubham; Sonnenschein, Nikolaus; Müller-Hannemann, Matthias; Hütt, Marc-Thorsten

    2012-12-07

    Few-node subgraphs are the smallest collective units in a network that can be investigated. They are beyond the scale of individual nodes but more local than, for example, communities. When statistically over- or under-represented, they are called network motifs. Network motifs have been interpreted as building blocks that shape the dynamic behaviour of networks. It is this promise of potentially explaining emergent properties of complex systems with relatively simple structures that led to an interest in network motifs in an ever-growing number of studies and across disciplines. Here, we discuss artefacts in the analysis of network motifs arising from discrepancies between the network under investigation and the pool of random graphs serving as a null model. Our aim was to provide a clear and accessible catalogue of such incongruities and their effect on the motif signature. As a case study, we explore the metabolic network of Escherichia coli and show that only by excluding ever more artefacts from the motif signature a strong and plausible correlation with the essentiality profile of metabolic reactions emerges.

  19. Artefacts in statistical analyses of network motifs: general framework and application to metabolic networks

    PubMed Central

    Beber, Moritz Emanuel; Fretter, Christoph; Jain, Shubham; Sonnenschein, Nikolaus; Müller-Hannemann, Matthias; Hütt, Marc-Thorsten

    2012-01-01

    Few-node subgraphs are the smallest collective units in a network that can be investigated. They are beyond the scale of individual nodes but more local than, for example, communities. When statistically over- or under-represented, they are called network motifs. Network motifs have been interpreted as building blocks that shape the dynamic behaviour of networks. It is this promise of potentially explaining emergent properties of complex systems with relatively simple structures that led to an interest in network motifs in an ever-growing number of studies and across disciplines. Here, we discuss artefacts in the analysis of network motifs arising from discrepancies between the network under investigation and the pool of random graphs serving as a null model. Our aim was to provide a clear and accessible catalogue of such incongruities and their effect on the motif signature. As a case study, we explore the metabolic network of Escherichia coli and show that only by excluding ever more artefacts from the motif signature a strong and plausible correlation with the essentiality profile of metabolic reactions emerges. PMID:22896565

  20. Neural Circuits: Male Mating Motifs.

    PubMed

    Benton, Richard

    2015-09-02

    Characterizing microcircuit motifs in intact nervous systems is essential to relate neural computations to behavior. In this issue of Neuron, Clowney et al. (2015) identify recurring, parallel feedforward excitatory and inhibitory pathways in male Drosophila's courtship circuitry, which might explain decisive mate choice.

  1. The Thiamin Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Dominiak, Paulina M.; Ciszak, Ewa M.

    2003-01-01

    Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits, two catalytic centers, common amino acid sequence, and specific contacts to provide a flip-flop, or alternate site, mechanism of action. Each catalytic center [PP:PYR] is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and aminopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core [PP:PYR]* within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GX@&(G)@XXGQ, and GDGX25-30 within the PP- domain, and the E&(G)@XXG@ within the PYR-domain, where Q, corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.

  2. The Thiamin Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Dominiak, P.; Ciszak, E.

    2003-01-01

    Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits and two catalytic centers. Each catalytic center (PP:PYR) is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and amhopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core (PP:PYR)(sub 2) within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GXPhiX(sub 4)(G)PhiXXGQ and GDGX(sub 25-30)NN in the PP-domain, and the EX(sub 4)(G)PhiXXGPhi in the PYR-domain, where Phi corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.

  3. Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs.

    PubMed

    Zheng, Yiyu; Li, Xiaoman; Hu, Haiyan

    2015-01-01

    Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/.

  4. A survey of DNA motif finding algorithms

    PubMed Central

    Das, Modan K; Dai, Ho-Kwok

    2007-01-01

    Background Unraveling the mechanisms that regulate gene expression is a major challenge in biology. An important task in this challenge is to identify regulatory elements, especially the binding sites in deoxyribonucleic acid (DNA) for transcription factors. These binding sites are short DNA segments that are called motifs. Recent advances in genome sequence availability and in high-throughput gene expression analysis technologies have allowed for the development of computational methods for motif finding. As a result, a large number of motif finding algorithms have been implemented and applied to various motif models over the past decade. This survey reviews the latest developments in DNA motif finding algorithms. Results Earlier algorithms use promoter sequences of coregulated genes from single genome and search for statistically overrepresented motifs. Recent algorithms are designed to use phylogenetic footprinting or orthologous sequences and also an integrated approach where promoter sequences of coregulated genes and phylogenetic footprinting are used. All the algorithms studied have been reported to correctly detect the motifs that have been previously detected by laboratory experimental approaches, and some algorithms were able to find novel motifs. However, most of these motif finding algorithms have been shown to work successfully in yeast and other lower organisms, but perform significantly worse in higher organisms. Conclusion Despite considerable efforts to date, DNA motif finding remains a complex challenge for biologists and computer scientists. Researchers have taken many different approaches in developing motif discovery tools and the progress made in this area of research is very encouraging. Performance comparison of different motif finding tools and identification of the best tools have proven to be a difficult task because tools are designed based on algorithms and motif models that are diverse and complex and our incomplete understanding of

  5. WildSpan: mining structured motifs from protein sequences

    PubMed Central

    2011-01-01

    Background Automatic extraction of motifs from biological sequences is an important research problem in study of molecular biology. For proteins, it is desired to discover sequence motifs containing a large number of wildcard symbols, as the residues associated with functional sites are usually largely separated in sequences. Discovering such patterns is time-consuming because abundant combinations exist when long gaps (a gap consists of one or more successive wildcards) are considered. Mining algorithms often employ constraints to narrow down the search space in order to increase efficiency. However, improper constraint models might degrade the sensitivity and specificity of the motifs discovered by computational methods. We previously proposed a new constraint model to handle large wildcard regions for discovering functional motifs of proteins. The patterns that satisfy the proposed constraint model are called W-patterns. A W-pattern is a structured motif that groups motif symbols into pattern blocks interleaved with large irregular gaps. Considering large gaps reflects the fact that functional residues are not always from a single region of protein sequences, and restricting motif symbols into clusters corresponds to the observation that short motifs are frequently present within protein families. To efficiently discover W-patterns for large-scale sequence annotation and function prediction, this paper first formally introduces the problem to solve and proposes an algorithm named WildSpan (sequential pattern mining across large wildcard regions) that incorporates several pruning strategies to largely reduce the mining cost. Results WildSpan is shown to efficiently find W-patterns containing conserved residues that are far separated in sequences. We conducted experiments with two mining strategies, protein-based and family-based mining, to evaluate the usefulness of W-patterns and performance of WildSpan. The protein-based mining mode of WildSpan is developed for

  6. Structural assessment of glycyl mutations in invariantly conserved motifs.

    PubMed

    Prakash, Tulika; Sandhu, Kuljeet Singh; Singh, Nitin Kumar; Bhasin, Yasha; Ramakrishnan, C; Brahmachari, Samir K

    2007-11-15

    Motifs that are evolutionarily conserved in proteins are crucial to their structure and function. In one of our earlier studies, we demonstrated that the conserved motifs occurring invariantly across several organisms could act as structural determinants of the proteins. We observed the abundance of glycyl residues in these invariantly conserved motifs. The role of glycyl residues in highly conserved motifs has not been studied extensively. Thus, it would be interesting to examine the structural perturbations induced by mutation in these conserved glycyl sites. In this work, we selected a representative set of invariant signature (IS) peptides for which both the PDB structure and mutation information was available. We thoroughly analyzed the conformational features of the glycyl sites and their local interactions with the surrounding residues. Using Ramachandran angles, we showed that the glycyl residues occurring in these IS peptides, which have undergone mutation, occurred more often in the L-disallowed as compared with the L-allowed region of the Ramachandran plot. Short range contacts around the mutation site were analyzed to study the steric effects. With the results obtained from our analysis, we hypothesize that any change of activity arising because of such mutations must be attributed to the long-range interaction(s) of the new residue if the glycyl residue in the IS peptide occurred in the L-allowed region of the Ramachandran plot. However, the mutation of those conserved glycyl residues that occurred in the L-disallowed region of the Ramachandran plot might lead to an altered activity of the protein as a result of an altered conformation of the backbone in the immediate vicinity of the glycyl residue, in addition to long range effects arising from the long side chains of the new residue. Thus, the loss of activity because of mutation in the conserved glycyl site might either relate to long range interactions or to local perturbations around the site

  7. The Thiamine-Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Ciszak, Ewa; Dominiak, Paulina

    2004-01-01

    Thiamin pyrophosphate (TPP), a derivative of vitamin B1, is a cofactor for enzymes performing catalysis in pathways of energy production including the well known decarboxylation of a-keto acid dehydrogenases followed by transketolation. TPP-dependent enzymes constitute a structurally and functionally diverse group exhibiting multimeric subunit organization, multiple domains and two chemically equivalent catalytic centers. Annotation of functional TPP-dependcnt enzymes, therefore, has not been trivial due to low sequence similarity related to this complex organization. Our approach to analysis of structures of known TPP-dependent enzymes reveals for the first time features common to this group, which we have termed the TPP-motif. The TPP-motif consists of specific spatial arrangements of structural elements and their specific contacts to provide for a flip-flop, or alternate site, enzymatic mechanism of action. Analysis of structural elements entrained in the flip-flop action displayed by TPP-dependent enzymes reveals a novel definition of the common amino acid sequences. These sequences allow for annotation of TPP-dependent enzymes, thus advancing functional proteomics. Further details of three-dimensional structures of TPP-dependent enzymes will be discussed.

  8. Signatures support program

    NASA Astrophysics Data System (ADS)

    Hawley, Chadwick T.

    2009-05-01

    The Signatures Support Program (SSP) leverages the full spectrum of signature-related activities (collections, processing, development, storage, maintenance, and dissemination) within the Department of Defense (DOD), the intelligence community (IC), other Federal agencies, and civil institutions. The Enterprise encompasses acoustic, seismic, radio frequency, infrared, radar, nuclear radiation, and electro-optical signatures. The SSP serves the war fighter, the IC, and civil institutions by supporting military operations, intelligence operations, homeland defense, disaster relief, acquisitions, and research and development. Data centers host and maintain signature holdings, collectively forming the national signatures pool. The geographically distributed organizations are the authoritative sources and repositories for signature data; the centers are responsible for data content and quality. The SSP proactively engages DOD, IC, other Federal entities, academia, and industry to locate signatures for inclusion in the distributed national signatures pool and provides world-wide 24/7 access via the SSP application.

  9. Novel motifs distinguish multiple homologues of Polycomb in vertebrates: expansion and diversification of the epigenetic toolkit

    PubMed Central

    2009-01-01

    Background Polycomb group (PcG) proteins maintain expression pattern of genes set early during development. Although originally isolated as regulators of homeotic genes, PcG members play a key role in epigenetic mechanism that maintains the expression state of a large number of genes. Polycomb (PC) is conserved during evolution and while invertebrates have one PC gene, vertebrates have five or more homologues. It remains unclear if different vertebrate PC homologues have distinct or overlapping functions. We have identified and compared the sequence of PC homologues in various organisms to analyze similarities and differences that shaped the evolutionary history of this key regulatory protein. Results All PC homologues have an N-terminal chromodomain and a C-terminal Polycomb Repressor box. We searched the protein and genome sequence database of various organisms for these signatures and identified ~100 PC homologues. Comparative analysis of these sequences led to the identification of a novel insect specific motif and several novel and signature motifs in the vertebrate homologue: two in CBX2 (Cx2.1 and Cx2.2), four in CBX4 (Cx4.1, Cx4.2, Cx4.3 and Cx4.4), three in CBX6 (Cx6.1, Cx6.2 and Cx6.3) and one in CBX8 (Cx8.1). Additionally, adjacent to the chromodomain, all the vertebrate homologues have a DNA binding motif - AT-Hook in case of CBX2, which was known earlier, and 'AT-Hook Like' motif, from this study, in other PC homologues. Conclusion Our analysis shows that PC is an ancient gene dating back to pre bilaterian origin that has not only been conserved but has also expanded during the evolution of complexity. Unique motifs acquired by each homologue have been maintained for more than 500 millions years indicating their functional relevance in boosting the epigenetic 'tool kit'. We report the presence of a DNA interaction motif adjacent to chromodomain in all vertebrate PC homologues and suggest a three-way 'PC-histoneH3-DNA' interaction that can restrict

  10. MSDmotif: exploring protein sites and motifs

    PubMed Central

    Golovin, Adel; Henrick, Kim

    2008-01-01

    Background Protein structures have conserved features – motifs, which have a sufficient influence on the protein function. These motifs can be found in sequence as well as in 3D space. Understanding of these fragments is essential for 3D structure prediction, modelling and drug-design. The Protein Data Bank (PDB) is the source of this information however present search tools have limited 3D options to integrate protein sequence with its 3D structure. Results We describe here a web application for querying the PDB for ligands, binding sites, small 3D structural and sequence motifs and the underlying database. Novel algorithms for chemical fragments, 3D motifs, ϕ/ψ sequences, super-secondary structure motifs and for small 3D structural motif associations searches are incorporated. The interface provides functionality for visualization, search criteria creation, sequence and 3D multiple alignment options. MSDmotif is an integrated system where a results page is also a search form. A set of motif statistics is available for analysis. This set includes molecule and motif binding statistics, distribution of motif sequences, occurrence of an amino-acid within a motif, correlation of amino-acids side-chain charges within a motif and Ramachandran plots for each residue. The binding statistics are presented in association with properties that include a ligand fragment library. Access is also provided through the distributed Annotation System (DAS) protocol. An additional entry point facilitates XML requests with XML responses. Conclusion MSDmotif is unique by combining chemical, sequence and 3D data in a single search engine with a range of search and visualisation options. It provides multiple views of data found in the PDB archive for exploring protein structures. PMID:18637174

  11. A survey of motif finding Web tools for detecting binding site motifs in ChIP-Seq data.

    PubMed

    Tran, Ngoc Tam L; Huang, Chun-Hsi

    2014-02-20

    ChIP-Seq (chromatin immunoprecipitation sequencing) has provided the advantage for finding motifs as ChIP-Seq experiments narrow down the motif finding to binding site locations. Recent motif finding tools facilitate the motif detection by providing user-friendly Web interface. In this work, we reviewed nine motif finding Web tools that are capable for detecting binding site motifs in ChIP-Seq data. We showed each motif finding Web tool has its own advantages for detecting motifs that other tools may not discover. We recommended the users to use multiple motif finding Web tools that implement different algorithms for obtaining significant motifs, overlapping resemble motifs, and non-overlapping motifs. Finally, we provided our suggestions for future development of motif finding Web tool that better assists researchers for finding motifs in ChIP-Seq data.

  12. Sampling Motif-Constrained Ensembles of Networks

    NASA Astrophysics Data System (ADS)

    Fischer, Rico; Leitão, Jorge C.; Peixoto, Tiago P.; Altmann, Eduardo G.

    2015-10-01

    The statistical significance of network properties is conditioned on null models which satisfy specified properties but that are otherwise random. Exponential random graph models are a principled theoretical framework to generate such constrained ensembles, but which often fail in practice, either due to model inconsistency or due to the impossibility to sample networks from them. These problems affect the important case of networks with prescribed clustering coefficient or number of small connected subgraphs (motifs). In this Letter we use the Wang-Landau method to obtain a multicanonical sampling that overcomes both these problems. We sample, in polynomial time, networks with arbitrary degree sequences from ensembles with imposed motifs counts. Applying this method to social networks, we investigate the relation between transitivity and homophily, and we quantify the correlation between different types of motifs, finding that single motifs can explain up to 60% of the variation of motif profiles.

  13. Temporal motifs in time-dependent networks

    NASA Astrophysics Data System (ADS)

    Kovanen, Lauri; Karsai, Márton; Kaski, Kimmo; Kertész, János; Saramäki, Jari

    2011-11-01

    Temporal networks are commonly used to represent systems where connections between elements are active only for restricted periods of time, such as telecommunication, neural signal processing, biochemical reaction and human social interaction networks. We introduce the framework of temporal motifs to study the mesoscale topological-temporal structure of temporal networks in which the events of nodes do not overlap in time. Temporal motifs are classes of similar event sequences, where the similarity refers not only to topology but also to the temporal order of the events. We provide a mapping from event sequences to coloured directed graphs that enables an efficient algorithm for identifying temporal motifs. We discuss some aspects of temporal motifs, including causality and null models, and present basic statistics of temporal motifs in a large mobile call network.

  14. Uncertainty in hydrological signatures

    NASA Astrophysics Data System (ADS)

    Westerberg, I. K.; McMillan, H. K.

    2015-09-01

    Information about rainfall-runoff processes is essential for hydrological analyses, modelling and water-management applications. A hydrological, or diagnostic, signature quantifies such information from observed data as an index value. Signatures are widely used, e.g. for catchment classification, model calibration and change detection. Uncertainties in the observed data - including measurement inaccuracy and representativeness as well as errors relating to data management - propagate to the signature values and reduce their information content. Subjective choices in the calculation method are a further source of uncertainty. We review the uncertainties relevant to different signatures based on rainfall and flow data. We propose a generally applicable method to calculate these uncertainties based on Monte Carlo sampling and demonstrate it in two catchments for common signatures including rainfall-runoff thresholds, recession analysis and basic descriptive signatures of flow distribution and dynamics. Our intention is to contribute to awareness and knowledge of signature uncertainty, including typical sources, magnitude and methods for its assessment. We found that the uncertainties were often large (i.e. typical intervals of ±10-40 % relative uncertainty) and highly variable between signatures. There was greater uncertainty in signatures that use high-frequency responses, small data subsets, or subsets prone to measurement errors. There was lower uncertainty in signatures that use spatial or temporal averages. Some signatures were sensitive to particular uncertainty types such as rating-curve form. We found that signatures can be designed to be robust to some uncertainty sources. Signature uncertainties of the magnitudes we found have the potential to change the conclusions of hydrological and ecohydrological analyses, such as cross-catchment comparisons or inferences about dominant processes.

  15. Efficient motif search in ranked lists and applications to variable gap motifs.

    PubMed

    Leibovich, Limor; Yakhini, Zohar

    2012-07-01

    Sequence elements, at all levels-DNA, RNA and protein, play a central role in mediating molecular recognition and thereby molecular regulation and signaling. Studies that focus on -measuring and investigating sequence-based recognition make use of statistical and computational tools, including approaches to searching sequence motifs. State-of-the-art motif searching tools are limited in their coverage and ability to address large motif spaces. We develop and present statistical and algorithmic approaches that take as input ranked lists of sequences and return significant motifs. The efficiency of our approach, based on suffix trees, allows searches over motif spaces that are not covered by existing tools. This includes searching variable gap motifs-two half sites with a flexible length gap in between-and searching long motifs over large alphabets. We used our approach to analyze several high-throughput measurement data sets and report some validation results as well as novel suggested motifs and motif refinements. We suggest a refinement of the known estrogen receptor 1 motif in humans, where we observe gaps other than three nucleotides that also serve as significant recognition sites, as well as a variable length motif related to potential tyrosine phosphorylation.

  16. [Psychopathological study of lie motif in schizophrenia].

    PubMed

    Otsuka, Koichiro; Kato, Satoshi

    2006-01-01

    The theme of a statement is called "lie motif" by the authors when schizophrenic patients say "I have lied to anybody". We tried to analyse of the psychopathological characteristics and anthropological meanings of the lie motifs in schizophrenia, which has not been thematically examined until now, based on 4 cases, and contrasting with the lie motif (Lügenmotiv) in depression taken up by A. Kraus (1989). We classified the lie motifs in schizophrenia into the following two types: a) the past directive lie motif: the patients speak about their real lie regarding it as a 'petty fault' in their distant past with self-guilty feeling, b) the present directive lie motif: the patients say repeatedly 'I have lied' (about their present speech and behavior), retreating from their previous commitments. The observed false confessions of innocent fault by the patients seem to belong to the present directed lie motif. In comparison with the lie motif in depression, it is characteristic for the lie motif in schizophrenia that the patients feel themselves to already have been caught out by others before they confess the lie. The lie motif in schizophrenia seems to come into being through the attribution process of taking the others' blame on ones' own shoulders, which has been pointed out to be common in the guilt experience in schizophrenia. The others' blame on this occasion is due to "the others' gaze" in the experience of the initial self-centralization (i.e. non delusional self-referential experience) in the early stage of schizophrenia (S. Kato 1999). The others' gaze is supposed to bring about the feeling of amorphous self-revelation which could also be regarded as the guilt feeling without content, to the patients. When the guilt feeling is bound with a past concrete fault, the patients tell the past directive lie motif. On the other hand, when the patients cannot find a past fixed content, and feel their present actions as uncertain and experience them as lies, the

  17. Isosteric and nonisosteric base pairs in RNA motifs: molecular dynamics and bioinformatics study of the sarcin-ricin internal loop.

    PubMed

    Havrila, Marek; Réblová, Kamila; Zirbel, Craig L; Leontis, Neocles B; Šponer, Jiří

    2013-11-21

    The sarcin-ricin RNA motif (SR motif) is one of the most prominent recurrent RNA building blocks that occurs in many different RNA contexts and folds autonomously, that is, in a context-independent manner. In this study, we combined bioinformatics analysis with explicit-solvent molecular dynamics (MD) simulations to better understand the relation between the RNA sequence and the evolutionary patterns of the SR motif. A SHAPE probing experiment was also performed to confirm the fidelity of the MD simulations. We identified 57 instances of the SR motif in a nonredundant subset of the RNA X-ray structure database and analyzed their base pairing, base-phosphate, and backbone-backbone interactions. We extracted sequences aligned to these instances from large rRNA alignments to determine the frequency of occurrence for different sequence variants. We then used a simple scoring scheme based on isostericity to suggest 10 sequence variants with a highly variable expected degree of compatibility with the SR motif 3D structure. We carried out MD simulations of SR motifs with these base substitutions. Nonisosteric base substitutions led to unstable structures, but so did isosteric substitutions which were unable to make key base-phosphate interactions. The MD technique explains why some potentially isosteric SR motifs are not realized during evolution. We also found that the inability to form stable cWW geometry is an important factor in the case of the first base pair of the flexible region of the SR motif. A comparison of structural, bioinformatics, SHAPE probing, and MD simulation data reveals that explicit solvent MD simulations neatly reflect the viability of different sequence variants of the SR motif. Thus, MD simulations can efficiently complement bioinformatics tools in studies of conservation patterns of RNA motifs and provide atomistic insight into the role of their different signature interactions.

  18. VARUN: discovering extensible motifs under saturation constraints.

    PubMed

    Apostolico, Alberto; Comin, Matteo; Parida, Laxmi

    2010-01-01

    The discovery of motifs in biosequences is frequently torn between the rigidity of the model on one hand and the abundance of candidates on the other hand. In particular, motifs that include wild cards or "don't cares" escalate exponentially with their number, and this gets only worse if a don't care is allowed to stretch up to some prescribed maximum length. In this paper, a notion of extensible motif in a sequence is introduced and studied, which tightly combines the structure of the motif pattern, as described by its syntactic specification, with the statistical measure of its occurrence count. It is shown that a combination of appropriate saturation conditions and the monotonicity of probabilistic scores over regions of constant frequency afford us significant parsimony in the generation and testing of candidate overrepresented motifs. A suite of software programs called Varun is described, implementing the discovery of extensible motifs of the type considered. The merits of the method are then documented by results obtained in a variety of experiments primarily targeting protein sequence families. Of equal importance seems the fact that the sets of all surprising motifs returned in each experiment are extracted faster and come in much more manageable sizes than would be obtained in the absence of saturation constraints.

  19. Stochastic motif extraction using hidden Markov model

    SciTech Connect

    Fujiwara, Yukiko; Asogawa, Minoru; Konagaya, Akihiko

    1994-12-31

    In this paper, we study the application of an HMM (hidden Markov model) to the problem of representing protein sequences by a stochastic motif. A stochastic protein motif represents the small segments of protein sequences that have a certain function or structure. The stochastic motif, represented by an HMM, has conditional probabilities to deal with the stochastic nature of the motif. This HMM directive reflects the characteristics of the motif, such as a protein periodical structure or grouping. In order to obtain the optimal HMM, we developed the {open_quotes}iterative duplication method{close_quotes} for HMM topology learning. It starts from a small fully-connected network and iterates the network generation and parameter optimization until it achieves sufficient discrimination accuracy. Using this method, we obtained an HMM for a leucine zipper motif. Compared to the accuracy of a symbolic pattern representation with accuracy of 14.8 percent, an HMM achieved 79.3 percent in prediction. Additionally, the method can obtain an HMM for various types of zinc finger motifs, and it might separate the mixed data. We demonstrated that this approach is applicable to the validation of the protein databases; a constructed HMM b as indicated that one protein sequence annotated as {open_quotes}lencine-zipper like sequence{close_quotes} in the database is quite different from other leucine-zipper sequences in terms of likelihood, and we found this discrimination is plausible.

  20. Sephardic signature in haplogroup T mitochondrial DNA.

    PubMed

    Bedford, Felice L

    2012-04-01

    A rare combination of mutations within mitochondrial DNA subhaplogroup T2e is identified as affiliated with Sephardic Jews, a group that has received relatively little attention. Four investigations were pursued: Search of the motif in 250 000 control region records across 8 databases, comparison of frequencies of T subhaplogroups (T1, T2b, T2c, T2e, T4, T(*)) across 11 diverse populations, creation of a phylogenic median-joining network from public T2e control region entries, and analysis of one Sephardic mitochondrial full genomic sequence with the motif. It was found that the rare motif belonged only to Sephardic descendents (Turkey, Bulgaria), to inhabitants of North American regions known for secret Spanish-Jewish colonization, or were consistent with Sephardic ancestry. The incidence of subhaplogroup T2e decreased from the Western Arabian Peninsula to Italy to Spain and into Western Europe. The ratio of sister subhaplogroups T2e to T2b was found to vary 40-fold across populations from a low in the British Isles to a high in Saudi Arabia with the ratio in Sephardim more similar to Saudi Arabia, Egypt, and Italy than to hosts Spain and Portugal. Coding region mutations of 2308G and 14499T may locate the Sephardic signature within T2e, but additional samples and reworking of current T2e phylogenetic branch structure is needed. The Sephardic Turkish community has a less pronounced founder effect than some Ashkenazi groups considered singly (eg, Polish), but other comparisons of interest await comparable averaging. Registries of signatures will benefit the study of populations with a large number of smaller-size founders.

  1. A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.

    PubMed

    Martínez-Bonet, Marta; Palladino, Claudia; Briz, Veronica; Rudolph, Jochen M; Fackler, Oliver T; Relloso, Miguel; Muñoz-Fernandez, Maria Angeles; Madrid, Ricardo

    2015-01-01

    To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection.

  2. A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities

    PubMed Central

    Martínez-Bonet, Marta; Palladino, Claudia; Briz, Veronica; Rudolph, Jochen M.; Fackler, Oliver T.; Relloso, Miguel; Muñoz-Fernandez, Maria Angeles; Madrid, Ricardo

    2015-01-01

    To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121–137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection. PMID:26700863

  3. The Frequency of Internal Shine-Dalgarno-like Motifs in Prokaryotes.

    PubMed

    Diwan, Gaurav D; Agashe, Deepa

    2016-06-14

    In prokaryotes, translation initiation typically depends on complementary binding between a G-rich Shine-Dalgarno (SD) motif in the 5' untranslated region of mRNAs, and the 3' tail of the 16S ribosomal RNA (the anti-SD sequence). In some cases, internal SD-like motifs in the coding region generate "programmed" ribosomal pauses that are beneficial for protein folding or accurate targeting. On the other hand, such pauses can also reduce protein production, generating purifying selection against internal SD-like motifs. This selection should be stronger in GC-rich genomes that are more likely to harbor the G-rich SD motif. However, the nature and consequences of selection acting on internal SD-like motifs within genomes and across species remains unclear. We analyzed the frequency of SD-like hexamers in the coding regions of 284 prokaryotes (277 with known anti-SD sequences and 7 without a typical SD mechanism). After accounting for GC content, we found that internal SD-like hexamers are avoided in 230 species, including three without a typical SD mechanism. The degree of avoidance was higher in GC-rich genomes, mesophiles, and N-terminal regions of genes. In contrast, 54 species either showed no signature of avoidance or were enriched in internal SD-like motifs. C-terminal gene regions were relatively enriched in SD-like hexamers, particularly for genes in operons or those followed closely by downstream genes. Together, our results suggest that the frequency of internal SD-like hexamers is governed by multiple factors including GC content and genome organization, and further empirical work is necessary to understand the evolution and functional roles of these motifs.

  4. Efficient motif search in ranked lists and applications to variable gap motifs

    PubMed Central

    Leibovich, Limor; Yakhini, Zohar

    2012-01-01

    Sequence elements, at all levels—DNA, RNA and protein, play a central role in mediating molecular recognition and thereby molecular regulation and signaling. Studies that focus on measuring and investigating sequence-based recognition make use of statistical and computational tools, including approaches to searching sequence motifs. State-of-the-art motif searching tools are limited in their coverage and ability to address large motif spaces. We develop and present statistical and algorithmic approaches that take as input ranked lists of sequences and return significant motifs. The efficiency of our approach, based on suffix trees, allows searches over motif spaces that are not covered by existing tools. This includes searching variable gap motifs—two half sites with a flexible length gap in between—and searching long motifs over large alphabets. We used our approach to analyze several high-throughput measurement data sets and report some validation results as well as novel suggested motifs and motif refinements. We suggest a refinement of the known estrogen receptor 1 motif in humans, where we observe gaps other than three nucleotides that also serve as significant recognition sites, as well as a variable length motif related to potential tyrosine phosphorylation. PMID:22416066

  5. RSAT peak-motifs: motif analysis in full-size ChIP-seq datasets.

    PubMed

    Thomas-Chollier, Morgane; Herrmann, Carl; Defrance, Matthieu; Sand, Olivier; Thieffry, Denis; van Helden, Jacques

    2012-02-01

    ChIP-seq is increasingly used to characterize transcription factor binding and chromatin marks at a genomic scale. Various tools are now available to extract binding motifs from peak data sets. However, most approaches are only available as command-line programs, or via a website but with size restrictions. We present peak-motifs, a computational pipeline that discovers motifs in peak sequences, compares them with databases, exports putative binding sites for visualization in the UCSC genome browser and generates an extensive report suited for both naive and expert users. It relies on time- and memory-efficient algorithms enabling the treatment of several thousand peaks within minutes. Regarding time efficiency, peak-motifs outperforms all comparable tools by several orders of magnitude. We demonstrate its accuracy by analyzing data sets ranging from 4000 to 1,28,000 peaks for 12 embryonic stem cell-specific transcription factors. In all cases, the program finds the expected motifs and returns additional motifs potentially bound by cofactors. We further apply peak-motifs to discover tissue-specific motifs in peak collections for the p300 transcriptional co-activator. To our knowledge, peak-motifs is the only tool that performs a complete motif analysis and offers a user-friendly web interface without any restriction on sequence size or number of peaks.

  6. Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas.

    PubMed

    Petrov, Anton I; Zirbel, Craig L; Leontis, Neocles B

    2013-10-01

    The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals that many internal and hairpin loops are modular, recurrent, and structured by conserved non-Watson-Crick base pairs. Structurally similar loops define RNA 3D motifs that are conserved in homologous RNA molecules, but can also occur at nonhomologous sites in diverse RNAs, and which often vary in sequence. To further our understanding of RNA motif structure and sequence variability and to provide a useful resource for structure modeling and prediction, we present a new method for automated classification of internal and hairpin loop RNA 3D motifs and a new online database called the RNA 3D Motif Atlas. To classify the motif instances, a representative set of internal and hairpin loops is automatically extracted from a nonredundant list of RNA-containing PDB files. Their structures are compared geometrically, all-against-all, using the FR3D program suite. The loops are clustered into motif groups, taking into account geometric similarity and structural annotations and making allowance for a variable number of bulged bases. The automated procedure that we have implemented identifies all hairpin and internal loop motifs previously described in the literature. All motif instances and motif groups are assigned unique and stable identifiers and are made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is automatically updated every four weeks. The RNA 3D Motif Atlas provides an interactive user interface for exploring motif diversity and tools for programmatic data access.

  7. Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas

    PubMed Central

    Petrov, Anton I.; Zirbel, Craig L.; Leontis, Neocles B.

    2013-01-01

    The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals that many internal and hairpin loops are modular, recurrent, and structured by conserved non-Watson–Crick base pairs. Structurally similar loops define RNA 3D motifs that are conserved in homologous RNA molecules, but can also occur at nonhomologous sites in diverse RNAs, and which often vary in sequence. To further our understanding of RNA motif structure and sequence variability and to provide a useful resource for structure modeling and prediction, we present a new method for automated classification of internal and hairpin loop RNA 3D motifs and a new online database called the RNA 3D Motif Atlas. To classify the motif instances, a representative set of internal and hairpin loops is automatically extracted from a nonredundant list of RNA-containing PDB files. Their structures are compared geometrically, all-against-all, using the FR3D program suite. The loops are clustered into motif groups, taking into account geometric similarity and structural annotations and making allowance for a variable number of bulged bases. The automated procedure that we have implemented identifies all hairpin and internal loop motifs previously described in the literature. All motif instances and motif groups are assigned unique and stable identifiers and are made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is automatically updated every four weeks. The RNA 3D Motif Atlas provides an interactive user interface for exploring motif diversity and tools for programmatic data access. PMID:23970545

  8. A cis-Regulatory Signature for Chordate Anterior Neuroectodermal Genes

    PubMed Central

    Christiaen, Lionel; Joly, Jean-Stéphane

    2010-01-01

    One of the striking findings of comparative developmental genetics was that expression patterns of core transcription factors are extraordinarily conserved in bilaterians. However, it remains unclear whether cis-regulatory elements of their target genes also exhibit common signatures associated with conserved embryonic fields. To address this question, we focused on genes that are active in the anterior neuroectoderm and non-neural ectoderm of the ascidian Ciona intestinalis. Following the dissection of a prototypic anterior placodal enhancer, we searched all genomic conserved non-coding elements for duplicated motifs around genes showing anterior neuroectodermal expression. Strikingly, we identified an over-represented pentamer motif corresponding to the binding site of the homeodomain protein OTX, which plays a pivotal role in the anterior development of all bilaterian species. Using an in vivo reporter gene assay, we observed that 10 of 23 candidate cis-regulatory elements containing duplicated OTX motifs are active in the anterior neuroectoderm, thus showing that this cis-regulatory signature is predictive of neuroectodermal enhancers. These results show that a common cis-regulatory signature corresponding to K50-Paired homeodomain transcription factors is found in non-coding sequences flanking anterior neuroectodermal genes in chordate embryos. Thus, field-specific selector genes impose architectural constraints in the form of combinations of short tags on their target enhancers. This could account for the strong evolutionary conservation of the regulatory elements controlling field-specific selector genes responsible for body plan formation. PMID:20419150

  9. Phosphorylation of poly(rC) binding protein 1 (PCBP1) contributes to stabilization of mu opioid receptor (MOR) mRNA via interaction with AU-rich element RNA-binding protein 1 (AUF1) and poly A binding protein (PABP)

    PubMed Central

    Hwang, Cheol Kyu; Wagley, Yadav; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H.

    2016-01-01

    Gene regulation at the post-transcriptional level is frequently based on cis- and trans-acting factors on target mRNAs. We found a C-rich element (CRE) in mu-opioid receptor (MOR) 3′-untranslated region (UTR) to which poly (rC) binding protein 1 (PCBP1) binds, resulting in MOR mRNA stabilization. RNA immunoprecipitation and RNA EMSA revealed the formation of PCBP1-RNA complexes at the element. Knockdown of PCBP1 decreased MOR mRNA half-life and protein expression. Stimulation by forskolin increased cytoplasmic localization of PCBP1 and PCBP1/MOR 3′-UTR interactions via increased serine phosphorylation that was blocked by protein kinase A (PKA) or (phosphatidyl inositol-3) PI3-kinase inhibitors. The forskolin treatment also enhanced serine- and tyrosine-phosphorylation of AU-rich element binding protein (AUF1), concurrent with its increased binding to the CRE, and led to an increased interaction of poly A binding protein (PABP) with the CRE and poly(A) sites. AUF1 phosphorylation also led to an increased interaction with PCBP1. These findings suggest that a single co-regulator, PCBP1, plays a crucial role in stabilizing MOR mRNA, and is induced by PKA signaling by conforming to AUF1 and PABP. PMID:27836661

  10. Digital Signature Management.

    ERIC Educational Resources Information Center

    Hassler, Vesna; Biely, Helmut

    1999-01-01

    Describes the Digital Signature Project that was developed in Austria to establish an infrastructure for applying smart card-based digital signatures in banking and electronic-commerce applications. Discusses the need to conform to international standards, an international certification infrastructure, and security features for a public directory…

  11. Network motif identification in stochastic networks

    NASA Astrophysics Data System (ADS)

    Jiang, Rui; Tu, Zhidong; Chen, Ting; Sun, Fengzhu

    2006-06-01

    Network motifs have been identified in a wide range of networks across many scientific disciplines and are suggested to be the basic building blocks of most complex networks. Nonetheless, many networks come with intrinsic and/or experimental uncertainties and should be treated as stochastic networks. The building blocks in these networks thus may also have stochastic properties. In this article, we study stochastic network motifs derived from families of mutually similar but not necessarily identical patterns of interconnections. We establish a finite mixture model for stochastic networks and develop an expectation-maximization algorithm for identifying stochastic network motifs. We apply this approach to the transcriptional regulatory networks of Escherichia coli and Saccharomyces cerevisiae, as well as the protein-protein interaction networks of seven species, and identify several stochastic network motifs that are consistent with current biological knowledge. expectation-maximization algorithm | mixture model | transcriptional regulatory network | protein-protein interaction network

  12. iMotifs: an integrated sequence motif visualization and analysis environment

    PubMed Central

    Piipari, Matias; Down, Thomas A.; Saini, Harpreet; Enright, Anton; Hubbard, Tim J.P.

    2010-01-01

    Motivation: Short sequence motifs are an important class of models in molecular biology, used most commonly for describing transcription factor binding site specificity patterns. High-throughput methods have been recently developed for detecting regulatory factor binding sites in vivo and in vitro and consequently high-quality binding site motif data are becoming available for increasing number of organisms and regulatory factors. Development of intuitive tools for the study of sequence motifs is therefore important. iMotifs is a graphical motif analysis environment that allows visualization of annotated sequence motifs and scored motif hits in sequences. It also offers motif inference with the sensitive NestedMICA algorithm, as well as overrepresentation and pairwise motif matching capabilities. All of the analysis functionality is provided without the need to convert between file formats or learn different command line interfaces. The application includes a bundled and graphically integrated version of the NestedMICA motif inference suite that has no outside dependencies. Problems associated with local deployment of software are therefore avoided. Availability: iMotifs is licensed with the GNU Lesser General Public License v2.0 (LGPL 2.0). The software and its source is available at http://wiki.github.com/mz2/imotifs and can be run on Mac OS X Leopard (Intel/PowerPC). We also provide a cross-platform (Linux, OS X, Windows) LGPL 2.0 licensed library libxms for the Perl, Ruby, R and Objective-C programming languages for input and output of XMS formatted annotated sequence motif set files. Contact: matias.piipari@gmail.com; imotifs@googlegroups.com PMID:20106815

  13. UV Signature Mutations †

    PubMed Central

    2014-01-01

    Sequencing complete tumor genomes and exomes has sparked the cancer field's interest in mutation signatures for identifying the tumor's carcinogen. This review and meta-analysis discusses signatures and their proper use. We first distinguish between a mutagen's canonical mutations – deviations from a random distribution of base changes to create a pattern typical of that mutagen – and the subset of signature mutations, which are unique to that mutagen and permit inference backward from mutations to mutagen. To verify UV signature mutations, we assembled literature datasets on cells exposed to UVC, UVB, UVA, or solar simulator light (SSL) and tested canonical UV mutation features as criteria for clustering datasets. A confirmed UV signature was: ≥60% of mutations are C→T at a dipyrimidine site, with ≥5% CC→TT. Other canonical features such as a bias for mutations on the non-transcribed strand or at the 3' pyrimidine had limited application. The most robust classifier combined these features with criteria for the rarity of non-UV canonical mutations. In addition, several signatures proposed for specific UV wavelengths were limited to specific genes or species; non-signature mutations induced by UV may cause melanoma BRAF mutations; and the mutagen for sunlight-related skin neoplasms may vary between continents. PMID:25354245

  14. An archaeal genomic signature

    NASA Technical Reports Server (NTRS)

    Graham, D. E.; Overbeek, R.; Olsen, G. J.; Woese, C. R.

    2000-01-01

    Comparisons of complete genome sequences allow the most objective and comprehensive descriptions possible of a lineage's evolution. This communication uses the completed genomes from four major euryarchaeal taxa to define a genomic signature for the Euryarchaeota and, by extension, the Archaea as a whole. The signature is defined in terms of the set of protein-encoding genes found in at least two diverse members of the euryarchaeal taxa that function uniquely within the Archaea; most signature proteins have no recognizable bacterial or eukaryal homologs. By this definition, 351 clusters of signature proteins have been identified. Functions of most proteins in this signature set are currently unknown. At least 70% of the clusters that contain proteins from all the euryarchaeal genomes also have crenarchaeal homologs. This conservative set, which appears refractory to horizontal gene transfer to the Bacteria or the Eukarya, would seem to reflect the significant innovations that were unique and fundamental to the archaeal "design fabric." Genomic protein signature analysis methods may be extended to characterize the evolution of any phylogenetically defined lineage. The complete set of protein clusters for the archaeal genomic signature is presented as supplementary material (see the PNAS web site, www.pnas.org).

  15. Twin Signature Schemes, Revisited

    NASA Astrophysics Data System (ADS)

    Schäge, Sven

    In this paper, we revisit the twin signature scheme by Naccache, Pointcheval and Stern from CCS 2001 that is secure under the Strong RSA (SRSA) assumption and improve its efficiency in several ways. First, we present a new twin signature scheme that is based on the Strong Diffie-Hellman (SDH) assumption in bilinear groups and allows for very short signatures and key material. A big advantage of this scheme is that, in contrast to the original scheme, it does not require a computationally expensive function for mapping messages to primes. We prove this new scheme secure under adaptive chosen message attacks. Second, we present a modification that allows to significantly increase efficiency when signing long messages. This construction uses collision-resistant hash functions as its basis. As a result, our improvements make the signature length independent of the message size. Our construction deviates from the standard hash-and-sign approach in which the hash value of the message is signed in place of the message itself. We show that in the case of twin signatures, one can exploit the properties of the hash function as an integral part of the signature scheme. This improvement can be applied to both the SRSA based and SDH based twin signature scheme.

  16. Characteristic motifs for families of allergenic proteins

    PubMed Central

    Ivanciuc, Ovidiu; Garcia, Tzintzuni; Torres, Miguel; Schein, Catherine H.; Braun, Werner

    2008-01-01

    The identification of potential allergenic proteins is usually done by scanning a database of allergenic proteins and locating known allergens with a high sequence similarity. However, there is no universally accepted cut-off value for sequence similarity to indicate potential IgE cross-reactivity. Further, overall sequence similarity may be less important than discrete areas of similarity in proteins with homologous structure. To identify such areas, we first classified all allergens and their subdomains in the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/) to their closest protein families as defined in Pfam, and identified conserved physicochemical property motifs characteristic of each group of sequences. Allergens populate only a small subset of all known Pfam families, as all allergenic proteins in SDAP could be grouped to only 130 (of 9318 total) Pfams, and 31 families contain more than four allergens. Conserved physicochemical property motifs for the aligned sequences of the most populated Pfam families were identified with the PCPMer program suite and catalogued in the webserver Motif-Mate (http://born.utmb.edu/motifmate/summary.php). We also determined specific motifs for allergenic members of a family that could distinguish them from non-allergenic ones. These allergen specific motifs should be most useful in database searches for potential allergens. We found that sequence motifs unique to the allergens in three families (seed storage proteins, Bet v 1, and tropomyosin) overlap with known IgE epitopes, thus providing evidence that our motif based approach can be used to assess the potential allergenicity of novel proteins. PMID:18951633

  17. Modeling gene regulatory network motifs using statecharts

    PubMed Central

    2012-01-01

    Background Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks. For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs. Results We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal. We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation. Conclusions We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed. PMID:22536967

  18. Are there molecular signatures?

    SciTech Connect

    Bennett, W.P.

    1995-10-01

    This report describes molecular signatures and mutational spectrum analysis. The mutation spectrum is defined as the type and location of DNA base change. There are currently about five well documented cases. Mutations and radon-associated tumors are discussed.

  19. Meteor signature interpretation

    SciTech Connect

    Canavan, G.H.

    1997-01-01

    Meteor signatures contain information about the constituents of space debris and present potential false alarms to early warnings systems. Better models could both extract the maximum scientific information possible and reduce their danger. Accurate predictions can be produced by models of modest complexity, which can be inverted to predict the sizes, compositions, and trajectories of object from their signatures for most objects of interest and concern.

  20. Invisibly Sanitizable Signature without Pairings

    NASA Astrophysics Data System (ADS)

    Yum, Dae Hyun; Lee, Pil Joong

    Sanitizable signatures allow sanitizers to delete some pre-determined parts of a signed document without invalidating the signature. While ordinary sanitizable signatures allow verifiers to know how many subdocuments have been sanitized, invisibly sanitizable signatures do not leave any clue to the sanitized subdocuments; verifiers do not know whether or not sanitizing has been performed. Previous invisibly sanitizable signature scheme was constructed based on aggregate signature with pairings. In this article, we present the first invisibly sanitizable signature without using pairings. Our proposed scheme is secure under the RSA assumption.

  1. Motif-based embedding for graph clustering

    NASA Astrophysics Data System (ADS)

    Lim, Sungsu; Lee, Jae-Gil

    2016-12-01

    Community detection in complex networks is a fundamental problem that has been extensively studied owing to its wide range of applications. However, because community detection methods typically rely on the relations between vertices in networks, they may fail to discover higher-order graph substructures, called the network motifs. In this paper, we propose a novel embedding method for graph clustering that considers higher-order relationships involving multiple vertices. We show that our embedding method, which we call motif-based embedding, is more effective in detecting communities than existing graph embedding methods, spectral embedding and force-directed embedding, both theoretically and experimentally.

  2. Crystal structure of interleukin-21 receptor (IL-21R) bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R.

    PubMed

    Hamming, Ole J; Kang, Lishan; Svensson, Anders; Karlsen, Jesper L; Rahbek-Nielsen, Henrik; Paludan, Søren R; Hjorth, Siv A; Bondensgaard, Kent; Hartmann, Rune

    2012-03-16

    IL-21 is a class I cytokine that exerts pleiotropic effects on both innate and adaptive immune responses. It signals through a heterodimeric receptor complex consisting of the IL-21 receptor (IL-21R) and the common γ-chain. A hallmark of the class I cytokine receptors is the class I cytokine receptor signature motif (WSXWS). The exact role of this motif has not been determined yet; however, it has been implicated in diverse functions, including ligand binding, receptor internalization, proper folding, and export, as well as signal transduction. Furthermore, the WXXW motif is known to be a consensus sequence for C-mannosylation. Here, we present the crystal structure of IL-21 bound to IL-21R and reveal that the WSXWS motif of IL-21R is C-mannosylated at the first tryptophan. We furthermore demonstrate that a sugar chain bridges the two fibronectin domains that constitute the extracellular domain of IL-21R and anchors at the WSXWS motif through an extensive hydrogen bonding network, including mannosylation. The glycan thus transforms the V-shaped receptor into an A-frame. This finding offers a novel structural explanation of the role of the class I cytokine signature motif.

  3. Crystal Structure of Interleukin-21 Receptor (IL-21R) Bound to IL-21 Reveals That Sugar Chain Interacting with WSXWS Motif Is Integral Part of IL-21R*

    PubMed Central

    Hamming, Ole J.; Kang, Lishan; Svensson, Anders; Karlsen, Jesper L.; Rahbek-Nielsen, Henrik; Paludan, Søren R.; Hjorth, Siv A.; Bondensgaard, Kent; Hartmann, Rune

    2012-01-01

    IL-21 is a class I cytokine that exerts pleiotropic effects on both innate and adaptive immune responses. It signals through a heterodimeric receptor complex consisting of the IL-21 receptor (IL-21R) and the common γ-chain. A hallmark of the class I cytokine receptors is the class I cytokine receptor signature motif (WSXWS). The exact role of this motif has not been determined yet; however, it has been implicated in diverse functions, including ligand binding, receptor internalization, proper folding, and export, as well as signal transduction. Furthermore, the WXXW motif is known to be a consensus sequence for C-mannosylation. Here, we present the crystal structure of IL-21 bound to IL-21R and reveal that the WSXWS motif of IL-21R is C-mannosylated at the first tryptophan. We furthermore demonstrate that a sugar chain bridges the two fibronectin domains that constitute the extracellular domain of IL-21R and anchors at the WSXWS motif through an extensive hydrogen bonding network, including mannosylation. The glycan thus transforms the V-shaped receptor into an A-frame. This finding offers a novel structural explanation of the role of the class I cytokine signature motif. PMID:22235133

  4. Network motifs modulate druggability of cellular targets

    PubMed Central

    Wu, Fan; Ma, Cong; Tan, Cheemeng

    2016-01-01

    Druggability refers to the capacity of a cellular target to be modulated by a small-molecule drug. To date, druggability is mainly studied by focusing on direct binding interactions between a drug and its target. However, druggability is impacted by cellular networks connected to a drug target. Here, we use computational approaches to reveal basic principles of network motifs that modulate druggability. Through quantitative analysis, we find that inhibiting self-positive feedback loop is a more robust and effective treatment strategy than inhibiting other regulations, and adding direct regulations to a drug-target generally reduces its druggability. The findings are explained through analytical solution of the motifs. Furthermore, we find that a consensus topology of highly druggable motifs consists of a negative feedback loop without any positive feedback loops, and consensus motifs with low druggability have multiple positive direct regulations and positive feedback loops. Based on the discovered principles, we predict potential genetic targets in Escherichia coli that have either high or low druggability based on their network context. Our work establishes the foundation toward identifying and predicting druggable targets based on their network topology. PMID:27824147

  5. The Motif of Meeting in Digital Education

    ERIC Educational Resources Information Center

    Sheail, Philippa

    2015-01-01

    This article draws on theoretical work which considers the composition of meetings, in order to think about the form of the meeting in digital environments for higher education. To explore the motif of meeting, I undertake a "compositional interpretation" (Rose, 2012) of the default interface offered by "Collaborate", an…

  6. Motifs and structural blocks retrieval by GHT

    NASA Astrophysics Data System (ADS)

    Cantoni, Virginio; Ferone, Alessio; Petrosino, Alfredo; Polat, Ozlem

    2014-06-01

    The structure of a protein gives more insight on the protein function than its amino acid sequence. Protein structure analysis and comparison are important for understanding the evolutionary relationships among proteins, predicting protein functions, and predicting protein folding. Proteins are formed by two basic regular 3D structural patterns, called Secondary Structures (SSs): helices and sheets. A structural motif is a compact 3D protein block referring to a small specific combination of secondary structural elements, which appears in a variety of molecules. In this paper we compare a few approaches for motif retrieval based on the Generalized Hough Transform (GHT). A primary technique is to adopt the single SS as structural primitives; alternatives are to adopt a SSs pair as primitive structural element, or a SSs triplet, and so on up-to an entire motif. The richer the primitive, the higher the time for pre-analysis and search, and the simpler the inspection process on the parameter space for analyzing the peaks. Performance comparisons, in terms of precision and computation time, are here presented considering the retrieval of motifs composed by three to five SSs for more than 15 million searches. The approach can be easily applied to the retrieval of greater blocks, up to protein domains, or even entire proteins.

  7. Practical quantum digital signature

    NASA Astrophysics Data System (ADS)

    Yin, Hua-Lei; Fu, Yao; Chen, Zeng-Bing

    2016-03-01

    Guaranteeing nonrepudiation, unforgeability as well as transferability of a signature is one of the most vital safeguards in today's e-commerce era. Based on fundamental laws of quantum physics, quantum digital signature (QDS) aims to provide information-theoretic security for this cryptographic task. However, up to date, the previously proposed QDS protocols are impractical due to various challenging problems and most importantly, the requirement of authenticated (secure) quantum channels between participants. Here, we present the first quantum digital signature protocol that removes the assumption of authenticated quantum channels while remaining secure against the collective attacks. Besides, our QDS protocol can be practically implemented over more than 100 km under current mature technology as used in quantum key distribution.

  8. Factor models for cancer signatures

    NASA Astrophysics Data System (ADS)

    Kakushadze, Zura; Yu, Willie

    2016-11-01

    We present a novel method for extracting cancer signatures by applying statistical risk models (http://ssrn.com/abstract=2732453) from quantitative finance to cancer genome data. Using 1389 whole genome sequenced samples from 14 cancers, we identify an "overall" mode of somatic mutational noise. We give a prescription for factoring out this noise and source code for fixing the number of signatures. We apply nonnegative matrix factorization (NMF) to genome data aggregated by cancer subtype and filtered using our method. The resultant signatures have substantially lower variability than those from unfiltered data. Also, the computational cost of signature extraction is cut by about a factor of 10. We find 3 novel cancer signatures, including a liver cancer dominant signature (96% contribution) and a renal cell carcinoma signature (70% contribution). Our method accelerates finding new cancer signatures and improves their overall stability. Reciprocally, the methods for extracting cancer signatures could have interesting applications in quantitative finance.

  9. Current signature sensor

    NASA Technical Reports Server (NTRS)

    Perotti, Jose M. (Inventor); Lucena, Angel (Inventor); Ihlefeld, Curtis (Inventor); Burns, Bradley (Inventor); Bassignani, Karin E. (Inventor)

    2005-01-01

    A solenoid health monitoring system uses a signal conditioner and controller assembly in one embodiment that includes analog circuitry and a DSP controller. The analog circuitry provides signal conditioning to the low-level raw signal coming from a signal acquisition assembly. Software running in a DSP analyzes the incoming data (recorded current signature) and determines the state of the solenoid whether it is energized, de-energized, or in a transitioning state. In one embodiment, the software identifies key features in the current signature during the transition phase and is able to determine the health of the solenoid.

  10. Current Signature Sensor

    NASA Technical Reports Server (NTRS)

    Perotti, Jose M. (Inventor); Lucena, Angel (Inventor); Ihlefeld, Curtis (Inventor); Burns, Bradley (Inventor); Bassignani, Mario (Inventor); Bassignani, Karin E. (Inventor)

    2005-01-01

    A solenoid health monitoring system uses a signal conditioner and controller assembly in one embodiment that includes analog circuitry and a DSP controller. The analog circuitry provides signal conditioning to the low-level raw signal coming from a signal acquisition assembly. Software running in a DSP analyzes the incoming data (recorded current signature) and determines the state of the solenoid whether it is energized, de-energized, or in a transitioning state. In one embodiment, the software identifies key features in the current signature during the transition phase and is able to determine the health of the solenoid.

  11. A survey of motif finding Web tools for detecting binding site motifs in ChIP-Seq data

    PubMed Central

    2014-01-01

    Abstract ChIP-Seq (chromatin immunoprecipitation sequencing) has provided the advantage for finding motifs as ChIP-Seq experiments narrow down the motif finding to binding site locations. Recent motif finding tools facilitate the motif detection by providing user-friendly Web interface. In this work, we reviewed nine motif finding Web tools that are capable for detecting binding site motifs in ChIP-Seq data. We showed each motif finding Web tool has its own advantages for detecting motifs that other tools may not discover. We recommended the users to use multiple motif finding Web tools that implement different algorithms for obtaining significant motifs, overlapping resemble motifs, and non-overlapping motifs. Finally, we provided our suggestions for future development of motif finding Web tool that better assists researchers for finding motifs in ChIP-Seq data. Reviewers This article was reviewed by Prof. Sandor Pongor, Dr. Yuriy Gusev, and Dr. Shyam Prabhakar (nominated by Prof. Limsoon Wong). PMID:24555784

  12. CombiMotif: A new algorithm for network motifs discovery in protein-protein interaction networks

    NASA Astrophysics Data System (ADS)

    Luo, Jiawei; Li, Guanghui; Song, Dan; Liang, Cheng

    2014-12-01

    Discovering motifs in protein-protein interaction networks is becoming a current major challenge in computational biology, since the distribution of the number of network motifs can reveal significant systemic differences among species. However, this task can be computationally expensive because of the involvement of graph isomorphic detection. In this paper, we present a new algorithm (CombiMotif) that incorporates combinatorial techniques to count non-induced occurrences of subgraph topologies in the form of trees. The efficiency of our algorithm is demonstrated by comparing the obtained results with the current state-of-the art subgraph counting algorithms. We also show major differences between unicellular and multicellular organisms. The datasets and source code of CombiMotif are freely available upon request.

  13. Ab initio coordination chemistry for nickel chelation motifs.

    PubMed

    Sudan, R Jesu Jaya; Kumari, J Lesitha Jeeva; Sudandiradoss, C

    2015-01-01

    Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

  14. Mitochondrial and Y chromosome haplotype motifs as diagnostic markers of Jewish ancestry: a reconsideration.

    PubMed

    Tofanelli, Sergio; Taglioli, Luca; Bertoncini, Stefania; Francalacci, Paolo; Klyosov, Anatole; Pagani, Luca

    2014-01-01

    Several authors have proposed haplotype motifs based on site variants at the mitochondrial genome (mtDNA) and the non-recombining portion of the Y chromosome (NRY) to trace the genealogies of Jewish people. Here, we analyzed their main approaches and test the feasibility of adopting motifs as ancestry markers through construction of a large database of mtDNA and NRY haplotypes from public genetic genealogical repositories. We verified the reliability of Jewish ancestry prediction based on the Cohen and Levite Modal Haplotypes in their "classical" 6 STR marker format or in the "extended" 12 STR format, as well as four founder mtDNA lineages (HVS-I segments) accounting for about 40% of the current population of Ashkenazi Jews. For this purpose we compared haplotype composition in individuals of self-reported Jewish ancestry with the rest of European, African or Middle Eastern samples, to test for non-random association of ethno-geographic groups and haplotypes. Overall, NRY and mtDNA based motifs, previously reported to differentiate between groups, were found to be more represented in Jewish compared to non-Jewish groups. However, this seems to stem from common ancestors of Jewish lineages being rather recent respect to ancestors of non-Jewish lineages with the same "haplotype signatures." Moreover, the polyphyly of haplotypes which contain the proposed motifs and the misuse of constant mutation rates heavily affected previous attempts to correctly dating the origin of common ancestries. Accordingly, our results stress the limitations of using the above haplotype motifs as reliable Jewish ancestry predictors and show its inadequacy for forensic or genealogical purposes.

  15. A Signature Style

    ERIC Educational Resources Information Center

    Smiles, Robin V.

    2005-01-01

    This article discusses Dr. Amalia Amaki and her approach to art as her signature style by turning everyday items into fine art. Amaki is an assistant professor of art, art history, and Black American studies at the University of Delaware. She loves taking unexpected an object and redefining it in the context of art--like a button, a fan, a faded…

  16. Spectroscopic Signatures and Structural Motifs in Isolated and Hydrated Xanthine: a Computational Study

    NASA Astrophysics Data System (ADS)

    Singh, Vipin Bahadur

    2016-06-01

    The conformational landscapes of xanthine and its hydrated complex have been investigated by MP2 and DFT methods. The ground state geometry optimization yield five lowest energy conformers of xanth1-(H2O)1 complex at the MP2/6-311++G(d,p) level of theory for the first time. We investigated the low-lying excited states of bare xanthine by means of coupled cluster singles and approximate doubles (CC2) and TDDFT methods and a satisfactory interpretation of the electronic absorption spectra1 is obtained. The difference between the S0-S1 transition energy due to the most stable and the second most stable stable conformation of xanthine was found to be 859 wn. One striking feature is the coexistence of the blue and red shift of the vertical excitation energy of the optically bright state S1 of xanthine upon forming complex with a water at C2=O and C6=O carbonyl sites, respectively. The lowest singlet ππ* excited-state of the xanth1-(H2O)1 complex involving C2=O carbonyl are strongly blue shifted which is in agreement with the result of R2PI spectra of singly hydrated xanthine. While for the most stable and the second most stable xanth1-(H2O)1 complexes involving C6=O carbonyl, the lowest singlet ππ* excited-state is red shifted. The effect of hydration on S1 excited state due to bulk water environment was mimicked by a combination of polarizable continuum solvent model (PCM) and conductor like screening model (COSMO), which also shows a blue shift in accordance with the result of electronic absorption spectra in aqueous solution. This hypsochromic shift, is expected to be the result of the changes in the π-electron delocalization extent of molecule because of hydrogen bond formation. The optimized structure of xanthine dimer, computed the first time by MP2 and DFT methods. The binding energy of this dimer linked by double N-H…O=C hydrogen bonds was found to be 88 kj/mole at the MP2/6-311++G(d,p) level of theory. Computed IR spectra is found in remarkable agreement with the experiment and the out of phase (C=O)2 stretching mode shows tripling of intensity upon dimerisation. The vertical excitation energy of the optically bright state S1 of xanthine monomer upon forming dimer is shifted towards red as well as blue. J. Chen and B.Kohler, Phys. Chem. Chem. Phys., 2012,14,10677-1068.

  17. A Review of Functional Motifs Utilized by Viruses

    PubMed Central

    Sobhy, Haitham

    2016-01-01

    Short linear motifs (SLiM) are short peptides that facilitate protein function and protein-protein interactions. Viruses utilize these motifs to enter into the host, interact with cellular proteins, or egress from host cells. Studying functional motifs may help to predict protein characteristics, interactions, or the putative cellular role of a protein. In virology, it may reveal aspects of the virus tropism and help find antiviral therapeutics. This review highlights the recent understanding of functional motifs utilized by viruses. Special attention was paid to the function of proteins harboring these motifs, and viruses encoding these proteins. The review highlights motifs involved in (i) immune response and post-translational modifications (e.g., ubiquitylation, SUMOylation or ISGylation); (ii) virus-host cell interactions, including virus attachment, entry, fusion, egress and nuclear trafficking; (iii) virulence and antiviral activities; (iv) virion structure; and (v) low-complexity regions (LCRs) or motifs enriched with residues (Xaa-rich motifs). PMID:28248213

  18. Functional Motifs in Biochemical Reaction Networks

    PubMed Central

    Tyson, John J.; Novák, Béla

    2013-01-01

    The signal-response characteristics of a living cell are determined by complex networks of interacting genes, proteins, and metabolites. Understanding how cells respond to specific challenges, how these responses are contravened in diseased cells, and how to intervene pharmacologically in the decision-making processes of cells requires an accurate theory of the information-processing capabilities of macromolecular regulatory networks. Adopting an engineer’s approach to control systems, we ask whether realistic cellular control networks can be decomposed into simple regulatory motifs that carry out specific functions in a cell. We show that such functional motifs exist and review the experimental evidence that they control cellular responses as expected. PMID:20055671

  19. On the Kernelization Complexity of Colorful Motifs

    NASA Astrophysics Data System (ADS)

    Ambalath, Abhimanyu M.; Balasundaram, Radheshyam; Rao H., Chintan; Koppula, Venkata; Misra, Neeldhara; Philip, Geevarghese; Ramanujan, M. S.

    The Colorful Motif problem asks if, given a vertex-colored graph G, there exists a subset S of vertices of G such that the graph induced by G on S is connected and contains every color in the graph exactly once. The problem is motivated by applications in computational biology and is also well-studied from the theoretical point of view. In particular, it is known to be NP-complete even on trees of maximum degree three [Fellows et al, ICALP 2007]. In their pioneering paper that introduced the color-coding technique, Alon et al. [STOC 1995] show, inter alia, that the problem is FPT on general graphs. More recently, Cygan et al. [WG 2010] showed that Colorful Motif is NP-complete on comb graphs, a special subclass of the set of trees of maximum degree three. They also showed that the problem is not likely to admit polynomial kernels on forests.

  20. Sequential motif profile of natural visibility graphs

    NASA Astrophysics Data System (ADS)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-11-01

    The concept of sequential visibility graph motifs—subgraphs appearing with characteristic frequencies in the visibility graphs associated to time series—has been advanced recently along with a theoretical framework to compute analytically the motif profiles associated to horizontal visibility graphs (HVGs). Here we develop a theory to compute the profile of sequential visibility graph motifs in the context of natural visibility graphs (VGs). This theory gives exact results for deterministic aperiodic processes with a smooth invariant density or stochastic processes that fulfill the Markov property and have a continuous marginal distribution. The framework also allows for a linear time numerical estimation in the case of empirical time series. A comparison between the HVG and the VG case (including evaluation of their robustness for short series polluted with measurement noise) is also presented.

  1. Chiral Alkyl Halides: Underexplored Motifs in Medicine

    PubMed Central

    Gál, Bálint; Bucher, Cyril; Burns, Noah Z.

    2016-01-01

    While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this review that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Our hope is that, by placing such compounds in the minds of the chemical community, they may gain more traction in drug discovery and inspire more synthetic chemists to develop methods for selective halogenation. PMID:27827902

  2. Anticipated synchronization in neuronal network motifs

    NASA Astrophysics Data System (ADS)

    Matias, F. S.; Gollo, L. L.; Carelli, P. V.; Copelli, M.; Mirasso, C. R.

    2013-01-01

    Two identical dynamical systems coupled unidirectionally (in a so called master-slave configuration) exhibit anticipated synchronization (AS) if the one which receives the coupling (the slave) also receives a negative delayed self-feedback. In oscillatory neuronal systems AS is characterized by a phase-locking with negative time delay τ between the spikes of the master and of the slave (slave fires before the master), while in the usual delayed synchronization (DS) regime τ is positive (slave fires after the master). A 3-neuron motif in which the slave self-feedback is replaced by a feedback loop mediated by an interneuron can exhibits both AS and DS regimes. Here we show that AS is robust in the presence of noise in a 3 Hodgkin-Huxley type neuronal motif. We also show that AS is stable for large values of τ in a chain of connected slaves-interneurons.

  3. Analyzing network reliability using structural motifs.

    PubMed

    Khorramzadeh, Yasamin; Youssef, Mina; Eubank, Stephen; Mowlaei, Shahir

    2015-04-01

    This paper uses the reliability polynomial, introduced by Moore and Shannon in 1956, to analyze the effect of network structure on diffusive dynamics such as the spread of infectious disease. We exhibit a representation for the reliability polynomial in terms of what we call structural motifs that is well suited for reasoning about the effect of a network's structural properties on diffusion across the network. We illustrate by deriving several general results relating graph structure to dynamical phenomena.

  4. Dynamic motifs in socio-economic networks

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Shao, Shuai; Stanley, H. Eugene; Havlin, Shlomo

    2014-12-01

    Socio-economic networks are of central importance in economic life. We develop a method of identifying and studying motifs in socio-economic networks by focusing on “dynamic motifs,” i.e., evolutionary connection patterns that, because of “node acquaintances” in the network, occur much more frequently than random patterns. We examine two evolving bi-partite networks: i) the world-wide commercial ship chartering market and ii) the ship build-to-order market. We find similar dynamic motifs in both bipartite networks, even though they describe different economic activities. We also find that “influence” and “persistence” are strong factors in the interaction behavior of organizations. When two companies are doing business with the same customer, it is highly probable that another customer who currently only has business relationship with one of these two companies, will become customer of the second in the future. This is the effect of influence. Persistence means that companies with close business ties to customers tend to maintain their relationships over a long period of time.

  5. Wake Signature Detection

    NASA Astrophysics Data System (ADS)

    Spedding, Geoffrey R.

    2014-01-01

    An accumulated body of quantitative evidence shows that bluff-body wakes in stably stratified environments have an unusual degree of coherence and organization, so characteristic geometries such as arrays of alternating-signed vortices have very long lifetimes, as measured in units of buoyancy timescales, or in the downstream distance scaled by a body length. The combination of pattern geometry and persistence renders the detection of these wakes possible in principle. It now appears that identifiable signatures can be found from many disparate sources: Islands, fish, and plankton all have been noted to generate features that can be detected by climate modelers, hopeful navigators in open oceans, or hungry predators. The various types of wakes are reviewed with notes on why their signatures are important and to whom. A general theory of wake pattern formation is lacking and would have to span many orders of magnitude in Reynolds number.

  6. SMAWT Signature Test

    DTIC Science & Technology

    1974-10-01

    were generally inversely proportional to the size assesments of the flash and smoke . Table 26 shows the percent of change in average judgments of...Average Time of Gunner’s View Obscuration by Smoke During Firings From the Wood Line .. .. ..... ..... ...... ..... .. 18 7. Average Obscuration Times...of Gunner’s View Obscuration by Smoke - Grass Line 19 8. Normalized Comparisons of the Relative Grades Assigned to Systems Signature Components

  7. Occurrence probability of structured motifs in random sequences.

    PubMed

    Robin, S; Daudin, J-J; Richard, H; Sagot, M-F; Schbath, S

    2002-01-01

    The problem of extracting from a set of nucleic acid sequences motifs which may have biological function is more and more important. In this paper, we are interested in particular motifs that may be implicated in the transcription process. These motifs, called structured motifs, are composed of two ordered parts separated by a variable distance and allowing for substitutions. In order to assess their statistical significance, we propose approximations of the probability of occurrences of such a structured motif in a given sequence. An application of our method to evaluate candidate promoters in E. coli and B. subtilis is presented. Simulations show the goodness of the approximations.

  8. CLIMP: Clustering Motifs via Maximal Cliques with Parallel Computing Design

    PubMed Central

    Chen, Yong

    2016-01-01

    A set of conserved binding sites recognized by a transcription factor is called a motif, which can be found by many applications of comparative genomics for identifying over-represented segments. Moreover, when numerous putative motifs are predicted from a collection of genome-wide data, their similarity data can be represented as a large graph, where these motifs are connected to one another. However, an efficient clustering algorithm is desired for clustering the motifs that belong to the same groups and separating the motifs that belong to different groups, or even deleting an amount of spurious ones. In this work, a new motif clustering algorithm, CLIMP, is proposed by using maximal cliques and sped up by parallelizing its program. When a synthetic motif dataset from the database JASPAR, a set of putative motifs from a phylogenetic foot-printing dataset, and a set of putative motifs from a ChIP dataset are used to compare the performances of CLIMP and two other high-performance algorithms, the results demonstrate that CLIMP mostly outperforms the two algorithms on the three datasets for motif clustering, so that it can be a useful complement of the clustering procedures in some genome-wide motif prediction pipelines. CLIMP is available at http://sqzhang.cn/climp.html. PMID:27487245

  9. No tradeoff between versatility and robustness in gene circuit motifs

    NASA Astrophysics Data System (ADS)

    Payne, Joshua L.

    2016-05-01

    Circuit motifs are small directed subgraphs that appear in real-world networks significantly more often than in randomized networks. In the Boolean model of gene circuits, most motifs are realized by multiple circuit genotypes. Each of a motif's constituent circuit genotypes may have one or more functions, which are embodied in the expression patterns the circuit forms in response to specific initial conditions. Recent enumeration of a space of nearly 17 million three-gene circuit genotypes revealed that all circuit motifs have more than one function, with the number of functions per motif ranging from 12 to nearly 30,000. This indicates that some motifs are more functionally versatile than others. However, the individual circuit genotypes that constitute each motif are less robust to mutation if they have many functions, hinting that functionally versatile motifs may be less robust to mutation than motifs with few functions. Here, I explore the relationship between versatility and robustness in circuit motifs, demonstrating that functionally versatile motifs are robust to mutation despite the inherent tradeoff between versatility and robustness at the level of an individual circuit genotype.

  10. Knowledge Signatures for Information Integration

    SciTech Connect

    Thomson, Judi; Cowell, Andrew J.; Paulson, Patrick R.; Butner, R. Scott; Whiting, Mark A.

    2003-10-25

    This paper introduces the notion of a knowledge signature: a concise, ontologically-driven representation of the semantic characteristics of data. Knowledge signatures provide programmatic access to data semantics while allowing comparisons to be made across different types of data such as text, images or video, enabling efficient, automated information integration. Through observation, which determines the degree of association between data and ontological concepts, and refinement, which uses the axioms and structure of the domain ontology to place the signature more accurately within the context of the domain, knowledge signatures can be created. A comparison of such signatures for two different pieces of data results in a measure of their semantic separation. This paper discusses the definition of knowledge signatures along with the design and prototype implementation of a knowledge signature generator.

  11. RNA structural motif recognition based on least-squares distance.

    PubMed

    Shen, Ying; Wong, Hau-San; Zhang, Shaohong; Zhang, Lin

    2013-09-01

    RNA structural motifs are recurrent structural elements occurring in RNA molecules. RNA structural motif recognition aims to find RNA substructures that are similar to a query motif, and it is important for RNA structure analysis and RNA function prediction. In view of this, we propose a new method known as RNA Structural Motif Recognition based on Least-Squares distance (LS-RSMR) to effectively recognize RNA structural motifs. A test set consisting of five types of RNA structural motifs occurring in Escherichia coli ribosomal RNA is compiled by us. Experiments are conducted for recognizing these five types of motifs. The experimental results fully reveal the superiority of the proposed LS-RSMR compared with four other state-of-the-art methods.

  12. Chaotic motif sampler: detecting motifs from biological sequences by using chaotic neurodynamics

    NASA Astrophysics Data System (ADS)

    Matsuura, Takafumi; Ikeguchi, Tohru

    Identification of a region in biological sequences, motif extraction problem (MEP) is solved in bioinformatics. However, the MEP is an NP-hard problem. Therefore, it is almost impossible to obtain an optimal solution within a reasonable time frame. To find near optimal solutions for NP-hard combinatorial optimization problems such as traveling salesman problems, quadratic assignment problems, and vehicle routing problems, chaotic search, which is one of the deterministic approaches, has been proposed and exhibits better performance than stochastic approaches. In this paper, we propose a new alignment method that employs chaotic dynamics to solve the MEPs. It is called the Chaotic Motif Sampler. We show that the performance of the Chaotic Motif Sampler is considerably better than that of the conventional methods such as the Gibbs Site Sampler and the Neighborhood Optimization for Multiple Alignment Discovery.

  13. Bases of motifs for generating repeated patterns with wild cards.

    PubMed

    Pisanti, Nadia; Crochemore, Maxime; Grossi, Roberto; Sagot, Marie-France

    2005-01-01

    Motif inference represents one of the most important areas of research in computational biology, and one of its oldest ones. Despite this, the problem remains very much open in the sense that no existing definition is fully satisfying, either in formal terms, or in relation to the biological questions that involve finding such motifs. Two main types of motifs have been considered in the literature: matrices (of letter frequency per position in the motif) and patterns. There is no conclusive evidence in favor of either, and recent work has attempted to integrate the two types into a single model. In this paper, we address the formal issue in relation to motifs as patterns. This is essential to get at a better understanding of motifs in general. In particular, we consider a promising idea that was recently proposed, which attempted to avoid the combinatorial explosion in the number of motifs by means of a generator set for the motifs. Instead of exhibiting a complete list of motifs satisfying some input constraints, what is produced is a basis of such motifs from which all the other ones can be generated. We study the computational cost of determining such a basis of repeated motifs with wild cards in a sequence. We give new upper and lower bounds on such a cost, introducing a notion of basis that is provably contained in (and, thus, smaller) than previously defined ones. Our basis can be computed in less time and space, and is still able to generate the same set of motifs. We also prove that the number of motifs in all bases defined so far grows exponentially with the quorum, that is, with the minimal number of times a motif must appear in a sequence, something unnoticed in previous work. We show that there is no hope to efficiently compute such bases unless the quorum is fixed.

  14. MINER: software for phylogenetic motif identification.

    PubMed

    La, David; Livesay, Dennis R

    2005-07-01

    MINER is web-based software for phylogenetic motif (PM) identification. PMs are sequence regions (fragments) that conserve the overall familial phylogeny. PMs have been shown to correspond to a wide variety of catalytic regions, substrate-binding sites and protein interfaces, making them ideal functional site predictions. The MINER output provides an intuitive interface for interactive PM sequence analysis and structural visualization. The web implementation of MINER is freely available at http://www.pmap.csupomona.edu/MINER/. Source code is available to the academic community on request.

  15. Signatures of nonthermal melting

    PubMed Central

    Zier, Tobias; Zijlstra, Eeuwe S.; Kalitsov, Alan; Theodonis, Ioannis; Garcia, Martin E.

    2015-01-01

    Intense ultrashort laser pulses can melt crystals in less than a picosecond but, in spite of over thirty years of active research, for many materials it is not known to what extent thermal and nonthermal microscopic processes cause this ultrafast phenomenon. Here, we perform ab-initio molecular-dynamics simulations of silicon on a laser-excited potential-energy surface, exclusively revealing nonthermal signatures of laser-induced melting. From our simulated atomic trajectories, we compute the decay of five structure factors and the time-dependent structure function. We demonstrate how these quantities provide criteria to distinguish predominantly nonthermal from thermal melting. PMID:26798822

  16. Signature CERN-URSS

    SciTech Connect

    2006-01-24

    Le DG W.Jentschke souhaite la bienvenue à l'assemblée et aux invités pour la signature du protocole entre le Cern et l'URSS qui est un événement important. C'est en 1955 que 55 visiteurs soviétiques ont visité le Cern pour la première fois. Le premier DG au Cern, F.Bloch, et Mons.Amaldi sont aussi présents. Tandis que le discours anglais de W.Jentschke est traduit en russe, le discours russe de Mons.Morozov est traduit en anglais.

  17. Transcription factor motif quality assessment requires systematic comparative analysis

    PubMed Central

    Kibet, Caleb Kipkurui; Machanick, Philip

    2016-01-01

    Transcription factor (TF) binding site prediction remains a challenge in gene regulatory research due to degeneracy and potential variability in binding sites in the genome. Dozens of algorithms designed to learn binding models (motifs) have generated many motifs available in research papers with a subset making it to databases like JASPAR, UniPROBE and Transfac. The presence of many versions of motifs from the various databases for a single TF and the lack of a standardized assessment technique makes it difficult for biologists to make an appropriate choice of binding model and for algorithm developers to benchmark, test and improve on their models. In this study, we review and evaluate the approaches in use, highlight differences and demonstrate the difficulty of defining a standardized motif assessment approach. We review scoring functions, motif length, test data and the type of performance metrics used in prior studies as some of the factors that influence the outcome of a motif assessment. We show that the scoring functions and statistics used in motif assessment influence ranking of motifs in a TF-specific manner. We also show that TF binding specificity can vary by source of genomic binding data. We also demonstrate that information content of a motif is not in isolation a measure of motif quality but is influenced by TF binding behaviour. We conclude that there is a need for an easy-to-use tool that presents all available evidence for a comparative analysis. PMID:27092243

  18. Cross-disciplinary detection and analysis of network motifs.

    PubMed

    Tran, Ngoc Tam L; DeLuccia, Luke; McDonald, Aidan F; Huang, Chun-Hsi

    2015-01-01

    The detection of network motifs has recently become an important part of network analysis across all disciplines. In this work, we detected and analyzed network motifs from undirected and directed networks of several different disciplines, including biological network, social network, ecological network, as well as other networks such as airlines, power grid, and co-purchase of political books networks. Our analysis revealed that undirected networks are similar at the basic three and four nodes, while the analysis of directed networks revealed the distinction between networks of different disciplines. The study showed that larger motifs contained the three-node motif as a subgraph. Topological analysis revealed that similar networks have similar small motifs, but as the motif size increases, differences arise. Pearson correlation coefficient showed strong positive relationship between some undirected networks but inverse relationship between some directed networks. The study suggests that the three-node motif is a building block of larger motifs. It also suggests that undirected networks share similar low-level structures. Moreover, similar networks share similar small motifs, but larger motifs define the unique structure of individuals. Pearson correlation coefficient suggests that protein structure networks, dolphin social network, and co-authorships in network science belong to a superfamily. In addition, yeast protein-protein interaction network, primary school contact network, Zachary's karate club network, and co-purchase of political books network can be classified into a superfamily.

  19. Promoter Motifs in NCLDVs: An Evolutionary Perspective.

    PubMed

    Oliveira, Graziele Pereira; Andrade, Ana Cláudia Dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Arantes, Thalita Souza; Boratto, Paulo Victor Miranda; Silva, Ludmila Karen Dos Santos; Dornas, Fábio Pio; Trindade, Giliane de Souza; Drumond, Betânia Paiva; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

    2017-01-20

    For many years, gene expression in the three cellular domains has been studied in an attempt to discover sequences associated with the regulation of the transcription process. Some specific transcriptional features were described in viruses, although few studies have been devoted to understanding the evolutionary aspects related to the spread of promoter motifs through related viral families. The discovery of giant viruses and the proposition of the new viral order Megavirales that comprise a monophyletic group, named nucleo-cytoplasmic large DNA viruses (NCLDV), raised new questions in the field. Some putative promoter sequences have already been described for some NCLDV members, bringing new insights into the evolutionary history of these complex microorganisms. In this review, we summarize the main aspects of the transcription regulation process in the three domains of life, followed by a systematic description of what is currently known about promoter regions in several NCLDVs. We also discuss how the analysis of the promoter sequences could bring new ideas about the giant viruses' evolution. Finally, considering a possible common ancestor for the NCLDV group, we discussed possible promoters' evolutionary scenarios and propose the term "MEGA-box" to designate an ancestor promoter motif ('TATATAAAATTGA') that could be evolved gradually by nucleotides' gain and loss and point mutations.

  20. Motif-directed redesign of enzyme specificity.

    PubMed

    Borgo, Benjamin; Havranek, James J

    2014-03-01

    Computational protein design relies on several approximations, including the use of fixed backbones and rotamers, to reduce protein design to a computationally tractable problem. However, allowing backbone and off-rotamer flexibility leads to more accurate designs and greater conformational diversity. Exhaustive sampling of this additional conformational space is challenging, and often impossible. Here, we report a computational method that utilizes a preselected library of native interactions to direct backbone flexibility to accommodate placement of these functional contacts. Using these native interaction modules, termed motifs, improves the likelihood that the interaction can be realized, provided that suitable backbone perturbations can be identified. Furthermore, it allows a directed search of the conformational space, reducing the sampling needed to find low energy conformations. We implemented the motif-based design algorithm in Rosetta, and tested the efficacy of this method by redesigning the substrate specificity of methionine aminopeptidase. In summary, native enzymes have evolved to catalyze a wide range of chemical reactions with extraordinary specificity. Computational enzyme design seeks to generate novel chemical activities by altering the target substrates of these existing enzymes. We have implemented a novel approach to redesign the specificity of an enzyme and demonstrated its effectiveness on a model system.

  1. Promoter Motifs in NCLDVs: An Evolutionary Perspective

    PubMed Central

    Oliveira, Graziele Pereira; Andrade, Ana Cláudia dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Arantes, Thalita Souza; Boratto, Paulo Victor Miranda; Silva, Ludmila Karen dos Santos; Dornas, Fábio Pio; Trindade, Giliane de Souza; Drumond, Betânia Paiva; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

    2017-01-01

    For many years, gene expression in the three cellular domains has been studied in an attempt to discover sequences associated with the regulation of the transcription process. Some specific transcriptional features were described in viruses, although few studies have been devoted to understanding the evolutionary aspects related to the spread of promoter motifs through related viral families. The discovery of giant viruses and the proposition of the new viral order Megavirales that comprise a monophyletic group, named nucleo-cytoplasmic large DNA viruses (NCLDV), raised new questions in the field. Some putative promoter sequences have already been described for some NCLDV members, bringing new insights into the evolutionary history of these complex microorganisms. In this review, we summarize the main aspects of the transcription regulation process in the three domains of life, followed by a systematic description of what is currently known about promoter regions in several NCLDVs. We also discuss how the analysis of the promoter sequences could bring new ideas about the giant viruses’ evolution. Finally, considering a possible common ancestor for the NCLDV group, we discussed possible promoters’ evolutionary scenarios and propose the term “MEGA-box” to designate an ancestor promoter motif (‘TATATAAAATTGA’) that could be evolved gradually by nucleotides’ gain and loss and point mutations. PMID:28117683

  2. Structural and functional insights into the regulation of Helicobacter pylori arginase activity by an evolutionary nonconserved motif.

    PubMed

    Srivastava, Abhishek; Meena, Shiv Kumar; Alam, Mashkoor; Nayeem, Shahid M; Deep, Shashank; Sau, Apurba Kumar

    2013-01-22

    Urea producing bimetallic arginases are essential for the synthesis of polyamine, DNA, and RNA. Despite conservation of the signature motifs in all arginases, a nonconserved ¹⁵³ESEEKAWQKLCSL¹⁶⁵ motif is found in the Helicobacter pylori enzyme, whose role is yet unknown. Using site-directed mutagenesis, kinetic assays, metal analyses, circular dichroism, heat-induced denaturation, molecular dynamics simulations and truncation studies, we report here the significance of this motif in catalytic function, metal retention, structural integrity, and stability of the protein. The enzyme did not exhibit detectable activity upon deletion of the motif as well as on individual mutation of Glu155 and Trp159 while Cys163Ala displayed significant decrease in the activity. Trp159Ala and Glu155Ala show severe loss of thermostability (14-17°) by a decrease in the α-helical structure. The role of Trp159 in stabilization of the structure with the surrounding aromatic residues is confirmed when Trp159Phe restored the structure and stability substantially compared to Trp159Ala. The simulation studies support the above results and show that the motif, which was previously solvent exposed, displays a loop-cum-small helix structure (Lys161-Cys163) and is located near the active-site through a novel Trp159-Asp126 interaction. This is consistent with the mutational analyses, where Trp159 and Asp126 are individually critical for retaining a bimetallic center and thereby for function. Furthermore, Cys163 of the helix is primarily important for dimerization, which is crucial for stimulation of the activity. Thus, these findings not only provide insights into the role of this motif but also offer a possibility to engineer it in human arginases for therapeutics against a number of carcinomas.

  3. Advanced spectral signature discrimination algorithm

    NASA Astrophysics Data System (ADS)

    Chakravarty, Sumit; Cao, Wenjie; Samat, Alim

    2013-05-01

    This paper presents a novel approach to the task of hyperspectral signature analysis. Hyperspectral signature analysis has been studied a lot in literature and there has been a lot of different algorithms developed which endeavors to discriminate between hyperspectral signatures. There are many approaches for performing the task of hyperspectral signature analysis. Binary coding approaches like SPAM and SFBC use basic statistical thresholding operations to binarize a signature which are then compared using Hamming distance. This framework has been extended to techniques like SDFC wherein a set of primate structures are used to characterize local variations in a signature together with the overall statistical measures like mean. As we see such structures harness only local variations and do not exploit any covariation of spectrally distinct parts of the signature. The approach of this research is to harvest such information by the use of a technique similar to circular convolution. In the approach we consider the signature as cyclic by appending the two ends of it. We then create two copies of the spectral signature. These three signatures can be placed next to each other like the rotating discs of a combination lock. We then find local structures at different circular shifts between the three cyclic spectral signatures. Texture features like in SDFC can be used to study the local structural variation for each circular shift. We can then create different measure by creating histogram from the shifts and thereafter using different techniques for information extraction from the histograms. Depending on the technique used different variant of the proposed algorithm are obtained. Experiments using the proposed technique show the viability of the proposed methods and their performances as compared to current binary signature coding techniques.

  4. Probabilistic models for semisupervised discriminative motif discovery in DNA sequences.

    PubMed

    Kim, Jong Kyoung; Choi, Seungjin

    2011-01-01

    Methods for discriminative motif discovery in DNA sequences identify transcription factor binding sites (TFBSs), searching only for patterns that differentiate two sets (positive and negative sets) of sequences. On one hand, discriminative methods increase the sensitivity and specificity of motif discovery, compared to generative models. On the other hand, generative models can easily exploit unlabeled sequences to better detect functional motifs when labeled training samples are limited. In this paper, we develop a hybrid generative/discriminative model which enables us to make use of unlabeled sequences in the framework of discriminative motif discovery, leading to semisupervised discriminative motif discovery. Numerical experiments on yeast ChIP-chip data for discovering DNA motifs demonstrate that the best performance is obtained between the purely-generative and the purely-discriminative and the semisupervised learning improves the performance when labeled sequences are limited.

  5. An Affinity Propagation-Based DNA Motif Discovery Algorithm.

    PubMed

    Sun, Chunxiao; Huo, Hongwei; Yu, Qiang; Guo, Haitao; Sun, Zhigang

    2015-01-01

    The planted (l, d) motif search (PMS) is one of the fundamental problems in bioinformatics, which plays an important role in locating transcription factor binding sites (TFBSs) in DNA sequences. Nowadays, identifying weak motifs and reducing the effect of local optimum are still important but challenging tasks for motif discovery. To solve the tasks, we propose a new algorithm, APMotif, which first applies the Affinity Propagation (AP) clustering in DNA sequences to produce informative and good candidate motifs and then employs Expectation Maximization (EM) refinement to obtain the optimal motifs from the candidate motifs. Experimental results both on simulated data sets and real biological data sets show that APMotif usually outperforms four other widely used algorithms in terms of high prediction accuracy.

  6. Network Motifs: Simple Building Blocks of Complex Networks

    NASA Astrophysics Data System (ADS)

    Milo, R.; Shen-Orr, S.; Itzkovitz, S.; Kashtan, N.; Chklovskii, D.; Alon, U.

    2002-10-01

    Complex networks are studied across many fields of science. To uncover their structural design principles, we defined ``network motifs,'' patterns of interconnections occurring in complex networks at numbers that are significantly higher than those in randomized networks. We found such motifs in networks from biochemistry, neurobiology, ecology, and engineering. The motifs shared by ecological food webs were distinct from the motifs shared by the genetic networks of Escherichia coli and Saccharomyces cerevisiae or from those found in the World Wide Web. Similar motifs were found in networks that perform information processing, even though they describe elements as different as biomolecules within a cell and synaptic connections between neurons in Caenorhabditis elegans. Motifs may thus define universal classes of networks. This approach may uncover the basic building blocks of most networks.

  7. Multimodal signature modeling of humans

    NASA Astrophysics Data System (ADS)

    Cathcart, J. Michael; Kocher, Brian; Prussing, Keith; Lane, Sarah; Thomas, Alan

    2010-04-01

    Georgia Tech been investigating method for the detection of covert personnel in traditionally difficult environments (e.g., urban, caves). This program focuses on a detailed phenomenological analysis of human physiology and signatures with the subsequent identification and characterization of potential observables. Both aspects are needed to support the development of personnel detection and tracking algorithms. The difficult nature of these personnel-related problems dictates a multimodal sensing approach. Human signature data of sufficient and accurate quality and quantity do not exist, thus the development of an accurate signature model for a human is needed. This model should also simulate various human activities to allow motion-based observables to be exploited. This paper will describe a multimodal signature modeling approach that incorporates human physiological aspects, thermoregulation, and dynamics into the signature calculation. This approach permits both passive and active signatures to be modeled. The focus of the current effort involved the computation of signatures in urban environments. This paper will discuss the development of a human motion model for use in simulating both electro-optical signatures and radar-based signatures. Video sequences of humans in a simulated urban environment will also be presented; results using these sequences for personnel tracking will be presented.

  8. Detecting DNA regulatory motifs by incorporating positional trendsin information content

    SciTech Connect

    Kechris, Katherina J.; van Zwet, Erik; Bickel, Peter J.; Eisen,Michael B.

    2004-05-04

    On the basis of the observation that conserved positions in transcription factor binding sites are often clustered together, we propose a simple extension to the model-based motif discovery methods. We assign position-specific prior distributions to the frequency parameters of the model, penalizing deviations from a specified conservation profile. Examples with both simulated and real data show that this extension helps discover motifs as the data become noisier or when there is a competing false motif.

  9. Gibbs motif sampling: detection of bacterial outer membrane protein repeats.

    PubMed Central

    Neuwald, A. F.; Liu, J. S.; Lawrence, C. E.

    1995-01-01

    The detection and alignment of locally conserved regions (motifs) in multiple sequences can provide insight into protein structure, function, and evolution. A new Gibbs sampling algorithm is described that detects motif-encoding regions in sequences and optimally partitions them into distinct motif models; this is illustrated using a set of immunoglobulin fold proteins. When applied to sequences sharing a single motif, the sampler can be used to classify motif regions into related submodels, as is illustrated using helix-turn-helix DNA-binding proteins. Other statistically based procedures are described for searching a database for sequences matching motifs found by the sampler. When applied to a set of 32 very distantly related bacterial integral outer membrane proteins, the sampler revealed that they share a subtle, repetitive motif. Although BLAST (Altschul SF et al., 1990, J Mol Biol 215:403-410) fails to detect significant pairwise similarity between any of the sequences, the repeats present in these outer membrane proteins, taken as a whole, are highly significant (based on a generally applicable statistical test for motifs described here). Analysis of bacterial porins with known trimeric beta-barrel structure and related proteins reveals a similar repetitive motif corresponding to alternating membrane-spanning beta-strands. These beta-strands occur on the membrane interface (as opposed to the trimeric interface) of the beta-barrel. The broad conservation and structural location of these repeats suggests that they play important functional roles. PMID:8520488

  10. Discriminative motif analysis of high-throughput dataset

    PubMed Central

    Yao, Zizhen; MacQuarrie, Kyle L.; Fong, Abraham P.; Tapscott, Stephen J.; Ruzzo, Walter L.; Gentleman, Robert C.

    2014-01-01

    Motivation: High-throughput ChIP-seq studies typically identify thousands of peaks for a single transcription factor (TF). It is common for traditional motif discovery tools to predict motifs that are statistically significant against a naïve background distribution but are of questionable biological relevance. Results: We describe a simple yet effective algorithm for discovering differential motifs between two sequence datasets that is effective in eliminating systematic biases and scalable to large datasets. Tested on 207 ENCODE ChIP-seq datasets, our method identifies correct motifs in 78% of the datasets with known motifs, demonstrating improvement in both accuracy and efficiency compared with DREME, another state-of-art discriminative motif discovery tool. More interestingly, on the remaining more challenging datasets, we identify common technical or biological factors that compromise the motif search results and use advanced features of our tool to control for these factors. We also present case studies demonstrating the ability of our method to detect single base pair differences in DNA specificity of two similar TFs. Lastly, we demonstrate discovery of key TF motifs involved in tissue specification by examination of high-throughput DNase accessibility data. Availability: The motifRG package is publically available via the bioconductor repository. Contact: yzizhen@fhcrc.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24162561

  11. An RNA motif that binds ATP

    NASA Technical Reports Server (NTRS)

    Sassanfar, M.; Szostak, J. W.

    1993-01-01

    RNAs that contain specific high-affinity binding sites for small molecule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecules. Here we describe a new in vitro selection procedure designed to ensure the isolation of RNAs that bind the ligand of interest in solution as well as on a solid support. We have used this method to isolate a remarkably small RNA motif that binds ATP, a substrate in numerous biological reactions and the universal biological high-energy intermediate. The selected ATP-binding RNAs contain a consensus sequence, embedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is characterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.

  12. Complex lasso: new entangled motifs in proteins

    NASA Astrophysics Data System (ADS)

    Niemyska, Wanda; Dabrowski-Tumanski, Pawel; Kadlof, Michal; Haglund, Ellinor; Sułkowski, Piotr; Sulkowska, Joanna I.

    2016-11-01

    We identify new entangled motifs in proteins that we call complex lassos. Lassos arise in proteins with disulfide bridges (or in proteins with amide linkages), when termini of a protein backbone pierce through an auxiliary surface of minimal area, spanned on a covalent loop. We find that as much as 18% of all proteins with disulfide bridges in a non-redundant subset of PDB form complex lassos, and classify them into six distinct geometric classes, one of which resembles supercoiling known from DNA. Based on biological classification of proteins we find that lassos are much more common in viruses, plants and fungi than in other kingdoms of life. We also discuss how changes in the oxidation/reduction potential may affect the function of proteins with lassos. Lassos and associated surfaces of minimal area provide new, interesting and possessing many potential applications geometric characteristics not only of proteins, but also of other biomolecules.

  13. Complex lasso: new entangled motifs in proteins

    PubMed Central

    Niemyska, Wanda; Dabrowski-Tumanski, Pawel; Kadlof, Michal; Haglund, Ellinor; Sułkowski, Piotr; Sulkowska, Joanna I.

    2016-01-01

    We identify new entangled motifs in proteins that we call complex lassos. Lassos arise in proteins with disulfide bridges (or in proteins with amide linkages), when termini of a protein backbone pierce through an auxiliary surface of minimal area, spanned on a covalent loop. We find that as much as 18% of all proteins with disulfide bridges in a non-redundant subset of PDB form complex lassos, and classify them into six distinct geometric classes, one of which resembles supercoiling known from DNA. Based on biological classification of proteins we find that lassos are much more common in viruses, plants and fungi than in other kingdoms of life. We also discuss how changes in the oxidation/reduction potential may affect the function of proteins with lassos. Lassos and associated surfaces of minimal area provide new, interesting and possessing many potential applications geometric characteristics not only of proteins, but also of other biomolecules. PMID:27874096

  14. Signature CERN-URSS

    ScienceCinema

    None

    2016-07-12

    Le DG W.Jentschke souhaite la bienvenue à l'assemblée et aux invités pour la signature du protocole entre le Cern et l'URSS qui est un événement important. C'est en 1955 que 55 visiteurs soviétiques ont visité le Cern pour la première fois. Le premier DG au Cern, F.Bloch, et Mons.Amaldi sont aussi présents. Tandis que le discours anglais de W.Jentschke est traduit en russe, le discours russe de Mons.Morozov est traduit en anglais.

  15. Signatures of aging revisited

    SciTech Connect

    Drell, S.; Jeanloz, R.; Cornwall, J.; Dyson, F.; Eardley, D.

    1998-03-18

    This study is a follow-on to the review made by JASON during its 1997 Summer Study of what is known about the aging of critical constituents, particularly the high explosives, metals (Pu, U), and polymers in the enduring stockpile. The JASON report (JSR-97-320) that summarized the findings was based on briefings by the three weapons labs (LANL, LLNL, SNL). They presented excellent technical analyses covering a broad range of scientific and engineering problems pertaining to determining signatures of aging. But the report also noted: `Missing, however, from the briefings and the written documents made available to us by the labs and DOE, was evidence of an adequately sharp focus and high priorities on a number of essential near-term needs of maintaining weapons in the stockpile.

  16. Landsat Signature Development Program

    NASA Technical Reports Server (NTRS)

    Hall, R. N.; Mcguire, K. G.; Bland, R. A.

    1976-01-01

    The Landsat Signature Development Program, LSDP, is designed to produce an unsupervised classification of a scene from a Landsat tape. This classification is based on the clustering tendencies of the multispectral scanner data processed from the scene. The program will generate a character map that, by identifying each of the general classes of surface features extracted from the scene data with a specific line printer symbol, indicates the approximate locations and distributions of these general classes within the scene. Also provided with the character map are a number of tables each of which describes either some aspect of the spectral properties of the resultant classes, some inter-class relationship, the incidence of picture elements assigned to the various classes in the character map classification of the scene, or some significant intermediate stage in the development of the final classes.

  17. Multisensors signature prediction workbench

    NASA Astrophysics Data System (ADS)

    Latger, Jean; Cathala, Thierry

    2015-10-01

    Guidance of weapon systems relies on sensors to analyze targets signature. Defense weapon systems also need to detect then identify threats also using sensors. The sensors performance is very dependent on conditions e.g. time of day, atmospheric propagation, background ... Visible camera are very efficient for diurnal fine weather conditions, long wave infrared sensors for night vision, radar systems very efficient for seeing through atmosphere and/or foliage ... Besides, multi sensors systems, combining several collocated sensors with associated algorithms of fusion, provide better efficiency (typically for Enhanced Vision Systems). But these sophisticated systems are all the more difficult to conceive, assess and qualify. In that frame, multi sensors simulation is highly required. This paper focuses on multi sensors simulation tools. A first part makes a state of the Art of such simulation workbenches with a special focus on SE-Workbench. SEWorkbench is described with regards to infrared/EO sensors, millimeter waves sensors, active EO sensors and GNSS sensors. Then a general overview of simulation of targets and backgrounds signature objectives is presented, depending on the type of simulation required (parametric studies, open loop simulation, closed loop simulation, hybridization of SW simulation and HW ...). After the objective review, the paper presents some basic requirements for simulation implementation such as the deterministic behavior of simulation, mandatory to repeat it many times for parametric studies... Several technical topics are then discussed, such as the rendering technique (ray tracing vs. rasterization), the implementation (CPU vs. GP GPU) and the tradeoff between physical accuracy and performance of computation. Examples of results using SE-Workbench are showed and commented.

  18. Signatures of dark matter

    NASA Astrophysics Data System (ADS)

    Baltz, Edward Anthony

    It is well known that most of the mass in the universe remains unobserved save for its gravitational effect on luminous matter. The nature of this ``dark matter'' remains a mystery. From measurements of the primordial deuterium abundance, the theory of big bang nucleosynthesis predicts that there are not enough baryons to account for the amount of dark matter observed, thus the missing mass must take an exotic form. Several promising candidates have been proposed. In this work I will describe my research along two main lines of inquiry into the dark matter puzzle. The first possibility is that the dark matter is exotic massive particles, such as those predicted by supersymmetric extensions to the standard model of particle physics. Such particles are generically called WIMPs, for weakly interacting massive particles. Focusing on the so-called neutralino in supersymmetric models, I discuss the possible signatures of such particles, including their direct detection via nuclear recoil experiments and their indirect detection via annihilations in the halos of galaxies, producing high energy antiprotons, positrons and gamma rays. I also discuss signatures of the possible slow decays of such particles. The second possibility is that there is a population of black holes formed in the early universe. Any dark objects in galactic halos, black holes included, are called MACHOs, for massive compact halo objects. Such objects can be detected by their gravitational microlensing effects. Several possibilities for sources of baryonic dark matter are also interesting for gravitational microlensing. These include brown dwarf stars and old, cool white dwarf stars. I discuss the theory of gravitational microlensing, focusing on the technique of pixel microlensing. I make predictions for several planned microlensing experiments with ground based and space based telescopes. Furthermore, I discuss binary lenses in the context of pixel microlensing. Finally, I develop a new technique for

  19. Signatures of AGN feedback

    NASA Astrophysics Data System (ADS)

    Wylezalek, D.; Zakamska, N.

    2016-06-01

    Feedback from active galactic nuclei (AGN) is widely considered to be the main driver in regulating the growth of massive galaxies. It operates by either heating or driving the gas that would otherwise be available for star formation out of the galaxy, preventing further increase in stellar mass. Observational proof for this scenario has, however, been hard to come by. We have assembled a large sample of 133 radio-quiet type-2 and red AGN at 0.1signatures are hosted in galaxies that are more `quenched' considering their stellar mass than galaxies with weaker outflow signatures. This correlation is only seen in AGN host galaxies with SFR >100 M_{⊙} yr^{-1} where presumably the coupling of the AGN-driven wind to the gas is strongest. This observation is consistent with the AGN having a net suppression, or `negative' impact, through feedback on the galaxies' star formation history.

  20. Motif-role-fingerprints: the building-blocks of motifs, clustering-coefficients and transitivities in directed networks.

    PubMed

    McDonnell, Mark D; Yaveroğlu, Ömer Nebil; Schmerl, Brett A; Iannella, Nicolangelo; Ward, Lawrence M

    2014-01-01

    Complex networks are frequently characterized by metrics for which particular subgraphs are counted. One statistic from this category, which we refer to as motif-role fingerprints, differs from global subgraph counts in that the number of subgraphs in which each node participates is counted. As with global subgraph counts, it can be important to distinguish between motif-role fingerprints that are 'structural' (induced subgraphs) and 'functional' (partial subgraphs). Here we show mathematically that a vector of all functional motif-role fingerprints can readily be obtained from an arbitrary directed adjacency matrix, and then converted to structural motif-role fingerprints by multiplying that vector by a specific invertible conversion matrix. This result demonstrates that a unique structural motif-role fingerprint exists for any given functional motif-role fingerprint. We demonstrate a similar result for the cases of functional and structural motif-fingerprints without node roles, and global subgraph counts that form the basis of standard motif analysis. We also explicitly highlight that motif-role fingerprints are elemental to several popular metrics for quantifying the subgraph structure of directed complex networks, including motif distributions, directed clustering coefficient, and transitivity. The relationships between each of these metrics and motif-role fingerprints also suggest new subtypes of directed clustering coefficients and transitivities. Our results have potential utility in analyzing directed synaptic networks constructed from neuronal connectome data, such as in terms of centrality. Other potential applications include anomaly detection in networks, identification of similar networks and identification of similar nodes within networks. Matlab code for calculating all stated metrics following calculation of functional motif-role fingerprints is provided as S1 Matlab File.

  1. Motif-Role-Fingerprints: The Building-Blocks of Motifs, Clustering-Coefficients and Transitivities in Directed Networks

    PubMed Central

    McDonnell, Mark D.; Yaveroğlu, Ömer Nebil; Schmerl, Brett A.; Iannella, Nicolangelo; Ward, Lawrence M.

    2014-01-01

    Complex networks are frequently characterized by metrics for which particular subgraphs are counted. One statistic from this category, which we refer to as motif-role fingerprints, differs from global subgraph counts in that the number of subgraphs in which each node participates is counted. As with global subgraph counts, it can be important to distinguish between motif-role fingerprints that are ‘structural’ (induced subgraphs) and ‘functional’ (partial subgraphs). Here we show mathematically that a vector of all functional motif-role fingerprints can readily be obtained from an arbitrary directed adjacency matrix, and then converted to structural motif-role fingerprints by multiplying that vector by a specific invertible conversion matrix. This result demonstrates that a unique structural motif-role fingerprint exists for any given functional motif-role fingerprint. We demonstrate a similar result for the cases of functional and structural motif-fingerprints without node roles, and global subgraph counts that form the basis of standard motif analysis. We also explicitly highlight that motif-role fingerprints are elemental to several popular metrics for quantifying the subgraph structure of directed complex networks, including motif distributions, directed clustering coefficient, and transitivity. The relationships between each of these metrics and motif-role fingerprints also suggest new subtypes of directed clustering coefficients and transitivities. Our results have potential utility in analyzing directed synaptic networks constructed from neuronal connectome data, such as in terms of centrality. Other potential applications include anomaly detection in networks, identification of similar networks and identification of similar nodes within networks. Matlab code for calculating all stated metrics following calculation of functional motif-role fingerprints is provided as S1 Matlab File. PMID:25486535

  2. Index of Spectrum Signature Data

    DTIC Science & Technology

    1985-05-01

    Frederick Research Corporation. Alexandria. VA 163 AN/APG-030 Radar Receiver Heasureaents Electromagnetic Coapatibilitv Analysis Center, US Navv Marine ... Electromagnetic Compatibility Characteristics of the W 86 Gun Fire Control Svstem. Naval HEapons Lab, Dahlgren, VA 501 Partial Spectrum Signature...ECAC-I-IO-(SS) DEPARTMENT OF DEFENSE Electromagnetic Compatibility Analysis Center Annapolis, Maryland 21402 INDEX OF SPECTRUM SIGNATURE DATA

  3. Cell short circuit, preshort signature

    NASA Technical Reports Server (NTRS)

    Lurie, C.

    1980-01-01

    Short-circuit events observed in ground test simulations of DSCS-3 battery in-orbit operations are analyzed. Voltage signatures appearing in the data preceding the short-circuit event are evaluated. The ground test simulation is briefly described along with performance during reconditioning discharges. Results suggest that a characteristic signature develops prior to a shorting event.

  4. Immunity related genes in dipterans share common enrichment of AT-rich motifs in their 5' regulatory regions that are potentially involved in nucleosome formation

    PubMed Central

    Hernandez-Romano, Jesus; Carlos-Rivera, Francisco J; Salgado, Heladia; Lamadrid-Figueroa, Hector; Valverde-Garduño, Veronica; Rodriguez, Mario H; Martinez-Barnetche, Jesus

    2008-01-01

    Background Understanding the transcriptional regulation mechanisms in response to environmental challenges is of fundamental importance in biology. Transcription factors associated to response elements and the chromatin structure had proven to play important roles in gene expression regulation. We have analyzed promoter regions of dipteran genes induced in response to immune challenge, in search for particular sequence patterns involved in their transcriptional regulation. Results 5' upstream regions of D. melanogaster and A. gambiae immunity-induced genes and their corresponding orthologous genes in 11 non-melanogaster drosophilid species and Ae. aegypti share enrichment in AT-rich short motifs. AT-rich motifs are associated with nucleosome formation as predicted by two different algorithms. In A. gambiae and D. melanogaster, many immunity genes 5' upstream sequences also showed NFκB response elements, located within 500 bp from the transcription start site. In A. gambiae, the frequency of ATAA motif near the NFκB response elements was increased, suggesting a functional link between nucleosome formation/remodelling and NFκB regulation of transcription. Conclusion AT-rich motif enrichment in 5' upstream sequences in A. gambiae, Ae. aegypti and the Drosophila genus immunity genes suggests a particular pattern of nucleosome formation/chromatin organization. The co-occurrence of such motifs with the NFκB response elements suggests that these sequence signatures may be functionally involved in transcriptional activation during dipteran immune response. AT-rich motif enrichment in regulatory regions in this group of co-regulated genes could represent an evolutionary constrained signature in dipterans and perhaps other distantly species. PMID:18613977

  5. MADMX: a strategy for maximal dense motif extraction.

    PubMed

    Grossi, Roberto; Pietracaprina, Andrea; Pisanti, Nadia; Pucci, Geppino; Upfal, Eli; Vandin, Fabio

    2011-04-01

    We develop, analyze, and experiment with a new tool, called MADMX, which extracts frequent motifs from biological sequences. We introduce the notion of density to single out the "significant" motifs. The density is a simple and flexible measure for bounding the number of don't cares in a motif, defined as the fraction of solid (i.e., different from don't care) characters in the motif. A maximal dense motif has density above a certain threshold, and any further specialization of a don't care symbol in it or any extension of its boundaries decreases its number of occurrences in the input sequence. By extracting only maximal dense motifs, MADMX reduces the output size and improves performance, while enhancing the quality of the discoveries. The efficiency of our approach relies on a newly defined combining operation, dubbed fusion, which allows for the construction of maximal dense motifs in a bottom-up fashion, while avoiding the generation of nonmaximal ones. We provide experimental evidence of the efficiency and the quality of the motifs returned by MADMX.

  6. DETAIL VIEW, MAIN ENTRANCE GATES, SHOWING A WINGED HOURGLASS MOTIF, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW, MAIN ENTRANCE GATES, SHOWING A WINGED HOURGLASS MOTIF, WHICH REFERS TO THE QUICK PASSAGE OF TIME AND THE SHORTNESS OF HUMAN LIFE. USE OF THIS MOTIF WAS A CARRYOVER FROM THE MCARTHUR GATES. - Woodlands Cemetery, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  7. Dynamic motifs of strategies in prisoner's dilemma games

    NASA Astrophysics Data System (ADS)

    Kim, Young Jin; Roh, Myungkyoon; Jeong, Seon-Young; Son, Seung-Woo

    2014-12-01

    We investigate the win-lose relations between strategies of iterated prisoner's dilemma games by using a directed network concept to display the replicator dynamics results. In the giant strongly-connected component of the win/lose network, we find win-lose circulations similar to rock-paper-scissors and analyze the fixed point and its stability. Applying the network motif concept, we introduce dynamic motifs, which describe the population dynamics relations among the three strategies. Through exact enumeration, we find 22 dynamic motifs and display their phase portraits. Visualization using directed networks and motif analysis is a useful method to make complex dynamic behavior simple in order to understand it more intuitively. Dynamic motifs can be building blocks for dynamic behavior among strategies when they are applied to other types of games.

  8. Different sequence signatures in the upstream regions of plant and animal tRNA genes shape distinct modes of regulation.

    PubMed

    Zhang, Gong; Lukoszek, Radoslaw; Mueller-Roeber, Bernd; Ignatova, Zoya

    2011-04-01

    In eukaryotes, the transcription of tRNA genes is initiated by the concerted action of transcription factors IIIC (TFIIIC) and IIIB (TFIIIB) which direct the recruitment of polymerase III. While TFIIIC recognizes highly conserved, intragenic promoter elements, TFIIIB binds to the non-coding 5'-upstream regions of the tRNA genes. Using a systematic bioinformatic analysis of 11 multicellular eukaryotic genomes we identified a highly conserved TATA motif followed by a CAA-motif in the tRNA upstream regions of all plant genomes. Strikingly, the 5'-flanking tRNA regions of the animal genomes are highly heterogeneous and lack a common conserved sequence signature. Interestingly, in the animal genomes the tRNA species that read the same codon share conserved motifs in their upstream regions. Deep-sequencing analysis of 16 human tissues revealed multiple splicing variants of two of the TFIIIB subunits, Bdp1 and Brf1, with tissue-specific expression patterns. These multiple forms most likely modulate the TFIIIB-DNA interactions and explain the lack of a uniform signature motif in the tRNA upstream regions of animal genomes. The anticodon-dependent 5'-flanking motifs provide a possible mechanism for independent regulation of the tRNA transcription in various human tissues.

  9. Comparative Whole-Genome Mapping To Determine Staphylococcus aureus Genome Size, Virulence Motifs, and Clonality

    PubMed Central

    Pantrang, Madhulatha; Stahl, Buffy; Briska, Adam M.; Stemper, Mary E.; Wagner, Trevor K.; Zentz, Emily B.; Callister, Steven M.; Lovrich, Steven D.; Henkhaus, John K.; Dykes, Colin W.

    2012-01-01

    Despite being a clonal pathogen, Staphylococcus aureus continues to acquire virulence and antibiotic-resistant genes located on mobile genetic elements such as genomic islands, prophages, pathogenicity islands, and the staphylococcal chromosomal cassette mec (SCCmec) by horizontal gene transfer from other staphylococci. The potential virulence of a S. aureus strain is often determined by comparing its pulsed-field gel electrophoresis (PFGE) or multilocus sequence typing profiles to that of known epidemic or virulent clones and by PCR of the toxin genes. Whole-genome mapping (formerly optical mapping), which is a high-resolution ordered restriction mapping of a bacterial genome, is a relatively new genomic tool that allows comparative analysis across entire bacterial genomes to identify regions of genomic similarities and dissimilarities, including small and large insertions and deletions. We explored whether whole-genome maps (WGMs) of methicillin-resistant S. aureus (MRSA) could be used to predict the presence of methicillin resistance, SCCmec type, and Panton-Valentine leukocidin (PVL)-producing genes on an S. aureus genome. We determined the WGMs of 47 diverse clinical isolates of S. aureus, including well-characterized reference MRSA strains, and annotated the signature restriction pattern in SCCmec types, arginine catabolic mobile element (ACME), and PVL-carrying prophage, PhiSa2 or PhiSa2-like regions on the genome. WGMs of these isolates accurately characterized them as MRSA or methicillin-sensitive S. aureus based on the presence or absence of the SCCmec motif, ACME and the unique signature pattern for the prophage insertion that harbored the PVL genes. Susceptibility to methicillin resistance and the presence of mecA, SCCmec types, and PVL genes were confirmed by PCR. A WGM clustering approach was further able to discriminate isolates within the same PFGE clonal group. These results showed that WGMs could be used not only to genotype S. aureus but also to

  10. Signatures of AGN feedback

    NASA Astrophysics Data System (ADS)

    Wylezalek, Dominika; Zakamska, Nadia L.; MaNGA-GMOS Team

    2017-01-01

    Feedback from actively accreting SMBHs (Active Galactic Nuclei, AGN) is now widely considered to be the main driver in regulating the growth of massive galaxies. Observational proof for this scenario has, however, been hard to come by. Many attempts at finding a conclusive observational proof that AGN may be able to quench star formation and regulate the host galaxies' growth have shown that this problem is highly complex.I will present results from several projects that focus on understanding the power, reach and impact of feedback processes exerted by AGN. I will describe recent efforts in our group of relating feedback signatures to the specific star formation rate in their host galaxies, where our results are consistent with the AGN having a `negative' impact through feedback on the galaxies' star formation history (Wylezalek+2016a,b). Furthermore, I will show that powerful AGN-driven winds can be easily hidden and not be apparent in the integrated spectrum of the galaxy. This implies that large IFU surveys, such as the SDSS-IV MaNGA survey, might uncover many previously unknown AGN and outflows that are potentially very relevant for understanding the role of AGN in galaxy evolution (Wylezalek+2016c)!

  11. Statistical clumped isotope signatures

    PubMed Central

    Röckmann, T.; Popa, M. E.; Krol, M. C.; Hofmann, M. E. G.

    2016-01-01

    High precision measurements of molecules containing more than one heavy isotope may provide novel constraints on element cycles in nature. These so-called clumped isotope signatures are reported relative to the random (stochastic) distribution of heavy isotopes over all available isotopocules of a molecule, which is the conventional reference. When multiple indistinguishable atoms of the same element are present in a molecule, this reference is calculated from the bulk (≈average) isotopic composition of the involved atoms. We show here that this referencing convention leads to apparent negative clumped isotope anomalies (anti-clumping) when the indistinguishable atoms originate from isotopically different populations. Such statistical clumped isotope anomalies must occur in any system where two or more indistinguishable atoms of the same element, but with different isotopic composition, combine in a molecule. The size of the anti-clumping signal is closely related to the difference of the initial isotope ratios of the indistinguishable atoms that have combined. Therefore, a measured statistical clumped isotope anomaly, relative to an expected (e.g. thermodynamical) clumped isotope composition, may allow assessment of the heterogeneity of the isotopic pools of atoms that are the substrate for formation of molecules. PMID:27535168

  12. De Novo Regulatory Motif Discovery Identifies Significant Motifs in Promoters of Five Classes of Plant Dehydrin Genes

    PubMed Central

    Zolotarov, Yevgen; Strömvik, Martina

    2015-01-01

    Plants accumulate dehydrins in response to osmotic stresses. Dehydrins are divided into five different classes, which are thought to be regulated in different manners. To better understand differences in transcriptional regulation of the five dehydrin classes, de novo motif discovery was performed on 350 dehydrin promoter sequences from a total of 51 plant genomes. Overrepresented motifs were identified in the promoters of five dehydrin classes. The Kn dehydrin promoters contain motifs linked with meristem specific expression, as well as motifs linked with cold/dehydration and abscisic acid response. KS dehydrin promoters contain a motif with a GATA core. SKn and YnSKn dehydrin promoters contain motifs that match elements connected with cold/dehydration, abscisic acid and light response. YnKn dehydrin promoters contain motifs that match abscisic acid and light response elements, but not cold/dehydration response elements. Conserved promoter motifs are present in the dehydrin classes and across different plant lineages, indicating that dehydrin gene regulation is likely also conserved. PMID:26114291

  13. A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain

    PubMed Central

    Wong, Szu S.; Østergaard, Søren; Hall, Gareth; Li, Chan; Williams, Philip M.; Stennicke, Henning

    2016-01-01

    Factor XI (FXI) is the zymogen of FXIa, which cleaves FIX in the intrinsic pathway of coagulation. FXI is known to exist as a dimer and interacts with multiple proteins via its 4 apple domains in the “saucer section” of the enzyme; however, to date, no complex crystal structure has been described. To investigate protein interactions of FXI, a large random peptide library consisting of 106 to 107 peptides was screened for FXI binding, which identified a series of FXI binding motifs containing the signature Asp-Phe-Pro (DFP) tripeptide. Motifs containing this core tripeptide were found in diverse proteins, including the known ligand high-molecular-weight kininogen (HK), as well as the extracellular matrix proteins laminin and collagen V. To define the binding site on FXI, we determined the crystal structure of FXI in complex with the HK-derived peptide NPISDFPDT. This revealed the location of the DFP peptide bound to the FXI apple 2 domain, and central to the interaction, the DFP phenylalanine side-chain inserts into a major hydrophobic pocket in the apple 2 domain and the isoleucine occupies a flanking minor pocket. Two further structures of FXI in complex with the laminin-derived peptide EFPDFP and a DFP peptide from the random screen demonstrated binding in the same pocket, although in a slightly different conformation, thus revealing some flexibility in the molecular interactions of the FXI apple 2 domain. PMID:27006387

  14. Single promoters as regulatory network motifs

    NASA Astrophysics Data System (ADS)

    Zopf, Christopher; Maheshri, Narendra

    2012-02-01

    At eukaryotic promoters, chromatin can influence the relationship between a gene's expression and transcription factor (TF) activity. This additional complexity might allow single promoters to exhibit dynamical behavior commonly attributed to regulatory motifs involving multiple genes. We investigate the role of promoter chromatin architecture in the kinetics of gene activation using a previously described set of promoter variants based on the phosphate-regulated PHO5 promoter in S. cerevisiae. Accurate quantitative measurement of transcription activation kinetics is facilitated by a controllable and observable TF input to a promoter of interest leading to an observable expression output in single cells. We find the particular architecture of these promoters can result in a significant delay in activation, filtering of noisy TF signals, and a memory of previous activation -- dynamical behaviors reminiscent of a feed-forward loop but only requiring a single promoter. We suggest this is a consequence of chromatin transactions at the promoter, likely passing through a long-lived ``primed'' state between its inactive and competent states. Finally, we show our experimental setup can be generalized as a ``gene oscilloscope'' to probe the kinetics of heterologous promoter architectures.

  15. Intrusion detection using secure signatures

    DOEpatents

    Nelson, Trent Darnel; Haile, Jedediah

    2014-09-30

    A method and device for intrusion detection using secure signatures comprising capturing network data. A search hash value, value employing at least one one-way function, is generated from the captured network data using a first hash function. The presence of a search hash value match in a secure signature table comprising search hash values and an encrypted rule is determined. After determining a search hash value match, a decryption key is generated from the captured network data using a second hash function, a hash function different form the first hash function. One or more of the encrypted rules of the secure signatures table having a hash value equal to the generated search hash value are then decrypted using the generated decryption key. The one or more decrypted secure signature rules are then processed for a match and one or more user notifications are deployed if a match is identified.

  16. Retail applications of signature verification

    NASA Astrophysics Data System (ADS)

    Zimmerman, Thomas G.; Russell, Gregory F.; Heilper, Andre; Smith, Barton A.; Hu, Jianying; Markman, Dmitry; Graham, Jon E.; Drews, Clemens

    2004-08-01

    The dramatic rise in identity theft, the ever pressing need to provide convenience in checkout services to attract and retain loyal customers, and the growing use of multi-function signature captures devices in the retail sector provides favorable conditions for the deployment of dynamic signature verification (DSV) in retail settings. We report on the development of a DSV system to meet the needs of the retail sector. We currently have a database of approximately 10,000 signatures collected from 600 subjects and forgers. Previous work at IBM on DSV has been merged and extended to achieve robust performance on pen position data available from commercial point of sale hardware, achieving equal error rates on skilled forgeries and authentic signatures of 1.5% to 4%.

  17. Triadic motifs in the dependence networks of virtual societies.

    PubMed

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-06-10

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.

  18. Triadic motifs in the dependence networks of virtual societies

    PubMed Central

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-01-01

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs. PMID:24912755

  19. Ballastic signature identification systems study

    NASA Technical Reports Server (NTRS)

    Reich, A.; Hine, T. L.

    1976-01-01

    The results are described of an attempt to establish a uniform procedure for documenting (recording) expended bullet signatures as effortlessly as possible and to build a comprehensive library of these signatures in a form that will permit the automated comparison of a new suspect bullet with the prestored library. The ultimate objective is to achieve a standardized format that will permit nationwide interaction between police departments, crime laboratories, and other interested law enforcement agencies.

  20. The TRTGn motif stabilizes the transcription initiation open complex.

    PubMed

    Voskuil, Martin I; Chambliss, Glenn H

    2002-09-20

    The effect on transcription initiation by the extended -10 motif (5'-TRTG(n)-3'), positioned upstream of the -10 region, was investigated using a series of base substitution mutations in the alpha-amylase promoter (amyP). The extended -10 motif, previously referred to as the -16 region, is found frequently in Gram-positive bacterial promoters and several extended -10 promoters from Escherichia coli. The inhibitory effects of the non-productive promoter site (amyP2), which overlaps the upstream region of amyP, were eliminated by mutagenesis of the -35 region and the TRTG motif of amyP2. Removal by mutagenesis of the competitive effects of amyP2 resulted in a reduced dependence of amyP on the TRTG motif. In the absence of the second promoter, mutations in the TRTG motif of amyP destabilized the open complex and prevented the maintenance of open complexes at low temperatures. The open complex half-life was up to 26-fold shorter in the mutant TRTG motif promoters than in the wild-type promoter. We demonstrate that the amyP TRTG motif dramatically stabilizes the open complex intermediate during transcription initiation. Even though the open complex is less stable in the mutant promoters, the region of melted DNA is the same in the wild-type and mutant promoters. However, upon addition of the first three nucleotides, which trap RNAP (RNA polymerase) in a stable initiating complex, the melted DNA region contracts at the 5'-end in a TRTG motif promoter mutant but not at the wild-type promoter, indicating that the motif contributes to maintaining DNA-strand separation.

  1. Automated motif extraction and classification in RNA tertiary structures

    PubMed Central

    Djelloul, Mahassine; Denise, Alain

    2008-01-01

    We used a novel graph-based approach to extract RNA tertiary motifs. We cataloged them all and clustered them using an innovative graph similarity measure. We applied our method to three widely studied structures: Haloarcula marismortui 50S (H.m 50S), Escherichia coli 50S (E. coli 50S), and Thermus thermophilus 16S (T.th 16S) RNAs. We identified 10 known motifs without any prior knowledge of their shapes or positions. We additionally identified four putative new motifs. PMID:18957493

  2. Coherent feedforward transcriptional regulatory motifs enhance drug resistance

    NASA Astrophysics Data System (ADS)

    Charlebois, Daniel A.; Balázsi, Gábor; Kærn, Mads

    2014-05-01

    Fluctuations in gene expression give identical cells access to a spectrum of phenotypes that can serve as a transient, nongenetic basis for natural selection by temporarily increasing drug resistance. In this study, we demonstrate using mathematical modeling and simulation that certain gene regulatory network motifs, specifically coherent feedforward loop motifs, can facilitate the development of nongenetic resistance by increasing cell-to-cell variability and the time scale at which beneficial phenotypic states can be maintained. Our results highlight how regulatory network motifs enabling transient, nongenetic inheritance play an important role in defining reproductive fitness in adverse environments and provide a selective advantage subject to evolutionary pressure.

  3. Seeing the B-A-C-H motif

    NASA Astrophysics Data System (ADS)

    Catravas, Palmyra

    2005-09-01

    Musical compositions can be thought of as complex, multidimensional data sets. Compositions based on the B-A-C-H motif (a four-note motif of the pitches of the last name of Johann Sebastian Bach) span several centuries of evolving compositional styles and provide an intriguing set for analysis since they contain a common feature, the motif, buried in dissimilar contexts. We will present analyses which highlight the content of this unusual set of pieces, with emphasis on visual display of information.

  4. Targeting functional motifs of a protein family

    NASA Astrophysics Data System (ADS)

    Bhadola, Pradeep; Deo, Nivedita

    2016-10-01

    The structural organization of a protein family is investigated by devising a method based on the random matrix theory (RMT), which uses the physiochemical properties of the amino acid with multiple sequence alignment. A graphical method to represent protein sequences using physiochemical properties is devised that gives a fast, easy, and informative way of comparing the evolutionary distances between protein sequences. A correlation matrix associated with each property is calculated, where the noise reduction and information filtering is done using RMT involving an ensemble of Wishart matrices. The analysis of the eigenvalue statistics of the correlation matrix for the β -lactamase family shows the universal features as observed in the Gaussian orthogonal ensemble (GOE). The property-based approach captures the short- as well as the long-range correlation (approximately following GOE) between the eigenvalues, whereas the previous approach (treating amino acids as characters) gives the usual short-range correlations, while the long-range correlations are the same as that of an uncorrelated series. The distribution of the eigenvector components for the eigenvalues outside the bulk (RMT bound) deviates significantly from RMT observations and contains important information about the system. The information content of each eigenvector of the correlation matrix is quantified by introducing an entropic estimate, which shows that for the β -lactamase family the smallest eigenvectors (low eigenmodes) are highly localized as well as informative. These small eigenvectors when processed gives clusters involving positions that have well-defined biological and structural importance matching with experiments. The approach is crucial for the recognition of structural motifs as shown in β -lactamase (and other families) and selectively identifies the important positions for targets to deactivate (activate) the enzymatic actions.

  5. Targeting functional motifs of a protein family.

    PubMed

    Bhadola, Pradeep; Deo, Nivedita

    2016-10-01

    The structural organization of a protein family is investigated by devising a method based on the random matrix theory (RMT), which uses the physiochemical properties of the amino acid with multiple sequence alignment. A graphical method to represent protein sequences using physiochemical properties is devised that gives a fast, easy, and informative way of comparing the evolutionary distances between protein sequences. A correlation matrix associated with each property is calculated, where the noise reduction and information filtering is done using RMT involving an ensemble of Wishart matrices. The analysis of the eigenvalue statistics of the correlation matrix for the β-lactamase family shows the universal features as observed in the Gaussian orthogonal ensemble (GOE). The property-based approach captures the short- as well as the long-range correlation (approximately following GOE) between the eigenvalues, whereas the previous approach (treating amino acids as characters) gives the usual short-range correlations, while the long-range correlations are the same as that of an uncorrelated series. The distribution of the eigenvector components for the eigenvalues outside the bulk (RMT bound) deviates significantly from RMT observations and contains important information about the system. The information content of each eigenvector of the correlation matrix is quantified by introducing an entropic estimate, which shows that for the β-lactamase family the smallest eigenvectors (low eigenmodes) are highly localized as well as informative. These small eigenvectors when processed gives clusters involving positions that have well-defined biological and structural importance matching with experiments. The approach is crucial for the recognition of structural motifs as shown in β-lactamase (and other families) and selectively identifies the important positions for targets to deactivate (activate) the enzymatic actions.

  6. Quantum messages with signatures forgeable in arbitrated quantum signature schemes

    NASA Astrophysics Data System (ADS)

    Kim, Taewan; Choi, Jeong Woon; Jho, Nam-Su; Lee, Soojoon

    2015-02-01

    Even though a method to perfectly sign quantum messages has not been known, the arbitrated quantum signature scheme has been considered as one of the good candidates. However, its forgery problem has been an obstacle to the scheme becoming a successful method. In this paper, we consider one situation, which is slightly different from the forgery problem, that we use to check whether at least one quantum message with signature can be forged in a given scheme, although all the messages cannot be forged. If there are only a finite number of forgeable quantum messages in the scheme, then the scheme can be secured against the forgery attack by not sending forgeable quantum messages, and so our situation does not directly imply that we check whether the scheme is secure against the attack. However, if users run a given scheme without any consideration of forgeable quantum messages, then a sender might transmit such forgeable messages to a receiver and in such a case an attacker can forge the messages if the attacker knows them. Thus it is important and necessary to look into forgeable quantum messages. We show here that there always exists such a forgeable quantum message-signature pair for every known scheme with quantum encryption and rotation, and numerically show that there are no forgeable quantum message-signature pairs that exist in an arbitrated quantum signature scheme.

  7. Simulating realistic predator signatures in quantitative fatty acid signature analysis

    USGS Publications Warehouse

    Bromaghin, Jeffrey F.

    2015-01-01

    Diet estimation is an important field within quantitative ecology, providing critical insights into many aspects of ecology and community dynamics. Quantitative fatty acid signature analysis (QFASA) is a prominent method of diet estimation, particularly for marine mammal and bird species. Investigators using QFASA commonly use computer simulation to evaluate statistical characteristics of diet estimators for the populations they study. Similar computer simulations have been used to explore and compare the performance of different variations of the original QFASA diet estimator. In both cases, computer simulations involve bootstrap sampling prey signature data to construct pseudo-predator signatures with known properties. However, bootstrap sample sizes have been selected arbitrarily and pseudo-predator signatures therefore may not have realistic properties. I develop an algorithm to objectively establish bootstrap sample sizes that generates pseudo-predator signatures with realistic properties, thereby enhancing the utility of computer simulation for assessing QFASA estimator performance. The algorithm also appears to be computationally efficient, resulting in bootstrap sample sizes that are smaller than those commonly used. I illustrate the algorithm with an example using data from Chukchi Sea polar bears (Ursus maritimus) and their marine mammal prey. The concepts underlying the approach may have value in other areas of quantitative ecology in which bootstrap samples are post-processed prior to their use.

  8. Linear array of conserved sequence motifs to discriminate protein subfamilies: study on pyridine nucleotide-disulfide reductases

    PubMed Central

    Avila, César L; Rapisarda, Viviana A; Farías, Ricardo N; De Las Rivas, Javier; Chehín, Rosana

    2007-01-01

    Background The pyridine nucleotide disulfide reductase (PNDR) is a large and heterogeneous protein family divided into two classes (I and II), which reflect the divergent evolution of its characteristic disulfide redox active site. However, not all the PNDR members fit into these categories and this suggests the need of further studies to achieve a more comprehensive classification of this complex family. Results A workflow to improve the clusterization of protein families based on the array of linear conserved motifs is designed. The method is applied to the PNDR large family finding two main groups, which correspond to PNDR classes I and II. However, two other separate protein clusters, previously classified as class I in most databases, are outgrouped: the peroxide reductases (NAOX, NAPE) and the type II NADH dehydrogenases (NDH-2). In this way, two novel PNDR classes III and IV for NAOX/NAPE and NDH-2 respectively are proposed. By knowledge-driven biochemical and functional data analyses done on the new class IV, a linear array of motifs putatively related to Cu(II)-reductase activity is detected in a specific subset of NDH-2. Conclusion The results presented are a novel contribution to the classification of the complex and large PNDR protein family, supporting its reclusterization into four classes. The linear array of motifs detected within the class IV PNDR subfamily could be useful as a signature for a particular subgroup of NDH-2. PMID:17367536

  9. Functional characterization of the guanine nucleotide exchange factor (GEF) motif of GIV protein reveals a threshold effect in signaling.

    PubMed

    Garcia-Marcos, Mikel; Kietrsunthorn, Patrick S; Pavlova, Yelena; Adia, Michelle A; Ghosh, Pradipta; Farquhar, Marilyn G

    2012-02-07

    Heterotrimeric G proteins are critical signal-transducing molecules controlled by a complex network of regulators. GIV (a.k.a. Girdin) is a unique component of this network and a nonreceptor guanine nucleotide exchange factor (GEF) that functions via a signature motif. GIV's GEF motif is involved in the regulation of critical biological processes such as phosphoinositide 3 kinase (PI3K)-Akt signaling, actin cytoskeleton remodeling, cell migration, and cancer metastasis. Here we investigated how the GEF function of GIV affects the wiring of its signaling pathway to shape different biological responses. Using a structure-guided approach, we designed a battery of GIV mutants with different Gαi-binding and -activating properties and used it to dissect the specific impact of changes in GIV's GEF activity on several cellular responses. In vivo signaling assays revealed a threshold effect of GEF activity for the activation of Akt by GIV in different cell lines and by different stimuli. Akt signaling is minimal at low GEF activity and is sharply increased to reach a maximum above a threshold of GEF activity, suggesting that GIV is a critical signal amplifier and that activation of Akt is ultrasensitive to changes in GIV's GEF activity. A similar threshold dependence was observed for other biological functions promoted by GIV such as remodeling of the actin cytoskeleton and cell migration. This functional characterization of GIV's GEF motif provides insights into the molecular interactions between nonreceptor GEFs and G proteins and the mechanisms that govern this signal transduction pathway.

  10. Significance Analysis of Prognostic Signatures

    PubMed Central

    Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.; Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John; Haibe-Kains, Benjamin

    2013-01-01

    A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that “random” gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated

  11. A million peptide motifs for the molecular biologist.

    PubMed

    Tompa, Peter; Davey, Norman E; Gibson, Toby J; Babu, M Madan

    2014-07-17

    A molecular description of functional modules in the cell is the focus of many high-throughput studies in the postgenomic era. A large portion of biomolecular interactions in virtually all cellular processes is mediated by compact interaction modules, referred to as peptide motifs. Such motifs are typically less than ten residues in length, occur within intrinsically disordered regions, and are recognized and/or posttranslationally modified by structured domains of the interacting partner. In this review, we suggest that there might be over a million instances of peptide motifs in the human proteome. While this staggering number suggests that peptide motifs are numerous and the most understudied functional module in the cell, it also holds great opportunities for new discoveries.

  12. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES OF GOLD LEAF AND BURNISHED GOLD LEAF WERE USED FOR THE INTERIOR FINISHES. - Anaconda Historic District, Washoe Theater, 305 Main Street, Anaconda, Deer Lodge County, MT

  13. 10. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES OF GOLD LEAF AND BURNISHED GOLD LEAF WERE USED FOR THE INTERIOR FINISHES - Anaconda Historic District, Washoe Theater, 305 Main Street, Anaconda, Deer Lodge County, MT

  14. Three-Dimensional DNA Nanostructures Assembled from DNA Star Motifs.

    PubMed

    Tian, Cheng; Zhang, Chuan

    2017-01-01

    Tile-based DNA self-assembly is a promising method in DNA nanotechnology and has produced a wide range of nanostructures by using a small set of unique DNA strands. DNA star motif, as one of DNA tiles, has been employed to assemble varieties of symmetric one-, two-, three-dimensional (1, 2, 3D) DNA nanostructures. Herein, we describe the design principles, assembly methods, and characterization methods of 3D DNA nanostructures assembled from the DNA star motifs.

  15. Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers

    PubMed Central

    Rogozin, Igor B.; Lada, Artem G.; Goncearenco, Alexander; Green, Michael R.; De, Subhajyoti; Nudelman, German; Panchenko, Anna R.; Koonin, Eugene V.; Pavlov, Youri I.

    2016-01-01

    Follicular lymphoma (FL) is an uncurable cancer characterized by progressive severity of relapses. We analyzed sequence context specificity of mutations in the B cells from a large cohort of FL patients. We revealed substantial excess of mutations within a novel hybrid nucleotide motif: the signature of somatic hypermutation (SHM) enzyme, Activation Induced Deaminase (AID), which overlaps the CpG methylation site. This finding implies that in FL the SHM machinery acts at genomic sites containing methylated cytosine. We identified the prevalence of this hybrid mutational signature in many other types of human cancer, suggesting that AID-mediated, CpG-methylation dependent mutagenesis is a common feature of tumorigenesis. PMID:27924834

  16. Signature molecular descriptor : advanced applications.

    SciTech Connect

    Visco, Donald Patrick, Jr.

    2010-04-01

    In this work we report on the development of the Signature Molecular Descriptor (or Signature) for use in the solution of inverse design problems as well as in highthroughput screening applications. The ultimate goal of using Signature is to identify novel and non-intuitive chemical structures with optimal predicted properties for a given application. We demonstrate this in three studies: green solvent design, glucocorticoid receptor ligand design and the design of inhibitors for Factor XIa. In many areas of engineering, compounds are designed and/or modified in incremental ways which rely upon heuristics or institutional knowledge. Often multiple experiments are performed and the optimal compound is identified in this brute-force fashion. Perhaps a traditional chemical scaffold is identified and movement of a substituent group around a ring constitutes the whole of the design process. Also notably, a chemical being evaluated in one area might demonstrate properties very attractive in another area and serendipity was the mechanism for solution. In contrast to such approaches, computer-aided molecular design (CAMD) looks to encompass both experimental and heuristic-based knowledge into a strategy that will design a molecule on a computer to meet a given target. Depending on the algorithm employed, the molecule which is designed might be quite novel (re: no CAS registration number) and/or non-intuitive relative to what is known about the problem at hand. While CAMD is a fairly recent strategy (dating to the early 1980s), it contains a variety of bottlenecks and limitations which have prevented the technique from garnering more attention in the academic, governmental and industrial institutions. A main reason for this is how the molecules are described in the computer. This step can control how models are developed for the properties of interest on a given problem as well as how to go from an output of the algorithm to an actual chemical structure. This report

  17. Finding specific RNA motifs: Function in a zeptomole world?

    PubMed Central

    KNIGHT, ROB; YARUS, MICHAEL

    2003-01-01

    We have developed a new method for estimating the abundance of any modular (piecewise) RNA motif within a longer random region. We have used this method to estimate the size of the active motifs available to modern SELEX experiments (picomoles of unique sequences) and to a plausible RNA World (zeptomoles of unique sequences: 1 zmole = 602 sequences). Unexpectedly, activities such as specific isoleucine binding are almost certainly present in zeptomoles of molecules, and even ribozymes such as self-cleavage motifs may appear (depending on assumptions about the minimal structures). The number of specified nucleotides is not the only important determinant of a motif’s rarity: The number of modules into which it is divided, and the details of this division, are also crucial. We propose three maxims for easily isolated motifs: the Maxim of Minimization, the Maxim of Multiplicity, and the Maxim of the Median. These maxims together state that selected motifs should be small and composed of as many separate, equally sized modules as possible. For evenly divided motifs with four modules, the largest accessible activity in picomole scale (1–1000 pmole) pools of length 100 is about 34 nucleotides; while for zeptomole scale (1–1000 zmole) pools it is about 20 specific nucleotides (50% probability of occurrence). This latter figure includes some ribozymes and aptamers. Consequently, an RNA metabolism apparently could have begun with only zeptomoles of RNA molecules. PMID:12554865

  18. Selection of peptide entry motifs by bacterial surface display.

    PubMed Central

    Taschner, Sabine; Meinke, Andreas; von Gabain, Alexander; Boyd, Aoife P

    2002-01-01

    Surface display technologies have been established previously to select peptides and polypeptides that interact with purified immobilized ligands. In the present study, we designed and implemented a surface display-based technique to identify novel peptide motifs that mediate entry into eukaryotic cells. An Escherichia coli library expressing surface-displayed peptides was combined with eukaryotic cells and the gentamicin protection assay was performed to select recombinant E. coli, which were internalized into eukaryotic cells by virtue of the displayed peptides. To establish the proof of principle of this approach, the fibronectin-binding motifs of the fibronectin-binding protein A of Staphylococcus aureus were inserted into the E. coli FhuA protein. Surface expression of the fusion proteins was demonstrated by functional assays and by FACS analysis. The fibronectin-binding motifs were shown to mediate entry of the bacteria into non-phagocytic eukaryotic cells and brought about the preferential selection of these bacteria over E. coli expressing parental FhuA, with an enrichment of 100000-fold. Four entry sequences were selected and identified using an S. aureus library of peptides displayed in the FhuA protein on the surface of E. coli. These sequences included novel entry motifs as well as integrin-binding Arg-Gly-Asp (RGD) motifs and promoted a high degree of bacterial entry. Bacterial surface display is thus a powerful tool to effectively select and identify entry peptide motifs. PMID:12144529

  19. Discovering Multidimensional Motifs in Physiological Signals for Personalized Healthcare.

    PubMed

    Balasubramanian, Arvind; Wang, Jun; Prabhakaran, Balakrishnan

    2016-08-01

    Personalized diagnosis and therapy requires monitoring patient activity using various body sensors. Sensor data generated during personalized exercises or tasks may be too specific or inadequate to be evaluated using supervised methods such as classification. We propose multidimensional motif (MDM) discovery as a means for patient activity monitoring, since such motifs can capture repeating patterns across multiple dimensions of the data, and can serve as conformance indicators. Previous studies pertaining to mining MDMs have proposed approaches that lack the capability of concurrently processing multiple dimensions, thus limiting their utility in online scenarios. In this paper, we propose an efficient real-time approach to MDM discovery in body sensor generated time series data for monitoring performance of patients during therapy. We present two alternative models for MDMs based on motif co-occurrences and temporal ordering among motifs across multiple dimensions, with detailed formulation of the concepts proposed. The proposed method uses an efficient hashing based record to enable speedy update and retrieval of motif sets, and identification of MDMs. Performance evaluation using synthetic and real body sensor data in unsupervised motif discovery tasks shows that the approach is effective for (a) concurrent processing of multidimensional time series information suitable for real-time applications, (b) finding unknown naturally occurring patterns with minimal delay, and

  20. The distribution of RNA motifs in natural sequences.

    PubMed

    Bourdeau, V; Ferbeyre, G; Pageau, M; Paquin, B; Cedergren, R

    1999-11-15

    Functional analysis of genome sequences has largely ignored RNA genes and their structures. We introduce here the notion of 'ribonomics' to describe the search for the distribution of and eventually the determination of the physiological roles of these RNA structures found in the sequence databases. The utility of this approach is illustrated here by the identification in the GenBank database of RNA motifs having known binding or chemical activity. The frequency of these motifs indicates that most have originated from evolutionary drift and are selectively neutral. On the other hand, their distribution among species and their location within genes suggest that the destiny of these motifs may be more elaborate. For example, the hammerhead motif has a skewed organismal presence, is phylogenetically stable and recent work on a schistosome version confirms its in vivo biological activity. The under-representation of the valine-binding motif and the Rev-binding element in GenBank hints at a detrimental effect on cell growth or viability. Data on the presence and the location of these motifs may provide critical guidance in the design of experiments directed towards the understanding and the manipulation of RNA complexes and activities in vivo.

  1. cWINNOWER Algorithm for Finding Fuzzy DNA Motifs

    NASA Technical Reports Server (NTRS)

    Liang, Shoudan

    2003-01-01

    The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein-binding signals. A signal is defined as any short nucleotide pattern having up to d mutations differing from a motif of length l. The algorithm finds such motifs if multiple mutated copies of the motif (i.e., the signals) are present in the DNA sequence in sufficient abundance. The cWINNOWER algorithm substantially improves the sensitivity of the winnower method of Pevzner and Sze by imposing a consensus constraint, enabling it to detect much weaker signals. We studied the minimum number of detectable motifs qc as a function of sequence length N for random sequences. We found that qc increases linearly with N for a fast version of the algorithm based on counting three-member sub-cliques. Imposing consensus constraints reduces qc, by a factor of three in this case, which makes the algorithm dramatically more sensitive. Our most sensitive algorithm, which counts four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a sequence of length N = 12000 for (l,d) = (15,4).

  2. Transcriptional Network Growing Models Using Motif-Based Preferential Attachment.

    PubMed

    Abdelzaher, Ahmed F; Al-Musawi, Ahmad F; Ghosh, Preetam; Mayo, Michael L; Perkins, Edward J

    2015-01-01

    Understanding relationships between architectural properties of gene-regulatory networks (GRNs) has been one of the major goals in systems biology and bioinformatics, as it can provide insights into, e.g., disease dynamics and drug development. Such GRNs are characterized by their scale-free degree distributions and existence of network motifs - i.e., small-node subgraphs that occur more abundantly in GRNs than expected from chance alone. Because these transcriptional modules represent "building blocks" of complex networks and exhibit a wide range of functional and dynamical properties, they may contribute to the remarkable robustness and dynamical stability associated with the whole of GRNs. Here, we developed network-construction models to better understand this relationship, which produce randomized GRNs by using transcriptional motifs as the fundamental growth unit in contrast to other methods that construct similar networks on a node-by-node basis. Because this model produces networks with a prescribed lower bound on the number of choice transcriptional motifs (e.g., downlinks, feed-forward loops), its fidelity to the motif distributions observed in model organisms represents an improvement over existing methods, which we validated by contrasting their resultant motif and degree distributions against existing network-growth models and data from the model organism of the bacterium Escherichia coli. These models may therefore serve as novel testbeds for further elucidating relationships between the topology of transcriptional motifs and network-wide dynamical properties.

  3. Signature Visualization of Software Binaries

    SciTech Connect

    Panas, T

    2008-07-01

    In this paper we present work on the visualization of software binaries. In particular, we utilize ROSE, an open source compiler infrastructure, to pre-process software binaries, and we apply a landscape metaphor to visualize the signature of each binary (malware). We define the signature of a binary as a metric-based layout of the functions contained in the binary. In our initial experiment, we visualize the signatures of a series of computer worms that all originate from the same line. These visualizations are useful for a number of reasons. First, the images reveal how the archetype has evolved over a series of versions of one worm. Second, one can see the distinct changes between version. This allows the viewer to form conclusions about the development cycle of a particular worm.

  4. Graph Analytics for Signature Discovery

    SciTech Connect

    Hogan, Emilie A.; Johnson, John R.; Halappanavar, Mahantesh; Lo, Chaomei

    2013-06-01

    Within large amounts of seemingly unstructured data it can be diffcult to find signatures of events. In our work we transform unstructured data into a graph representation. By doing this we expose underlying structure in the data and can take advantage of existing graph analytics capabilities, as well as develop new capabilities. Currently we focus on applications in cybersecurity and communication domains. Within cybersecurity we aim to find signatures for perpetrators using the pass-the-hash attack, and in communications we look for emails or phone calls going up or down a chain of command. In both of these areas, and in many others, the signature we look for is a path with certain temporal properties. In this paper we discuss our methodology for finding these temporal paths within large graphs.

  5. Measurement of sniper infrared signatures

    NASA Astrophysics Data System (ADS)

    Kastek, M.; Dulski, R.; Trzaskawka, P.; Bieszczad, G.

    2009-09-01

    The paper presents some practical aspects of sniper IR signature measurements. Description of particular signatures for sniper and background in typical scenarios has been presented. We take into consideration sniper activities in open area as well as in urban environment. The measurements were made at field test ground. High precision laboratory measurements were also performed. Several infrared cameras were used during measurements to cover all measurement assumptions. Some of the cameras are measurement class devices with high accuracy and speed. The others are microbolometer cameras with FPA detector similar to those used in real commercial counter-sniper systems. The registration was made in SWIR and LWIR spectral bands simultaneously. An ultra fast visual camera was also used for visible spectra registration. Exemplary sniper IR signatures for typical situation were presented.

  6. Textural signatures for wetland vegetation

    NASA Technical Reports Server (NTRS)

    Whitman, R. I.; Marcellus, K. L.

    1973-01-01

    This investigation indicates that unique textural signatures do exist for specific wetland communities at certain times in the growing season. When photographs with the proper resolution are obtained, the textural features can identify the spectral features of the vegetation community seen with lower resolution mapping data. The development of a matrix of optimum textural signatures is the goal of this research. Seasonal variations of spectral and textural features are particularly important when performing a vegetations analysis of fresh water marshes. This matrix will aid in flight planning, since expected seasonal variations and resolution requirements can be established prior to a given flight mission.

  7. Ballistic Signature Identification System Study

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The first phase of a research project directed toward development of a high speed automatic process to be used to match gun barrel signatures imparted to fired bullets was documented. An optical projection technique has been devised to produce and photograph a planar image of the entire signature, and the phototransparency produced is subjected to analysis using digital Fourier transform techniques. The success of this approach appears to be limited primarily by the accuracy of the photographic step since no significant processing limitations have been encountered.

  8. Mechanisms of Zero-Lag Synchronization in Cortical Motifs

    PubMed Central

    Gollo, Leonardo L.; Mirasso, Claudio; Sporns, Olaf; Breakspear, Michael

    2014-01-01

    Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of “dynamical relaying” – a mechanism that relies on a specific network motif – has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair – a “resonance pair” – plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying) from those that do not (such as the common driving triad). Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain. PMID:24763382

  9. NetMODE: Network Motif Detection without Nauty

    PubMed Central

    Wang, Haidong; Deng, Hualiang; Liu, Xiaoguang; Wang, Gang

    2012-01-01

    A motif in a network is a connected graph that occurs significantly more frequently as an induced subgraph than would be expected in a similar randomized network. By virtue of being atypical, it is thought that motifs might play a more important role than arbitrary subgraphs. Recently, a flurry of advances in the study of network motifs has created demand for faster computational means for identifying motifs in increasingly larger networks. Motif detection is typically performed by enumerating subgraphs in an input network and in an ensemble of comparison networks; this poses a significant computational problem. Classifying the subgraphs encountered, for instance, is typically performed using a graph canonical labeling package, such as Nauty, and will typically be called billions of times. In this article, we describe an implementation of a network motif detection package, which we call NetMODE. NetMODE can only perform motif detection for -node subgraphs when , but does so without the use of Nauty. To avoid using Nauty, NetMODE has an initial pretreatment phase, where -node graph data is stored in memory (). For we take a novel approach, which relates to the Reconstruction Conjecture for directed graphs. We find that NetMODE can perform up to around times faster than its predecessors when and up to around times faster when (the exact improvement varies considerably). NetMODE also (a) includes a method for generating comparison graphs uniformly at random, (b) can interface with external packages (e.g. R), and (c) can utilize multi-core architectures. NetMODE is available from netmode.sf.net. PMID:23272055

  10. Hydrazidase, a Novel Amidase Signature Enzyme That Hydrolyzes Acylhydrazides

    PubMed Central

    Oinuma, Ken-Ichi; Takuwa, Atsushi; Taniyama, Kosuke; Doi, Yuki

    2015-01-01

    The degradation mechanisms of natural and artificial hydrazides have been elucidated. Here we screened and isolated bacteria that utilize the acylhydrazide 4-hydroxybenzoic acid 1-phenylethylidene hydrazide (HBPH) from soils. Physiological and phylogenetic studies identified one bacterium as Microbacterium sp. strain HM58-2, from which we purified intracellular hydrazidase, cloned its gene, and prepared recombinant hydrazidase using an Escherichia coli expression system. The Microbacterium sp. HM58-2 hydrazidase is a 631-amino-acid monomer that was 31% identical to indoleacetamide hydrolase isolated from Bradyrhizobium japonicum. Phylogenetic studies indicated that the Microbacterium sp. HM58-2 hydrazidase constitutes a novel hydrazidase group among amidase signature proteins that are distributed within proteobacteria, actinobacteria, and firmicutes. The hydrazidase stoichiometrically hydrolyzed the acylhydrazide residue of HBPH to the corresponding acid and hydrazine derivative. Steady-state kinetics showed that the enzyme hydrolyzes structurally related 4-hydrozybenzamide to hydroxybenzoic acid at a lower rate than HBPH, indicating that the hydrazidase prefers hydrazide to amide. The hydrazidase contains the catalytic Ser-Ser-Lys motif that is conserved among members of the amidase signature family; it shares a catalytic mechanism with amidases, according to mutagenesis findings, and another hydrazidase-specific mechanism must exist that compensates for the absence of the catalytic Ser residue. The finding that an environmental bacterium produces hydrazidase implies the existence of a novel bacterial mechanism of hydrazide degradation that impacts its ecological role. PMID:25583978

  11. Improved method of signature extraction

    NASA Technical Reports Server (NTRS)

    Christianson, D.; Gordon, M.; Kistler, R.; Kriegler, F. J.; Lampert, S.; Marshall, R. E.; Mclaughlin, R.; Smith, V.

    1977-01-01

    System promises capability of rapidly processing large amounts of data generated by currently available and planned multispectral sensors, such as those utilized on aircraft and spacecraft. Techniques developed for system, greatly decrease operator time required for signature extraction from multispectral data base.

  12. Topological Signatures for Population Admixture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Topological Signatures for Population AdmixtureDeniz Yorukoglu1, Filippo Utro1, David Kuhn2, Saugata Basu3 and Laxmi Parida1* Abstract Background: As populations with multi-linear transmission (i.e., mixing of genetic material from two parents, say) evolve over generations, the genetic transmission...

  13. MK 66 Rocket Signature Reduction

    DTIC Science & Technology

    1982-04-01

    Indian Head, Maryland. ’The objec- tive of the study was to reduce the visible signature of the rocket motor. The rocket motor used for demonstration tests...15 6. Actual Emmiissions . . . . . . ........... . 16 7. Human Eye Adjusted Emmissions ..................... .. 16 8. Cross...altered. Additives are commonly used in gun propellants for elimination of muzzle flash. Their use in tactical rockets has been very limited, and

  14. Disaster relief through composite signatures

    NASA Astrophysics Data System (ADS)

    Hawley, Chadwick T.; Hyde, Brian; Carpenter, Tom; Nichols, Steve

    2012-06-01

    A composite signature is a group of signatures that are related in such a way to more completely or further define a target or operational endeavor at a higher fidelity. This paper builds on previous work developing innovative composite signatures associated with civil disasters, including physical, chemical and pattern/behavioral. For the composite signature approach to be successful it requires effective data fusion and visualization. This plays a key role in both preparedness and the response and recovery which are critical to saving lives. Visualization tools enhance the overall understanding of the crisis by pulling together and analyzing the data, and providing a clear and complete analysis of the information to the organizations/agencies dependant on it for a successful operation. An example of this, Freedom Web, is an easy-to-use data visualization and collaboration solution for use in homeland security, emergency preparedness, situational awareness, and event management. The solution provides a nationwide common operating picture for all levels of government through a web based, map interface. The tool was designed to be utilized by non-geospatial experts and is easily tailored to the specific needs of the users. Consisting of standard COTS and open source databases and a web server, users can view, edit, share, and highlight information easily and quickly through a standard internet browser.

  15. IQ-motif peptides as novel anti-microbial agents.

    PubMed

    McLean, Denise T F; Lundy, Fionnuala T; Timson, David J

    2013-04-01

    The IQ-motif is an amphipathic, often positively charged, α-helical, calmodulin binding sequence found in a number of eukaryote signalling, transport and cytoskeletal proteins. They share common biophysical characteristics with established, cationic α-helical antimicrobial peptides, such as the human cathelicidin LL-37. Therefore, we tested eight peptides encoding the sequences of IQ-motifs derived from the human cytoskeletal scaffolding proteins IQGAP2 and IQGAP3. Some of these peptides were able to inhibit the growth of Escherichia coli and Staphylococcus aureus with minimal inhibitory concentrations (MIC) comparable to LL-37. In addition some IQ-motifs had activity against the fungus Candida albicans. This antimicrobial activity is combined with low haemolytic activity (comparable to, or lower than, that of LL-37). Those IQ-motifs with anti-microbial activity tended to be able to bind to lipopolysaccharide. Some of these were also able to permeabilise the cell membranes of both Gram positive and Gram negative bacteria. These results demonstrate that IQ-motifs are viable lead sequences for the identification and optimisation of novel anti-microbial peptides. Thus, further investigation of the anti-microbial properties of this diverse group of sequences is merited.

  16. Interconnected Network Motifs Control Podocyte Morphology and Kidney Function

    PubMed Central

    Azeloglu, Evren U.; Hardy, Simon V.; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y.; Fang, Wei; Xiong, Huabao; Neves, Susana R.; Jain, Mohit R.; Li, Hong; Ma’ayan, Avi; Gordon, Ronald E.; He, John Cijiang; Iyengar, Ravi

    2014-01-01

    Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3′,5′-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element–binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor–driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease. PMID:24497609

  17. cWINNOWER algorithm for finding fuzzy dna motifs

    NASA Technical Reports Server (NTRS)

    Liang, S.; Samanta, M. P.; Biegel, B. A.

    2004-01-01

    The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein-binding signals. A signal is defined as any short nucleotide pattern having up to d mutations differing from a motif of length l. The algorithm finds such motifs if a clique consisting of a sufficiently large number of mutated copies of the motif (i.e., the signals) is present in the DNA sequence. The cWINNOWER algorithm substantially improves the sensitivity of the winnower method of Pevzner and Sze by imposing a consensus constraint, enabling it to detect much weaker signals. We studied the minimum detectable clique size qc as a function of sequence length N for random sequences. We found that qc increases linearly with N for a fast version of the algorithm based on counting three-member sub-cliques. Imposing consensus constraints reduces qc by a factor of three in this case, which makes the algorithm dramatically more sensitive. Our most sensitive algorithm, which counts four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a sequence of length N = 12,000 for (l, d) = (15, 4). Copyright Imperial College Press.

  18. Fitting a mixture model by expectation maximization to discover motifs in biopolymers

    SciTech Connect

    Bailey, T.L.; Elkan, C.

    1994-12-31

    The algorithm described in this paper discovers one or more motifs in a collection of DNA or protein sequences by using the technique of expectation maximization to fit a two-component finite mixture model to the set of sequences. Multiple motifs are found by fitting a mixture model to the data, probabilistically erasing the occurrences of the motif thus found, and repeating the process to find successive motifs. The algorithm requires only a set of unaligned sequences and a number specifying the width of the motifs as input. It returns a model of each motif and a threshold which together can be used as a Bayes-optimal classifier for searching for occurrences of the motif in other databases. The algorithm estimates how many times each motif occurs in each sequence in the dataset and outputs an alignment of the occurrences of the motif. The algorithm is capable of discovering several different motifs with differing numbers of occurrences in a single dataset.

  19. Mutations at the signature sequence of CFTR create a Cd(2+)-gated chloride channel.

    PubMed

    Wang, Xiaohui; Bompadre, Silvia G; Li, Min; Hwang, Tzyh-Chang

    2009-01-01

    The canonical sequence LSGGQ, also known as the signature sequence, defines the adenosine triphosphate (ATP)-binding cassette transporter superfamily. Crystallographic studies reveal that the signature sequence, together with the Walker A and Walker B motifs, forms the ATP-binding pocket upon dimerization of the two nucleotide-binding domains (NBDs) in a head-to-tail configuration. The importance of the signature sequence is attested by the fact that a glycine to aspartate mutation (i.e., G551D) in cystic fibrosis transmembrane conductance regulator (CFTR) results in a severe phenotype of cystic fibrosis. We previously showed that the G551D mutation completely eliminates ATP-dependent gating of the CFTR chloride channel. Here, we report that micromolar [Cd(2+)] can dramatically increase the activity of G551D-CFTR in the absence of ATP. This effect of Cd(2+) is not seen in wild-type channels or in G551A. Pretreatment of G551D-CFTR with the cysteine modification reagent 2-aminoethyl methane thiosulfonate hydrobromide protects the channel from Cd(2+) activation, suggesting an involvement of endogenous cysteine residue(s) in mediating this effect of Cd(2+). The mutants G551C, L548C, and S549C, all in the signature sequence of CFTR's NBD1, show robust response to Cd(2+). On the other hand, negligible effects of Cd(2+) were seen with T547C, Q552C, and R553C, indicating that a specific region of the signature sequence is involved in transmitting the signal of Cd(2+) binding to the gate. Collectively, these results suggest that the effect of Cd(2+) is mediated by a metal bridge formation between yet to be identified cysteine residue(s) and the engineered aspartate or cysteine in the signature sequence. We propose that the signature sequence serves as a switch that transduces the signal of ligand binding to the channel gate.

  20. Block truncation signature coding for hyperspectral analysis

    NASA Astrophysics Data System (ADS)

    Chakravarty, Sumit; Chang, Chein-I.

    2008-08-01

    This paper introduces a new signature coding which is designed based on the well-known Block Truncation Coding (BTC). It comprises of bit-maps of the signature blocks generated by different threshold criteria. Two new BTC-based algorithms are developed for signature coding, to be called Block Truncation Signature Coding (BTSC) and 2-level BTSC (2BTSC). In order to compare the developed BTC based algorithms with current binary signature coding schemes such as Spectral Program Analysis Manager (SPAM) developed by Mazer et al. and Spectral Feature-based Binary Coding (SFBC) by Qian et al., three different thresholding functions, local block mean, local block gradient, local block correlation are derived to improve the BTSC performance where the combined bit-maps generated by these thresholds can provide better spectral signature characterization. Experimental results reveal that the new BTC-based signature coding performs more effectively in characterizing spectral variations than currently available binary signature coding methods.

  1. Partially Blind Signatures Based on Quantum Cryptography

    NASA Astrophysics Data System (ADS)

    Cai, Xiao-Qiu; Niu, Hui-Fang

    2012-12-01

    In a partially blind signature scheme, the signer explicitly includes pre-agreed common information in the blind signature, which can improve the availability and performance. We present a new partially blind signature scheme based on fundamental properties of quantum mechanics. In addition, we analyze the security of this scheme, and show it is not possible to forge valid partially blind signatures. Moreover, the comparisons between this scheme and those based on public-key cryptography are also discussed.

  2. Selection against spurious promoter motifs correlates withtranslational efficiency across bacteria

    SciTech Connect

    Froula, Jeffrey L.; Francino, M. Pilar

    2007-05-01

    Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the -10 promoter motifs that bind the {sigma}{sup 70} subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of -10 motifs in regulatory sequences while eliminating them from the nonfunctional and, in most cases, from the protein coding regions. In some genomes, however, -10 sites are over-represented in the coding sequences; these sites could induce pauses effecting regulatory roles throughout the length of a transcriptional unit. For nonfunctional sequences, the extent of motif under-representation varies across genomes in a manner that broadly correlates with the number of tRNA genes, a good indicator of translational speed and growth rate. This suggests that minimizing the time invested in gene transcription is an important selective pressure against spurious binding. However, selection against spurious binding is detectable in the reduced genomes of host-restricted bacteria that grow at slow rates, indicating that components of efficiency other than speed may also be important. Minimizing the number of RNAP molecules per cell required for transcription, and the corresponding energetic expense, may be most relevant in slow growers. These results indicate that genome-level properties affecting the efficiency of transcription and translation can respond in an integrated manner to optimize gene expression. The detection of selection against promoter motifs in nonfunctional regions also implies that no sequence may evolve free of selective constraints, at least in the relatively small and unstructured genomes of bacteria.

  3. [Specific motifs in the genomes of the family Chlamydiaceae].

    PubMed

    Demkin, V V; Kirillova, N V

    2012-01-01

    Specific motifs in the genomes of the family Chlamydiaceae were discussed. The search for genetic markers ofbacteria identification and typing is an urgent problem. The progress in sequencing technology resulted in compilation of the database of genomic nucleotide sequences of bacteria. This raised the problem of the search and selection of genetic targets for identification and typing in bacterial genes based on comparative analysis of complete genomic sequences. The goal of this work was to implement comparative genetic analysis of different species of the family Chlamydiaceae. This analysis was focused to detection of specific motifs capable of serving as genetic marker of this family. The consensus domains were detected using the Visual Basic for Application software for MS Excel. Complete coincidence of segments 25 nucleotide long was used as the test for consensus domain selection. One complete genomic sequence for each of 8 bacterial species was taken for the experiment. The experimental sample did not contain complete sequence of C. suis, because at the moment of this research this species was absence in the database GenBank. Comparative assay of the sequences of the C. trachomatis and other representatives of the family Chlamydiaceae revealed 41 common motifs for 8 Chlamydiaceae species tested in this work. The maximal number of consensus motifs was observed in genes of ribosomal RNA and t-RNA. In addition to genes of r-RNA and t-RNA consensus motifs were observed in 5 genes and 6 intergene segments. The gene CTL0299, CTLO800, dagA, and hctA consensus motifs detected in this work can be regarded as identification domains of the family Chlamydiaceae.

  4. Specific RNA self-assembly with minimal paranemic motifs.

    PubMed

    Afonin, Kirill A; Cieply, Dennis J; Leontis, Neocles B

    2008-01-09

    The paranemic crossover (PX) is a motif for assembling two nucleic acid molecules using Watson-Crick (WC) basepairing without unfolding preformed secondary structure in the individual molecules. Once formed, the paranemic assembly motif comprises adjacent parallel double helices that crossover at every possible point over the length of the motif. The interaction is reversible as it does not require denaturation of basepairs internal to each interacting molecular unit. Paranemic assembly has been demonstrated for DNA but not for RNA and only for motifs with four or more crossover points and lengths of five or more helical half-turns. Here we report the design of RNA molecules that paranemically assemble with the minimum number of two crossovers spanning the major groove to form paranemic motifs with a length of three half turns (3HT). Dissociation constants (Kd's) were measured for a series of molecules in which the number of basepairs between the crossover points was varied from five to eight basepairs. The paranemic 3HT complex with six basepairs (3HT_6M) was found to be the most stable with Kd = 1 x 10-8 M. The half-time for kinetic exchange of the 3HT_6M complex was determined to be approximately 100 min, from which we calculated association and dissociation rate constants ka = 5.11 x 103 M-1s-1 and kd = 5.11 x 10-5 s-1. RNA paranemic assembly of 3HT and 5HT complexes is blocked by single-base substitutions that disrupt individual intermolecular Watson-Crick basepairs and is restored by compensatory substitutions that restore those basepairs. The 3HT motif appears suitable for specific, programmable, and reversible tecto-RNA self-assembly for constructing artificial RNA molecular machines.

  5. Characterizing regulatory path motifs in integrated networks using perturbational data

    PubMed Central

    2010-01-01

    We introduce Pathicular http://bioinformatics.psb.ugent.be/software/details/Pathicular, a Cytoscape plugin for studying the cellular response to perturbations of transcription factors by integrating perturbational expression data with transcriptional, protein-protein and phosphorylation networks. Pathicular searches for 'regulatory path motifs', short paths in the integrated physical networks which occur significantly more often than expected between transcription factors and their targets in the perturbational data. A case study in Saccharomyces cerevisiae identifies eight regulatory path motifs and demonstrates their biological significance. PMID:20230615

  6. A Command Editor Tool for X and Motif

    DTIC Science & Technology

    1993-07-01

    1of 16 h.. . . .. .. . . . . . .I .... . . . .. . . . . . . .- I m arble X/Motlf Design Document for Contract # DAAH01-93-C-R013 minimal implementation...Motif 2 of 18 m arble X/Motif Design Document for Contract # DAAH01-93-C-R013 ing of modified system widgets, proides to the developer the full source...oa’rutmz ol"croidctv fteseilmd h A iandEio olfrX n oi f1 i~lol’lot m arble Xfflotlf De*ign Documnent for Contract # DAAHOI-93-C-R013 user has just

  7. 48 CFR 4.102 - Contractor's signature.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Contractor's signature. 4... ADMINISTRATIVE MATTERS Contract Execution 4.102 Contractor's signature. (a) Individuals. A contract with an... be signed by that individual, and the signature shall be followed by the individual's typed,...

  8. Signatures of topological Josephson junctions

    NASA Astrophysics Data System (ADS)

    Peng, Yang; Pientka, Falko; Berg, Erez; Oreg, Yuval; von Oppen, Felix

    2016-08-01

    Quasiparticle poisoning and diabatic transitions may significantly narrow the window for the experimental observation of the 4 π -periodic dc Josephson effect predicted for topological Josephson junctions. Here, we show that switching-current measurements provide accessible and robust signatures for topological superconductivity which persist in the presence of quasiparticle poisoning processes. Such measurements provide access to the phase-dependent subgap spectrum and Josephson currents of the topological junction when incorporating it into an asymmetric SQUID together with a conventional Josephson junction with large critical current. We also argue that pump-probe experiments with multiple current pulses can be used to measure the quasiparticle poisoning rates of the topological junction. The proposed signatures are particularly robust, even in the presence of Zeeman fields and spin-orbit coupling, when focusing on short Josephson junctions. Finally, we also consider microwave excitations of short topological Josephson junctions which may complement switching-current measurements.

  9. Polarization signatures of airborne particulates

    NASA Astrophysics Data System (ADS)

    Raman, Prashant; Fuller, Kirk A.; Gregory, Don A.

    2013-07-01

    Exploratory research has been conducted with the aim of completely determining the polarization signatures of selected particulates as a function of wavelength. This may lead to a better understanding of the interaction between electromagnetic radiation and such materials, perhaps leading to the point detection of bio-aerosols present in the atmosphere. To this end, a polarimeter capable of measuring the complete Mueller matrix of highly scattering samples in transmission and reflection (with good spectral resolution from 300 to 1100 nm) has been developed. The polarization properties of Bacillus subtilis (surrogate for anthrax spore) are compared to ambient particulate matter species such as pollen, dust, and soot. Differentiating features in the polarization signatures of these samples have been identified, thus demonstrating the potential applicability of this technique for the detection of bio-aerosol in the ambient atmosphere.

  10. Signatures of a shadow biosphere.

    PubMed

    Davies, Paul C W; Benner, Steven A; Cleland, Carol E; Lineweaver, Charles H; McKay, Christopher P; Wolfe-Simon, Felisa

    2009-03-01

    Astrobiologists are aware that extraterrestrial life might differ from known life, and considerable thought has been given to possible signatures associated with weird forms of life on other planets. So far, however, very little attention has been paid to the possibility that our own planet might also host communities of weird life. If life arises readily in Earth-like conditions, as many astrobiologists contend, then it may well have formed many times on Earth itself, which raises the question whether one or more shadow biospheres have existed in the past or still exist today. In this paper, we discuss possible signatures of weird life and outline some simple strategies for seeking evidence of a shadow biosphere.

  11. Nonlinear analysis of dynamic signature

    NASA Astrophysics Data System (ADS)

    Rashidi, S.; Fallah, A.; Towhidkhah, F.

    2013-12-01

    Signature is a long trained motor skill resulting in well combination of segments like strokes and loops. It is a physical manifestation of complex motor processes. The problem, generally stated, is that how relative simplicity in behavior emerges from considerable complexity of perception-action system that produces behavior within an infinitely variable biomechanical and environmental context. To solve this problem, we present evidences which indicate that motor control dynamic in signing process is a chaotic process. This chaotic dynamic may explain a richer array of time series behavior in motor skill of signature. Nonlinear analysis is a powerful approach and suitable tool which seeks for characterizing dynamical systems through concepts such as fractal dimension and Lyapunov exponent. As a result, they can be analyzed in both horizontal and vertical for time series of position and velocity. We observed from the results that noninteger values for the correlation dimension indicates low dimensional deterministic dynamics. This result could be confirmed by using surrogate data tests. We have also used time series to calculate the largest Lyapunov exponent and obtain a positive value. These results constitute significant evidence that signature data are outcome of chaos in a nonlinear dynamical system of motor control.

  12. Nephila clavipes Flagelliform Silk-like GGX Motifs Contribute to Extensibility and Spacer Motifs Contribute to Strength in Synthetic Spider Silk Fibers

    PubMed Central

    Adrianos, Sherry L.; Teulé, Florence; Hinman, Michael B.; Jones, Justin A.; Weber, Warner S.; Yarger, Jeffery L.; Lewis, Randolph V.

    2013-01-01

    Flagelliform spider silk is the most extensible silk fiber produced by orb weaver spiders, though not as strong as the dragline silk of the spider. The motifs found in the core of the Nephila clavipes flagelliform Flag protein are: GGX, spacer, and GPGGX. Flag does not contain the polyalanine motif known to provide the strength of dragline silk. To investigate the source of flagelliform fiber strength, four recombinant proteins were produced containing variations of the three core motifs of the Nephila clavipes flagelliform Flag protein that produces this type of fiber. The as-spun fibers were processed in 80% aqueous isopropanol using a standardized process for all four fiber types, which produced improved mechanical properties. Mechanical testing of the recombinant proteins determined that the GGX motif contributes extensibility and the spacer motif contributes strength to the recombinant fibers. Recombinant protein fibers containing the spacer motif were stronger than the proteins constructed without the spacer that contained only the GGX motif or the combination of the GGX and GPGGX motifs. The mechanical and structural X-ray diffraction analysis of the recombinant fibers provide data that suggests a functional role of the spacer motif that produces tensile strength though the spacer motif is not clearly defined structurally. These results indicate that the spacer is likely a primary contributor of strength with the GGX motif supplying mobility to the protein network of native N. clavipes flagelliform silk fibers. PMID:23646825

  13. Nephila clavipes Flagelliform silk-like GGX motifs contribute to extensibility and spacer motifs contribute to strength in synthetic spider silk fibers.

    PubMed

    Adrianos, Sherry L; Teulé, Florence; Hinman, Michael B; Jones, Justin A; Weber, Warner S; Yarger, Jeffery L; Lewis, Randolph V

    2013-06-10

    Flagelliform spider silk is the most extensible silk fiber produced by orb weaver spiders, though not as strong as the dragline silk of the spider. The motifs found in the core of the Nephila clavipes flagelliform Flag protein are GGX, spacer, and GPGGX. Flag does not contain the polyalanine motif known to provide the strength of dragline silk. To investigate the source of flagelliform fiber strength, four recombinant proteins were produced containing variations of the three core motifs of the Nephila clavipes flagelliform Flag protein that produces this type of fiber. The as-spun fibers were processed in 80% aqueous isopropanol using a standardized process for all four fiber types, which produced improved mechanical properties. Mechanical testing of the recombinant proteins determined that the GGX motif contributes extensibility and the spacer motif contributes strength to the recombinant fibers. Recombinant protein fibers containing the spacer motif were stronger than the proteins constructed without the spacer that contained only the GGX motif or the combination of the GGX and GPGGX motifs. The mechanical and structural X-ray diffraction analysis of the recombinant fibers provide data that suggests a functional role of the spacer motif that produces tensile strength, though the spacer motif is not clearly defined structurally. These results indicate that the spacer is likely a primary contributor of strength, with the GGX motif supplying mobility to the protein network of native N. clavipes flagelliform silk fibers.

  14. Core signalling motif displaying multistability through multi-state enzymes

    PubMed Central

    Feng, Song; Sáez, Meritxell; Wiuf, Carsten; Feliu, Elisenda

    2016-01-01

    Bistability, and more generally multistability, is a key system dynamics feature enabling decision-making and memory in cells. Deciphering the molecular determinants of multistability is thus crucial for a better understanding of cellular pathways and their (re)engineering in synthetic biology. Here, we show that a key motif found predominantly in eukaryotic signalling systems, namely a futile signalling cycle, can display bistability when featuring a two-state kinase. We provide necessary and sufficient mathematical conditions on the kinetic parameters of this motif that guarantee the existence of multiple steady states. These conditions foster the intuition that bistability arises as a consequence of competition between the two states of the kinase. Extending from this result, we find that increasing the number of kinase states linearly translates into an increase in the number of steady states in the system. These findings reveal, to our knowledge, a new mechanism for the generation of bistability and multistability in cellular signalling systems. Further the futile cycle featuring a two-state kinase is among the smallest bistable signalling motifs. We show that multi-state kinases and the described competition-based motif are part of several natural signalling systems and thereby could enable them to implement complex information processing through multistability. These results indicate that multi-state kinases in signalling systems are readily exploited by natural evolution and could equally be used by synthetic approaches for the generation of multistable information processing systems at the cellular level. PMID:27733693

  15. Conditional graphical models for protein structural motif recognition.

    PubMed

    Liu, Yan; Carbonell, Jaime; Gopalakrishnan, Vanathi; Weigele, Peter

    2009-05-01

    Determining protein structures is crucial to understanding the mechanisms of infection and designing drugs. However, the elucidation of protein folds by crystallographic experiments can be a bottleneck in the development process. In this article, we present a probabilistic graphical model framework, conditional graphical models, for predicting protein structural motifs. It represents the structure characteristics of a structural motif using a graph, where the nodes denote the secondary structure elements, and the edges indicate the side-chain interactions between the components either within one protein chain or between chains. Then the model defines the optimal segmentation of a protein sequence against the graph by maximizing its "conditional" probability so that it can take advantages of the discriminative training approach. Efficient approximate inference algorithms using reversible jump Markov Chain Monte Carlo (MCMC) algorithm are developed to handle the resulting complex graphical models. We test our algorithm on four important structural motifs, and our method outperforms other state-of-art algorithms for motif recognition. We also hypothesize potential membership proteins of target folds from Swiss-Prot, which further supports the evolutionary hypothesis about viral folds.

  16. Motifs in triadic random graphs based on Steiner triple systems

    NASA Astrophysics Data System (ADS)

    Winkler, Marco; Reichardt, Jörg

    2013-08-01

    Conventionally, pairwise relationships between nodes are considered to be the fundamental building blocks of complex networks. However, over the last decade, the overabundance of certain subnetwork patterns, i.e., the so-called motifs, has attracted much attention. It has been hypothesized that these motifs, instead of links, serve as the building blocks of network structures. Although the relation between a network's topology and the general properties of the system, such as its function, its robustness against perturbations, or its efficiency in spreading information, is the central theme of network science, there is still a lack of sound generative models needed for testing the functional role of subgraph motifs. Our work aims to overcome this limitation. We employ the framework of exponential random graph models (ERGMs) to define models based on triadic substructures. The fact that only a small portion of triads can actually be set independently poses a challenge for the formulation of such models. To overcome this obstacle, we use Steiner triple systems (STSs). These are partitions of sets of nodes into pair-disjoint triads, which thus can be specified independently. Combining the concepts of ERGMs and STSs, we suggest generative models capable of generating ensembles of networks with nontrivial triadic Z-score profiles. Further, we discover inevitable correlations between the abundance of triad patterns, which occur solely for statistical reasons and need to be taken into account when discussing the functional implications of motif statistics. Moreover, we calculate the degree distributions of our triadic random graphs analytically.

  17. Forward and Back: Motifs of Inhibition in Olfactory Processing

    PubMed Central

    Bazhenov, Maxim; Stopfer, Mark

    2016-01-01

    The remarkable performance of the olfactory system in classifying and categorizing the complex olfactory environment is built upon several basic neural circuit motifs. These include forms of inhibition that may play comparable roles in widely divergent species. In this issue of Neuron, a new study by Stokes and Isaacson sheds light on how elementary types of inhibition dynamically interact. PMID:20696373

  18. Insights into the motif preference of APOBEC3 enzymes.

    PubMed

    Ebrahimi, Diako; Alinejad-Rokny, Hamid; Davenport, Miles P

    2014-01-01

    We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3' end (in +1 and +2 positions) were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3'polypurine tracts (PPTs) which remain double stranded during the HIV reverse transcription. GGGG motifs outside the PPTs were also disfavoured. The motifs GGAG and GAGG were also found to be disfavoured targets for APOBEC3. The motif-dependent mutation of G within the HIV genome by members of the APOBEC3 family other than APOBEC3G was limited to GA→AA changes. The results did not show evidence of other types of context dependent G-to-A changes in the HIV genome.

  19. Insights into the Motif Preference of APOBEC3 Enzymes

    PubMed Central

    Ebrahimi, Diako; Alinejad-Rokny, Hamid; Davenport, Miles P.

    2014-01-01

    We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3′ end (in +1 and +2 positions) were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3′polypurine tracts (PPTs) which remain double stranded during the HIV reverse transcription. GGGG motifs outside the PPTs were also disfavoured. The motifs GGAG and GAGG were also found to be disfavoured targets for APOBEC3. The motif-dependent mutation of G within the HIV genome by members of the APOBEC3 family other than APOBEC3G was limited to GA→AA changes. The results did not show evidence of other types of context dependent G-to-A changes in the HIV genome. PMID:24498164

  20. 5. DETAIL VIEW OF THE EGYPTIAN MOTIF DECORATIVE ELEMENTS OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. DETAIL VIEW OF THE EGYPTIAN MOTIF DECORATIVE ELEMENTS OF BUILDING 1'S MAIN ENTRY TOWER (INCLUDING THE ENGAGED COLUMN CAPITALS, PILASTERS & CAPITALS, CORNICES, AND TERRA COTTA EAGLES); LOOKING SW FROM THE E WING ROOF. (Ryan) - Veterans Administration Medical Center, Building No. 1, Old State Route 13 West, Marion, Williamson County, IL

  1. DNA containing CpG motifs induces angiogenesis

    NASA Astrophysics Data System (ADS)

    Zheng, Mei; Klinman, Dennis M.; Gierynska, Malgorzata; Rouse, Barry T.

    2002-06-01

    New blood vessel formation in the cornea is an essential step in the pathogenesis of a blinding immunoinflammatory reaction caused by ocular infection with herpes simplex virus (HSV). By using a murine corneal micropocket assay, we found that HSV DNA (which contains a significant excess of potentially bioactive "CpG" motifs when compared with mammalian DNA) induces angiogenesis. Moreover, synthetic oligodeoxynucleotides containing CpG motifs attract inflammatory cells and stimulate the release of vascular endothelial growth factor (VEGF), which in turn triggers new blood vessel formation. In vitro, CpG DNA induces the J774A.1 murine macrophage cell line to produce VEGF. In vivo CpG-induced angiogenesis was blocked by the administration of anti-mVEGF Ab or the inclusion of "neutralizing" oligodeoxynucleotides that specifically oppose the stimulatory activity of CpG DNA. These findings establish that DNA containing bioactive CpG motifs induces angiogenesis, and suggest that CpG motifs in HSV DNA may contribute to the blinding lesions of stromal keratitis.

  2. Crystal Structure of (+)-[delta]-Cadinene Synthase from Gossypium arboreum and Evolutionary Divergence of Metal Binding Motifs for Catalysis

    SciTech Connect

    Gennadios, Heather A.; Gonzalez, Veronica; Di Costanzo, Luigi; Li, Amang; Yu, Fanglei; Miller, David J.; Allemann, Rudolf K.; Christianson, David W.

    2009-09-11

    (+)-{delta}-Cadinene synthase (DCS) from Gossypium arboreum (tree cotton) is a sesquiterpene cyclase that catalyzes the cyclization of farnesyl diphosphate in the first committed step of the biosynthesis of gossypol, a phytoalexin that defends the plant from bacterial and fungal pathogens. Here, we report the X-ray crystal structure of unliganded DCS at 2.4 {angstrom} resolution and the structure of its complex with three putative Mg{sup 2+} ions and the substrate analogue inhibitor 2-fluorofarnesyl diphosphate (2F-FPP) at 2.75 {angstrom} resolution. These structures illuminate unusual features that accommodate the trinuclear metal cluster required for substrate binding and catalysis. Like other terpenoid cyclases, DCS contains a characteristic aspartate-rich D{sup 307}DTYD{sup 311} motif on helix D that interacts with Mg{sub A}{sup 2+} and Mg{sub C}{sup 2+}. However, DCS appears to be unique among terpenoid cyclases in that it does not contain the 'NSE/DTE' motif on helix H that specifically chelates Mg{sub B}{sup 2+}, which is usually found as the signature sequence (N,D)D(L,I,V)X(S,T)XXXE (boldface indicates Mg{sub B}{sup 2+} ligands). Instead, DCS contains a second aspartate-rich motif, D{sup 451}DVAE{sup 455}, that interacts with Mg{sub B}{sup 2+}. In this regard, DCS is more similar to the isoprenoid chain elongation enzyme farnesyl diphosphate synthase, which also contains two aspartate-rich motifs, rather than the greater family of terpenoid cyclases. Nevertheless, the structure of the DCS-2F-FPP complex shows that the structure of the trinuclear magnesium cluster is generally similar to that of other terpenoid cyclases despite the alternative Mg{sub B}{sup 2+} binding motif. Analyses of DCS mutants with alanine substitutions in the D{sup 307}DTYD{sup 311} and D{sup 451}DVAE{sup 455} segments reveal the contributions of these segments to catalysis.

  3. The impact of RNA binding motif protein 4-regulated splicing cascade on the progression and metabolism of colorectal cancer cells.

    PubMed

    Liang, Yu-Chih; Lin, Wei-Cheng; Lin, Ying-Ju; Lin, Jung-Chun

    2015-11-10

    Dysregulated splicing of pre-messenger (m)RNA is considered a molecular occasion of carcinogenesis. However, the underlying mechanism is complex and remains to be investigated. Herein, we report that the upregulated miR-92a reduced the RNA-binding motif 4 (RBM4) protein expression, leading to the imbalanced expression of the neuronal polypyrimidine tract-binding (nPTB) protein through alternative splicing-coupled nonsense mediated decay (NMD) mechanism. Increase in nPTB protein enhances the relative level of fibroblast growth factor receptor 2 IIIc (FGFR2) and pyruvate kinase M2 (PKM2) transcripts which contribute to the progression and metabolic signature of CRC cells. Expression profiles of RBM4 and downstream alternative splicing events are consistently observed in cancerous tissues compared to adjacent normal tissues. These results constitute a mechanistic understanding of RBM4 on repressing the carcinogenesis of colorectal cells.

  4. Stress-caused anergy of leukocytes towards Staphylococcal enterotoxin B and exposure transcriptome signatures.

    PubMed

    Muhie, S; Hammamieh, R; Cummings, C; Yang, D; Jett, M

    2015-01-01

    Leucocytes from soldiers exposed to battlefield-like stress (RASP: Rangers Assessment and Selection Program) were exposed in vitro to Staphylococcal enterotoxin B (SEB). We assayed SEB-induced regulation of gene expression, both in the presence and absence of severe stress, to generate two sets of gene profiles. One set of transcripts and microRNAs were specific to post-RASP SEB exposure, and another set were signatures of SEB exposure common to both the pre- and post-RASP leucocytes. Pathways and upstream regulatory analyses indicated that the post-RASP SEB-signature transcripts were manifestation of the anergic state of post-RASP leucocytes. These were further verified using expression-based predictions of cellular processes and literature searches. Specificity of the second set of transcripts to SEB exposure was verified using machine-learning algorithms on our and four other (Gene Expression Omnibus) data sets. Cell adhesion, coagulation, hypoxia and vascular endothelial growth factor-mediated vascular leakage were SEB-specific pathways even under the background of severe stress. Hsa-miR-155-3p was the top SEB exposure predictor in our data set, and C-X-C motif chemokine ligand 9 was SEB specific in all the analyzed data sets. The SEB-signature transcripts (which also showed distinct expression signatures from Yersinia pestis and dengue virus) may serve as potential biomarkers of SEB exposure even under the background of stress.

  5. The noncatalytic triad of alpha-amylases: a novel structural motif involved in conformational stability.

    PubMed

    Marx, Jean-Claude; Poncin, Johan; Simorre, Jean-Pierre; Ramteke, Pramod W; Feller, Georges

    2008-02-01

    Chloride-activated alpha-amylases contain a noncatalytic triad, independent of the glycosidic active site, perfectly mimicking the catalytic triad of serine-proteases and of other active serine hydrolytic enzymes. Mutagenesis of Glu, His, and Ser residues in various alpha-amylases shows that this pattern is a structural determinant of the enzyme conformation that cannot be altered without losing the intrinsic stability of the protein. (1)H-(15)N NMR spectra of a bacterial alpha-amylase reveal proton signals that are identical with the NMR signature of catalytic triads and especially a deshielded proton involving a protonated histidine and displaying properties similar to that of a low barrier hydrogen bond. It is proposed that the H-bond between His and Glu of the noncatalytic triad is an unusually strong interaction, responsible for the observed NMR signal and for the weak stability of the triad mutants. Furthermore, a stringent template-based search of the Protein Data Bank demonstrated that this motif is not restricted to alpha-amylases, but is also found in 80 structures from 33 different proteins, amongst which SH2 domain-containing proteins are the best representatives.

  6. The transcription factor Spn1 regulates gene expression via a highly conserved novel structural motif

    PubMed Central

    Pujari, Venugopal; Radebaugh, Catherine A.; Chodaparambil, Jayanth V.; Muthurajan, Uma M.; Almeida, Adam R.; Fischbeck, Julie A.; Luger, Karolin; Stargell, Laurie A.

    2010-01-01

    Spn1 plays essential roles in the regulation of gene expression by RNA Polymerase II (RNAPII), and it is highly conserved in organisms ranging from yeast to humans. Spn1 physically and/or genetically interacts with RNAPII, TBP, TFIIS and a number of chromatin remodeling factors (Swi/Snf and Spt6). The central domain of Spn1 (residues 141-305 out of 410) is necessary and sufficient for performing the essential functions of SPN1 in yeast cells. Here we report the high-resolution (1.85Å) crystal structure of the conserved central domain of Saccharomyces cerevisiae Spn1. The central domain is comprised of eight alpha-helices in a right handed super helical arrangement, and exhibits structural similarity to domain I of TFIIS. A unique structural feature of Spn1 is a highly conserved loop, which defines one side of a pronounced cavity. The loop and the other residues forming the cavity are highly conserved at the amino acid level among all Spn1 family members, suggesting that this is a signature motif for Spn1 orthologs. The locations and the molecular characterization of temperature-sensitive mutations in Spn1 indicate that the cavity is a key attribute of Spn1 that is critical for its regulatory functions during RNAPII-mediated transcriptional activity. PMID:20875428

  7. The transcription factor Spn1 regulates gene expression via a highly conserved novel structural motif.

    PubMed

    Pujari, Venugopal; Radebaugh, Catherine A; Chodaparambil, Jayanth V; Muthurajan, Uma M; Almeida, Adam R; Fischbeck, Julie A; Luger, Karolin; Stargell, Laurie A

    2010-11-19

    Spn1/Iws1 plays essential roles in the regulation of gene expression by RNA polymerase II (RNAPII), and it is highly conserved in organisms ranging from yeast to humans. Spn1 physically and/or genetically interacts with RNAPII, TBP (TATA-binding protein), TFIIS (transcription factor IIS), and a number of chromatin remodeling factors (Swi/Snf and Spt6). The central domain of Spn1 (residues 141-305 out of 410) is necessary and sufficient for performing the essential functions of SPN1 in yeast cells. Here, we report the high-resolution (1.85 Å) crystal structure of the conserved central domain of Saccharomyces cerevisiae Spn1. The central domain is composed of eight α-helices in a right-handed superhelical arrangement and exhibits structural similarity to domain I of TFIIS. A unique structural feature of Spn1 is a highly conserved loop, which defines one side of a pronounced cavity. The loop and the other residues forming the cavity are highly conserved at the amino acid level among all Spn1 family members, suggesting that this is a signature motif for Spn1 orthologs. The locations and the molecular characterization of temperature-sensitive mutations in Spn1 indicate that the cavity is a key attribute of Spn1 that is critical for its regulatory functions during RNAPII-mediated transcriptional activity.

  8. Motivated Proteins: A web application for studying small three-dimensional protein motifs

    PubMed Central

    Leader, David P; Milner-White, E James

    2009-01-01

    Background Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are αβ-motifs, asx-motifs, asx-turns, β-bulges, β-bulge loops, β-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns. We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. Description The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. Conclusion Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schema. PMID:19210785

  9. Forensic handwriting examiners' expertise for signature comparison.

    PubMed

    Sita, Jodi; Found, Bryan; Rogers, Douglas K

    2002-09-01

    This paper reports on the performance of forensic document examiners (FDEs) in a signature comparison task that was designed to address the issue of expertise. The opinions of FDEs regarding 150 genuine and simulated questioned signatures were compared with a control group of non-examiners' opinions. On the question of expertise, results showed that FDEs were statistically better than the control group at accurately determining the genuineness or non-genuineness of questioned signatures. The FDE group made errors (by calling a genuine signature simulated or by calling a simulated signature genuine) in 3.4% of their opinions while 19.3% of the control group's opinions were erroneous. The FDE group gave significantly more inconclusive opinions than the control group. Analysis of FDEs' responses showed that more correct opinions were expressed regarding simulated signatures and more inconclusive opinions were made on genuine signatures. Further, when the complexity of a signature was taken into account, FDEs made more correct opinions on high complexity signatures than on signatures of lower complexity. There was a wide range of skill amongst FDEs and no significant relationship was found between the number of years FDEs had been practicing and their correct, inconclusive and error rates.

  10. Clustered somatic mutations are frequent in transcription factor binding motifs within proximal promoter regions in melanoma and other cutaneous malignancies

    PubMed Central

    Colebatch, Andrew J.; Di Stefano, Leon; Wong, Stephen Q.; Hannan, Ross D.; Waring, Paul M.; Dobrovic, Alexander

    2016-01-01

    Most cancer DNA sequencing studies have prioritized recurrent non-synonymous coding mutations in order to identify novel cancer-related mutations. Although attention is increasingly being paid to mutations in non-coding regions, standard approaches to identifying significant mutations may not be appropriate and there has been limited analysis of mutational clusters in functionally annotated non-coding regions. We sought to identify clustered somatic mutations (hotspot regions across samples) in functionally annotated regions in melanoma and other cutaneous malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma). Sliding window analyses revealed numerous recurrent clustered hotspot mutations in proximal promoters, with some specific clusters present in up to 25% of cases. Mutations in melanoma were clustered within ETS and Sp1 transcription factor binding motifs, had a UV signature and were identified in other cutaneous malignancies. Clinicopathologic correlation and mutation analysis support a causal role for chronic UV irradiation generating somatic mutations in transcription factor binding motifs of proximal promoters. PMID:27611953

  11. Genetic signatures of heroin addiction.

    PubMed

    Chen, Shaw-Ji; Liao, Ding-Lieh; Shen, Tsu-Wang; Yang, Hsin-Chou; Chen, Kuang-Chi; Chen, Chia-Hsiang

    2016-08-01

    Heroin addiction is a complex psychiatric disorder with a chronic course and a high relapse rate, which results from the interaction between genetic and environmental factors. Heroin addiction has a substantial heritability in its etiology; hence, identification of individuals with a high genetic propensity to heroin addiction may help prevent the occurrence and relapse of heroin addiction and its complications. The study aimed to identify a small set of genetic signatures that may reliably predict the individuals with a high genetic propensity to heroin addiction. We first measured the transcript level of 13 genes (RASA1, PRKCB, PDK1, JUN, CEBPG, CD74, CEBPB, AUTS2, ENO2, IMPDH2, HAT1, MBD1, and RGS3) in lymphoblastoid cell lines in a sample of 124 male heroin addicts and 124 male control subjects using real-time quantitative PCR. Seven genes (PRKCB, PDK1, JUN, CEBPG, CEBPB, ENO2, and HAT1) showed significant differential expression between the 2 groups. Further analysis using 3 statistical methods including logistic regression analysis, support vector machine learning analysis, and a computer software BIASLESS revealed that a set of 4 genes (JUN, CEBPB, PRKCB, ENO2, or CEBPG) could predict the diagnosis of heroin addiction with the accuracy rate around 85% in our dataset. Our findings support the idea that it is possible to identify genetic signatures of heroin addiction using a small set of expressed genes. However, the study can only be considered as a proof-of-concept study. As the establishment of lymphoblastoid cell line is a laborious and lengthy process, it would be more practical in clinical settings to identify genetic signatures for heroin addiction directly from peripheral blood cells in the future study.

  12. Infrared signatures for remote sensing

    SciTech Connect

    McDowell, R.S.; Sharpe, S.W.; Kelly, J.F.

    1994-04-01

    PNL`s capabilities for infrared and near-infrared spectroscopy include tunable-diode-laser (TDL) systems covering 300--3,000 cm{sup {minus}1} at <10-MHz bandwidth; a Bruker Fourier-transform infrared (FTIR) spectrometer for the near- to far-infrared at 50-MHz resolution; and a stable line-tunable, 12-w cw CO{sub 2} laser. PNL also has a beam expansion source with a 12-cm slit, which provides a 3-m effective path for gases at {approximately}10 K, giving a Doppler width of typically 10 MHz; and long-path static gas cells (to 100 m). In applying this equipment to signatures work, the authors emphasize the importance of high spectral resolution for detecting and identifying atmospheric interferences; for identifying the optimum analytical frequencies; for deriving, by spectroscopic analysis, the molecular parameters needed for modeling; and for obtaining data on species and/or bands that are not in existing databases. As an example of such spectroscopy, the authors have assigned and analyzed the C-Cl stretching region of CCl{sub 4} at 770--800 cm{sup {minus}1}. This is an important potential signature species whose IR absorption has remained puzzling because of the natural isotopic mix, extensive hot-band structure, and a Fermi resonance involving a nearby combination band. Instrument development projects include the IR sniffer, a small high-sensitivity, high-discrimination (Doppler-limited) device for fence-line or downwind monitoring that is effective even in regions of atmospheric absorption; preliminary work has achieved sensitivities at the low-ppb level. Other work covers trace species detection with TDLs, and FM-modulated CO{sub 2} laser LIDAR. The authors are planning a field experiment to interrogate the Hanford tank farm for signature species from Rattlesnake Mountain, a standoff of ca. 15 km, to be accompanied by simultaneous ground-truthing at the tanks.

  13. Signature of anisotropic bubble collisions

    SciTech Connect

    Salem, Michael P.

    2010-09-15

    Our universe may have formed via bubble nucleation in an eternally inflating background. Furthermore, the background may have a compact dimension--the modulus of which tunnels out of a metastable minimum during bubble nucleation--which subsequently grows to become one of our three large spatial dimensions. When in this scenario our bubble universe collides with other ones like it, the collision geometry is constrained by the reduced symmetry of the tunneling instanton. While the regions affected by such bubble collisions still appear (to leading order) as disks in an observer's sky, the centers of these disks all lie on a single great circle, providing a distinct signature of anisotropic bubble nucleation.

  14. Spectroscopic signature for ferroelectric ice

    NASA Astrophysics Data System (ADS)

    Wójcik, Marek J.; Gług, Maciej; Boczar, Marek; Boda, Łukasz

    2014-09-01

    Various forms of ice exist within our galaxy. Particularly intriguing type of ice - ‘ferroelectric ice' was discovered experimentally and is stable in temperatures below 72 K. This form of ice can generate enormous electric fields and can play an important role in planetary formation. In this letter we present Car-Parrinello simulation of infrared spectra of ferroelectric ice and compare them with spectra of hexagonal ice. Librational region of the spectra can be treated as spectroscopic signature of ice XI and can be of help to identify ferroelectric ice in the Universe.

  15. Satellite signatures in SLR observations

    NASA Technical Reports Server (NTRS)

    Appleby, G. M.

    1993-01-01

    We examine the evidence for the detection of satellite-dependent signatures in the laser range observations obtained by the UK single-photon Satellite Laser Ranging (SLR) System models of the expected observation distributions from Ajisai and Lageos are developed from the published satellite spread functions and from the characteristics of the SLR System and compared with the observations. The effects of varying return strengths are discussed using the models and by experimental observations of Ajisai, during which a range of return levels from single to multiple photons is achieved. The implications of these results for system-dependent center for mass corrections are discussed.

  16. Observational Signatures of Magnetic Reconnection

    NASA Technical Reports Server (NTRS)

    Savage, Sabrina

    2014-01-01

    Magnetic reconnection is often referred to as the primary source of energy release during solar flares. Directly observing reconnection occurring in the solar atmosphere, however, is not trivial considering that the scale size of the diffusion region is magnitudes smaller than the observational capabilities of current instrumentation, and coronal magnetic field measurements are not currently sufficient to capture the process. Therefore, predicting and studying observationally feasible signatures of the precursors and consequences of reconnection is necessary for guiding and verifying the simulations that dominate our understanding. I will present a set of such observations, particularly in connection with long-duration solar events, and compare them with recent simulations and theoretical predictions.

  17. Gut microbiota signatures of longevity.

    PubMed

    Kong, Fanli; Hua, Yutong; Zeng, Bo; Ning, Ruihong; Li, Ying; Zhao, Jiangchao

    2016-09-26

    An aging global population poses substantial challenges to society [1]. Centenarians are a model for healthy aging because they have reached the extreme limit of life by escaping, surviving, or delaying chronic diseases [2]. The genetics of centenarians have been extensively examined [3], but less is known about their gut microbiotas. Recently, Biagi et al.[4] characterized the gut microbiota in Italian centenarians and semi-supercentenarians. Here, we compare the gut microbiota of Chinese long-living people with younger age groups, and with the results from the Italian population [4], to identify gut-microbial signatures of healthy aging.

  18. Quantum broadcasting multiple blind signature with constant size

    NASA Astrophysics Data System (ADS)

    Xiao, Min; Li, Zhenli

    2016-09-01

    Using quantum homomorphic signature in quantum network, we propose a quantum broadcasting multiple blind signature scheme. Different from classical signature and current quantum signature schemes, the multi-signature proposed in our scheme is not generated by simply putting the individual signatures together, but by aggregating the individual signatures based on homomorphic property. Therefore, the size of the multi-signature is constant. Furthermore, based on a wide range of investigation for the security of existing quantum signature protocols, our protocol is designed to resist possible forgery attacks against signature and message from the various attack sources and disavowal attacks from participants.

  19. A Bioinformatics Approach for Detecting Repetitive Nested Motifs using Pattern Matching

    PubMed Central

    Romero, José R.; Carballido, Jessica A.; Garbus, Ingrid; Echenique, Viviana C.; Ponzoni, Ignacio

    2016-01-01

    The identification of nested motifs in genomic sequences is a complex computational problem. The detection of these patterns is important to allow the discovery of transposable element (TE) insertions, incomplete reverse transcripts, deletions, and/or mutations. In this study, a de novo strategy for detecting patterns that represent nested motifs was designed based on exhaustive searches for pairs of motifs and combinatorial pattern analysis. These patterns can be grouped into three categories, motifs within other motifs, motifs flanked by other motifs, and motifs of large size. The methodology used in this study, applied to genomic sequences from the plant species Aegilops tauschii and Oryza sativa, revealed that it is possible to identify putative nested TEs by detecting these three types of patterns. The results were validated through BLAST alignments, which revealed the efficacy and usefulness of the new method, which is called Mamushka. PMID:27812277

  20. FPGA implementation of motifs-based neuronal network and synchronization analysis

    NASA Astrophysics Data System (ADS)

    Deng, Bin; Zhu, Zechen; Yang, Shuangming; Wei, Xile; Wang, Jiang; Yu, Haitao

    2016-06-01

    Motifs in complex networks play a crucial role in determining the brain functions. In this paper, 13 kinds of motifs are implemented with Field Programmable Gate Array (FPGA) to investigate the relationships between the networks properties and motifs properties. We use discretization method and pipelined architecture to construct various motifs with Hindmarsh-Rose (HR) neuron as the node model. We also build a small-world network based on these motifs and conduct the synchronization analysis of motifs as well as the constructed network. We find that the synchronization properties of motif determine that of motif-based small-world network, which demonstrates effectiveness of our proposed hardware simulation platform. By imitation of some vital nuclei in the brain to generate normal discharges, our proposed FPGA-based artificial neuronal networks have the potential to replace the injured nuclei to complete the brain function in the treatment of Parkinson's disease and epilepsy.

  1. Convergent evolution and mimicry of protein linear motifs in host-pathogen interactions.

    PubMed

    Chemes, Lucía Beatriz; de Prat-Gay, Gonzalo; Sánchez, Ignacio Enrique

    2015-06-01

    Pathogen linear motif mimics are highly evolvable elements that facilitate rewiring of host protein interaction networks. Host linear motifs and pathogen mimics differ in sequence, leading to thermodynamic and structural differences in the resulting protein-protein interactions. Moreover, the functional output of a mimic depends on the motif and domain repertoire of the pathogen protein. Regulatory evolution mediated by linear motifs can be understood by measuring evolutionary rates, quantifying positive and negative selection and performing phylogenetic reconstructions of linear motif natural history. Convergent evolution of linear motif mimics is widespread among unrelated proteins from viral, prokaryotic and eukaryotic pathogens and can also take place within individual protein phylogenies. Statistics, biochemistry and laboratory models of infection link pathogen linear motifs to phenotypic traits such as tropism, virulence and oncogenicity. In vitro evolution experiments and analysis of natural sequences suggest that changes in linear motif composition underlie pathogen adaptation to a changing environment.

  2. A Bioinformatics Approach for Detecting Repetitive Nested Motifs using Pattern Matching.

    PubMed

    Romero, José R; Carballido, Jessica A; Garbus, Ingrid; Echenique, Viviana C; Ponzoni, Ignacio

    2016-01-01

    The identification of nested motifs in genomic sequences is a complex computational problem. The detection of these patterns is important to allow the discovery of transposable element (TE) insertions, incomplete reverse transcripts, deletions, and/or mutations. In this study, a de novo strategy for detecting patterns that represent nested motifs was designed based on exhaustive searches for pairs of motifs and combinatorial pattern analysis. These patterns can be grouped into three categories, motifs within other motifs, motifs flanked by other motifs, and motifs of large size. The methodology used in this study, applied to genomic sequences from the plant species Aegilops tauschii and Oryza sativa, revealed that it is possible to identify putative nested TEs by detecting these three types of patterns. The results were validated through BLAST alignments, which revealed the efficacy and usefulness of the new method, which is called Mamushka.

  3. Visual signatures in video visualization.

    PubMed

    Chen, Min; Botchen, Ralf P; Hashim, Rudy R; Weiskopf, Daniel; Ertl, Thomas; Thornton, Ian M

    2006-01-01

    Video visualization is a computation process that extracts meaningful information from original video data sets and conveys the extracted information to users in appropriate visual representations. This paper presents a broad treatment of the subject, following a typical research pipeline involving concept formulation, system development, a path-finding user study, and a field trial with real application data. In particular, we have conducted a fundamental study on the visualization of motion events in videos. We have, for the first time, deployed flow visualization techniques in video visualization. We have compared the effectiveness of different abstract visual representations of videos. We have conducted a user study to examine whether users are able to learn to recognize visual signatures of motions, and to assist in the evaluation of different visualization techniques. We have applied our understanding and the developed techniques to a set of application video clips. Our study has demonstrated that video visualization is both technically feasible and cost-effective. It has provided the first set of evidence confirming that ordinary users can be accustomed to the visual features depicted in video visualizations, and can learn to recognize visual signatures of a variety of motion events.

  4. Association of branched oligonucleotides into the i-motif.

    PubMed

    Robidoux, S; Klinck, R; Gehring, K; Damha, M J

    1997-12-01

    The unique architecture of branched oligonucleotides mimicking lariat RNA introns [Wallace and Edmons, Proc. Natl. Acad. Sci. USA 80, 950-954 (1983)] was exploited to study compounds that associate as two parallel duplexes with intercalating C/C+ base pairs (i-motif DNA) [Gehring et al. Nature 363, 561-565 (1993)]. The formation of a branched cytosine tetrad was induced by joining the 5'-ends of pair of pentadeoxycytidine strands with a branching riboadenosine (rA) linker. This arrangement causes the orientation of the dC strands to be parallel, and forces the formation of a C/C+ duplex that self-associates into i-DNA. Presence of the i-motif in this structure is supported by thermal denaturation, native gel electrophoresis, CD, and NMR spectroscopy.

  5. Factoring local sequence composition in motif significance analysis.

    PubMed

    Ng, Patrick; Keich, Uri

    2008-01-01

    We recently introduced a biologically realistic and reliable significance analysis of the output of a popular class of motif finders. In this paper we further improve our significance analysis by incorporating local base composition information. Relying on realistic biological data simulation, as well as on FDR analysis applied to real data, we show that our method is significantly better than the increasingly popular practice of using the normal approximation to estimate the significance of a finder's output. Finally we turn to leveraging our reliable significance analysis to improve the actual motif finding task. Specifically, endowing a variant of the Gibbs Sampler with our improved significance analysis we demonstrate that de novo finders can perform better than has been perceived. Significantly, our new variant outperforms all the finders reviewed in a recently published comprehensive analysis of the Harbison genome-wide binding location data. Interestingly, many of these finders incorporate additional information such as nucleosome positioning and the significance of binding data.

  6. Finding sequence motifs in groups of functionally related proteins.

    PubMed

    Smith, H O; Annau, T M; Chandrasegaran, S

    1990-01-01

    We have developed a method for rapidly finding patterns of conserved amino acid residues (motifs) in groups of functionally related proteins. All 3-amino acid patterns in a group of proteins of the type aa1 d1 aa2 d2 aa3, where d1 and d2 are distances that can be varied in a range up to 24 residues, are accumulated into an array. Segments of the proteins containing those patterns that occur most frequently are aligned on each other by a scoring method that obtains an average relatedness value for all the amino acids in each column of the aligned sequence block based on the Dayhoff relatedness odds matrix. The automated method successfully finds and displays nearly all of the sequence motifs that have been previously reported to occur in 33 reverse transcriptases, 18 DNA integrases, and 30 DNA methyltransferases.

  7. Graph animals, subgraph sampling, and motif search in large networks.

    PubMed

    Baskerville, Kim; Grassberger, Peter; Paczuski, Maya

    2007-09-01

    We generalize a sampling algorithm for lattice animals (connected clusters on a regular lattice) to a Monte Carlo algorithm for "graph animals," i.e., connected subgraphs in arbitrary networks. As with the algorithm in [N. Kashtan et al., Bioinformatics 20, 1746 (2004)], it provides a weighted sample, but the computation of the weights is much faster (linear in the size of subgraphs, instead of superexponential). This allows subgraphs with up to ten or more nodes to be sampled with very high statistics, from arbitrarily large networks. Using this together with a heuristic algorithm for rapidly classifying isomorphic graphs, we present results for two protein interaction networks obtained using the tandem affinity purification (TAP) method: one of Escherichia coli with 230 nodes and 695 links, and one for yeast (Saccharomyces cerevisiae) with roughly ten times more nodes and links. We find in both cases that most connected subgraphs are strong motifs (Z scores >10) or antimotifs (Z scores <-10) when the null model is the ensemble of networks with fixed degree sequence. Strong differences appear between the two networks, with dominant motifs in E. coli being (nearly) bipartite graphs and having many pairs of nodes that connect to the same neighbors, while dominant motifs in yeast tend towards completeness or contain large cliques. We also explore a number of methods that do not rely on measurements of Z scores or comparisons with null models. For instance, we discuss the influence of specific complexes like the 26S proteasome in yeast, where a small number of complexes dominate the k cores with large k and have a decisive effect on the strongest motifs with 6-8 nodes. We also present Zipf plots of counts versus rank. They show broad distributions that are not power laws, in contrast to the case when disconnected subgraphs are included.

  8. A survey of motif discovery methods in an integrated framework

    PubMed Central

    Sandve, Geir Kjetil; Drabløs, Finn

    2006-01-01

    Background There has been a growing interest in computational discovery of regulatory elements, and a multitude of motif discovery methods have been proposed. Computational motif discovery has been used with some success in simple organisms like yeast. However, as we move to higher organisms with more complex genomes, more sensitive methods are needed. Several recent methods try to integrate additional sources of information, including microarray experiments (gene expression and ChlP-chip). There is also a growing awareness that regulatory elements work in combination, and that this combinatorial behavior must be modeled for successful motif discovery. However, the multitude of methods and approaches makes it difficult to get a good understanding of the current status of the field. Results This paper presents a survey of methods for motif discovery in DNA, based on a structured and well defined framework that integrates all relevant elements. Existing methods are discussed according to this framework. Conclusion The survey shows that although no single method takes all relevant elements into consideration, a very large number of different models treating the various elements separately have been tried. Very often the choices that have been made are not explicitly stated, making it difficult to compare different implementations. Also, the tests that have been used are often not comparable. Therefore, a stringent framework and improved test methods are needed to evaluate the different approaches in order to conclude which ones are most promising. Reviewers: This article was reviewed by Eugene V. Koonin, Philipp Bucher (nominated by Mikhail Gelfand) and Frank Eisenhaber. PMID:16600018

  9. A Combinatorial Code for Splicing Silencing: UAGG and GGGG Motifs

    PubMed Central

    An, Ping; Burge, Christopher B

    2005-01-01

    Alternative pre-mRNA splicing is widely used to regulate gene expression by tuning the levels of tissue-specific mRNA isoforms. Few regulatory mechanisms are understood at the level of combinatorial control despite numerous sequences, distinct from splice sites, that have been shown to play roles in splicing enhancement or silencing. Here we use molecular approaches to identify a ternary combination of exonic UAGG and 5′-splice-site-proximal GGGG motifs that functions cooperatively to silence the brain-region-specific CI cassette exon (exon 19) of the glutamate NMDA R1 receptor (GRIN1) transcript. Disruption of three components of the motif pattern converted the CI cassette into a constitutive exon, while predominant skipping was conferred when the same components were introduced, de novo, into a heterologous constitutive exon. Predominant exon silencing was directed by the motif pattern in the presence of six competing exonic splicing enhancers, and this effect was retained after systematically repositioning the two exonic UAGGs within the CI cassette. In this system, hnRNP A1 was shown to mediate silencing while hnRNP H antagonized silencing. Genome-wide computational analysis combined with RT-PCR testing showed that a class of skipped human and mouse exons can be identified by searches that preserve the sequence and spatial configuration of the UAGG and GGGG motifs. This analysis suggests that the multi-component silencing code may play an important role in the tissue-specific regulation of the CI cassette exon, and that it may serve more generally as a molecular language to allow for intricate adjustments and the coordination of splicing patterns from different genes. PMID:15828859

  10. Graph animals, subgraph sampling, and motif search in large networks

    NASA Astrophysics Data System (ADS)

    Baskerville, Kim; Grassberger, Peter; Paczuski, Maya

    2007-09-01

    We generalize a sampling algorithm for lattice animals (connected clusters on a regular lattice) to a Monte Carlo algorithm for “graph animals,” i.e., connected subgraphs in arbitrary networks. As with the algorithm in [N. Kashtan , Bioinformatics 20, 1746 (2004)], it provides a weighted sample, but the computation of the weights is much faster (linear in the size of subgraphs, instead of superexponential). This allows subgraphs with up to ten or more nodes to be sampled with very high statistics, from arbitrarily large networks. Using this together with a heuristic algorithm for rapidly classifying isomorphic graphs, we present results for two protein interaction networks obtained using the tandem affinity purification (TAP) method: one of Escherichia coli with 230 nodes and 695 links, and one for yeast (Saccharomyces cerevisiae) with roughly ten times more nodes and links. We find in both cases that most connected subgraphs are strong motifs ( Z scores >10 ) or antimotifs ( Z scores <-10 ) when the null model is the ensemble of networks with fixed degree sequence. Strong differences appear between the two networks, with dominant motifs in E. coli being (nearly) bipartite graphs and having many pairs of nodes that connect to the same neighbors, while dominant motifs in yeast tend towards completeness or contain large cliques. We also explore a number of methods that do not rely on measurements of Z scores or comparisons with null models. For instance, we discuss the influence of specific complexes like the 26S proteasome in yeast, where a small number of complexes dominate the k cores with large k and have a decisive effect on the strongest motifs with 6-8 nodes. We also present Zipf plots of counts versus rank. They show broad distributions that are not power laws, in contrast to the case when disconnected subgraphs are included.

  11. Motif, the basics: an overview of the widget set

    SciTech Connect

    McClurg, F.R.

    1992-10-01

    The Motif library provides programmers with a rich set of tools for building a graphical user interface with a three-dimensional appearance and a consistent method of interaction for controlling an Unix application. This Xt-based, high-level library presents an object-oriented'' approach to program design for programmers and allows end-users the flexibility to modify attributes of the interface.

  12. Motif, the basics: an overview of the widget set

    SciTech Connect

    McClurg, F.R.

    1992-10-01

    The Motif library provides programmers with a rich set of tools for building a graphical user interface with a three-dimensional appearance and a consistent method of interaction for controlling an Unix application. This Xt-based, high-level library presents an ``object-oriented`` approach to program design for programmers and allows end-users the flexibility to modify attributes of the interface.

  13. Secure Obfuscation for Encrypted Group Signatures

    PubMed Central

    Fan, Hongfei; Liu, Qin

    2015-01-01

    In recent years, group signature techniques are widely used in constructing privacy-preserving security schemes for various information systems. However, conventional techniques keep the schemes secure only in normal black-box attack contexts. In other words, these schemes suppose that (the implementation of) the group signature generation algorithm is running in a platform that is perfectly protected from various intrusions and attacks. As a complementary to existing studies, how to generate group signatures securely in a more austere security context, such as a white-box attack context, is studied in this paper. We use obfuscation as an approach to acquire a higher level of security. Concretely, we introduce a special group signature functionality-an encrypted group signature, and then provide an obfuscator for the proposed functionality. A series of new security notions for both the functionality and its obfuscator has been introduced. The most important one is the average-case secure virtual black-box property w.r.t. dependent oracles and restricted dependent oracles which captures the requirement of protecting the output of the proposed obfuscator against collision attacks from group members. The security notions fit for many other specialized obfuscators, such as obfuscators for identity-based signatures, threshold signatures and key-insulated signatures. Finally, the correctness and security of the proposed obfuscator have been proven. Thereby, the obfuscated encrypted group signature functionality can be applied to variants of privacy-preserving security schemes and enhance the security level of these schemes. PMID:26167686

  14. Input apparatus for dynamic signature verification systems

    DOEpatents

    EerNisse, Errol P.; Land, Cecil E.; Snelling, Jay B.

    1978-01-01

    The disclosure relates to signature verification input apparatus comprising a writing instrument and platen containing piezoelectric transducers which generate signals in response to writing pressures.

  15. Structure and ubiquitin binding of the ubiquitin-interacting motif

    SciTech Connect

    Fisher,R.; Wang, B.; Alam, S.; Higginson, D.; Robinson, H.; Sundquist, C.; Hill, C.

    2003-01-01

    Ubiquitylation is used to target proteins into a large number of different biological processes including proteasomal degradation, endocytosis, virus budding, and vacuolar protein sorting (Vps). Ubiquitylated proteins are typically recognized using one of several different conserved ubiquitin binding modules. Here, we report the crystal structure and ubiquitin binding properties of one such module, the ubiquitin-interacting motif (UIM). We found that UIM peptides from several proteins involved in endocytosis and vacuolar protein sorting including Hrs, Vps27p, Stam1, and Eps15 bound specifically, but with modest affinity (K{sub d} = 0.1-1 mM), to free ubiquitin. Full affinity ubiquitin binding required the presence of conserved acidic patches at the N and C terminus of the UIM, as well as highly conserved central alanine and serine residues. NMR chemical shift perturbation mapping experiments demonstrated that all of these UIM peptides bind to the I44 surface of ubiquitin. The 1.45 {angstrom} resolution crystal structure of the second yeast Vps27p UIM (Vps27p-2) revealed that the ubiquitin-interacting motif forms an amphipathic helix. Although Vps27p-2 is monomeric in solution, the motif unexpectedly crystallized as an antiparallel four-helix bundle, and the potential biological implications of UIM oligomerization are therefore discussed.

  16. Maximum likelihood density modification by pattern recognition of structural motifs

    DOEpatents

    Terwilliger, Thomas C.

    2004-04-13

    An electron density for a crystallographic structure having protein regions and solvent regions is improved by maximizing the log likelihood of a set of structures factors {F.sub.h } using a local log-likelihood function: (x)+p(.rho.(x).vertline.SOLV)p.sub.SOLV (x)+p(.rho.(x).vertline.H)p.sub.H (x)], where p.sub.PROT (x) is the probability that x is in the protein region, p(.rho.(x).vertline.PROT) is the conditional probability for .rho.(x) given that x is in the protein region, and p.sub.SOLV (x) and p(.rho.(x).vertline.SOLV) are the corresponding quantities for the solvent region, p.sub.H (x) refers to the probability that there is a structural motif at a known location, with a known orientation, in the vicinity of the point x; and p(.rho.(x).vertline.H) is the probability distribution for electron density at this point given that the structural motif actually is present. One appropriate structural motif is a helical structure within the crystallographic structure.

  17. Retroviruses integrate into a shared, non-palindromic DNA motif.

    PubMed

    Kirk, Paul D W; Huvet, Maxime; Melamed, Anat; Maertens, Goedele N; Bangham, Charles R M

    2016-11-14

    Many DNA-binding factors, such as transcription factors, form oligomeric complexes with structural symmetry that bind to palindromic DNA sequences(1). Palindromic consensus nucleotide sequences are also found at the genomic integration sites of retroviruses(2-6) and other transposable elements(7-9), and it has been suggested that this palindromic consensus arises as a consequence of the structural symmetry in the integrase complex(2,3). However, we show here that the palindromic consensus sequence is not present in individual integration sites of human T-cell lymphotropic virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1), but arises in the population average as a consequence of the existence of a non-palindromic nucleotide motif that occurs in approximately equal proportions on the plus strand and the minus strand of the host genome. We develop a generally applicable algorithm to sort the individual integration site sequences into plus-strand and minus-strand subpopulations, and use this to identify the integration site nucleotide motifs of five retroviruses of different genera: HTLV-1, HIV-1, murine leukaemia virus (MLV), avian sarcoma leucosis virus (ASLV) and prototype foamy virus (PFV). The results reveal a non-palindromic motif that is shared between these retroviruses.

  18. STEME: efficient EM to find motifs in large data sets.

    PubMed

    Reid, John E; Wernisch, Lorenz

    2011-10-01

    MEME and many other popular motif finders use the expectation-maximization (EM) algorithm to optimize their parameters. Unfortunately, the running time of EM is linear in the length of the input sequences. This can prohibit its application to data sets of the size commonly generated by high-throughput biological techniques. A suffix tree is a data structure that can efficiently index a set of sequences. We describe an algorithm, Suffix Tree EM for Motif Elicitation (STEME), that approximates EM using suffix trees. To the best of our knowledge, this is the first application of suffix trees to EM. We provide an analysis of the expected running time of the algorithm and demonstrate that STEME runs an order of magnitude more quickly than the implementation of EM used by MEME. We give theoretical bounds for the quality of the approximation and show that, in practice, the approximation has a negligible effect on the outcome. We provide an open source implementation of the algorithm that we hope will be used to speed up existing and future motif search algorithms.

  19. Caveats in modeling a common motif in genetic circuits

    NASA Astrophysics Data System (ADS)

    Labavić, Darka; Nagel, Hannes; Janke, Wolfhard; Meyer-Ortmanns, Hildegard

    2013-06-01

    From a coarse-grained perspective, the motif of a self-activating species, activating a second species that acts as its own repressor, is widely found in biological systems, in particular in genetic systems with inherent oscillatory behavior. Here we consider a specific realization of this motif as a genetic circuit, termed the bistable frustrated unit, in which genes are described as directly producing proteins. Upon an improved resolution in time, we focus on the effect that inherent time scales on the underlying scale can have on the bifurcation patterns on a coarser scale. Time scales are set by the binding and unbinding rates of the transcription factors to the promoter regions of the genes. Depending on the ratio of these rates to the decay times of both proteins, the appropriate averaging procedure for obtaining a coarse-grained description changes and leads to sets of deterministic equations, which considerably differ in their bifurcation structure. In particular, the desired intermediate range of regular limit cycles fades away when the binding rates of genes are not fast as compared to the decay time of the proteins. Our analysis illustrates that the common topology of the widely found motif alone does not imply universal features in the dynamics.

  20. An update on cell surface proteins containing extensin-motifs.

    PubMed

    Borassi, Cecilia; Sede, Ana R; Mecchia, Martin A; Salgado Salter, Juan D; Marzol, Eliana; Muschietti, Jorge P; Estevez, Jose M

    2016-01-01

    In recent years it has become clear that there are several molecular links that interconnect the plant cell surface continuum, which is highly important in many biological processes such as plant growth, development, and interaction with the environment. The plant cell surface continuum can be defined as the space that contains and interlinks the cell wall, plasma membrane and cytoskeleton compartments. In this review, we provide an updated view of cell surface proteins that include modular domains with an extensin (EXT)-motif followed by a cytoplasmic kinase-like domain, known as PERKs (for proline-rich extensin-like receptor kinases); with an EXT-motif and an actin binding domain, known as formins; and with extracellular hybrid-EXTs. We focus our attention on the EXT-motifs with the short sequence Ser-Pro(3-5), which is found in several different protein contexts within the same extracellular space, highlighting a putative conserved structural and functional role. A closer understanding of the dynamic regulation of plant cell surface continuum and its relationship with the downstream signalling cascade is a crucial forthcoming challenge.

  1. The bioactive acidic serine- and aspartate-rich motif peptide.

    PubMed

    Minamizaki, Tomoko; Yoshiko, Yuji

    2015-01-01

    The organic component of the bone matrix comprises 40% dry weight of bone. The organic component is mostly composed of type I collagen and small amounts of non-collagenous proteins (NCPs) (10-15% of the total bone protein content). The small integrin-binding ligand N-linked glycoprotein (SIBLING) family, a NCP, is considered to play a key role in bone mineralization. SIBLING family of proteins share common structural features and includes the arginine-glycine-aspartic acid (RGD) motif and acidic serine- and aspartic acid-rich motif (ASARM). Clinical manifestations of gene mutations and/or genetically modified mice indicate that SIBLINGs play diverse roles in bone and extraskeletal tissues. ASARM peptides might not be primary responsible for the functional diversity of SIBLINGs, but this motif is suggested to be a key domain of SIBLINGs. However, the exact function of ASARM peptides is poorly understood. In this article, we discuss the considerable progress made in understanding the role of ASARM as a bioactive peptide.

  2. QuateXelero: An Accelerated Exact Network Motif Detection Algorithm

    PubMed Central

    Khakabimamaghani, Sahand; Sharafuddin, Iman; Dichter, Norbert; Koch, Ina; Masoudi-Nejad, Ali

    2013-01-01

    Finding motifs in biological, social, technological, and other types of networks has become a widespread method to gain more knowledge about these networks’ structure and function. However, this task is very computationally demanding, because it is highly associated with the graph isomorphism which is an NP problem (not known to belong to P or NP-complete subsets yet). Accordingly, this research is endeavoring to decrease the need to call NAUTY isomorphism detection method, which is the most time-consuming step in many existing algorithms. The work provides an extremely fast motif detection algorithm called QuateXelero, which has a Quaternary Tree data structure in the heart. The proposed algorithm is based on the well-known ESU (FANMOD) motif detection algorithm. The results of experiments on some standard model networks approve the overal superiority of the proposed algorithm, namely QuateXelero, compared with two of the fastest existing algorithms, G-Tries and Kavosh. QuateXelero is especially fastest in constructing the central data structure of the algorithm from scratch based on the input network. PMID:23874498

  3. A novel swarm intelligence algorithm for finding DNA motifs.

    PubMed

    Lei, Chengwei; Ruan, Jianhua

    2009-01-01

    Discovering DNA motifs from co-expressed or co-regulated genes is an important step towards deciphering complex gene regulatory networks and understanding gene functions. Despite significant improvement in the last decade, it still remains one of the most challenging problems in computational molecular biology. In this work, we propose a novel motif finding algorithm that finds consensus patterns using a population-based stochastic optimisation technique called Particle Swarm Optimisation (PSO), which has been shown to be effective in optimising difficult multidimensional problems in continuous domains. We propose to use a word dissimilarity graph to remap the neighborhood structure of the solution space of DNA motifs, and propose a modification of the naive PSO algorithm to accommodate discrete variables. In order to improve efficiency, we also propose several strategies for escaping from local optima and for automatically determining the termination criteria. Experimental results on simulated challenge problems show that our method is both more efficient and more accurate than several existing algorithms. Applications to several sets of real promoter sequences also show that our approach is able to detect known transcription factor binding sites, and outperforms two of the most popular existing algorithms.

  4. MAR characteristic motifs mediate episomal vector in CHO cells.

    PubMed

    Lin, Yan; Li, Zhaoxi; Wang, Tianyun; Wang, Xiaoyin; Wang, Li; Dong, Weihua; Jing, Changqin; Yang, Xianjun

    2015-04-01

    An ideal gene therapy vector should enable persistent transgene expression without limitations in safety and reproducibility. Recent researches' insight into the ability of chromosomal matrix attachment regions (MARs) to mediate episomal maintenance of genetic elements allowed the development of a circular episomal vector. Although a MAR-mediated engineered vector has been developed, little is known on which motifs of MAR confer this function during interaction with the host genome. Here, we report an artificially synthesized DNA fragment containing only characteristic motif sequences that served as an alternative to human beta-interferon matrix attachment region sequence. The potential of the vector to mediate gene transfer in CHO cells was investigated. The short synthetic MAR motifs were found to mediate episomal vector at a low copy number for many generations without integration into the host genome. Higher transgene expression was maintained for at least 4 months. In addition, MAR was maintained episomally and conferred sustained EGFP expression even in nonselective CHO cells. All the results demonstrated that MAR characteristic sequence-based vector can function as stable episomes in CHO cells, supporting long-term and effective transgene expression.

  5. Event Networks and the Identification of Crime Pattern Motifs

    PubMed Central

    2015-01-01

    In this paper we demonstrate the use of network analysis to characterise patterns of clustering in spatio-temporal events. Such clustering is of both theoretical and practical importance in the study of crime, and forms the basis for a number of preventative strategies. However, existing analytical methods show only that clustering is present in data, while offering little insight into the nature of the patterns present. Here, we show how the classification of pairs of events as close in space and time can be used to define a network, thereby generalising previous approaches. The application of graph-theoretic techniques to these networks can then offer significantly deeper insight into the structure of the data than previously possible. In particular, we focus on the identification of network motifs, which have clear interpretation in terms of spatio-temporal behaviour. Statistical analysis is complicated by the nature of the underlying data, and we provide a method by which appropriate randomised graphs can be generated. Two datasets are used as case studies: maritime piracy at the global scale, and residential burglary in an urban area. In both cases, the same significant 3-vertex motif is found; this result suggests that incidents tend to occur not just in pairs, but in fact in larger groups within a restricted spatio-temporal domain. In the 4-vertex case, different motifs are found to be significant in each case, suggesting that this technique is capable of discriminating between clustering patterns at a finer granularity than previously possible. PMID:26605544

  6. Event Networks and the Identification of Crime Pattern Motifs.

    PubMed

    Davies, Toby; Marchione, Elio

    2015-01-01

    In this paper we demonstrate the use of network analysis to characterise patterns of clustering in spatio-temporal events. Such clustering is of both theoretical and practical importance in the study of crime, and forms the basis for a number of preventative strategies. However, existing analytical methods show only that clustering is present in data, while offering little insight into the nature of the patterns present. Here, we show how the classification of pairs of events as close in space and time can be used to define a network, thereby generalising previous approaches. The application of graph-theoretic techniques to these networks can then offer significantly deeper insight into the structure of the data than previously possible. In particular, we focus on the identification of network motifs, which have clear interpretation in terms of spatio-temporal behaviour. Statistical analysis is complicated by the nature of the underlying data, and we provide a method by which appropriate randomised graphs can be generated. Two datasets are used as case studies: maritime piracy at the global scale, and residential burglary in an urban area. In both cases, the same significant 3-vertex motif is found; this result suggests that incidents tend to occur not just in pairs, but in fact in larger groups within a restricted spatio-temporal domain. In the 4-vertex case, different motifs are found to be significant in each case, suggesting that this technique is capable of discriminating between clustering patterns at a finer granularity than previously possible.

  7. Automatic Network Fingerprinting through Single-Node Motifs

    PubMed Central

    Echtermeyer, Christoph; da Fontoura Costa, Luciano; Rodrigues, Francisco A.; Kaiser, Marcus

    2011-01-01

    Complex networks have been characterised by their specific connectivity patterns (network motifs), but their building blocks can also be identified and described by node-motifs—a combination of local network features. One technique to identify single node-motifs has been presented by Costa et al. (L. D. F. Costa, F. A. Rodrigues, C. C. Hilgetag, and M. Kaiser, Europhys. Lett., 87, 1, 2009). Here, we first suggest improvements to the method including how its parameters can be determined automatically. Such automatic routines make high-throughput studies of many networks feasible. Second, the new routines are validated in different network-series. Third, we provide an example of how the method can be used to analyse network time-series. In conclusion, we provide a robust method for systematically discovering and classifying characteristic nodes of a network. In contrast to classical motif analysis, our approach can identify individual components (here: nodes) that are specific to a network. Such special nodes, as hubs before, might be found to play critical roles in real-world networks. PMID:21297963

  8. A Novel Bayesian DNA Motif Comparison Method for Clustering and Retrieval

    PubMed Central

    Margalit, Hanah; Friedman, Nir

    2008-01-01

    Characterizing the DNA-binding specificities of transcription factors is a key problem in computational biology that has been addressed by multiple algorithms. These usually take as input sequences that are putatively bound by the same factor and output one or more DNA motifs. A common practice is to apply several such algorithms simultaneously to improve coverage at the price of redundancy. In interpreting such results, two tasks are crucial: clustering of redundant motifs, and attributing the motifs to transcription factors by retrieval of similar motifs from previously characterized motif libraries. Both tasks inherently involve motif comparison. Here we present a novel method for comparing and merging motifs, based on Bayesian probabilistic principles. This method takes into account both the similarity in positional nucleotide distributions of the two motifs and their dissimilarity to the background distribution. We demonstrate the use of the new comparison method as a basis for motif clustering and retrieval procedures, and compare it to several commonly used alternatives. Our results show that the new method outperforms other available methods in accuracy and sensitivity. We incorporated the resulting motif clustering and retrieval procedures in a large-scale automated pipeline for analyzing DNA motifs. This pipeline integrates the results of various DNA motif discovery algorithms and automatically merges redundant motifs from multiple training sets into a coherent annotated library of motifs. Application of this pipeline to recent genome-wide transcription factor location data in S. cerevisiae successfully identified DNA motifs in a manner that is as good as semi-automated analysis reported in the literature. Moreover, we show how this analysis elucidates the mechanisms of condition-specific preferences of transcription factors. PMID:18463706

  9. Decreased RNA-binding motif 5 expression is associated with tumor progression in gastric cancer.

    PubMed

    Kobayashi, Takahiko; Ishida, Junich; Shimizu, Yuichi; Kawakami, Hiroshi; Suda, Goki; Muranaka, Tetsuhito; Komatsu, Yoshito; Asaka, Masahiro; Sakamoto, Naoya

    2017-03-01

    RNA-binding motif 5 is a putative tumor suppressor gene that modulates cell cycle arrest and apoptosis. We recently demonstrated that RNA-binding motif 5 inhibits cell growth through the p53 pathway. This study evaluated the clinical significance of RNA-binding motif 5 expression in gastric cancer and the effects of altered RNA-binding motif 5 expression on cancer biology in gastric cancer cells. RNA-binding motif 5 protein expression was evaluated by immunohistochemistry using the surgical specimens of 106 patients with gastric cancer. We analyzed the relationships of RNA-binding motif 5 expression with clinicopathological parameters and patient prognosis. We further explored the effects of RNA-binding motif 5 downregulation with short hairpin RNA on cell growth and p53 signaling in MKN45 gastric cancer cells. Immunohistochemistry revealed that RNA-binding motif 5 expression was decreased in 29 of 106 (27.4%) gastric cancer specimens. Decreased RNA-binding motif 5 expression was correlated with histological differentiation, depth of tumor infiltration, nodal metastasis, tumor-node-metastasis stage, and prognosis. RNA-binding motif 5 silencing enhanced gastric cancer cell proliferation and decreased p53 transcriptional activity in reporter gene assays. Conversely, restoration of RNA-binding motif 5 expression suppressed cell growth and recovered p53 transactivation in RNA-binding motif 5-silenced cells. Furthermore, RNA-binding motif 5 silencing reduced the messenger RNA and protein expression of the p53 target gene p21. Our results suggest that RNA-binding motif 5 downregulation is involved in gastric cancer progression and that RNA-binding motif 5 behaves as a tumor suppressor gene in gastric cancer.

  10. The kinetic analysis of the substrate specificity of motif 5 in a HAD hydrolase-type phosphosugar phosphatase of Arabidopsis thaliana.

    PubMed

    Caparrós-Martín, José A; McCarthy-Suárez, Iva; Culiáñez-Macià, Francisco A

    2014-09-01

    The Arabidopsis thaliana gene AtSgpp (locus tag At2g38740), encodes a protein whose sequence motifs and expected structure reveal that it belongs to the HAD hydrolases subfamily I, with the C1-type cap domain (Caparrós-Martín et al. in Planta 237:943-954, 2013). In the presence of Mg(2+) ions, the enzyme has a phosphatase activity over a wide range of phosphosugar substrates. AtSgpp promiscuity is preferentially detectable on D-ribose-5-phosphate, 2-deoxy-D-ribose-5-phosphate, 2-deoxy-D-glucose-6-phosphate, D-mannose-6-phosphate, D-fructose-1-phosphate, D-glucose-6-phosphate, DL-glycerol-3-phosphate, and D-fructose-6-phosphate. Site-directed mutagenesis analysis of the putative signature sequence motif-5 (IAGKH), which defines its specific chemistry, brings to light the active-site residues Ala-69 and His-72. Mutation A69M, changes the pH dependence of AtSgpp catalysis, and mutant protein AtSgpp-H72K was inactive in phosphomonoester dephosphorylation. It was also observed that substitutions I68M and K71R slightly affect the substrate specificity, while the replacement of the entire motif for that of homologous DL-glycerol-3-phosphatase AtGpp (MMGRK) does not switch AtSgpp activity to the specific targeting for DL-glycerol-3-phosphate.

  11. Signature spectrale des grains interstellaires.

    NASA Astrophysics Data System (ADS)

    Léger, A.

    Notre connaissance de la nature des grains interstellaires reposait sur un nombre très restreint de signatures spectrales dans la courbe d'extinction du milieu interstellaire. Une information considérable est contenue dans les 40 bandes interstellaires diffuses dans le visible, mais reste inexploitée. L'interprétation récente des cinq bandes IR en émission, en terme de molécules d'hydrocarbures aromatiques polycycliques, est développée. Elle permet l'utilisation d'une information spectroscopique comparable, à elle seule, à ce sur quoi était basée jusqu'alors notre connaissance de la matière interstellaire condensée. Différentes implications de cette mise en évidence sont proposées.

  12. Identification of cancer-related genes and motifs in the human gene regulatory network.

    PubMed

    Carson, Matthew B; Gu, Jianlei; Yu, Guangjun; Lu, Hui

    2015-08-01

    The authors investigated the regulatory network motifs and corresponding motif positions of cancer-related genes. First, they mapped disease-related genes to a transcription factor regulatory network. Next, they calculated statistically significant motifs and subsequently identified positions within these motifs that were enriched in cancer-related genes. Potential mechanisms of these motifs and positions are discussed. These results could be used to identify other disease- and cancer-related genes and could also suggest mechanisms for how these genes relate to co-occurring diseases.

  13. Metabolic Signatures of Bacterial Vaginosis

    PubMed Central

    Morgan, Martin T.; Fiedler, Tina L.; Djukovic, Danijel; Hoffman, Noah G.; Raftery, Daniel; Marrazzo, Jeanne M.

    2015-01-01

    ABSTRACT Bacterial vaginosis (BV) is characterized by shifts in the vaginal microbiota from Lactobacillus dominant to a microbiota with diverse anaerobic bacteria. Few studies have linked specific metabolites with bacteria found in the human vagina. Here, we report dramatic differences in metabolite compositions and concentrations associated with BV using a global metabolomics approach. We further validated important metabolites using samples from a second cohort of women and a different platform to measure metabolites. In the primary study, we compared metabolite profiles in cervicovaginal lavage fluid from 40 women with BV and 20 women without BV. Vaginal bacterial representation was determined using broad-range PCR with pyrosequencing and concentrations of bacteria by quantitative PCR. We detected 279 named biochemicals; levels of 62% of metabolites were significantly different in women with BV. Unsupervised clustering of metabolites separated women with and without BV. Women with BV have metabolite profiles marked by lower concentrations of amino acids and dipeptides, concomitant with higher levels of amino acid catabolites and polyamines. Higher levels of the signaling eicosanoid 12-hydroxyeicosatetraenoic acid (12-HETE), a biomarker for inflammation, were noted in BV. Lactobacillus crispatus and Lactobacillus jensenii exhibited similar metabolite correlation patterns, which were distinct from correlation patterns exhibited by BV-associated bacteria. Several metabolites were significantly associated with clinical signs and symptoms (Amsel criteria) used to diagnose BV, and no metabolite was associated with all four clinical criteria. BV has strong metabolic signatures across multiple metabolic pathways, and these signatures are associated with the presence and concentrations of particular bacteria. PMID:25873373

  14. Irma multisensor predictive signature model

    NASA Astrophysics Data System (ADS)

    Watson, John S.; Flynn, David S.; Wellfare, Michael R.; Richards, Mike; Prestwood, Lee

    1995-06-01

    The Irma synthetic signature model was one of the first high resolution synthetic infrared (IR) target and background signature models to be developed for tactical air-to-surface weapon scenarios. Originally developed in 1980 by the Armament Directorate of the Air Force Wright Laboratory (WL/MN), the Irma model was used exclusively to generate IR scenes for smart weapons research and development. In 1988, a number of significant upgrades to Irma were initiated including the addition of a laser channel. This two channel version, Irma 3.0, was released to the user community in 1990. In 1992, an improved scene generator was incorporated into the Irma model which supported correlated frame-to-frame imagery. This and other improvements were released in Irma 2.2. Recently, Irma 3.2, a passive IR/millimeter wave (MMW) code, was completed. Currently, upgrades are underway to include an active MMW channel. Designated Irma 4.0, this code will serve as a cornerstone of sensor fusion research in the laboratory from 6.1 concept development to 6.3 technology demonstration programs for precision guided munitions. Several significant milestones have been reached in this development process and are demonstrated. The Irma 4.0 software design has been developed and interim results are available. Irma is being developed to facilitate multi-sensor smart weapons research and development. It is currently in distribution to over 80 agencies within the U.S. Air Force, U.S. Army, U.S. Navy, ARPA, NASA, Department of Transportation, academia, and industry.

  15. Signature properties of water: Their molecular electronic origins

    PubMed Central

    Jones, Andrew P.; Cipcigan, Flaviu S.; Crain, Jason; Martyna, Glenn J.

    2015-01-01

    Water challenges our fundamental understanding of emergent materials properties from a molecular perspective. It exhibits a uniquely rich phenomenology including dramatic variations in behavior over the wide temperature range of the liquid into water’s crystalline phases and amorphous states. We show that many-body responses arising from water’s electronic structure are essential mechanisms harnessed by the molecule to encode for the distinguishing features of its condensed states. We treat the complete set of these many-body responses nonperturbatively within a coarse-grained electronic structure derived exclusively from single-molecule properties. Such a “strong coupling” approach generates interaction terms of all symmetries to all orders, thereby enabling unique transferability to diverse local environments such as those encountered along the coexistence curve. The symmetries of local motifs that can potentially emerge are not known a priori. Consequently, electronic responses unfiltered by artificial truncation are then required to embody the terms that tip the balance to the correct set of structures. Therefore, our fully responsive molecular model produces, a simple, accurate, and intuitive picture of water’s complexity and its molecular origin, predicting water’s signature physical properties from ice, through liquid–vapor coexistence, to the critical point. PMID:25941394

  16. Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

    PubMed

    Jain, Shruti; Bhattacharyya, Kausik; Bakshi, Rachit; Narang, Ankita; Brahmachari, Vani

    2017-04-01

    The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc.

  17. The Pedagogic Signature of the Teaching Profession

    ERIC Educational Resources Information Center

    Kiel, Ewald; Lerche, Thomas; Kollmannsberger, Markus; Oubaid, Viktor; Weiss, Sabine

    2016-01-01

    Lee S. Shulman deplores that the field of education as a profession does not have a pedagogic signature, which he characterizes as a synthesis of cognitive, practical and moral apprenticeship. In this context, the following study has three goals: 1) In the first theoretical part, the basic problems of constructing a pedagogic signature are…

  18. 21 CFR 11.50 - Signature manifestations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ELECTRONIC RECORDS; ELECTRONIC SIGNATURES Electronic Records § 11.50 Signature manifestations. (a) Signed electronic... the same controls as for electronic records and shall be included as part of any human readable...

  19. 48 CFR 4.102 - Contractor's signature.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contractor's signature. 4.102 Section 4.102 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Contract Execution 4.102 Contractor's signature. (a) Individuals. A contract with...

  20. A Real Quantum Designated Verifier Signature Scheme

    NASA Astrophysics Data System (ADS)

    Shi, Wei-Min; Zhou, Yi-Hua; Yang, Yu-Guang

    2015-09-01

    The effectiveness of most quantum signature schemes reported in the literature can be verified by a designated person, however, those quantum signature schemes aren't the real traditional designated verifier signature schemes, because the designated person hasn't the capability to efficiently simulate a signature which is indistinguishable from a signer, which cannot satisfy the requirements in some special environments such as E-voting, call for tenders and software licensing. For solving this problem, a real quantum designated verifier signature scheme is proposed in this paper. According to the property of unitary transformation and quantum one-way function, only a verifier designated by a signer can verify the "validity of a signature" and the designated verifier cannot prove to a third party that the signature was produced by the signer or by himself through a transcript simulation algorithm. Moreover, the quantum key distribution and quantum encryption algorithm guarantee the unconditional security of this scheme. Analysis results show that this new scheme satisfies the main security requirements of designated verifier signature scheme and the major attack strategies.

  1. Does Social Work Have a Signature Pedagogy?

    ERIC Educational Resources Information Center

    Earls Larrison, Tara; Korr, Wynne S.

    2013-01-01

    This article contributes to discourse on signature pedagogy by reconceptualizing how our pedagogies are understood and defined for social work education. We critique the view that field education is social work's signature pedagogy and consider what pedagogies are distinct about the teaching and learning of social work. Using Shulman's…

  2. 5 CFR 850.106 - Electronic signatures.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be... signature of an electronic communication may be deemed to satisfy any statutory or regulatory requirement... section, an electronic signature is a method of signing an electronic communication, including...

  3. Association between targeted somatic mutation (TSM) signatures and HGS-OvCa progression.

    PubMed

    Lindley, Robyn A; Humbert, Patrick; Larner, Cliff; Akmeemana, Eric H; Pendlebury, Christopher R R

    2016-09-01

    Evidence already exists that the activation-induced cytidine deaminase (AID/APOBEC) and the adenosine deaminase (ADAR) families of enzymes are implicated as powerful mutagens in oncogenic processes in many somatic tissues. Each deaminase is identified by the DNA or RNA nucleotide sequence ("motif") surrounding the nucleotide targeted for deamination. The primary objective of this study is to develop an in silico approach to identify nucleotide sequence changes of the target motifs of key deaminases during oncogenesis. If successful, a secondary objective is to investigate if such changes are associated with disease progression indicators that include disease stage and progression-free survival time. Using a discovery cohort of 194 high-grade serous ovarian adenocarcinoma (HGS-OvCa) exomes, the results confirm the ability of the novel in silico approach used to identify changes in the preferred target motifs for AID, APOBEC3G, APOBEC3B, and ADAR1 during oncogenesis. Using this approach, a set of new cancer-progression associated signatures (C-PASs) were identified. Furthermore, it was found that the C-PAS identified can be used to differentiate between the cohort of patients that remained progression-free for longer than 60 months, from those in which disease progressed within 60 months (sensitivity 95%, specificity 90%). The spectrum of outcomes observed here could provide a foundation for future clinical assessment of susceptibility variants in ovarian, and several other cancers as disease progresses. The ability of the in silico methodology used to identify changes in deaminase motifs during oncogenesis also suggests new links between immune system function and tumorigenesis.

  4. Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer

    PubMed Central

    Chen, Zhong; Lan, Xun; Thomas-Ahner, Jennifer M; Wu, Dayong; Liu, Xiangtao; Ye, Zhenqing; Wang, Liguo; Sunkel, Benjamin; Grenade, Cassandra; Chen, Junsheng; Zynger, Debra L; Yan, Pearlly S; Huang, Jiaoti; Nephew, Kenneth P; Huang, Tim H-M; Lin, Shili; Clinton, Steven K; Li, Wei; Jin, Victor X; Wang, Qianben

    2015-01-01

    Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific motifs. By using a motif-resolution chromatin immunoprecipitation-exonuclease (ChIP-exo) approach, we find that agonist-liganded human androgen receptor (AR) and antagonist-liganded AR bind to two distinctly different motifs, leading to distinct transcriptional outcomes in prostate cancer cells. Further analysis on clinical prostate tissues reveals that the binding of AR to these two distinct motifs is involved in prostate carcinogenesis. Together, these results suggest that unique ligands may switch DNA motifs recognized by ligand-dependent transcription factors in vivo. Our findings also provide a broad mechanistic foundation for understanding ligand-specific induction of gene expression profiles. PMID:25535248

  5. Signatures of mutational processes in human cancer

    PubMed Central

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Wedge, David C.; Aparicio, Samuel A.J.R.; Behjati, Sam; Biankin, Andrew V.; Bignell, Graham R.; Bolli, Niccolo; Borg, Ake; Børresen-Dale, Anne-Lise; Boyault, Sandrine; Burkhardt, Birgit; Butler, Adam P.; Caldas, Carlos; Davies, Helen R.; Desmedt, Christine; Eils, Roland; Eyfjörd, Jórunn Erla; Foekens, John A.; Greaves, Mel; Hosoda, Fumie; Hutter, Barbara; Ilicic, Tomislav; Imbeaud, Sandrine; Imielinsk, Marcin; Jäger, Natalie; Jones, David T.W.; Jones, David; Knappskog, Stian; Kool, Marcel; Lakhani, Sunil R.; López-Otín, Carlos; Martin, Sancha; Munshi, Nikhil C.; Nakamura, Hiromi; Northcott, Paul A.; Pajic, Marina; Papaemmanuil, Elli; Paradiso, Angelo; Pearson, John V.; Puente, Xose S.; Raine, Keiran; Ramakrishna, Manasa; Richardson, Andrea L.; Richter, Julia; Rosenstiel, Philip; Schlesner, Matthias; Schumacher, Ton N.; Span, Paul N.; Teague, Jon W.; Totoki, Yasushi; Tutt, Andrew N.J.; Valdés-Mas, Rafael; van Buuren, Marit M.; van ’t Veer, Laura; Vincent-Salomon, Anne; Waddell, Nicola; Yates, Lucy R.; Zucman-Rossi, Jessica; Futreal, P. Andrew; McDermott, Ultan; Lichter, Peter; Meyerson, Matthew; Grimmond, Sean M.; Siebert, Reiner; Campo, Elías; Shibata, Tatsuhiro; Pfister, Stefan M.; Campbell, Peter J.; Stratton, Michael R.

    2013-01-01

    All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy. PMID:23945592

  6. Real time gamma-ray signature identifier

    DOEpatents

    Rowland, Mark [Alamo, CA; Gosnell, Tom B [Moraga, CA; Ham, Cheryl [Livermore, CA; Perkins, Dwight [Livermore, CA; Wong, James [Dublin, CA

    2012-05-15

    A real time gamma-ray signature/source identification method and system using principal components analysis (PCA) for transforming and substantially reducing one or more comprehensive spectral libraries of nuclear materials types and configurations into a corresponding concise representation/signature(s) representing and indexing each individual predetermined spectrum in principal component (PC) space, wherein an unknown gamma-ray signature may be compared against the representative signature to find a match or at least characterize the unknown signature from among all the entries in the library with a single regression or simple projection into the PC space, so as to substantially reduce processing time and computing resources and enable real-time characterization and/or identification.

  7. MISCORE: a new scoring function for characterizing DNA regulatory motifs in promoter sequences

    PubMed Central

    2012-01-01

    Background Computational approaches for finding DNA regulatory motifs in promoter sequences are useful to biologists in terms of reducing the experimental costs and speeding up the discovery process of de novo binding sites. It is important for rule-based or clustering-based motif searching schemes to effectively and efficiently evaluate the similarity between a k-mer (a k-length subsequence) and a motif model, without assuming the independence of nucleotides in motif models or without employing computationally expensive Markov chain models to estimate the background probabilities of k-mers. Also, it is interesting and beneficial to use a priori knowledge in developing advanced searching tools. Results This paper presents a new scoring function, termed as MISCORE, for functional motif characterization and evaluation. Our MISCORE is free from: (i) any assumption on model dependency; and (ii) the use of Markov chain model for background modeling. It integrates the compositional complexity of motif instances into the function. Performance evaluations with comparison to the well-known Maximum a Posteriori (MAP) score and Information Content (IC) have shown that MISCORE has promising capabilities to separate and recognize functional DNA motifs and its instances from non-functional ones. Conclusions MISCORE is a fast computational tool for candidate motif characterization, evaluation and selection. It enables to embed priori known motif models for computing motif-to-motif similarity, which is more advantageous than IC and MAP score. In addition to these merits mentioned above, MISCORE can automatically filter out some repetitive k-mers from a motif model due to the introduction of the compositional complexity in the function. Consequently, the merits of our proposed MISCORE in terms of both motif signal modeling power and computational efficiency will make it more applicable in the development of computational motif discovery tools. PMID:23282090

  8. Dynamic characteristics of signatures: effects of writer style on genuine and simulated signatures.

    PubMed

    Mohammed, Linton; Found, Bryan; Caligiuri, Michael; Rogers, Doug

    2015-01-01

    The aims of this study were to determine if computer-measured dynamic features (duration, size, velocity, jerk, and pen pressure) differ between genuine and simulated signatures. Sixty subjects (3 equal groups of 3 signature styles) each provided 10 naturally written (genuine) signatures. Each of these subjects then provided 15 simulations of each of three model signatures. The genuine (N = 600) and simulated (N = 2700) signatures were collected using a digitizing tablet. MovAlyzeR(®) software was used to estimate kinematic parameters for each pen stroke. Stroke duration, velocity, and pen pressure were found to discriminate between genuine and simulated signatures regardless of the simulator's own style of signature or the style of signature being simulated. However, there was a significant interaction between style and condition for size and jerk (a measure of smoothness). The results of this study, based on quantitative analysis and dynamic handwriting features, indicate that the style of the simulator's own signature and the style of signature being simulated can impact the characteristics of handwriting movements for simulations. Writer style characteristics might therefore need to be taken into consideration as potentially significant when evaluating signature features with a view to forming opinions regarding authenticity.

  9. DNA nanotechnology based on i-motif structures.

    PubMed

    Dong, Yuanchen; Yang, Zhongqiang; Liu, Dongsheng

    2014-06-17

    CONSPECTUS: Most biological processes happen at the nanometer scale, and understanding the energy transformations and material transportation mechanisms within living organisms has proved challenging. To better understand the secrets of life, researchers have investigated artificial molecular motors and devices over the past decade because such systems can mimic certain biological processes. DNA nanotechnology based on i-motif structures is one system that has played an important role in these investigations. In this Account, we summarize recent advances in functional DNA nanotechnology based on i-motif structures. The i-motif is a DNA quadruplex that occurs as four stretches of cytosine repeat sequences form C·CH(+) base pairs, and their stabilization requires slightly acidic conditions. This unique property has produced the first DNA molecular motor driven by pH changes. The motor is reliable, and studies show that it is capable of millisecond running speeds, comparable to the speed of natural protein motors. With careful design, the output of these types of motors was combined to drive micrometer-sized cantilevers bend. Using established DNA nanostructure assembly and functionalization methods, researchers can easily integrate the motor within other DNA assembled structures and functional units, producing DNA molecular devices with new functions such as suprahydrophobic/suprahydrophilic smart surfaces that switch, intelligent nanopores triggered by pH changes, molecular logic gates, and DNA nanosprings. Recently, researchers have produced motors driven by light and electricity, which have allowed DNA motors to be integrated within silicon-based nanodevices. Moreover, some devices based on i-motif structures have proven useful for investigating processes within living cells. The pH-responsiveness of the i-motif structure also provides a way to control the stepwise assembly of DNA nanostructures. In addition, because of the stability of the i-motif, this

  10. Motif discovery with data mining in 3D protein structure databases: discovery, validation and prediction of the U-shape zinc binding ("Huf-Zinc") motif.

    PubMed

    Maurer-Stroh, Sebastian; Gao, He; Han, Hao; Baeten, Lies; Schymkowitz, Joost; Rousseau, Frederic; Zhang, Louxin; Eisenhaber, Frank

    2013-02-01

    Data mining in protein databases, derivatives from more fundamental protein 3D structure and sequence databases, has considerable unearthed potential for the discovery of sequence motif--structural motif--function relationships as the finding of the U-shape (Huf-Zinc) motif, originally a small student's project, exemplifies. The metal ion zinc is critically involved in universal biological processes, ranging from protein-DNA complexes and transcription regulation to enzymatic catalysis and metabolic pathways. Proteins have evolved a series of motifs to specifically recognize and bind zinc ions. Many of these, so called zinc fingers, are structurally independent globular domains with discontinuous binding motifs made up of residues mostly far apart in sequence. Through a systematic approach starting from the BRIX structure fragment database, we discovered that there exists another predictable subset of zinc-binding motifs that not only have a conserved continuous sequence pattern but also share a characteristic local conformation, despite being included in totally different overall folds. While this does not allow general prediction of all Zn binding motifs, a HMM-based web server, Huf-Zinc, is available for prediction of these novel, as well as conventional, zinc finger motifs in protein sequences. The Huf-Zinc webserver can be freely accessed through this URL (http://mendel.bii.a-star.edu.sg/METHODS/hufzinc/).

  11. Identifying combinatorial regulation of transcription factors and binding motifs

    PubMed Central

    Kato, Mamoru; Hata, Naoya; Banerjee, Nilanjana; Futcher, Bruce; Zhang, Michael Q

    2004-01-01

    Background Combinatorial interaction of transcription factors (TFs) is important for gene regulation. Although various genomic datasets are relevant to this issue, each dataset provides relatively weak evidence on its own. Developing methods that can integrate different sequence, expression and localization data have become important. Results Here we use a novel method that integrates chromatin immunoprecipitation (ChIP) data with microarray expression data and with combinatorial TF-motif analysis. We systematically identify combinations of transcription factors and of motifs. The various combinations of TFs involved multiple binding mechanisms. We reconstruct a new combinatorial regulatory map of the yeast cell cycle in which cell-cycle regulation can be drawn as a chain of extended TF modules. We find that the pairwise combination of a TF for an early cell-cycle phase and a TF for a later phase is often used to control gene expression at intermediate times. Thus the number of distinct times of gene expression is greater than the number of transcription factors. We also see that some TF modules control branch points (cell-cycle entry and exit), and in the presence of appropriate signals they can allow progress along alternative pathways. Conclusions Combining different data sources can increase statistical power as demonstrated by detecting TF interactions and composite TF-binding motifs. The original picture of a chain of simple cell-cycle regulators can be extended to a chain of composite regulatory modules: different modules may share a common TF component in the same pathway or a TF component cross-talking to other pathways. PMID:15287978

  12. CENTDIST: discovery of co-associated factors by motif distribution

    PubMed Central

    Zhang, Zhizhuo; Chang, Cheng Wei; Goh, Wan Ling; Sung, Wing-Kin; Cheung, Edwin

    2011-01-01

    Transcription factors (TFs) do not function alone but work together with other TFs (called co-TFs) in a combinatorial fashion to precisely control the transcription of target genes. Mining co-TFs is thus important to understand the mechanism of transcriptional regulation. Although existing methods can identify co-TFs, their accuracy depends heavily on the chosen background model and other parameters such as the enrichment window size and the PWM score cut-off. In this study, we have developed a novel web-based co-motif scanning program called CENTDIST (http://compbio.ddns.comp.nus.edu.sg/~chipseq/centdist/). In comparison to current co-motif scanning programs, CENTDIST does not require the input of any user-specific parameters and background information. Instead, CENTDIST automatically determines the best set of parameters and ranks co-TF motifs based on their distribution around ChIP-seq peaks. We tested CENTDIST on 14 ChIP-seq data sets and found CENTDIST is more accurate than existing methods. In particular, we applied CENTDIST on an Androgen Receptor (AR) ChIP-seq data set from a prostate cancer cell line and correctly predicted all known co-TFs (eight TFs) of AR in the top 20 hits as well as discovering AP4 as a novel co-TF of AR (which was missed by existing methods). Taken together, CENTDIST, which exploits the imbalanced nature of co-TF binding, is a user-friendly, parameter-less and powerful predictive web-based program for understanding the mechanism of transcriptional co-regulation. PMID:21602269

  13. Identification of imine reductase-specific sequence motifs.

    PubMed

    Fademrecht, Silvia; Scheller, Philipp N; Nestl, Bettina M; Hauer, Bernhard; Pleiss, Jürgen

    2016-05-01

    Chiral amines are valuable building blocks for the production of a variety of pharmaceuticals, agrochemicals and other specialty chemicals. Only recently, imine reductases (IREDs) were discovered which catalyze the stereoselective reduction of imines to chiral amines. Although several IREDs were biochemically characterized in the last few years, knowledge of the reaction mechanism and the molecular basis of substrate specificity and stereoselectivity is limited. To gain further insights into the sequence-function relationships, the Imine Reductase Engineering Database (www.IRED.BioCatNet.de) was established and a systematic analysis of 530 putative IREDs was performed. A standard numbering scheme based on R-IRED-Sk was introduced to facilitate the identification and communication of structurally equivalent positions in different proteins. A conservation analysis revealed a highly conserved cofactor binding region and a predominantly hydrophobic substrate binding cleft. Two IRED-specific motifs were identified, the cofactor binding motif GLGxMGx(5 )[ATS]x(4) Gx(4) [VIL]WNR[TS]x(2) [KR] and the active site motif Gx[DE]x[GDA]x[APS]x(3){K}x[ASL]x[LMVIAG]. Our results indicate a preference toward NADPH for all IREDs and explain why, despite their sequence similarity to β-hydroxyacid dehydrogenases (β-HADs), no conversion of β-hydroxyacids has been observed. Superfamily-specific conservations were investigated to explore the molecular basis of their stereopreference. Based on our analysis and previous experimental results on IRED mutants, an exclusive role of standard position 187 for stereoselectivity is excluded. Alternatively, two standard positions 139 and 194 were identified which are superfamily-specifically conserved and differ in R- and S-selective enzymes.

  14. Genomic analysis of membrane protein families: abundance and conserved motifs

    PubMed Central

    Liu, Yang; Engelman, Donald M; Gerstein, Mark

    2002-01-01

    Background Polytopic membrane proteins can be related to each other on the basis of the number of transmembrane helices and sequence similarities. Building on the Pfam classification of protein domain families, and using transmembrane-helix prediction and sequence-similarity searching, we identified a total of 526 well-characterized membrane protein families in 26 recently sequenced genomes. To this we added a clustering of a number of predicted but unclassified membrane proteins, resulting in a total of 637 membrane protein families. Results Analysis of the occurrence and composition of these families revealed several interesting trends. The number of assigned membrane protein domains has an approximately linear relationship to the total number of open reading frames (ORFs) in 26 genomes studied. Caenorhabditis elegans is an apparent outlier, because of its high representation of seven-span transmembrane (7-TM) chemoreceptor families. In all genomes, including that of C. elegans, the number of distinct membrane protein families has a logarithmic relation to the number of ORFs. Glycine, proline, and tyrosine locations tend to be conserved in transmembrane regions within families, whereas isoleucine, valine, and methionine locations are relatively mutable. Analysis of motifs in putative transmembrane helices reveals that GxxxG and GxxxxxxG (which can be written GG4 and GG7, respectively; see Materials and methods) are among the most prevalent. This was noted in earlier studies; we now find these motifs are particularly well conserved in families, however, especially those corresponding to transporters, symporters, and channels. Conclusions We carried out a genome-wide analysis on patterns of the classified polytopic membrane protein families and analyzed the distribution of conserved amino acids and motifs in the transmembrane helix regions in these families. PMID:12372142

  15. The Assembly Motif of a Bacterial Small Multidrug Resistance Protein*

    PubMed Central

    Poulsen, Bradley E.; Rath, Arianna; Deber, Charles M.

    2009-01-01

    Multidrug transporters such as the small multidrug resistance (SMR) family of bacterial integral membrane proteins are capable of conferring clinically significant resistance to a variety of common therapeutics. As antiporter proteins of ∼100 amino acids, SMRs must self-assemble into homo-oligomeric structures for efflux of drug molecules. Oligomerization centered at transmembrane helix four (TM4) has been implicated in SMR assembly, but the full complement of residues required to mediate its self-interaction remains to be characterized. Here, we use Hsmr, the 110-residue SMR family member of the archaebacterium Halobacterium salinarum, to determine the TM4 residue motif required to mediate drug resistance and SMR self-association. Twelve single point mutants that scan the central portion of the TM4 helix (residues 85–104) were constructed and were tested for their ability to confer resistance to the cytotoxic compound ethidium bromide. Six residues were found to be individually essential for drug resistance activity (Gly90, Leu91, Leu93, Ile94, Gly97, and Val98), defining a minimum activity motif of 90GLXLIXXGV98 within TM4. When the propensity of these mutants to dimerize on SDS-PAGE was examined, replacements of all but Ile resulted in ∼2-fold reduction of dimerization versus the wild-type antiporter. Our work defines a minimum activity motif of 90GLXLIXXGV98 within TM4 and suggests that this sequence mediates TM4-based SMR dimerization along a single helix surface, stabilized by a small residue heptad repeat sequence. These TM4-TM4 interactions likely constitute the highest affinity locus for disruption of SMR function by directly targeting its self-assembly mechanism. PMID:19224913

  16. Short sequence motifs, overrepresented in mammalian conservednon-coding sequences

    SciTech Connect

    Minovitsky, Simon; Stegmaier, Philip; Kel, Alexander; Kondrashov,Alexey S.; Dubchak, Inna

    2007-02-21

    Background: A substantial fraction of non-coding DNAsequences of multicellular eukaryotes is under selective constraint. Inparticular, ~;5 percent of the human genome consists of conservednon-coding sequences (CNSs). CNSs differ from other genomic sequences intheir nucleotide composition and must play important functional roles,which mostly remain obscure.Results: We investigated relative abundancesof short sequence motifs in all human CNSs present in the human/mousewhole-genome alignments vs. three background sets of sequences: (i)weakly conserved or unconserved non-coding sequences (non-CNSs); (ii)near-promoter sequences (located between nucleotides -500 and -1500,relative to a start of transcription); and (iii) random sequences withthe same nucleotide composition as that of CNSs. When compared tonon-CNSs and near-promoter sequences, CNSs possess an excess of AT-richmotifs, often containing runs of identical nucleotides. In contrast, whencompared to random sequences, CNSs contain an excess of GC-rich motifswhich, however, lack CpG dinucleotides. Thus, abundance of short sequencemotifs in human CNSs, taken as a whole, is mostly determined by theiroverall compositional properties and not by overrepresentation of anyspecific short motifs. These properties are: (i) high AT-content of CNSs,(ii) a tendency, probably due to context-dependent mutation, of A's andT's to clump, (iii) presence of short GC-rich regions, and (iv) avoidanceof CpG contexts, due to their hypermutability. Only a small number ofshort motifs, overrepresented in all human CNSs are similar to bindingsites of transcription factors from the FOX family.Conclusion: Human CNSsas a whole appear to be too broad a class of sequences to possess strongfootprints of any short sequence-specific functions. Such footprintsshould be studied at the level of functional subclasses of CNSs, such asthose which flank genes with a particular pattern of expression. Overallproperties of CNSs are affected by patterns in

  17. On "A new quantum blind signature with unlinkability"

    NASA Astrophysics Data System (ADS)

    Luo, Yi-Ping; Tsai, Shang-Lun; Hwang, Tzonelih; Kao, Shih-Hung

    2017-04-01

    This article points out a security loophole in Shi et al.'s quantum blind signature scheme. By using the modification attack, a message owner can cheat a signature receiver with a fake message-signature pair without being detected.

  18. 21 CFR 11.200 - Electronic signature components and controls.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other...

  19. 76 FR 411 - Regulatory Guidance Concerning Electronic Signatures and Documents

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... Federal Motor Carrier Safety Administration Regulatory Guidance Concerning Electronic Signatures and... guidance. SUMMARY: FMCSA issues regulatory guidance concerning the use of electronic signatures and... information regarding FMCSA's acceptance of electronic signature on documents required by the Federal...

  20. 21 CFR 11.200 - Electronic signature components and controls.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other...

  1. 21 CFR 11.200 - Electronic signature components and controls.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other...

  2. 21 CFR 11.200 - Electronic signature components and controls.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other...

  3. 21 CFR 11.200 - Electronic signature components and controls.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... signature components and controls. (a) Electronic signatures that are not based upon biometrics shall: (1... signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other...

  4. Evolving DNA motifs to predict GeneChip probe performance

    PubMed Central

    Langdon, WB; Harrison, AP

    2009-01-01

    Background Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe. Results Regular expressions can be automatically created from a Backus-Naur form (BNF) context-free grammar using strongly typed genetic programming. Conclusion The automatically produced motif is better at predicting poor DNA sequences than an existing human generated RE, suggesting runs of Cytosine and Guanine and mixtures should all be avoided. PMID:19298675

  5. Nucleic Acid i-Motif Structures in Analytical Chemistry.

    PubMed

    Alba, Joan Josep; Sadurní, Anna; Gargallo, Raimundo

    2016-09-02

    Under the appropriate experimental conditions of pH and temperature, cytosine-rich segments in DNA or RNA sequences may produce a characteristic folded structure known as an i-motif. Besides its potential role in vivo, which is still under investigation, this structure has attracted increasing interest in other fields due to its sharp, fast and reversible pH-driven conformational changes. This "on/off" switch at molecular level is being used in nanotechnology and analytical chemistry to develop nanomachines and sensors, respectively. This paper presents a review of the latest applications of this structure in the field of chemical analysis.

  6. Recurring sequence-structure motifs in (βα)8-barrel proteins and experimental optimization of a chimeric protein designed based on such motifs.

    PubMed

    Wang, Jichao; Zhang, Tongchuan; Liu, Ruicun; Song, Meilin; Wang, Juncheng; Hong, Jiong; Chen, Quan; Liu, Haiyan

    2017-02-01

    An interesting way of generating novel artificial proteins is to combine sequence motifs from natural proteins, mimicking the evolutionary path suggested by natural proteins comprising recurring motifs. We analyzed the βα and αβ modules of TIM barrel proteins by structure alignment-based sequence clustering. A number of preferred motifs were identified. A chimeric TIM was designed by using recurring elements as mutually compatible interfaces. The foldability of the designed TIM protein was then significantly improved by six rounds of directed evolution. The melting temperature has been improved by more than 20°C. A variety of characteristics suggested that the resulting protein is well-folded. Our analysis provided a library of peptide motifs that is potentially useful for different protein engineering studies. The protein engineering strategy of using recurring motifs as interfaces to connect partial natural proteins may be applied to other protein folds.

  7. Fast and Accurate Discovery of Degenerate Linear Motifs in Protein Sequences

    PubMed Central

    Levy, Emmanuel D.; Michnick, Stephen W.

    2014-01-01

    Linear motifs mediate a wide variety of cellular functions, which makes their characterization in protein sequences crucial to understanding cellular systems. However, the short length and degenerate nature of linear motifs make their discovery a difficult problem. Here, we introduce MotifHound, an algorithm particularly suited for the discovery of small and degenerate linear motifs. MotifHound performs an exact and exhaustive enumeration of all motifs present in proteins of interest, including all of their degenerate forms, and scores the overrepresentation of each motif based on its occurrence in proteins of interest relative to a background (e.g., proteome) using the hypergeometric distribution. To assess MotifHound, we benchmarked it together with state-of-the-art algorithms. The benchmark consists of 11,880 sets of proteins from S. cerevisiae; in each set, we artificially spiked-in one motif varying in terms of three key parameters, (i) number of occurrences, (ii) length and (iii) the number of degenerate or “wildcard” positions. The benchmark enabled the evaluation of the impact of these three properties on the performance of the different algorithms. The results showed that MotifHound and SLiMFinder were the most accurate in detecting degenerate linear motifs. Interestingly, MotifHound was 15 to 20 times faster at comparable accuracy and performed best in the discovery of highly degenerate motifs. We complemented the benchmark by an analysis of proteins experimentally shown to bind the FUS1 SH3 domain from S. cerevisiae. Using the full-length protein partners as sole information, MotifHound recapitulated most experimentally determined motifs binding to the FUS1 SH3 domain. Moreover, these motifs exhibited properties typical of SH3 binding peptides, e.g., high intrinsic disorder and evolutionary conservation, despite the fact that none of these properties were used as prior information. MotifHound is available (http://michnick.bcm.umontreal.ca or http

  8. What Signatures Dominantly Associate with Gene Age?

    PubMed Central

    Yin, Hongyan; Wang, Guangyu; Ma, Lina; Yi, Soojin V.; Zhang, Zhang

    2016-01-01

    As genes originate at different evolutionary times, they harbor distinctive genomic signatures of evolutionary ages. Although previous studies have investigated different gene age-related signatures, what signatures dominantly associate with gene age remains unresolved. Here we address this question via a combined approach of comprehensive assignment of gene ages, gene family identification, and multivariate analyses. We first provide a comprehensive and improved gene age assignment by combining homolog clustering with phylogeny inference and categorize human genes into 26 age classes spanning the whole tree of life. We then explore the dominant age-related signatures based on a collection of 10 potential signatures (including gene composition, gene length, selection pressure, expression level, connectivity in protein–protein interaction network and DNA methylation). Our results show that GC content and connectivity in protein–protein interaction network (PPIN) associate dominantly with gene age. Furthermore, we investigate the heterogeneity of dominant signatures in duplicates and singletons. We find that GC content is a consistent primary factor of gene age in duplicates and singletons, whereas PPIN is more strongly associated with gene age in singletons than in duplicates. Taken together, GC content and PPIN are two dominant signatures in close association with gene age, exhibiting heterogeneity in duplicates and singletons and presumably reflecting complex differential interplays between natural selection and mutation. PMID:27609935

  9. SLiMDisc: short, linear motif discovery, correcting for common evolutionary descent

    PubMed Central

    Davey, Norman E.; Shields, Denis C.; Edwards, Richard J.

    2006-01-01

    Many important interactions of proteins are facilitated by short, linear motifs (SLiMs) within a protein's primary sequence. Our aim was to establish robust methods for discovering putative functional motifs. The strongest evidence for such motifs is obtained when the same motifs occur in unrelated proteins, evolving by convergence. In practise, searches for such motifs are often swamped by motifs shared in related proteins that are identical by descent. Prediction of motifs among sets of biologically related proteins, including those both with and without detectable similarity, were made using the TEIRESIAS algorithm. The number of motif occurrences arising through common evolutionary descent were normalized based on treatment of BLAST local alignments. Motifs were ranked according to a score derived from the product of the normalized number of occurrences and the information content. The method was shown to significantly outperform methods that do not discount evolutionary relatedness, when applied to known SLiMs from a subset of the eukaryotic linear motif (ELM) database. An implementation of Multiple Spanning Tree weighting outperformed two other weighting schemes, in a variety of settings. PMID:16855291

  10. Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments

    PubMed Central

    Kheradpour, Pouya; Kellis, Manolis

    2014-01-01

    Recent advances in technology have led to a dramatic increase in the number of available transcription factor ChIP-seq and ChIP-chip data sets. Understanding the motif content of these data sets is an important step in understanding the underlying mechanisms of regulation. Here we provide a systematic motif analysis for 427 human ChIP-seq data sets using motifs curated from the literature and also discovered de novo using five established motif discovery tools. We use a systematic pipeline for calculating motif enrichment in each data set, providing a principled way for choosing between motif variants found in the literature and for flagging potentially problematic data sets. Our analysis confirms the known specificity of 41 of the 56 analyzed factor groups and reveals motifs of potential cofactors. We also use cell type-specific binding to find factors active in specific conditions. The resource we provide is accessible both for browsing a small number of factors and for performing large-scale systematic analyses. We provide motif matrices, instances and enrichments in each of the ENCODE data sets. The motifs discovered here have been used in parallel studies to validate the specificity of antibodies, understand cooperativity between data sets and measure the variation of motif binding across individuals and species. PMID:24335146

  11. Molecular signatures of major depression.

    PubMed

    Cai, Na; Chang, Simon; Li, Yihan; Li, Qibin; Hu, Jingchu; Liang, Jieqin; Song, Li; Kretzschmar, Warren; Gan, Xiangchao; Nicod, Jerome; Rivera, Margarita; Deng, Hong; Du, Bo; Li, Keqing; Sang, Wenhu; Gao, Jingfang; Gao, Shugui; Ha, Baowei; Ho, Hung-Yao; Hu, Chunmei; Hu, Jian; Hu, Zhenfei; Huang, Guoping; Jiang, Guoqing; Jiang, Tao; Jin, Wei; Li, Gongying; Li, Kan; Li, Yi; Li, Yingrui; Li, Youhui; Lin, Yu-Ting; Liu, Lanfen; Liu, Tiebang; Liu, Ying; Liu, Yuan; Lu, Yao; Lv, Luxian; Meng, Huaqing; Qian, Puyi; Sang, Hong; Shen, Jianhua; Shi, Jianguo; Sun, Jing; Tao, Ming; Wang, Gang; Wang, Guangbiao; Wang, Jian; Wang, Linmao; Wang, Xueyi; Wang, Xumei; Yang, Huanming; Yang, Lijun; Yin, Ye; Zhang, Jinbei; Zhang, Kerang; Sun, Ning; Zhang, Wei; Zhang, Xiuqing; Zhang, Zhen; Zhong, Hui; Breen, Gerome; Wang, Jun; Marchini, Jonathan; Chen, Yiping; Xu, Qi; Xu, Xun; Mott, Richard; Huang, Guo-Jen; Kendler, Kenneth; Flint, Jonathan

    2015-05-04

    Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual's somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10(-42), odds ratio 1.33 [95% confidence interval [CI] = 1.29-1.37]) and telomere length (p = 2.84 × 10(-14), odds ratio 0.85 [95% CI = 0.81-0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease.

  12. SIRUS spectral signature analysis code

    NASA Astrophysics Data System (ADS)

    Bishop, Gary J.; Caola, Mike J.; Geatches, Rachel M.; Roberts, Nick C.

    2003-09-01

    The Advanced Technology Centre (ATC) is responsible for developing IR signature prediction capabilities for its parent body, BAE SYSTEMS. To achieve this, the SIRUS code has been developed and used on a variety of projects for well over a decade. SIRUS is capable of providing accurate IR predictions for air breathing and rocket motor propelled vehicles. SIRUS models various physical components to derive its predictions. A key component is the radiance reflected from the surface of the modeled vehicle. This is modeled by fitting parameters to the measured Bi-Directional Reflectance Function (BDRF) of the surface material(s). The ATC have successfully implemented a parameterization scheme based on the published OPTASM model, and this is described. However, inconsistencies between reflectance measurements and values calculated from the parameterized fit have led to an elliptical parameter enhancement. The implementation of this is also described. Finally, an end-to-end measurement-parameterization capability is described, based on measurements taken with SOC600 instrumentation.

  13. Molecular signatures of vaccine adjuvants.

    PubMed

    Olafsdottir, Thorunn; Lindqvist, Madelene; Harandi, Ali M

    2015-09-29

    Mass vaccination has saved millions of human lives and improved the quality of life in both developing and developed countries. The emergence of new pathogens and inadequate protection conferred by some of the existing vaccines such as vaccines for tuberculosis, influenza and pertussis especially in certain age groups have resulted in a move from empirically developed vaccines toward more pathogen tailored and rationally engineered vaccines. A deeper understanding of the interaction of innate and adaptive immunity at molecular level enables the development of vaccines that selectively target certain type of immune responses without excessive reactogenicity. Adjuvants constitute an imperative element of modern vaccines. Although a variety of candidate adjuvants have been evaluated in the past few decades, only a limited number of vaccine adjuvants are currently available for human use. A better understanding of the mode of action of adjuvants is pivotal to harness the potential of existing and new adjuvants in shaping a desired immune response. Recent advancement in systems biology powered by the emerging cutting edge omics technology has led to the identification of molecular signatures rapidly induced after vaccination in the blood that correlate and predict a later protective immune response or vaccine safety. This can pave ways to prospectively determine the potency and safety of vaccines and adjuvants. This review is intended to highlight the importance of big data analysis in advancing our understanding of the mechanisms of actions of adjuvants to inform rational development of future human vaccines.

  14. Transcriptional Signatures in Huntington's Disease

    PubMed Central

    2007-01-01

    While selective neuronal death has been an influential theme in Huntington's disease (HD), there is now a preponderance of evidence that significant neuronal dysfunction precedes frank neuronal death. The best evidence for neuronal dysfunction is the observation that gene expression is altered in HD brain, suggesting that transcriptional dysregulation is a central mechanism. Studies of altered gene expression began with careful observations of post-mortem human HD brain and subsequently were accelerated by the development of transgenic mouse models. The application of DNA microarray technology has spurred tremendous progress with respect to the altered transcriptional processes that occur in HD, through gene expression studies of both transgenic mouse models as well as cellular models of HD. Gene expression profiles are remarkably comparable across these models, bolstering the idea that transcriptional signatures reflect an essential feature of disease pathogenesis. Finally, gene expression studies have been applied to human HD, thus not only validating the approach of using model systems, but also solidifying the idea that altered transcription is a key mechanism in HD pathogenesis. In the future, gene expression profiling will be used as a readout in clinical trials aimed at correcting transcriptional dysregulation in Huntington's disease. PMID:17467140

  15. Infrared signatures from bomb detonations

    NASA Astrophysics Data System (ADS)

    Orson, Jay A.; Bagby, William F.; Perram, Glen P.

    2003-04-01

    Remote observations of the temporal and spectral characteristics of the infrared emissions from bomb detonations have been correlated with explosion conditions. A Fourier transform interferometer was used to record spectra in the 1.6-20 μm range at spectral resolutions of 4-16 cm -1 and temporal resolutions of 0.047-0.123 s. Field observations of 56 detonation events included a set of aircraft delivered ordinance and a series of static ground detonations for a variety of bomb sizes, types and environmental conditions. The emission is well represented by a gray body with continuously decreasing temperature and characteristic decay times of 1-4 s, providing only limited variability with detonation conditions. However, the fireball size times the emissivity as a function of time can be determined from the spectra without imaging and provides a more sensitive signature. The degree of temporal overlap as a function of frequency for a pair of detonation events provides a very sensitive discriminator for explosion conditions. The temporal overlap decreases with increasing emission frequency for all the observed events, indicating more information content at higher frequencies.

  16. Molecular Signatures of Major Depression

    PubMed Central

    Cai, Na; Chang, Simon; Li, Yihan; Li, Qibin; Hu, Jingchu; Liang, Jieqin; Song, Li; Kretzschmar, Warren; Gan, Xiangchao; Nicod, Jerome; Rivera, Margarita; Deng, Hong; Du, Bo; Li, Keqing; Sang, Wenhu; Gao, Jingfang; Gao, Shugui; Ha, Baowei; Ho, Hung-Yao; Hu, Chunmei; Hu, Jian; Hu, Zhenfei; Huang, Guoping; Jiang, Guoqing; Jiang, Tao; Jin, Wei; Li, Gongying; Li, Kan; Li, Yi; Li, Yingrui; Li, Youhui; Lin, Yu-Ting; Liu, Lanfen; Liu, Tiebang; Liu, Ying; Liu, Yuan; Lu, Yao; Lv, Luxian; Meng, Huaqing; Qian, Puyi; Sang, Hong; Shen, Jianhua; Shi, Jianguo; Sun, Jing; Tao, Ming; Wang, Gang; Wang, Guangbiao; Wang, Jian; Wang, Linmao; Wang, Xueyi; Wang, Xumei; Yang, Huanming; Yang, Lijun; Yin, Ye; Zhang, Jinbei; Zhang, Kerang; Sun, Ning; Zhang, Wei; Zhang, Xiuqing; Zhang, Zhen; Zhong, Hui; Breen, Gerome; Wang, Jun; Marchini, Jonathan; Chen, Yiping; Xu, Qi; Xu, Xun; Mott, Richard; Huang, Guo-Jen; Kendler, Kenneth; Flint, Jonathan

    2015-01-01

    Summary Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease. PMID:25913401

  17. (abstract) Topographic Signatures in Geology

    NASA Technical Reports Server (NTRS)

    Farr, Tom G.; Evans, Diane L.

    1996-01-01

    Topographic information is required for many Earth Science investigations. For example, topography is an important element in regional and global geomorphic studies because it reflects the interplay between the climate-driven processes of erosion and the tectonic processes of uplift. A number of techniques have been developed to analyze digital topographic data, including Fourier texture analysis. A Fourier transform of the topography of an area allows the spatial frequency content of the topography to be analyzed. Band-pass filtering of the transform produces images representing the amplitude of different spatial wavelengths. These are then used in a multi-band classification to map units based on their spatial frequency content. The results using a radar image instead of digital topography showed good correspondence to a geologic map, however brightness variations in the image unrelated to topography caused errors. An additional benefit to the use of Fourier band-pass images for the classification is that the textural signatures of the units are quantative measures of the spatial characteristics of the units that may be used to map similar units in similar environments.

  18. MicroRNA and AU-rich element regulation of prostaglandin synthesis

    PubMed Central

    Moore, Ashleigh E.; Young, Lisa E.

    2012-01-01

    Many liness of evidence demonstrate that prostaglandins play an important role in cancer, and enhanced synthesis of prostaglandin E2 (PGE2) is often observed in various human malignancies often associated with poor prognosis. PGE2 synthesis is initiated with the release of arachidonic acid by phospholipase enzymes, where it is then converted into the intermediate prostaglandin prostaglandin H2 (PGH2) by members of the cyclooxygenase family. The synthesis of PGE2 from PGH2 is facilitated by three different PGE synthases, and functional PGE2 can promote tumor growth by binding to four EP receptors to activate signaling pathways that control cell proliferation, migration, apoptosis, and angiogenesis. An integral method of controlling gene expression is by posttranscriptional mechanisms that regulate mRNA stability and protein translation. Messenger RNA regulatory elements typically reside within the 3′ untranslated region (3′UTR) of the transcript and play a critical role in targeting specific mRNAs for posttranscriptional regulation through micro-RNA (miRNA) binding and adenylate- and uridylate-rich element RNA-binding proteins. In this review, we highlight the current advances in our understanding of the impact these RNA sequence elements have upon regulating PGE2 levels. We also identify various RNA sequence elements consistently observed within the 3′UTRs of the genes involved in the PGE2 pathway, indicating these binding sites for miRNAs and RNA-binding proteins to be central regulators of PGE2 synthesis and function. These findings may provide a rationale for the development of new therapeutic approaches to control tumor growth and metastasis promoted by elevated PGE2 levels. PMID:22005950

  19. Recognizing impactor signatures in the planetary record

    NASA Technical Reports Server (NTRS)

    Schultz, Peter H.; Gault, Donald E.

    1992-01-01

    Crater size reflects the target response to the combined effects of impactor size, density, and velocity. Isolating the effects of each variable in the cratering record is generally considered masked, if not lost, during late stages of crater modification (e.g., floor uplift and rim collapse). Important clues, however, come from the distinctive signatures of the impactor created by oblique impacts. In summary, oblique impacts allow for the identification of distinctive signatures of the impactor created during early penetration. Such signatures may further allow first-order testing of scaling relations for late crater excavation from the planetary surface record. Other aspects of this study are discussed.

  20. Timing signatures of large scale solar eruptions

    NASA Astrophysics Data System (ADS)

    Balasubramaniam, K. S.; Hock-Mysliwiec, Rachel; Henry, Timothy; Kirk, Michael S.

    2016-05-01

    We examine the timing signatures of large solar eruptions resulting in flares, CMEs and Solar Energetic Particle events. We probe solar active regions from the chromosphere through the corona, using data from space and ground-based observations, including ISOON, SDO, GONG, and GOES. Our studies include a number of flares and CMEs of mostly the M- and X-strengths as categorized by GOES. We find that the chromospheric signatures of these large eruptions occur 5-30 minutes in advance of coronal high temperature signatures. These timing measurements are then used as inputs to models and reconstruct the eruptive nature of these systems, and explore their utility in forecasts.

  1. Remote Sensing of Body Signs and Signatures

    DTIC Science & Technology

    1985-10-01

    REMOTE SENSING OF BODY SIGNS AND SIGNATURES LPrepared For Naval Medical Research and Development Command National Naval Medical Center, Bethesda...BODY SIGNS AND SIGNATURES S~By James C. Lin and Karen H. Chan Department of Bioengineering University of Illinois at Chicago Chicago, IL 60680 Abstract...Filters Di-t lb io. I AN!ý,z.biiity Codes I’ A.IDist jor p REMOTE SENSING OF BODY SIGNS AND SIGNATURES By James C. Lin and Karen H. Chan Department

  2. Synchronization patterns: from network motifs to hierarchical networks

    NASA Astrophysics Data System (ADS)

    Krishnagopal, Sanjukta; Lehnert, Judith; Poel, Winnie; Zakharova, Anna; Schöll, Eckehard

    2017-03-01

    We investigate complex synchronization patterns such as cluster synchronization and partial amplitude death in networks of coupled Stuart-Landau oscillators with fractal connectivities. The study of fractal or self-similar topology is motivated by the network of neurons in the brain. This fractal property is well represented in hierarchical networks, for which we present three different models. In addition, we introduce an analytical eigensolution method and provide a comprehensive picture of the interplay of network topology and the corresponding network dynamics, thus allowing us to predict the dynamics of arbitrarily large hierarchical networks simply by analysing small network motifs. We also show that oscillation death can be induced in these networks, even if the coupling is symmetric, contrary to previous understanding of oscillation death. Our results show that there is a direct correlation between topology and dynamics: hierarchical networks exhibit the corresponding hierarchical dynamics. This helps bridge the gap between mesoscale motifs and macroscopic networks. This article is part of the themed issue 'Horizons of cybernetical physics'.

  3. Prevalent RNA recognition motif duplication in the human genome.

    PubMed

    Tsai, Yihsuan S; Gomez, Shawn M; Wang, Zefeng

    2014-05-01

    The sequence-specific recognition of RNA by proteins is mediated through various RNA binding domains, with the RNA recognition motif (RRM) being the most frequent and present in >50% of RNA-binding proteins (RBPs). Many RBPs contain multiple RRMs, and it is unclear how each RRM contributes to the binding specificity of the entire protein. We found that RRMs within the same RBP (i.e., sibling RRMs) tend to have significantly higher similarity than expected by chance. Sibling RRM pairs from RBPs shared by multiple species tend to have lower similarity than those found only in a single species, suggesting that multiple RRMs within the same protein might arise from domain duplication followed by divergence through random mutations. This finding is exemplified by a recent RRM domain duplication in DAZ proteins and an ancient duplication in PABP proteins. Additionally, we found that different similarities between sibling RRMs are associated with distinct functions of an RBP and that the RBPs tend to contain repetitive sequences with low complexity. Taken together, this study suggests that the number of RBPs with multiple RRMs has expanded in mammals and that the multiple sibling RRMs may recognize similar target motifs in a cooperative manner.

  4. Functional implications of local DNA structures in regulatory motifs.

    PubMed

    Xiang, Qian

    2013-01-01

    The three-dimensional structure of DNA has been proposed to be a major determinant for functional transcription factors (TFs) and DNA interaction. Here, we use hydroxyl radical cleavage pattern as a measure of local DNA structure. We compared the conservation between DNA sequence and structure in terms of information content and attempted to assess the functional implications of DNA structures in regulatory motifs. We used statistical methods to evaluate the structural divergence of substituting a single position within a binding site and applied them to a collection of putative regulatory motifs. The following are our major observations: (i) we observed more information in structural alignment than in the corresponding sequence alignment for most of the transcriptional factors; (ii) for each TF, majority of positions have more information in the structural alignment as compared to the sequence alignment; (iii) we further defined a DNA structural divergence score (SD score) for each wild-type and mutant pair that is distinguished by single-base mutation. The SD score for benign mutations is significantly lower than that of switch mutations. This indicates structural conservation is also important for TFBS to be functional and DNA structures will provide previously unappreciated information for TF to realize the binding specificity.

  5. Applying Side-chain Flexibility in Motifs for Protein Docking

    PubMed Central

    Liu, Hui; Lin, Feng; Yang, Jian-Li; Wang, Hong-Rui; Liu, Xiu-Ling

    2015-01-01

    Conventional rigid docking algorithms have been unsatisfactory in their computational results, largely due to the fact that protein structures are flexible in live environments. In response, we propose to introduce the side-chain flexibility in protein motif into the docking. First, the Morse theory is applied to curvature labeling and surface region growing, for segmentation of the protein surface into smaller patches. Then, the protein is described by an ensemble of conformations that incorporate the flexibility of interface side chains and are sampled using rotamers. Next, a 3D rotation invariant shape descriptor is proposed to deal with the flexible motifs and surface patches; thus, pairwise complementarity matching is needed only between the convex patches of ligand and the concave patches of receptor. The iterative closest point (ICP) algorithm is implemented for geometric alignment of the two 3D protein surface patches. Compared with the fast Fourier transform-based global geometric matching algorithm and other methods, our FlexDock system generates much less false-positive docking results, which benefits identification of the complementary candidates. Our computational experiments show the advantages of the proposed flexible docking algorithm over its counterparts. PMID:26508871

  6. Identifying DNA Binding Motifs by Combining Data from Different Sources

    SciTech Connect

    Mao, Linyong; Resat, Haluk; Nagib Callaos; Katsuhisa Horimoto; Jake Chen; Amy Sze Chan

    2004-07-19

    A transcription factor regulates the expression of its target genes by binding to their operator regions. It functions by affecting the interactions between RNA polymerases and the gene's promoter. Many transcription factors bind to their targets by recognizing a specific DNA sequence pattern, which is referred to as a consensus sequence or a motif. Since it would remove the possible biases, combining biological data from different sources can be expected to improve the quality of the information extracted from the biological data. We analyzed the microarray gene expression data and the organism's genome sequence jointly to determine the transcription factor recognition sequences with more accuracy. Utilizing such a data integration approach, we have investigated the regulation of the photosynthesis genes of the purple non-sulphur photosynthetic bacterium Rhodobacter sphaeroides. The photosynthesis genes in this organism are tightly regulated as a function of environmental growth conditions by three major regulatory systems, PrrB/PrrA, AppA/PpsR and FnrL. In this study, we have detected a previously undefined PrrA consensus sequence, improved the previously known DNA-binding motif of PpsR, and confirmed the consensus sequence of the global regulator FnrL.

  7. Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases

    PubMed Central

    Zhao, Bryan M.; Keasey, Sarah L.; Tropea, Joseph E.; Lountos, George T.; Dyas, Beverly K.; Cherry, Scott; Raran-Kurussi, Sreejith; Waugh, David S.; Ulrich, Robert G.

    2015-01-01

    Protein tyrosine phosphatases dephosphorylate tyrosine residues of proteins, whereas, dual specificity phosphatases (DUSPs) are a subgroup of protein tyrosine phosphatases that dephosphorylate not only Tyr(P) residue, but also the Ser(P) and Thr(P) residues of proteins. The DUSPs are linked to the regulation of many cellular functions and signaling pathways. Though many cellular targets of DUSPs are known, the relationship between catalytic activity and substrate specificity is poorly defined. We investigated the interactions of peptide substrates with select DUSPs of four types: MAP kinases (DUSP1 and DUSP7), atypical (DUSP3, DUSP14, DUSP22 and DUSP27), viral (variola VH1), and Cdc25 (A-C). Phosphatase recognition sites were experimentally determined by measuring dephosphorylation of 6,218 microarrayed Tyr(P) peptides representing confirmed and theoretical phosphorylation motifs from the cellular proteome. A broad continuum of dephosphorylation was observed across the microarrayed peptide substrates for all phosphatases, suggesting a complex relationship between substrate sequence recognition and optimal activity. Further analysis of peptide dephosphorylation by hierarchical clustering indicated that DUSPs could be organized by substrate sequence motifs, and peptide-specificities by phylogenetic relationships among the catalytic domains. The most highly dephosphorylated peptides represented proteins from 29 cell-signaling pathways, greatly expanding the list of potential targets of DUSPs. These newly identified DUSP substrates will be important for examining structure-activity relationships with physiologically relevant targets. PMID:26302245

  8. Discovering interacting domains and motifs in protein-protein interactions.

    PubMed

    Hugo, Willy; Sung, Wing-Kin; Ng, See-Kiong

    2013-01-01

    Many important biological processes, such as the signaling pathways, require protein-protein interactions (PPIs) that are designed for fast response to stimuli. These interactions are usually transient, easily formed, and disrupted, yet specific. Many of these transient interactions involve the binding of a protein domain to a short stretch (3-10) of amino acid residues, which can be characterized by a sequence pattern, i.e., a short linear motif (SLiM). We call these interacting domains and motifs domain-SLiM interactions. Existing methods have focused on discovering SLiMs in the interacting proteins' sequence data. With the recent increase in protein structures, we have a new opportunity to detect SLiMs directly from the proteins' 3D structures instead of their linear sequences. In this chapter, we describe a computational method called SLiMDIet to directly detect SLiMs on domain interfaces extracted from 3D structures of PPIs. SLiMDIet comprises two steps: (1) interaction interfaces belonging to the same domain are extracted and grouped together using structural clustering and (2) the extracted interaction interfaces in each cluster are structurally aligned to extract the corresponding SLiM. Using SLiMDIet, de novo SLiMs interacting with protein domains can be computationally detected from structurally clustered domain-SLiM interactions for PFAM domains which have available 3D structures in the PDB database.

  9. Synchronization patterns: from network motifs to hierarchical networks.

    PubMed

    Krishnagopal, Sanjukta; Lehnert, Judith; Poel, Winnie; Zakharova, Anna; Schöll, Eckehard

    2017-03-06

    We investigate complex synchronization patterns such as cluster synchronization and partial amplitude death in networks of coupled Stuart-Landau oscillators with fractal connectivities. The study of fractal or self-similar topology is motivated by the network of neurons in the brain. This fractal property is well represented in hierarchical networks, for which we present three different models. In addition, we introduce an analytical eigensolution method and provide a comprehensive picture of the interplay of network topology and the corresponding network dynamics, thus allowing us to predict the dynamics of arbitrarily large hierarchical networks simply by analysing small network motifs. We also show that oscillation death can be induced in these networks, even if the coupling is symmetric, contrary to previous understanding of oscillation death. Our results show that there is a direct correlation between topology and dynamics: hierarchical networks exhibit the corresponding hierarchical dynamics. This helps bridge the gap between mesoscale motifs and macroscopic networks.This article is part of the themed issue 'Horizons of cybernetical physics'.

  10. Computational definition of sequence motifs governing constitutive exon splicing.

    PubMed

    Zhang, Xiang H-F; Chasin, Lawrence A

    2004-06-01

    We have searched for sequence motifs that contribute to the recognition of human pre-mRNA splice sites by comparing the frequency of 8-mers in internal noncoding exons versus unspliced pseudo exons and 5' untranslated regions (5' untranslated regions [UTRs]) of transcripts of intronless genes. This type of comparison avoids the isolation of sequences that are distinguished by their protein-coding information. We classified sequence families comprising 2069 putative exonic enhancers and 974 putative exonic silencers. Representatives of each class functioned as enhancers or silencers when inserted into a test exon and assayed in transfected mammalian cells. As a class, the enhancer sequencers were more prevalent and the silencer elements less prevalent in all exons compared with introns. A survey of 58 reported exonic splicing mutations showed good agreement between the splicing phenotype and the effect of the mutation on the motifs defined here. The large number of effective sequences implied by these results suggests that sequences that influence splicing may be very abundant in pre-mRNA.

  11. The helix bundle: A reversible lipid binding motif

    PubMed Central

    Narayanaswami, Vasanthy; Kiss, Robert S.; Weers, Paul M.M.

    2009-01-01

    Apolipoproteins are the protein components of lipoproteins that have the innate ability to inter convert between a lipid-free and a lipid-bound form in a facile manner, a remarkable property conferred by the helix bundle motif. Composed of a series of four or five amphipathic α-helices that fold to form a helix bundle, this motif allows the en face orientation of the hydrophobic faces of the α-helices in the protein interior in the lipid-free state. A conformational switch then permits helix-helix interactions to be substituted by helix-lipid interactions upon lipid binding interaction. This review compares the apolipoprotein high resolution structures and the factors that trigger this switch in insect apolipophorin III and the mammalian apolipoproteins, apolipoprotein E and apolipoprotein A-I, pointing out the commonalities and key differences in the mode of lipid interaction. Further insights into the lipid bound conformation of apolipoproteins are required to fully understand their functional role under physiological conditions. PMID:19770066

  12. Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

    PubMed Central

    Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

    2013-01-01

    Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

  13. Exhaustive Search for Over-represented DNA Sequence Motifs with CisFinder

    PubMed Central

    Sharov, Alexei A.; Ko, Minoru S.H.

    2009-01-01

    We present CisFinder software, which generates a comprehensive list of motifs enriched in a set of DNA sequences and describes them with position frequency matrices (PFMs). A new algorithm was designed to estimate PFMs directly from counts of n-mer words with and without gaps; then PFMs are extended over gaps and flanking regions and clustered to generate non-redundant sets of motifs. The algorithm successfully identified binding motifs for 12 transcription factors (TFs) in embryonic stem cells based on published chromatin immunoprecipitation sequencing data. Furthermore, CisFinder successfully identified alternative binding motifs of TFs (e.g. POU5F1, ESRRB, and CTCF) and motifs for known and unknown co-factors of genes associated with the pluripotent state of ES cells. CisFinder also showed robust performance in the identification of motifs that were only slightly enriched in a set of DNA sequences. PMID:19740934

  14. Blind Quantum Signature with Blind Quantum Computation

    NASA Astrophysics Data System (ADS)

    Li, Wei; Shi, Ronghua; Guo, Ying

    2017-04-01

    Blind quantum computation allows a client without quantum abilities to interact with a quantum server to perform a unconditional secure computing protocol, while protecting client's privacy. Motivated by confidentiality of blind quantum computation, a blind quantum signature scheme is designed with laconic structure. Different from the traditional signature schemes, the signing and verifying operations are performed through measurement-based quantum computation. Inputs of blind quantum computation are securely controlled with multi-qubit entangled states. The unique signature of the transmitted message is generated by the signer without leaking information in imperfect channels. Whereas, the receiver can verify the validity of the signature using the quantum matching algorithm. The security is guaranteed by entanglement of quantum system for blind quantum computation. It provides a potential practical application for e-commerce in the cloud computing and first-generation quantum computation.

  15. Electronic Signatures for Public Procurement across Europe

    NASA Astrophysics Data System (ADS)

    Ølnes, Jon; Andresen, Anette; Arbia, Stefano; Ernst, Markus; Hagen, Martin; Klein, Stephan; Manca, Giovanni; Rossi, Adriano; Schipplick, Frank; Tatti, Daniele; Wessolowski, Gesa; Windheuser, Jan

    The PEPPOL (Pan-European Public Procurement On-Line) project is a large scale pilot under the CIP programme of the EU, exploring electronic public procurement in a unified European market. An important element is interoperability of electronic signatures across borders, identified today as a major obstacle to cross-border procurement. PEPPOL will address use of signatures in procurement processes, in particular tendering but also post-award processes like orders and invoices. Signature policies, i.e. quality requirements and requirements on information captured in the signing process, will be developed. This as well as technical interoperability of e-signatures across Europe will finally be piloted in demonstrators starting late 2009 or early 2010.

  16. Blind Quantum Signature with Blind Quantum Computation

    NASA Astrophysics Data System (ADS)

    Li, Wei; Shi, Ronghua; Guo, Ying

    2016-12-01

    Blind quantum computation allows a client without quantum abilities to interact with a quantum server to perform a unconditional secure computing protocol, while protecting client's privacy. Motivated by confidentiality of blind quantum computation, a blind quantum signature scheme is designed with laconic structure. Different from the traditional signature schemes, the signing and verifying operations are performed through measurement-based quantum computation. Inputs of blind quantum computation are securely controlled with multi-qubit entangled states. The unique signature of the transmitted message is generated by the signer without leaking information in imperfect channels. Whereas, the receiver can verify the validity of the signature using the quantum matching algorithm. The security is guaranteed by entanglement of quantum system for blind quantum computation. It provides a potential practical application for e-commerce in the cloud computing and first-generation quantum computation.

  17. 15 CFR 908.16 - Signature.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... SUBMITTING REPORTS ON WEATHER MODIFICATION ACTIVITIES § 908.16 Signature. All reports filed with the National... or intending to conduct the weather modification activities referred to therein by such...

  18. Analysis of multispectral signatures of the shot

    NASA Astrophysics Data System (ADS)

    Kastek, Mariusz; Dulski, Rafał; Piątkowski, Tadeusz; Madura, Henryk; Bareła, Jarosław; Polakowski, Henryk

    2011-06-01

    The paper presents some practical aspects of sniper IR signature measurements. Description of particular signatures for sniper shot in typical scenarios has been presented. We take into consideration sniper activities in the open area as well as in urban environment. The measurements were made at field test ground. High precision laboratory measurements were also performed. Several infrared cameras were used during measurements to cover all measurement assumptions. Some of the cameras are measurement-class devices with high accuracy and frame rates. The registrations were simultaneously made in UV, NWIR, SWIR and LWIR spectral bands. The infrared cameras have possibilities to install optical filters for multispectral measurement. An ultra fast visual camera was also used for visible spectra registration. Exemplary sniper IR signatures for typical situation were presented. LWIR imaging spectroradiometer HyperCam was also used during the laboratory measurements and field experiments. The signatures collected by HyperCam were useful for the determination of spectral characteristics of shot.

  19. Secure quantum signatures using insecure quantum channels

    NASA Astrophysics Data System (ADS)

    Amiri, Ryan; Wallden, Petros; Kent, Adrian; Andersson, Erika

    2016-03-01

    Digital signatures are widely used in modern communication to guarantee authenticity and transferability of messages. The security of currently used classical schemes relies on computational assumptions. We present a quantum signature scheme that does not require trusted quantum channels. We prove that it is unconditionally secure against the most general coherent attacks, and show that it requires the transmission of significantly fewer quantum states than previous schemes. We also show that the quantum channel noise threshold for our scheme is less strict than for distilling a secure key using quantum key distribution. This shows that "direct" quantum signature schemes can be preferable to signature schemes relying on secret shared keys generated using quantum key distribution.

  20. Isotopic signatures by bulk analyses

    SciTech Connect

    Efurd, D.W.; Rokop, D.J.

    1997-12-01

    Los Alamos National Laboratory has developed a series of measurement techniques for identification of nuclear signatures by analyzing bulk samples. Two specific applications for isotopic fingerprinting to identify the origin of anthropogenic radioactivity in bulk samples are presented. The first example is the analyses of environmental samples collected in the US Arctic to determine the impact of dumping of radionuclides in this polar region. Analyses of sediment and biota samples indicate that for the areas sampled the anthropogenic radionuclide content of sediments was predominantly the result of the deposition of global fallout. The anthropogenic radionuclide concentrations in fish, birds and mammals were very low. It can be surmised that marine food chains are presently not significantly affected. The second example is isotopic fingerprinting of water and sediment samples from the Rocky Flats Facility (RFP). The largest source of anthropogenic radioactivity presently affecting surface-waters at RFP is the sediments that are currently residing in the holding ponds. One gram of sediment from a holding pond contains approximately 50 times more plutonium than 1 liter of water from the pond. Essentially 100% of the uranium in Ponds A-1 and A-2 originated as depleted uranium. The largest source of radioactivity in the terminal Ponds A-4, B-5 and C-2 was naturally occurring uranium and its decay product radium. The uranium concentrations in the waters collected from the terminal ponds contained 0.05% or less of the interim standard calculated derived concentration guide for uranium in waters available to the public. All of the radioactivity observed in soil, sediment and water samples collected at RFP was naturally occurring, the result of processes at RFP or the result of global fallout. No extraneous anthropogenic alpha, beta or gamma activities were detected. The plutonium concentrations in Pond C-2 appear to vary seasonally.

  1. ACCRETING CIRCUMPLANETARY DISKS: OBSERVATIONAL SIGNATURES

    SciTech Connect

    Zhu, Zhaohuan

    2015-01-20

    I calculate the spectral energy distributions of accreting circumplanetary disks using atmospheric radiative transfer models. Circumplanetary disks only accreting at 10{sup –10} M {sub ☉} yr{sup –1} around a 1 M{sub J} planet can be brighter than the planet itself. A moderately accreting circumplanetary disk ( M-dot ∼10{sup −8} M{sub ⊙} yr{sup −1}; enough to form a 10 M{sub J} planet within 1 Myr) around a 1 M{sub J} planet has a maximum temperature of ∼2000 K, and at near-infrared wavelengths (J, H, K bands), this disk is as bright as a late-M-type brown dwarf or a 10 M{sub J} planet with a ''hot start''. To use direct imaging to find the accretion disks around low-mass planets (e.g., 1 M{sub J} ) and distinguish them from brown dwarfs or hot high-mass planets, it is crucial to obtain photometry at mid-infrared bands (L', M, N bands) because the emission from circumplanetary disks falls off more slowly toward longer wavelengths than those of brown dwarfs or planets. If young planets have strong magnetic fields (≳100 G), fields may truncate slowly accreting circumplanetary disks ( M-dot ≲10{sup −9} M{sub ⊙} yr{sup −1}) and lead to magnetospheric accretion, which can provide additional accretion signatures, such as UV/optical excess from the accretion shock and line emission.

  2. Irma multisensor predictive signature model

    NASA Astrophysics Data System (ADS)

    Watson, John S.; Wellfare, Michael R.; Chenault, David B.; Talele, Sunjay E.; Blume, Bradley T.; Richards, Mike; Prestwood, Lee

    1997-06-01

    Development of target acquisition and target recognition algorithms in highly cluttered backgrounds in a variety of battlefield conditions demands a flexible, high fidelity capability for synthetic image generation. Cost effective smart weapons research and testing also requires extensive scene generation capability. The Irma software package addresses this need through a first principles, phenomenology based scene generator that enhances research into new algorithms, novel sensors, and sensor fusion approaches. Irma was one of the first high resolution synthetic infrared target and background signature models developed for tactical air-to-surface weapon scenarios. Originally developed in 1980 by the Armament Directorate of the Air Force Wright Laboratory, the Irma model was used exclusively to generate IR scenes for smart weapons research and development. in 1987, Nichols Research Corporation took over the maintenance of Irma and has since added substantial capabilities. The development of Irma has culminated in a program that includes not only passive visible, IR, and millimeter wave (MMW) channels but also active MMW and ladar channels. Each of these channels is co-registered providing the capability to develop algorithms for multi-band sensor fusion concepts and associated algorithms. In this paper, the capabilities of the latest release of Irma, Irma 4.0, will be described. A brief description of the elements of the software that are common to all channels will be provided. Each channel will be described briefly including a summary of the phenomenological effects and the sensor effects modeled in the software. Examples of Irma multi- channel imagery will be presented.

  3. Geochemical and Sulfur-Isotopic Signatures of Volcanogenic Massive Sulfide Deposits on Prince of Wales Island and Vicinity, Southeastern Alaska

    USGS Publications Warehouse

    Slack, John F.; Shanks, Wayne C.; Karl, Susan M.; Gemery, Pamela A.; Bittenbender, Peter E.; Ridley, W. Ian

    2007-01-01

    example, Mn, As, Sb, and Tl in pyrite from the Moira Sound unit), whereas in other samples the signatures are varyingly annealed, owing to metamorphic overprinting. A limited LA-ICP-MS database for sphalerite indicates that low-Fe sphalerite is preferentially associated with the most Au rich deposits, the Niblack and Nutkwa. Sulfur-isotopic values for sulfide minerals in the VMS deposits in the Wales Group range from 5.9 to 17.4 permil (avg 11.5?2.7 permil), about 5 to 6 permil higher than those in the Moira Sound unit, which range from -2.8 to 10.4 permil (avg 6.1?4.0 permil). This difference in 34Ssulfide values reflects a dominantly seawater sulfate source of the sulfides and is linked to the 34S values of contemporaneous seawater sulfate, which were slightly higher during the Late Proterozoic through Cambrian than during the Ordovician through Early Silurian.

  4. The postprocessing of quantum digital signatures

    NASA Astrophysics Data System (ADS)

    Wang, Tian-Yin; Ma, Jian-Feng; Cai, Xiao-Qiu

    2017-01-01

    Many novel quantum digital signature proposals have been proposed, which can effectively guarantee the information-theoretic security of the signature for a singe bit against forging and denying. Using the current basic building blocks of signing a single bit, we give a new proposal to construct an entire protocol for signing a long message. Compared with the previous work, it can improve at least 33.33% efficiency.

  5. Signature-based store checking buffer

    DOEpatents

    Sridharan, Vilas; Gurumurthi, Sudhanva

    2015-06-02

    A system and method for optimizing redundant output verification, are provided. A hardware-based store fingerprint buffer receives multiple instances of output from multiple instances of computation. The store fingerprint buffer generates a signature from the content included in the multiple instances of output. When a barrier is reached, the store fingerprint buffer uses the signature to verify the content is error-free.

  6. Research Plan for Fire Signatures and Detection

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Viewgraphs on the prevention, suppression, and detection of fires aboard a spacecraft is presented. The topics include: 1) Fire Prevention, Detection, and Suppression Sub-Element Products; 2) FPDS Organizing Questions; 3) FPDS Organizing Questions; 4) Signatures, Sensors, and Simulations; 5) Quantification of Fire and Pre-Fire Signatures; 6) Smoke; 7) DAFT Hardware; 8) Additional Benefits of DAFT; 9) Development and Characterization of Sensors 10) Simulation of the Transport of Smoke and Fire Precursors; and 11) FPDS Organizing Questions.

  7. Mining bridge and brick motifs from complex biological networks for functionally and statistically significant discovery.

    PubMed

    Cheng, Chia-Ying; Huang, Chung-Yuan; Sun, Chuen-Tsai

    2008-02-01

    A major task for postgenomic systems biology researchers is to systematically catalogue molecules and their interactions within living cells. Advancements in complex-network theory are being made toward uncovering organizing principles that govern cell formation and evolution, but we lack understanding of how molecules and their interactions determine how complex systems function. Molecular bridge motifs include isolated motifs that neither interact nor overlap with others, whereas brick motifs act as network foundations that play a central role in defining global topological organization. To emphasize their structural organizing and evolutionary characteristics, we define bridge motifs as consisting of weak links only and brick motifs as consisting of strong links only, then propose a method for performing two tasks simultaneously, which are as follows: 1) detecting global statistical features and local connection structures in biological networks and 2) locating functionally and statistically significant network motifs. To further understand the role of biological networks in system contexts, we examine functional and topological differences between bridge and brick motifs for predicting biological network behaviors and functions. After observing brick motif similarities between E. coli and S. cerevisiae, we note that bridge motifs differentiate C. elegans from Drosophila and sea urchin in three types of networks. Similarities (differences) in bridge and brick motifs imply similar (different) key circuit elements in the three organisms. We suggest that motif-content analyses can provide researchers with global and local data for real biological networks and assist in the search for either isolated or functionally and topologically overlapping motifs when investigating and comparing biological system functions and behaviors.

  8. Transcription factor and microRNA-regulated network motifs for cancer and signal transduction networks

    PubMed Central

    2015-01-01

    Abstract Background Molecular networks are the basis of biological processes. Such networks can be decomposed into smaller modules, also known as network motifs. These motifs show interesting dynamical behaviors, in which co-operativity effects between the motif components play a critical role in human diseases. We have developed a motif-searching algorithm, which is able to identify common motif types from the cancer networks and signal transduction networks (STNs). Some of the network motifs are interconnected which can be merged together and form more complex structures, the so-called coupled motif structures (CMS). These structures exhibit mixed dynamical behavior, which may lead biological organisms to perform specific functions. Results In this study, we integrate transcription factors (TFs), microRNAs (miRNAs), miRNA targets and network motifs information to build the cancer-related TF-miRNA-motif networks (TMMN). This allows us to examine the role of network motifs in cancer formation at different levels of regulation, i.e. transcription initiation (TF → miRNA), gene-gene interaction (CMS), and post-transcriptional regulation (miRNA → target genes). Among the cancer networks and STNs we considered, it is found that there is a substantial amount of crosstalking through motif interconnections, in particular, the crosstalk between prostate cancer network and PI3K-Akt STN. Conclusions To validate the role of network motifs in cancer formation, several examples are presented which demonstrated the effectiveness of the present approach. A web-based platform has been set up which can be accessed at: http://ppi.bioinfo.asia.edu.tw/pathway/. It is very likely that our results can supply very specific CMS missing information for certain cancer types, it is an indispensable tool for cancer biology research. PMID:25707690

  9. Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages

    PubMed Central

    2011-01-01

    Background Deficiency of the transcription factor MafB, which is normally expressed in macrophages, can underlie cellular dysfunction associated with a range of autoimmune diseases and arteriosclerosis. MafB has important roles in cell differentiation and regulation of target gene expression; however, the mechanisms of this regulation and the identities of other transcription factors with which MafB interacts remain uncertain. Bioinformatics methods provide a valuable approach for elucidating the nature of these interactions with transcriptional regulatory elements from a large number of DNA sequences. In particular, identification of patterns of co-occurrence of regulatory cis-elements (motifs) offers a robust approach. Results Here, the directional relationships among several functional motifs were evaluated using the Log-linear Graphical Model (LGM) after extraction and search for evolutionarily conserved motifs. This analysis highlighted GATA-1 motifs and 5’AT-rich half Maf recognition elements (MAREs) in promoter regions of 18 genes that were down-regulated in Mafb deficient macrophages. GATA-1 motifs and MafB motifs could regulate expression of these genes in both a negative and positive manner, respectively. The validity of this conclusion was tested with data from a luciferase assay that used a C1qa promoter construct carrying both the GATA-1 motifs and MAREs. GATA-1 was found to inhibit the activity of the C1qa promoter with the GATA-1 motifs and MafB motifs. Conclusions These observations suggest that both the GATA-1 motifs and MafB motifs are important for lineage specific expression of C1qa. In addition, these findings show that analysis of combinations of evolutionarily conserved motifs can be successfully used to identify patterns of gene regulation. PMID:22784578

  10. Kinematics of Signature Writing in Healthy Aging*

    PubMed Central

    Caligiuri, Michael P.; Kim, Chi; Landy, Kelly M.

    2014-01-01

    Forensic document examiners (FDE) called upon to distinguish a genuine from a forged signature of an elderly person are often required to consider the question of age-related deterioration and whether the available exemplars reliably capture the natural effects of aging of the original writer. An understanding of the statistical relationship between advanced age and handwriting movements can reduce the uncertainty that may exist in an examiner’s approach to questioned signatures formed by elderly writers. The primary purpose of this study was to systematically examine age-related changes in signature kinematics in healthy writers. Forty-two healthy subjects between the ages of 60–91 years participated in this study. Signatures were recorded using a digitizing tablet and commercial software was used to examine the temporal and spatial stroke kinematics and pen pressure. Results indicated that vertical stroke duration and dysfluency increased with age, whereas vertical stroke amplitude and velocity decreased with age. Pen pressure decreased with age. We found that a linear model characterized the best-fit relationship between advanced age and handwriting movement parameters for signature formation. Male writers exhibited stronger age effects than female writers, especially for pen pressure and stroke dysfluency. The present study contributes to an understanding of how advanced age alters signature formation in otherwise healthy adults. PMID:24673648

  11. Chemical and Physical Signatures for Microbial Forensics

    SciTech Connect

    Cliff, John B.; Kreuzer, Helen W.; Ehrhardt, Christopher J.; Wunschel, David S.

    2012-01-03

    Chemical and physical signatures for microbial forensics John Cliff and Helen Kreuzer-Martin, eds. Humana Press Chapter 1. Introduction: Review of history and statement of need. Randy Murch, Virginia Tech Chapter 2. The Microbe: Structure, morphology, and physiology of the microbe as they relate to potential signatures of growth conditions. Joany Jackman, Johns Hopkins University Chapter 3. Science for Forensics: Special considerations for the forensic arena - quality control, sample integrity, etc. Mark Wilson (retired FBI): Western Carolina University Chapter 4. Physical signatures: Light and electron microscopy, atomic force microscopy, gravimetry etc. Joseph Michael, Sandia National Laboratory Chapter 5. Lipids: FAME, PLFA, steroids, LPS, etc. James Robertson, Federal Bureau of Investigation Chapter 6. Carbohydrates: Cell wall components, cytoplasm components, methods Alvin Fox, University of South Carolina School of Medicine David Wunschel, Pacific Northwest National Laboratory Chapter 7. Peptides: Peptides, proteins, lipoproteins David Wunschel, Pacific Northwest National Laboratory Chapter 8. Elemental content: CNOHPS (treated in passing), metals, prospective cell types John Cliff, International Atomic Energy Agency Chapter 9. Isotopic signatures: Stable isotopes C,N,H,O,S, 14C dating, potential for heavy elements. Helen Kreuzer-Martin, Pacific Northwest National Laboratory Michaele Kashgarian, Lawrence Livermore National Laboratory Chapter 10. Extracellular signatures: Cellular debris, heme, agar, headspace, spent media, etc Karen Wahl, Pacific Northwest National Laboratory Chapter 11. Data Reduction and Integrated Microbial Forensics: Statistical concepts, parametric and multivariate statistics, integrating signatures Kristin Jarman, Pacific Northwest National Laboratory

  12. Assessing the Quality of Bioforensic Signatures

    SciTech Connect

    Sego, Landon H.; Holmes, Aimee E.; Gosink, Luke J.; Webb-Robertson, Bobbie-Jo M.; Kreuzer, Helen W.; Anderson, Richard M.; Brothers, Alan J.; Corley, Courtney D.; Tardiff, Mark F.

    2013-06-04

    We present a mathematical framework for assessing the quality of signature systems in terms of fidelity, cost, risk, and utility—a method we refer to as Signature Quality Metrics (SQM). We demonstrate the SQM approach by assessing the quality of a signature system designed to predict the culture medium used to grow a microorganism. The system consists of four chemical assays designed to identify various ingredients that could be used to produce the culture medium. The analytical measurements resulting from any combination of these four assays can be used in a Bayesian network to predict the probabilities that the microorganism was grown using one of eleven culture media. We evaluated fifteen combinations of the signature system by removing one or more of the assays from the Bayes network. We demonstrated that SQM can be used to distinguish between the various combinations in terms of attributes of interest. The approach assisted in clearly identifying assays that were least informative, largely in part because they only could discriminate between very few culture media, and in particular, culture media that are rarely used. There are limitations associated with the data that were used to train and test the signature system. Consequently, our intent is not to draw formal conclusions regarding this particular bioforensic system, but rather to illustrate an analytical approach that could be useful in comparing one signature system to another.

  13. Signature extension through the application of cluster matching algorithms to determine appropriate signature transformations

    NASA Technical Reports Server (NTRS)

    Lambeck, P. F.; Rice, D. P.

    1976-01-01

    Signature extension is intended to increase the space-time range over which a set of training statistics can be used to classify data without significant loss of recognition accuracy. A first cluster matching algorithm MASC (Multiplicative and Additive Signature Correction) was developed at the Environmental Research Institute of Michigan to test the concept of using associations between training and recognition area cluster statistics to define an average signature transformation. A more recent signature extension module CROP-A (Cluster Regression Ordered on Principal Axis) has shown evidence of making significant associations between training and recognition area cluster statistics, with the clusters to be matched being selected automatically by the algorithm.

  14. RNAMotifScanX: a graph alignment approach for RNA structural motif identification.

    PubMed

    Zhong, Cuncong; Zhang, Shaojie

    2015-03-01

    RNA structural motifs are recurrent three-dimensional (3D) components found in the RNA architecture. These RNA structural motifs play important structural or functional roles and usually exhibit highly conserved 3D geometries and base-interaction patterns. Analysis of the RNA 3D structures and elucidation of their molecular functions heavily rely on efficient and accurate identification of these motifs. However, efficient RNA structural motif search tools are lacking due to the high complexity of these motifs. In this work, we present RNAMotifScanX, a motif search tool based on a base-interaction graph alignment algorithm. This novel algorithm enables automatic identification of both partially and fully matched motif instances. RNAMotifScanX considers noncanonical base-pairing interactions, base-stacking interactions, and sequence conservation of the motifs, which leads to significantly improved sensitivity and specificity as compared with other state-of-the-art search tools. RNAMotifScanX also adopts a carefully designed branch-and-bound technique, which enables ultra-fast search of large kink-turn motifs against a 23S rRNA. The software package RNAMotifScanX is implemented using GNU C++, and is freely available from http://genome.ucf.edu/RNAMotifScanX.

  15. Analysis of Genomic Sequence Motifs for Deciphering Transcription Factor Binding and Transcriptional Regulation in Eukaryotic Cells

    PubMed Central

    Boeva, Valentina

    2016-01-01

    Eukaryotic genomes contain a variety of structured patterns: repetitive elements, binding sites of DNA and RNA associated proteins, splice sites, and so on. Often, these structured patterns can be formalized as motifs and described using a proper mathematical model such as position weight matrix and IUPAC consensus. Two key tasks are typically carried out for motifs in the context of the analysis of genomic sequences. These are: identification in a set of DNA regions of over-represented motifs from a particular motif database, and de novo discovery of over-represented motifs. Here we describe existing methodology to perform these two tasks for motifs characterizing transcription factor binding. When applied to the output of ChIP-seq and ChIP-exo experiments, or to promoter regions of co-modulated genes, motif analysis techniques allow for the prediction of transcription factor binding events and enable identification of transcriptional regulators and co-regulators. The usefulness of motif analysis is further exemplified in this review by how motif discovery improves peak calling in ChIP-seq and ChIP-exo experiments and, when coupled with information on gene expression, allows insights into physical mechanisms of transcriptional modulation. PMID:26941778

  16. WordSpy: identifying transcription factor binding motifs by building a dictionary and learning a grammar

    PubMed Central

    Wang, Guandong; Yu, Taotao; Zhang, Weixiong

    2005-01-01

    Transcription factor (TF) binding sites or motifs (TFBMs) are functional cis-regulatory DNA sequences that play an essential role in gene transcriptional regulation. Although many experimental and computational methods have been developed, finding TFBMs remains a challenging problem. We propose and develop a novel dictionary based motif finding algorithm, which we call WordSpy. One significant feature of WordSpy is the combination of a word counting method and a statistical model which consists of a dictionary of motifs and a grammar specifying their usage. The algorithm is suitable for genome-wide motif finding; it is capable of discovering hundreds of motifs from a large set of promoters in a single run. We further enhance WordSpy by applying gene expression information to separate true TFBMs from spurious ones, and by incorporating negative sequences to identify discriminative motifs. In addition, we also use randomly selected promoters from the genome to evaluate the significance of the discovered motifs. The output from WordSpy consists of an ordered list of putative motifs and a set of regulatory sequences with motif binding sites highlighted. The web server of WordSpy is available at . PMID:15980501

  17. cisExpress: motif detection in DNA sequences

    PubMed Central

    Triska, Martin; Grocutt, David; Southern, James; Murphy, Denis J.; Tatarinova, Tatiana

    2013-01-01

    Motivation: One of the major challenges for contemporary bioinformatics is the analysis and accurate annotation of genomic datasets to enable extraction of useful information about the functional role of DNA sequences. This article describes a novel genome-wide statistical approach to the detection of specific DNA sequence motifs based on similarities between the promoters of similarly expressed genes. This new tool, cisExpress, is especially designed for use with large datasets, such as those generated by publicly accessible whole genome and transcriptome projects. cisExpress uses a task farming algorithm to exploit all available computational cores within a shared memory node. We demonstrate the robust nature and validity of the proposed method. It is applicable for use with a wide range of genomic databases for any species of interest. Availability: cisExpress is available at www.cisexpress.org. Contact: tatiana.tatarinova@usc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23793750

  18. Bacteria-mimicking nanoparticle surface functionalization with targeting motifs

    NASA Astrophysics Data System (ADS)

    Lai, Mei-Hsiu; Clay, Nicholas E.; Kim, Dong Hyun; Kong, Hyunjoon

    2015-04-01

    In recent years, surface modification of nanocarriers with targeting motifs has been explored to modulate delivery of various diagnostic, sensing and therapeutic molecular cargo to desired sites of interest in in vitro bioengineering platforms and in vivo pathologic tissue. However, most surface functionalization approaches are often plagued by complex chemical modifications and effortful purifications. To resolve such challenges, this study demonstrates a unique method to immobilize antibodies that can act as targeting motifs on the surfaces of nanocarriers, inspired by a process that bacteria use for immobilization of the host's antibodies. We hypothesized that alkylated Staphylococcus aureus protein A (SpA) would self-assemble with micelles and subsequently induce stable coupling of antibodies to the micelles. We examined this hypothesis by using poly(2-hydroxyethyl-co-octadecyl aspartamide) (PHEA-g-C18) as a model polymer to form micelles. The self-assembly between the micelles and alkylated SpA became more thermodynamically favorable by increasing the degree of substitution of octadecyl chains to PHEA-g-C18, due to a positive entropy change. Lastly, the mixing of SpA-PA-coupled micelles with antibodies resulted in the coating of micelles with antibodies, as confirmed with a fluorescence resonance energy transfer (FRET) assay. The micelles coated with antibodies to VCAM-1 or integrin αv displayed a higher binding affinity to substrates coated with VCAM-1 and integrin αvβ3, respectively, than other controls, as evaluated with surface plasmon resonance (SPR) spectroscopy and a circulation-simulating flow chamber. We envisage that this bacteria-inspired protein immobilization approach will be useful to improve the quality of targeted delivery of nanoparticles, and can be extended to modify the surface of a wide array of nanocarriers.In recent years, surface modification of nanocarriers with targeting motifs has been explored to modulate delivery of various

  19. Sulfur-induced structural motifs on copper and gold surfaces

    SciTech Connect

    Walen, Holly

    2016-01-01

    The interaction of sulfur with copper and gold surfaces plays a fundamental role in important phenomena that include coarsening of surface nanostructures, and self-assembly of alkanethiols. Here, we identify and analyze unique sulfur-induced structural motifs observed on the low-index surfaces of these two metals. We seek out these structures in an effort to better understand the fundamental interactions between these metals and sulfur that lends to the stability and favorability of metal-sulfur complexes vs. chemisorbed atomic sulfur. The experimental observations presented here—made under identical conditions—together with extensive DFT analyses, allow comparisons and insights into factors that favor the existence of metal-sulfur complexes, vs. chemisorbed atomic sulfur, on metal terraces. We believe this data will be instrumental in better understanding the complex phenomena occurring between the surfaces of coinage metals and sulfur.

  20. RNA Sociology: Group Behavioral Motifs of RNA Consortia

    PubMed Central

    Witzany, Guenther

    2014-01-01

    RNA sociology investigates the behavioral motifs of RNA consortia from the social science perspective. Besides the self-folding of RNAs into single stem loop structures, group building of such stem loops results in a variety of essential agents that are highly active in regulatory processes in cellular and non-cellular life. RNA stem loop self-folding and group building do not depend solely on sequence syntax; more important are their contextual (functional) needs. Also, evolutionary processes seem to occur through RNA stem loop consortia that may act as a complement. This means the whole entity functions only if all participating parts are coordinated, although the complementary building parts originally evolved for different functions. If complementary groups, such as rRNAs and tRNAs, are placed together in selective pressure contexts, new evolutionary features may emerge. Evolution initiated by competent agents in natural genome editing clearly contrasts with statistical error replication narratives. PMID:25426799

  1. Study on online community user motif using web usage mining

    NASA Astrophysics Data System (ADS)

    Alphy, Meera; Sharma, Ajay

    2016-04-01

    The Web usage mining is the application of data mining, which is used to extract useful information from the online community. The World Wide Web contains at least 4.73 billion pages according to Indexed Web and it contains at least 228.52 million pages according Dutch Indexed web on 6th august 2015, Thursday. It’s difficult to get needed data from these billions of web pages in World Wide Web. Here is the importance of web usage mining. Personalizing the search engine helps the web user to identify the most used data in an easy way. It reduces the time consumption; automatic site search and automatic restore the useful sites. This study represents the old techniques to latest techniques used in pattern discovery and analysis in web usage mining from 1996 to 2015. Analyzing user motif helps in the improvement of business, e-commerce, personalisation and improvement of websites.

  2. Sequential dynamics in the motif of excitatory coupled elements

    NASA Astrophysics Data System (ADS)

    Korotkov, Alexander G.; Kazakov, Alexey O.; Osipov, Grigory V.

    2015-11-01

    In this article a new model of motif (small ensemble) of neuron-like elements is proposed. It is built with the use of the generalized Lotka-Volterra model with excitatory couplings. The main motivation for this work comes from the problems of neuroscience where excitatory couplings are proved to be the predominant type of interaction between neurons of the brain. In this paper it is shown that there are two modes depending on the type of coupling between the elements: the mode with a stable heteroclinic cycle and the mode with a stable limit cycle. Our second goal is to examine the chaotic dynamics of the generalized three-dimensional Lotka-Volterra model.

  3. 21 CFR 11.70 - Signature/record linking.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ELECTRONIC RECORDS; ELECTRONIC SIGNATURES Electronic Records § 11.70 Signature/record linking. Electronic signatures and handwritten signatures executed to electronic records shall be linked to their...

  4. Subduction signature in backarc mantle?

    NASA Astrophysics Data System (ADS)

    Nelson, W. R.; Snow, J. E.; Brandon, A. D.; Ohara, Y.

    2013-12-01

    Abyssal peridotites exposed during seafloor extension provide a rare glimpse into the processes occurring within the oceanic mantle. Whole rock and mineral-scale major element data from abyssal peridotites record processes intimately associated with melt-depletion and melt-rock interaction occurring just prior to exposure of the mantle at the surface. Isotopic data, however, can provide insight into the long-term evolution of the oceanic mantle. A number of studies of mantle material exposed along mid-ocean ridges have demonstrated that abyssal peridotites from Mid-Atlantic Ridge, Gakkel Ridge, and Southwest Indian Ridge commonly display a range of whole rock Os isotopic ratios (187Os/188Os = 0.118- 0.130; Brandon et al., 2000; Standish et al., 2002; Alard et al., 2005; Harvey et al., 2006; Liu et al., 2008). The range of isotopic values in each region demonstrates that the oceanic mantle does not melt uniformly over time. Instead, anciently depleted regions (187Os/188Os ≈ 0.118) are juxtaposed against relatively fertile regions (187Os/188Os ≈ 0.130) that are isotopically similar to established primitive mantle values (187Os/188Os = 0.1296; Meisel et al. 2001). Abyssal peridotites from the Godzilla Megamullion and Chaotic Terrain in the backarc Parece Vela Basin (Philippine Sea) display a range of Os isotopic values extending to similar unradiogenic values. However, some of the backarc basin abyssal peridotites record more radiogenic 187Os/188Os values (0.135-0.170) than mid-ocean ridge peridotites. Comparable radiogenic signatures are reported only in highly weathered abyssal peridotites (187Os/188Os ≤ 0.17, Standish et al., 2002) and subduction-related volcanic arc peridotites (187Os/188Os ≤ 0.16, Brandon et al., 1996; Widom et al., 2003). In both the weathered peridotites and arc peridotites, the 187Os/188Os value is negatively correlated with Os abundance: the most radiogenic value has the lowest Os abundance (< 1 ppb) making them highly susceptible to

  5. Polyproline and triple helix motifs in host-pathogen recognition.

    PubMed

    Berisio, Rita; Vitagliano, Luigi

    2012-12-01

    Secondary structure elements often mediate protein-protein interactions. Despite their low abundance in folded proteins, polyproline II (PPII) and its variant, the triple helix, are frequently involved in protein-protein interactions, likely due to their peculiar propensity to be solvent-exposed. We here review the role of PPII and triple helix in mediating hostpathogen interactions, with a particular emphasis to the structural aspects of these processes. After a brief description of the basic structural features of these elements, examples of host-pathogen interactions involving these motifs are illustrated. Literature data suggest that the role played by PPII motif in these processes is twofold. Indeed, PPII regions may directly mediate interactions between proteins of the host and the pathogen. Alternatively, PPII may act as structural spacers needed for the correct positioning of the elements needed for adhesion and infectivity. Recent investigations have highlighted that collagen triple helix is also a common target for bacterial adhesins. Although structural data on complexes between adhesins and collagen models are rather limited, experimental and theoretical studies have unveiled some interesting clues of the recognition process. Interestingly, very recent data show that not only is the triple helix used by pathogens as a target in the host-pathogen interaction but it may also act as a bait in these processes since bacterial proteins containing triple helix regions have been shown to interact with host proteins. As both PPII and triple helix expose several main chain non-satisfied hydrogen bond acceptors and donors, both elements are highly solvated. The preservation of the solvation state of both PPII and triple helix upon protein-protein interaction is an emerging aspect that will be here thoroughly discussed.

  6. Multivalent dendrimer vectors with DNA intercalation motifs for gene delivery.

    PubMed

    Wong, Pamela T; Tang, Kenny; Coulter, Alexa; Tang, Shengzhuang; Baker, James R; Choi, Seok Ki

    2014-11-10

    Poly(amido amine) (PAMAM) dendrimers constitute an important class of nonviral, cationic vectors in gene delivery. Here we report on a new concept for dendrimer vector design based on the incorporation of dual binding motifs: DNA intercalation, and receptor recognition for targeted delivery. We prepared a series of dendrimer conjugates derived from a fifth generation (G5) PAMAM dendrimer, each conjugated with multiple folate (FA) or riboflavin (RF) ligands for cell receptor targeting, and with 3,8-diamino-6-phenylphenanthridinium ("DAPP")-derived ligands for anchoring a DNA payload. Polyplexes of each dendrimer with calf thymus dsDNA were made and characterized by surface plasmon resonance (SPR) spectroscopy, dynamic light scattering (DLS) and zeta potential measurement. These studies provided evidence supporting polyplex formation based on the observation of tight DNA-dendrimer adhesion, and changes in particle size and surface charge upon coincubation. Further SPR studies to investigate the adhesion of the polyplex to a model surface immobilized with folate binding protein (FBP), demonstrated that the DNA payload has only a minimal effect on the receptor binding activity of the polyplex: KD = 0.22 nM for G5(FA)(DAPP) versus 0.98 nM for its polyplex. Finally, we performed in vitro transfection assays to determine the efficiency of conjugate mediated delivery of a luciferase-encoding plasmid into the KB cancer cell line and showed that RF-conjugated dendrimers were 1 to 2 orders of magnitude more effective in enhancing luciferase gene transfection than a plasmid only control. In summary, this study serves as a proof of concept for DNA-ligand intercalation as a motif in the design of multivalent dendrimer vectors for targeted gene delivery.

  7. Efficient Unrestricted Identity-Based Aggregate Signature Scheme

    PubMed Central

    Yuan, Yumin; Zhan, Qian; Huang, Hua

    2014-01-01

    An aggregate signature scheme allows anyone to compress multiple individual signatures from various users into a single compact signature. The main objective of such a scheme is to reduce the costs on storage, communication and computation. However, among existing aggregate signature schemes in the identity-based setting, some of them fail to achieve constant-length aggregate signature or require a large amount of pairing operations which grows linearly with the number of signers, while others have some limitations on the aggregated signatures. The main challenge in building efficient aggregate signature scheme is to compress signatures into a compact, constant-length signature without any restriction. To address the above drawbacks, by using the bilinear pairings, we propose an efficient unrestricted identity-based aggregate signature. Our scheme achieves both full aggregation and constant pairing computation. We prove that our scheme has existential unforgeability under the computational Diffie-Hellman assumption. PMID:25329777

  8. Efficient unrestricted identity-based aggregate signature scheme.

    PubMed

    Yuan, Yumin; Zhan, Qian; Huang, Hua

    2014-01-01

    An aggregate signature scheme allows anyone to compress multiple individual signatures from various users into a single compact signature. The main objective of such a scheme is to reduce the costs on storage, communication and computation. However, among existing aggregate signature schemes in the identity-based setting, some of them fail to achieve constant-length aggregate signature or require a large amount of pairing operations which grows linearly with the number of signers, while others have some limitations on the aggregated signatures. The main challenge in building efficient aggregate signature scheme is to compress signatures into a compact, constant-length signature without any restriction. To address the above drawbacks, by using the bilinear pairings, we propose an efficient unrestricted identity-based aggregate signature. Our scheme achieves both full aggregation and constant pairing computation. We prove that our scheme has existential unforgeability under the computational Diffie-Hellman assumption.

  9. Improved K-means clustering algorithm for exploring local protein sequence motifs representing common structural property.

    PubMed

    Zhong, Wei; Altun, Gulsah; Harrison, Robert; Tai, Phang C; Pan, Yi

    2005-09-01

    Information about local protein sequence motifs is very important to the analysis of biologically significant conserved regions of protein sequences. These conserved regions can potentially determine the diverse conformation and activities of proteins. In this work, recurring sequence motifs of proteins are explored with an improved K-means clustering algorithm on a new dataset. The structural similarity of these recurring sequence clusters to produce sequence motifs is studied in order to evaluate the relationship between sequence motifs and their structures. To the best of our knowledge, the dataset used by our research is the most updated dataset among similar studies for sequence motifs. A new greedy initialization method for the K-means algorithm is proposed to improve traditional K-means clustering techniques. The new initialization method tries to choose suitable initial points, which are well separated and have the potential to form high-quality clusters. Our experiments indicate that the improved K-means algorithm satisfactorily increases the percentage of sequence segments belonging to clusters with high structural similarity. Careful comparison of sequence motifs obtained by the improved and traditional algorithms also suggests that the improved K-means clustering algorithm may discover some relatively weak and subtle sequence motifs, which are undetectable by the traditional K-means algorithms. Many biochemical tests reported in the literature show that these sequence motifs are biologically meaningful. Experimental results also indicate that the improved K-means algorithm generates more detailed sequence motifs representing common structures than previous research. Furthermore, these motifs are universally conserved sequence patterns across protein families, overcoming some weak points of other popular sequence motifs. The satisfactory result of the experiment suggests that this new K-means algorithm may be applied to other areas of bioinformatics

  10. Assembly of supramolecular DNA complexes containing both G-quadruplexes and i-motifs by enhancing the G-repeat-bearing capacity of i-motifs

    PubMed Central

    Cao, Yanwei; Gao, Shang; Yan, Yuting; Bruist, Michael F.; Wang, Bing; Guo, Xinhua

    2017-01-01

    The single-step assembly of supramolecular complexes containing both i-motifs and G-quadruplexes (G4s) is demonstrated. This can be achieved because the formation of four-stranded i-motifs appears to be little affected by certain terminal residues: a five-cytosine tetrameric i-motif can bear ten-base flanking residues. However, things become complex when different lengths of guanine-repeats are added at the 3′ or 5′ ends of the cytosine-repeats. Here, a series of oligomers d(XGiXC5X) and d(XC5XGiX) (X = A, T or none; i < 5) are designed to study the impact of G-repeats on the formation of tetrameric i-motifs. Our data demonstrate that tetramolecular i-motif structure can tolerate specific flanking G-repeats. Assemblies of these oligonucleotides are polymorphic, but may be controlled by solution pH and counter ion species. Importantly, we find that the sequences d(TGiAC5) can form the tetrameric i-motif in large quantities. This leads to the design of two oligonucleotides d(TG4AC7) and d(TGBrGGBrGAC7) that self-assemble to form quadruplex supramolecules under certain conditions. d(TG4AC7) forms supramolecules under acidic conditions in the presence of K+ that are mainly V-shaped or ring-like containing parallel G4s and antiparallel i-motifs. d(TGBrGGBrGAC7) forms long linear quadruplex wires under acidic conditions in the presence of Na+ that consist of both antiparallel G4s and i-motifs. PMID:27899568

  11. Terahertz signature characterization of bio-simulants

    NASA Astrophysics Data System (ADS)

    Majewski, Alexander J.; Miller, Peter; Abreu, Rene; Grotts, Jeffrey; Globus, Tatiana; Brown, Elliott

    2005-05-01

    Collaboration with the University of Virginia (UVa) and the University of California, Santa Barbara (UCSB) has resulted in the collection of signature data in the THz region of the spectrum for ovalbumin, Bacillus Subtilis (BG) and RNA from MS2 phage. Two independent experimental measurement systems were used to characterize the bio-simulants. Prior to our efforts, only a limited signature database existed. The goal was to evaluate a larger ensemble of biological agent simulants (BG, MS2 and ovalbumin) by measuring their THz absorption spectra. UCSB used a photomixer spectrometer and UVa a Fourier Transform spectrometer to measure absorption spectra. Each group used different sample preparation techniques and made multiple measurements to provide reliable statistics. Data processing culminated in applying proprietary algorithms to develop detection filters for each simulant. Through a covariance matrix approach, the detection filters extract signatures over regions with strong absorption and ignore regions with large signature variation (noise). The discrimination capability of these filters was also tested. The probability of detection and false alarm for each simulant was analyzed by each simulant specific filter. We analyzed a limited set of Bacillus thuringiensis (BT) data (a near neighbor to BG) and were capable of discriminating between BT and BG. The signal processing and filter construction demonstrates signature specificity and filter discrimination capabilities.

  12. Wayward Warriors: The Viking Motif in Swedish and English Children's Literature

    ERIC Educational Resources Information Center

    Sundmark, Björn

    2014-01-01

    In this article the Viking motif in children's literature is explored--from its roots in (adult) nationalist and antiquarian discourse, over pedagogical and historical texts for children, to the eventual diversification (or dissolution) of the motif into different genres and forms. The focus is on Swedish Viking narratives, but points of…

  13. Base motif recognition and design of DNA templates for fluorescent silver clusters by machine learning.

    PubMed

    Copp, Stacy M; Bogdanov, Petko; Debord, Mark; Singh, Ambuj; Gwinn, Elisabeth

    2014-09-03

    Discriminative base motifs within DNA templates for fluorescent silver clusters are identified using methods that combine large experimental data sets with machine learning tools for pattern recognition. Combining the discovery of certain multibase motifs important for determining fluorescence brightness with a generative algorithm, the probability of selecting DNA templates that stabilize fluorescent silver clusters is increased by a factor of >3.

  14. Bayesian multiple-instance motif discovery with BAMBI: inference of recombinase and transcription factor binding sites

    PubMed Central

    Jajamovich, Guido H.; Wang, Xiaodong; Arkin, Adam P.; Samoilov, Michael S.

    2011-01-01

    Finding conserved motifs in genomic sequences represents one of essential bioinformatic problems. However, achieving high discovery performance without imposing substantial auxiliary constraints on possible motif features remains a key algorithmic challenge. This work describes BAMBI—a sequential Monte Carlo motif-identification algorithm, which is based on a position weight matrix model that does not require additional constraints and is able to estimate such motif properties as length, logo, number of instances and their locations solely on the basis of primary nucleotide sequence data. Furthermore, should biologically meaningful information about motif attributes be available, BAMBI takes advantage of this knowledge to further refine the discovery results. In practical applications, we show that the proposed approach can be used to find sites of such diverse DNA-binding molecules as the cAMP receptor protein (CRP) and Din-family site-specific serine recombinases. Results obtained by BAMBI in these and other settings demonstrate better statistical performance than any of the four widely-used profile-based motif discovery methods: MEME, BioProspector with BioOptimizer, SeSiMCMC and Motif Sampler as measured by the nucleotide-level correlation coefficient. Additionally, in the case of Din-family recombinase target site discovery, the BAMBI-inferred motif is found to be the only one functionally accurate from the underlying biochemical mechanism standpoint. C++ and Matlab code is available at http://www.ee.columbia.edu/~guido/BAMBI or http://genomics.lbl.gov/BAMBI/. PMID:21948794

  15. Physical-chemical property based sequence motifs and methods regarding same

    DOEpatents

    Braun, Werner; Mathura, Venkatarajan S.; Schein, Catherine H.

    2008-09-09

    A data analysis system, program, and/or method, e.g., a data mining/data exploration method, using physical-chemical property motifs. For example, a sequence database may be searched for identifying segments thereof having physical-chemical properties similar to the physical-chemical property motifs.

  16. Computational generation and screening of RNA motifs in large nucleotide sequence pools

    PubMed Central

    Kim, Namhee; Izzo, Joseph A.; Elmetwaly, Shereef; Gan, Hin Hark; Schlick, Tamar

    2010-01-01

    Although identification of active motifs in large random sequence pools is central to RNA in vitro selection, no systematic computational equivalent of this process has yet been developed. We develop a computational approach that combines target pool generation, motif scanning and motif screening using secondary structure analysis for applications to 1012–1014-sequence pools; large pool sizes are made possible using program redesign and supercomputing resources. We use the new protocol to search for aptamer and ribozyme motifs in pools up to experimental pool size (1014 sequences). We show that motif scanning, structure matching and flanking sequence analysis, respectively, reduce the initial sequence pool by 6–8, 1–2 and 1 orders of magnitude, consistent with the rare occurrence of active motifs in random pools. The final yields match the theoretical yields from probability theory for simple motifs and overestimate experimental yields, which constitute lower bounds, for aptamers because screening analyses beyond secondary structure information are not considered systematically. We also show that designed pools using our nucleotide transition probability matrices can produce higher yields for RNA ligase motifs than random pools. Our methods for generating, analyzing and designing large pools can help improve RNA design via simulation of aspects of in vitro selection. PMID:20448026

  17. The PXDLS linear motif regulates circadian rhythmicity through protein–protein interactions

    PubMed Central

    Shalev, Moran; Aviram, Rona; Adamovich, Yaarit; Kraut-Cohen, Judith; Shamia, Tal; Ben-Dor, Shifra; Golik, Marina; Asher, Gad

    2014-01-01

    The circadian core clock circuitry relies on interlocked transcription-translation feedback loops that largely count on multiple protein interactions. The molecular mechanisms implicated in the assembly of these protein complexes are relatively unknown. Our bioinformatics analysis of short linear motifs, implicated in protein interactions, reveals an enrichment of the Pro-X-Asp-Leu-Ser (PXDLS) motif within circadian transcripts. We show that the PXDLS motif can bind to BMAL1/CLOCK and disrupt circadian oscillations in a cell-autonomous manner. Remarkably, the motif is evolutionary conserved in the core clock protein REV-ERBα, and additional proteins implicated in the clock's function (NRIP1, CBP). In this conjuncture, we uncover a novel cross talk between the two principal core clock feedback loops and show that BMAL/CLOCK and REV-ERBα interact and that the PXDLS motif of REV-ERBα participates in their binding. Furthermore, we demonstrate that the PXDLS motifs of NRIP1 and CBP are involved in circadian rhythmicity. Our findings suggest that the PXDLS motif plays an important role in circadian rhythmicity through regulation of protein interactions within the clock circuitry and that short linear motifs can be employed to modulate circadian oscillations. PMID:25260595

  18. Population genomics and transcriptional consequences of regulatory motif variation in globally diverse Saccharomyces cerevisiae strains.

    PubMed

    Connelly, Caitlin F; Skelly, Daniel A; Dunham, Maitreya J; Akey, Joshua M

    2013-07-01

    Noncoding genetic variation is known to significantly influence gene expression levels in a growing number of specific cases; however, the patterns of genome-wide noncoding variation present within populations, the evolutionary forces acting on noncoding variants, and the relative effects of regulatory polymorphisms on transcript abundance are not well characterized. Here, we address these questions by analyzing patterns of regulatory variation in motifs for 177 DNA binding proteins in 37 strains of Saccharomyces cerevisiae. Between S. cerevisiae strains, we found considerable polymorphism in regulatory motifs across strains (mean π = 0.005) as well as diversity in regulatory motifs (mean 0.91 motifs differences per regulatory region). Population genetics analyses reveal that motifs are under purifying selection, and there is considerable heterogeneity in the magnitude of selection across different motifs. Finally, we obtained RNA-Seq data in 22 strains and identified 49 polymorphic DNA sequence motifs in 30 distinct genes that are significantly associated with transcriptional differences between strains. In 22 of these genes, there was a single polymorphic motif associated with expression in the upstream region. Our results provide comprehensive insights into the evolutionary trajectory of regulatory variation in yeast and the characteristics of a compendium of regulatory alleles.

  19. Redemptive Rhetoric: The Continuity Motif in the Rhetoric of Right to Life.

    ERIC Educational Resources Information Center

    Solomon, Martha

    1980-01-01

    Traces the use of the "continuity" motif in the Right to Life movement's rhetoric and its influence on the depiction of the abortion controversy. Analyzes how the motif functions rhetorically to aid the movement in defining its activities and involvement. (PD)

  20. Neutral red as a specific light-up fluorescent probe for i-motif DNA.

    PubMed

    Xu, Lijun; Wang, Jine; Sun, Na; Liu, Min; Cao, Yi; Wang, Zhili; Pei, Renjun

    2016-12-06

    We report a specific light-up fluorescent probe for i-motif DNA for the first time. Compared with the previously reported probes, neutral red could selectively interact with an i-motif and show a significant increase in its fluorescence. This feature makes it advantageous for designing label-free fluorescent sensing systems.

  1. An Examination of Four Key Motifs Found in High Fantasy for Children.

    ERIC Educational Resources Information Center

    Cohen, John Arthur

    The purpose of this study was to come to a greater understanding of contemporary high fantasy for children by analyzing in depth the nature and functions of four key motifs of this sub-genre of fantasy. These motifs are created worlds, time displacement, quest, and combat between good and evil. The 47 books chosen for analysis were recommended in…

  2. Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated

    PubMed Central

    2010-01-01

    Background DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS") but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) not to be biological transcription factor binding sites ("empirical TFBS"). We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding. Results Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation. Conclusions Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation. PMID:20875111

  3. GOmotif: A web server for investigating the biological role of protein sequence motifs

    PubMed Central

    2011-01-01

    Background Many proteins contain conserved sequence patterns (motifs) that contribute to their functionality. The process of experimentally identifying and validating novel protein motifs can be difficult, expensive, and time consuming. A means for helping to identify in advance the possible function of a novel motif is important to test hypotheses concerning the biological relevance of these motifs, thus reducing experimental trial-and-error. Results GOmotif accepts PROSITE and regular expression formatted motifs as input and searches a Gene Ontology annotated protein database using motif search tools. The search returns the set of proteins containing matching motifs and their associated Gene Ontology terms. These results are presented as: 1) a hierarchical, navigable tree separated into the three Gene Ontology biological domains - biological process, cellular component, and molecular function; 2) corresponding pie charts indicating raw and statistically adjusted distributions of the results, and 3) an interactive graphical network view depicting the location of the results in the Gene Ontology. Conclusions GOmotif is a web-based tool designed to assist researchers in investigating the biological role of novel protein motifs. GOmotif can be freely accessed at http://www.gomotif.ca PMID:21943350

  4. Population Genomics and Transcriptional Consequences of Regulatory Motif Variation in Globally Diverse Saccharomyces cerevisiae Strains

    PubMed Central

    Connelly, Caitlin F.; Skelly, Daniel A.; Dunham, Maitreya J.; Akey, Joshua M.

    2013-01-01

    Noncoding genetic variation is known to significantly influence gene expression levels in a growing number of specific cases; however, the patterns of genome-wide noncoding variation present within populations, the evolutionary forces acting on noncoding variants, and the relative effects of regulatory polymorphisms on transcript abundance are not well characterized. Here, we address these questions by analyzing patterns of regulatory variation in motifs for 177 DNA binding proteins in 37 strains of Saccharomyces cerevisiae. Between S. cerevisiae strains, we found considerable polymorphism in regulatory motifs across strains (mean π = 0.005) as well as diversity in regulatory motifs (mean 0.91 motifs differences per regulatory region). Population genetics analyses reveal that motifs are under purifying selection, and there is considerable heterogeneity in the magnitude of selection across different motifs. Finally, we obtained RNA-Seq data in 22 strains and identified 49 polymorphic DNA sequence motifs in 30 distinct genes that are significantly associated with transcriptional differences between strains. In 22 of these genes, there was a single polymorphic motif associated with expression in the upstream region. Our results provide comprehensive insights into the evolutionary trajectory of regulatory variation in yeast and the characteristics of a compendium of regulatory alleles. PMID:23619145

  5. Stabilization of i-motif structures by 2′-β-fluorination of DNA

    PubMed Central

    Assi, Hala Abou; Harkness, Robert W.; Martin-Pintado, Nerea; Wilds, Christopher J.; Campos-Olivas, Ramón; Mittermaier, Anthony K.; González, Carlos; Damha, Masad J.

    2016-01-01

    i-Motifs are four-stranded DNA structures consisting of two parallel DNA duplexes held together by hemi-protonated and intercalated cytosine base pairs (C:CH+). They have attracted considerable research interest for their potential role in gene regulation and their use as pH responsive switches and building blocks in macromolecular assemblies. At neutral and basic pH values, the cytosine bases deprotonate and the structure unfolds into single strands. To avoid this limitation and expand the range of environmental conditions supporting i-motif folding, we replaced the sugar in DNA by 2-deoxy-2-fluoroarabinose. We demonstrate that such a modification significantly stabilizes i-motif formation over a wide pH range, including pH 7. Nuclear magnetic resonance experiments reveal that 2-deoxy-2-fluoroarabinose adopts a C2′-endo conformation, instead of the C3′-endo conformation usually found in unmodified i-motifs. Nevertheless, this substitution does not alter the overall i-motif structure. This conformational change, together with the changes in charge distribution in the sugar caused by the electronegative fluorine atoms, leads to a number of favorable sequential and inter-strand electrostatic interactions. The availability of folded i-motifs at neutral pH will aid investigations into the biological function of i-motifs in vitro, and will expand i-motif applications in nanotechnology. PMID:27166371

  6. The EDLL motif: a potent plant transcriptional activation domain from AP2/ERF transcription factors.

    PubMed

    Tiwari, Shiv B; Belachew, Alemu; Ma, Siu Fong; Young, Melinda; Ade, Jules; Shen, Yu; Marion, Colleen M; Holtan, Hans E; Bailey, Adina; Stone, Jeffrey K; Edwards, Leslie; Wallace, Andreah D; Canales, Roger D; Adam, Luc; Ratcliffe, Oliver J; Repetti, Peter P

    2012-06-01

    In plants, the ERF/EREBP family of transcriptional regulators plays a key role in adaptation to various biotic and abiotic stresses. These proteins contain a conserved AP2 DNA-binding domain and several uncharacterized motifs. Here, we describe a short motif, termed 'EDLL', that is present in AtERF98/TDR1 and other clade members from the same AP2 sub-family. We show that the EDLL motif, which has a unique arrangement of acidic amino acids and hydrophobic leucines, functions as a strong activation domain. The motif is transferable to other proteins, and is active at both proximal and distal positions of target promoters. As such, the EDLL motif is able to partly overcome the repression conferred by the AtHB2 transcription factor, which contains an ERF-associated amphiphilic repression (EAR) motif. We further examined the activation potential of EDLL by analysis of the regulation of flowering time by NF-Y (nuclear factor Y) proteins. Genetic evidence indicates that NF-Y protein complexes potentiate the action of CONSTANS in regulation of flowering in Arabidopsis; we show that the transcriptional activation function of CONSTANS can be substituted by direct fusion of the EDLL activation motif to NF-YB subunits. The EDLL motif represents a potent plant activation domain that can be used as a tool to confer transcriptional activation potential to heterologous DNA-binding proteins.

  7. A generalized profile syntax for biomolecular sequence motifs and its function in automatic sequence interpretation

    SciTech Connect

    Bucher, P.; Bairoch, A.

    1994-12-31

    A general syntax for expressing bimolecular sequence motifs is described, which will be used in future releases of the PROSITE data bank and in a similar collection of nucleic acid sequence motifs currently under development. The central part of the syntax is a regular structure which can be viewed as a generalization of the profiles introduced by Gribskov and coworkers. Accessory features implement specific motif search strategies and provide information helpful for the interpretation of predicted matches. Two contrasting examples, representing E. coli promoters and SH3 domains respectively, are shown to demonstrate the versatility of the syntax, and its compatibility with diverse motif search methods. It is argued, that a comprehensive machine-readable motif collection based on the new syntax, in conjunction with a standard search program, can serve as a general-purpose sequence interpretation and function prediction tool.

  8. Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences

    PubMed Central

    Wright, Elisé P.; Day, Henry A.; Ibrahim, Ali M.; Kumar, Jeethendra; Boswell, Leo J. E.; Huguin, Camille; Stevenson, Clare E. M.; Pors, Klaus; Waller, Zoë A. E.

    2016-01-01

    There are hundreds of ligands which can interact with G-quadruplex DNA, yet very few which target i-motif. To appreciate an understanding between the dynamics between these structures and how they can be affected by intervention with small molecule ligands, more i-motif binding compounds are required. Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. Additionally, mitoxantrone was found to bind i-motif forming sequences preferentially over double helical DNA. We also describe the stabilisation properties of analogues of mitoxantrone. This offers a new family of ligands with potential for use in experiments into the structure and function of i-motif forming DNA sequences. PMID:28004744

  9. The dimerization motif of the glycophorin A transmembrane segment in membranes: importance of glycine residues.

    PubMed

    Brosig, B; Langosch, D

    1998-04-01

    The glycophorin A transmembrane segment homo-dimerizes to a right-handed pair of alpha-helices. Here, we identified the amino acid motif mediating this interaction within a natural membrane environment. Critical residues were grafted onto two different hydrophobic host sequences in a stepwise manner and self-assembly of the hybrid sequences was determined with the ToxR transcription activator system. Our results show that the motif LIxxGxxxGxxxT elicits a level of self-association equivalent to that of the original glycophorin A transmembrane segment. This motif is very similar to the one previously established in detergent solution. Interestingly, the central GxxxG motif by itself already induced strong self-assembly of host sequences and the three-residue spacing between both glycines proved to be optimal for the interaction. The GxxxG element thus appears to be the most crucial part of the interaction motif.

  10. The dimerization motif of the glycophorin A transmembrane segment in membranes: importance of glycine residues.

    PubMed Central

    Brosig, B.; Langosch, D.

    1998-01-01

    The glycophorin A transmembrane segment homo-dimerizes to a right-handed pair of alpha-helices. Here, we identified the amino acid motif mediating this interaction within a natural membrane environment. Critical residues were grafted onto two different hydrophobic host sequences in a stepwise manner and self-assembly of the hybrid sequences was determined with the ToxR transcription activator system. Our results show that the motif LIxxGxxxGxxxT elicits a level of self-association equivalent to that of the original glycophorin A transmembrane segment. This motif is very similar to the one previously established in detergent solution. Interestingly, the central GxxxG motif by itself already induced strong self-assembly of host sequences and the three-residue spacing between both glycines proved to be optimal for the interaction. The GxxxG element thus appears to be the most crucial part of the interaction motif. PMID:9568912

  11. Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences

    NASA Astrophysics Data System (ADS)

    Wright, Elisé P.; Day, Henry A.; Ibrahim, Ali M.; Kumar, Jeethendra; Boswell, Leo J. E.; Huguin, Camille; Stevenson, Clare E. M.; Pors, Klaus; Waller, Zoë A. E.

    2016-12-01

    There are hundreds of ligands which can interact with G-quadruplex DNA, yet very few which target i-motif. To appreciate an understanding between the dynamics between these structures and how they can be affected by intervention with small molecule ligands, more i-motif binding compounds are required. Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. Additionally, mitoxantrone was found to bind i-motif forming sequences preferentially over double helical DNA. We also describe the stabilisation properties of analogues of mitoxantrone. This offers a new family of ligands with potential for use in experiments into the structure and function of i-motif forming DNA sequences.

  12. Growing scale-free networks with tunable distributions of triad motifs

    NASA Astrophysics Data System (ADS)

    Li, Shuguang; Yuan, Jianping; Shi, Yong; Zagal, Juan Cristóbal

    2015-06-01

    Network motifs are local structural patterns and elementary functional units of complex networks in real world, which can have significant impacts on the global behavior of these systems. Many models are able to reproduce complex networks mimicking a series of global features of real systems, however the local features such as motifs in real networks have not been well represented. We propose a model to grow scale-free networks with tunable motif distributions through a combined operation of preferential attachment and triad motif seeding steps. Numerical experiments show that the constructed networks have adjustable distributions of the local triad motifs, meanwhile preserving the global features of power-law distributions of node degree, short average path lengths of nodes, and highly clustered structures.

  13. Motif-based construction of a functional map for mammalian olfactory receptors.

    PubMed

    Liu, Agatha H; Zhang, Xinmin; Stolovitzky, Gustavo A; Califano, Andrea; Firestein, Stuart J

    2003-05-01

    We applied an automatic and unsupervised system to a nearly complete database of mammalian odor receptor genes. The generated motifs and gene classification were subjected to extensive and systematic downstream analysis to obtain biological insights. Two major results from this analysis were: (1) a map of sequence motifs that may correlate with function and (2) the corresponding receptor classes in which members of each class are likely to share specific functions. We have discovered motifs that have been implicated in structural integrity and posttranslational modification, as well as motifs very likely to be directly involved in ligand binding. We further propose a combinatorial molecular hypothesis, based on unique combinations of the observed motifs, that provides a foundation for understanding the generation of a large number of ligand binding sites.

  14. Combinatorial Information Theoretical Measurement of the Semantic Significance of Semantic Graph Motifs

    SciTech Connect

    Joslyn, Cliff A.; al-Saffar, Sinan; Haglin, David J.; Holder, Larry

    2011-06-14

    Given an arbitrary semantic graph data set, perhaps one lacking in explicit ontological information, we wish to first identify its significant semantic structures, and then measure the extent of their significance. Casting a semantic graph dataset as an edge-labeled, directed graph, this task can be built on the ability to mine frequent {\\em labeled} subgraphs in edge-labeled, directed graphs. We begin by considering the fundamentals of the enumerative combinatorics of subgraph motif structures in edge-labeled directed graphs. We identify its frequent labeled, directed subgraph motif patterns, and measure the significance of the resulting motifs by the information gain relative to the expected value of the motif based on the empirical frequency distribution of the link types which compose them, assuming indpendence. We illustrate the method on a small test graph, and discuss results obtained for small linear motifs (link type bigrams and trigrams) in a larger graph structure.

  15. Estimating physiological skin parameters from hyperspectral signatures.

    PubMed

    Vyas, Saurabh; Banerjee, Amit; Burlina, Philippe

    2013-05-01

    We describe an approach for estimating human skin parameters, such as melanosome concentration, collagen concentration, oxygen saturation, and blood volume, using hyperspectral radiometric measurements (signatures) obtained from in vivo skin. We use a computational model based on Kubelka-Munk theory and the Fresnel equations. This model forward maps the skin parameters to a corresponding multiband reflectance spectra. Machine-learning-based regression is used to generate the inverse map, and hence estimate skin parameters from hyperspectral signatures. We test our methods using synthetic and in vivo skin signatures obtained in the visible through the short wave infrared domains from 24 patients of both genders and Caucasian, Asian, and African American ethnicities. Performance validation shows promising results: good agreement with the ground truth and well-established physiological precepts. These methods have potential use in the characterization of skin abnormalities and in minimally-invasive prescreening of malignant skin cancers.

  16. Estimating physiological skin parameters from hyperspectral signatures

    NASA Astrophysics Data System (ADS)

    Vyas, Saurabh; Banerjee, Amit; Burlina, Philippe

    2013-05-01

    We describe an approach for estimating human skin parameters, such as melanosome concentration, collagen concentration, oxygen saturation, and blood volume, using hyperspectral radiometric measurements (signatures) obtained from in vivo skin. We use a computational model based on Kubelka-Munk theory and the Fresnel equations. This model forward maps the skin parameters to a corresponding multiband reflectance spectra. Machine-learning-based regression is used to generate the inverse map, and hence estimate skin parameters from hyperspectral signatures. We test our methods using synthetic and in vivo skin signatures obtained in the visible through the short wave infrared domains from 24 patients of both genders and Caucasian, Asian, and African American ethnicities. Performance validation shows promising results: good agreement with the ground truth and well-established physiological precepts. These methods have potential use in the characterization of skin abnormalities and in minimally-invasive prescreening of malignant skin cancers.

  17. Biomarker Gene Signature Discovery Integrating Network Knowledge

    PubMed Central

    Cun, Yupeng; Fröhlich, Holger

    2012-01-01

    Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step towards a better personalized medicine. During the last decade various methods, mainly coming from the machine learning or statistical domain, have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Here we review the current state of research in this field by giving an overview about so-far proposed approaches. PMID:24832044

  18. Explosives Detection: Exploitation of the Physical Signatures

    NASA Astrophysics Data System (ADS)

    Atkinson, David

    2010-10-01

    Explosives based terrorism is an ongoing threat that is evolving with respect to implementation, configuration and materials used. There are a variety of devices designed to detect explosive devices, however, each technology has limitations and operational constraints. A full understanding of the signatures available for detection coupled with the array of detection choices can be used to develop a conceptual model of an explosives screening operation. Physics based sensors provide a robust approach to explosives detection, typically through the identification of anomalies, and are currently used for screening in airports around the world. The next generation of detectors for explosives detection will need to be more sensitive and selective, as well as integrate seamlessly with devices focused on chemical signatures. An appreciation for the details of the physical signature exploitation in cluttered environments with time, space, and privacy constraints is necessary for effective explosives screening of people, luggage, cargo, and vehicles.

  19. A Novel Quantum Proxy Blind Signature Scheme

    NASA Astrophysics Data System (ADS)

    Guo, Wei; Xie, Shu-Cui; Zhang, Jian-Zhong

    2017-02-01

    A novel quantum proxy blind signature scheme is proposed. In this scheme, a special type of non-maximally entangled three-qubit state is introduced as a quantum channel, which can realize perfect teleportation. The message sender U blinds his message by means of preparing two groups of non-orthogonal single-photon states. According to the original signer Charlie's delegation message, the proxy signer Alice generates a corresponding signature. The arbitrator Trent can help the receiver Bob verify the signature, and also prevent Bob from doing any damage. The above-mentioned advantages make this scheme different from some existing schemes. It is showed that our scheme has the properties of undeniability, unforgeability, blindness, untraceability. Moreover, it is free from intercept-resend attack.

  20. Nitrogen isotopic signatures in the Acapulco meteorite

    NASA Technical Reports Server (NTRS)

    Sturgeon, G.; Marti, K.

    1991-01-01

    N isotopic abundances are reported for a bulk sample of the unique meteorite Acapulco. Although the mineral chemistry indicates a high degree of recrystallization under redox conditions between those of H and E chondrites (Palme et al., 1981), the presence of two distinct N isotopic signatures shows that the carriers of these N components were not equilibrated. In stepwise pyrolysis, the larger (65 percent) N component is released mostly below 1000 C and reveals a signature of delta(N-15) = 8.9 + or - 1.2 per mil, which is within the range observed in chondrites. A second 'light' component appears above 1000 C and has a signature of delta(N-15) less than or equal to -110.5 + or - 4.0 per mil (uncorrected for spallation N-15).

  1. Molecular signature in HCV-positive lymphomas.

    PubMed

    De Re, Valli; Caggiari, Laura; Garziera, Marica; De Zorzi, Mariangela; Repetto, Ombretta

    2012-01-01

    Hepatitis C virus (HCV) is a positive, single-stranded RNA virus, which has been associated to different subtypes of B-cell non-Hodgkin lymphoma (B-NHL). Cumulative evidence suggests an HCV-related antigen driven process in the B-NHL development. The underlying molecular signature associated to HCV-related B-NHL has to date remained obscure. In this review, we discuss the recent developments in this field with a special mention to different sets of genes whose expression is associated with BCR coupled to Blys signaling which in turn was found to be linked to B-cell maturation stages and NF-κb transcription factor. Even if recent progress on HCV-B-NHL signature has been made, the precise relationship between HCV and lymphoma development and phenotype signature remain to be clarified.

  2. Quantum mechanical stabilization of Minkowski signature wormholes

    SciTech Connect

    Visser, M.

    1989-05-19

    When one attempts to construct classical wormholes in Minkowski signature Lorentzian spacetimes violations of both the weak energy hypothesis and averaged weak energy hypothesis are encountered. Since the weak energy hypothesis is experimentally known to be violated quantum mechanically, this suggests that a quantum mechanical analysis of Minkowski signature wormholes is in order. In this note I perform a minisuperspace analysis of a simple class of Minkowski signature wormholes. By solving the Wheeler-de Witt equation for pure Einstein gravity on this minisuperspace the quantum mechanical wave function of the wormhole is obtained in closed form. The wormhole is shown to be quantum mechanically stabilized with an average radius of order the Planck length. 8 refs.

  3. Ritual and signature in serial sexual homicide.

    PubMed

    Schlesinger, Louis B; Kassen, Martin; Mesa, V Blair; Pinizzotto, Anthony J

    2010-01-01

    Ritual and signature are fantasy-driven, repetitive crime scene behaviors that have been found to occur in serial sexual homicide. Notwithstanding numerous anecdotal case reports, ritual and signature have rarely been studied empirically. In a national sample of 38 offenders and their 162 victims, we examined behavioral and thematic consistency, as well as the evolution and uniqueness of these crime scene actions. The notion that serial sexual murderers engage in the same rituals and leave unique signatures at every scene was not supported by our data. In fact, the results suggest that the crime scene conduct of this group of offenders is fairly complex and varied. Implications of these findings for forensic assessments and criminal investigations are discussed.

  4. Orbital debris characterization with impact flash signatures

    SciTech Connect

    Ang, J.A.

    1991-12-31

    Orbital debris is recognized as a serious and growing threat to man`s utilization and exploration of space. While some information is available on the material composition of orbital debris, most measurements of orbital debris size and velocity distributions do not distinguish material type. The analysis and understanding of impact flash signatures can lead to an in-situ detector system with the ability to determine size and impact velocity distribution for orbital debris segregated by material type. This detector concept is based on an understanding of how material shock properties govern the flash signature arising from the impact of a piece of orbital debris (impactor) against a witness plate (target). Analytical results are presented that identify the most promising witness plate materials with respect to producing impact flash signatures that characterize the orbital debris material. 7 refs.

  5. Orbital debris characterization with impact flash signatures

    SciTech Connect

    Ang, J.A.

    1991-01-01

    Orbital debris is recognized as a serious and growing threat to man's utilization and exploration of space. While some information is available on the material composition of orbital debris, most measurements of orbital debris size and velocity distributions do not distinguish material type. The analysis and understanding of impact flash signatures can lead to an in-situ detector system with the ability to determine size and impact velocity distribution for orbital debris segregated by material type. This detector concept is based on an understanding of how material shock properties govern the flash signature arising from the impact of a piece of orbital debris (impactor) against a witness plate (target). Analytical results are presented that identify the most promising witness plate materials with respect to producing impact flash signatures that characterize the orbital debris material. 7 refs.

  6. Selection signatures in worldwide sheep populations.

    PubMed

    Fariello, Maria-Ines; Servin, Bertrand; Tosser-Klopp, Gwenola; Rupp, Rachel; Moreno, Carole; San Cristobal, Magali; Boitard, Simon

    2014-01-01

    The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments.

  7. A Methodology for Calculating Radiation Signatures

    SciTech Connect

    Klasky, Marc Louis; Wilcox, Trevor; Bathke, Charles G.; James, Michael R.

    2015-05-01

    A rigorous formalism is presented for calculating radiation signatures from both Special Nuclear Material (SNM) as well as radiological sources. The use of MCNP6 in conjunction with CINDER/ORIGEN is described to allow for the determination of both neutron and photon leakages from objects of interest. In addition, a description of the use of MCNP6 to properly model the background neutron and photon sources is also presented. Examinations of the physics issues encountered in the modeling are investigated so as to allow for guidance in the user discerning the relevant physics to incorporate into general radiation signature calculations. Furthermore, examples are provided to assist in delineating the pertinent physics that must be accounted for. Finally, examples of detector modeling utilizing MCNP are provided along with a discussion on the generation of Receiver Operating Curves, which are the suggested means by which to determine detectability radiation signatures emanating from objects.

  8. Selection Signatures in Worldwide Sheep Populations

    PubMed Central

    Fariello, Maria-Ines; Servin, Bertrand; Tosser-Klopp, Gwenola; Rupp, Rachel; Moreno, Carole; Cristobal, Magali San; Boitard, Simon

    2014-01-01

    The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments. PMID:25126940

  9. Bioinformatics study of cancer-related mutations within p53 phosphorylation site motifs.

    PubMed

    Ji, Xiaona; Huang, Qiang; Yu, Long; Nussinov, Ruth; Ma, Buyong

    2014-07-29

    p53 protein has about thirty phosphorylation sites located at the N- and C-termini and in the core domain. The phosphorylation sites are relatively less mutated than other residues in p53. To understand why and how p53 phosphorylation sites are rarely mutated in human cancer, using a bioinformatics approaches, we examined the phosphorylation site and its nearby flanking residues, focusing on the consensus phosphorylation motif pattern, amino-acid correlations within the phosphorylation motifs, the propensity of structural disorder of the phosphorylation motifs, and cancer mutations observed within the phosphorylation motifs. Many p53 phosphorylation sites are targets for several kinases. The phosphorylation sites match 17 consensus sequence motifs out of the 29 classified. In addition to proline, which is common in kinase specificity-determining sites, we found high propensity of acidic residues to be adjacent to phosphorylation sites. Analysis of human cancer mutations in the phosphorylation motifs revealed that motifs with adjacent acidic residues generally have fewer mutations, in contrast to phosphorylation sites near proline residues. p53 phosphorylation motifs are mostly disordered. However, human cancer mutations within phosphorylation motifs tend to decrease the disorder propensity. Our results suggest that combination of acidic residues Asp and Glu with phosphorylation sites provide charge redundancy which may safe guard against loss-of-function mutations, and that the natively disordered nature of p53 phosphorylation motifs may help reduce mutational damage. Our results further suggest that engineering acidic amino acids adjacent to potential phosphorylation sites could be a p53 gene therapy strategy.

  10. An improved poly(A) motifs recognition method based on decision level fusion.

    PubMed

    Zhang, Shanxin; Han, Jiuqiang; Liu, Jun; Zheng, Jiguang; Liu, Ruiling

    2015-02-01

    Polyadenylation is the process of addition of poly(A) tail to mRNA 3' ends. Identification of motifs controlling polyadenylation plays an essential role in improving genome annotation accuracy and better understanding of the mechanisms governing gene regulation. The bioinformatics methods used for poly(A) motifs recognition have demonstrated that information extracted from sequences surrounding the candidate motifs can differentiate true motifs from the false ones greatly. However, these methods depend on either domain features or string kernels. To date, methods combining information from different sources have not been found yet. Here, we proposed an improved poly(A) motifs recognition method by combing different sources based on decision level fusion. First of all, two novel prediction methods was proposed based on support vector machine (SVM): one method is achieved by using the domain-specific features and principle component analysis (PCA) method to eliminate the redundancy (PCA-SVM); the other method is based on Oligo string kernel (Oligo-SVM). Then we proposed a novel machine-learning method for poly(A) motif prediction by marrying four poly(A) motifs recognition methods, including two state-of-the-art methods (Random Forest (RF) and HMM-SVM), and two novel proposed methods (PCA-SVM and Oligo-SVM). A decision level information fusion method was employed to combine the decision values of different classifiers by applying the DS evidence theory. We evaluated our method on a comprehensive poly(A) dataset that consists of 14,740 samples on 12 variants of poly(A) motifs and 2750 samples containing none of these motifs. Our method has achieved accuracy up to 86.13%. Compared with the four classifiers, our evidence theory based method reduces the average error rate by about 30%, 27%, 26% and 16%, respectively. The experimental results suggest that the proposed method is more effective for poly(A) motif recognition.

  11. DNA Methylation Signatures of the Plant Chromomethyltransferases

    PubMed Central

    Baulcombe, David C.

    2016-01-01

    DNA methylation in plants is traditionally partitioned into CG, CHG and CHH contexts (with H any nucleotide but G). By investigating DNA methylation patterns in trinucleotide contexts in four angiosperm species, we show that such a representation hides spatial and functional partitioning of different methylation pathways and is incomplete. CG methylation (mCG) is largely context-independent whereas, at CHG motifs, there is under-representation of mCCG in pericentric regions of A. thaliana and tomato and throughout the chromosomes of maize and rice. In A. thaliana the biased representation of mCCG in heterochromatin is related to specificities of H3K9 methyltransferase SUVH family members. At CHH motifs there is an over-representation of different variant forms of mCHH that, similarly to mCCG hypomethylation, is partitioned into the pericentric regions of the two dicots but dispersed in the monocot chromosomes. The over-represented mCHH motifs in A. thaliana associate with specific types of transposon including both class I and II elements. At mCHH the contextual bias is due to the involvement of various chromomethyltransferases whereas the context-independent CHH methylation in A. thaliana and tomato is mediated by the RNA-directed DNA methylation process that is most active in the gene-rich euchromatin. This analysis therefore reveals that the sequence context of the methylome of plant genomes is informative about the mechanisms associated with maintenance of methylation and the overlying chromatin structure. PMID:27997534

  12. CpG island erosion, polycomb occupancy and sequence motif enrichment at bivalent promoters in mammalian embryonic stem cells.

    PubMed

    Mantsoki, Anna; Devailly, Guillaume; Joshi, Anagha

    2015-11-19

    In embryonic stem (ES) cells, developmental regulators have a characteristic bivalent chromatin signature marked by simultaneous presence of both activation (H3K4me3) and repression (H3K27me3) signals and are thought to be in a 'poised' state for subsequent activation or silencing during differentiation. We collected eleven pairs (H3K4me3 and H3K27me3) of ChIP sequencing datasets in human ES cells and eight pairs in murine ES cells, and predicted high-confidence (HC) bivalent promoters. Over 85% of H3K27me3 marked promoters were bivalent in human and mouse ES cells. We found that (i) HC bivalent promoters were enriched for developmental factors and were highly likely to be differentially expressed upon transcription factor perturbation; (ii) murine HC bivalent promoters were occupied by both polycomb repressive component classes (PRC1 and PRC2) and grouped into four distinct clusters with different biological functions; (iii) HC bivalent and active promoters were CpG rich while H3K27me3-only promoters lacked CpG islands. Binding enrichment of distinct sets of regulators distinguished bivalent from active promoters. Moreover, a 'TCCCC' sequence motif was specifically enriched in bivalent promoters. Finally, this analysis will serve as a resource for future studies to further understand transcriptional regulation during embryonic development.

  13. CpG island erosion, polycomb occupancy and sequence motif enrichment at bivalent promoters in mammalian embryonic stem cells

    PubMed Central

    Mantsoki, Anna; Devailly, Guillaume; Joshi, Anagha

    2015-01-01

    In embryonic stem (ES) cells, developmental regulators have a characteristic bivalent chromatin signature marked by simultaneous presence of both activation (H3K4me3) and repression (H3K27me3) signals and are thought to be in a ‘poised’ state for subsequent activation or silencing during differentiation. We collected eleven pairs (H3K4me3 and H3K27me3) of ChIP sequencing datasets in human ES cells and eight pairs in murine ES cells, and predicted high-confidence (HC) bivalent promoters. Over 85% of H3K27me3 marked promoters were bivalent in human and mouse ES cells. We found that (i) HC bivalent promoters were enriched for developmental factors and were highly likely to be differentially expressed upon transcription factor perturbation; (ii) murine HC bivalent promoters were occupied by both polycomb repressive component classes (PRC1 and PRC2) and grouped into four distinct clusters with different biological functions; (iii) HC bivalent and active promoters were CpG rich while H3K27me3-only promoters lacked CpG islands. Binding enrichment of distinct sets of regulators distinguished bivalent from active promoters. Moreover, a ‘TCCCC’ sequence motif was specifically enriched in bivalent promoters. Finally, this analysis will serve as a resource for future studies to further understand transcriptional regulation during embryonic development. PMID:26582124

  14. An efficient and provably secure proxy signature scheme

    NASA Astrophysics Data System (ADS)

    Zhang, Jianhong; Liu, Xue; Gao, Shengnan

    2010-08-01

    Proxy signature is a special signature, it allows an original signer to delegate her signing capability to a proxy signer and the proxy signer can produce a signature on behalf of the original signer. At present, most of proxy signature in essence consists of two signatures. To overcome the problem, we propose a short efficient proxy signature scheme based on a certificateless signature scheme. And we show that the proposed scheme is secure in the random oracle model. The security of the scheme is related to Inverse Computational Diffie-Hellman Problem and the k-CCA problem. Comparison with Huang et.al scheme, our scheme has an advantage over Huang et.al's scheme in terms of the size of proxy signature. Since the length of proxy signature in our scheme is 160bit, it is very suitable for mobile devices.

  15. Transient thermal camouflage and heat signature control

    NASA Astrophysics Data System (ADS)

    Yang, Tian-Zhi; Su, Yishu; Xu, Weikai; Yang, Xiao-Dong

    2016-09-01

    Thermal metamaterials have been proposed to manipulate heat flux as a new way to cloak or camouflage objects in the infrared world. To date, however, thermal metamaterials only operate in the steady-state and exhibit detectable, transient heat signatures. In this letter, the theoretical basis for a thermal camouflaging technique with controlled transient diffusion is presented. This technique renders an object invisible in real time. More importantly, the thermal camouflaging device instantaneously generates a pre-designed heat signature and behaves as a perfect thermal illusion device. A metamaterial coating with homogeneous and isotropic thermal conductivity, density, and volumetric heat capacity was fabricated and very good camouflaging performance was achieved.

  16. KEA-71 Smart Current Signature Sensor (SCSS)

    NASA Technical Reports Server (NTRS)

    Perotti, Jose M.

    2010-01-01

    This slide presentation reviews the development and uses of the Smart Current Signature Sensor (SCSS), also known as the Valve Health Monitor (VHM) system. SCSS provides a way to not only monitor real-time the valve's operation in a non invasive manner, but also to monitor its health (Fault Detection and Isolation) and identify potential faults and/or degradation in the near future (Prediction/Prognosis). This technology approach is not only applicable for solenoid valves, and it could be extrapolated to other electrical components with repeatable electrical current signatures such as motors.

  17. Plasma Signatures of Radial Field Power Dropouts

    SciTech Connect

    Lucek, E.A.; Horbury, T.S.; Balogh, A.; McComas, D.J.

    1998-10-04

    A class of small scale structures, with a near-radial magnetic field and a drop in magnetic field fluctuation power, have recently been identified in the polar solar wind. An earlier study of 24 events, each lasting for 6 hours or more, identified no clear plasma signature. In an extension of that work, radial intervals lasting for 4 hours or more (89 in total), have been used to search for a statistically significant plasma signature. It was found that, despite considerable variations between intervals, there was a small but significant drop, on average, in plasma temperature, density and {beta} during these events.

  18. Plasma signatures of radial field power dropouts

    SciTech Connect

    Lucek, E.A.; Balogh, A.; Horbury, T.S.; McComas, D.J.

    1999-06-01

    A class of small scale structures, with a near-radial magnetic field and a drop in magnetic field fluctuation power, have recently been identified in the polar solar wind. An earlier study of 24 events, each lasting for 6 hours or more, identified no clear plasma signature. In an extension of that work, radial intervals lasting for 4 hours or more (89 in total), have been used to search for a statistically significant plasma signature. It was found that, despite considerable variations between intervals, there was a small but significant drop, on average, in plasma temperature, density and {beta} during these events. {copyright} {ital 1999 American Institute of Physics.}

  19. Cryptanalysis of the Quantum Group Signature Protocols

    NASA Astrophysics Data System (ADS)

    Zhang, Ke-Jia; Sun, Ying; Song, Ting-Ting; Zuo, Hui-Juan

    2013-11-01

    Recently, the researches of quantum group signature (QGS) have attracted a lot of attentions and some typical protocols have been designed for e-payment system, e-government, e-business, etc. In this paper, we analyze the security of the quantum group signature with the example of two novel protocols. It can be seen that both of them cannot be implemented securely since the arbitrator cannot solve the disputes fairly. In order to show that, some possible attack strategies, which can be used by the malicious participants, are proposed. Moreover, the further discussions of QGS are presented finally, including some insecurity factors and improved ideas.

  20. Characterization of marine macroalgae by fluorescence signatures

    NASA Technical Reports Server (NTRS)

    Topinka, J. A.; Bellows, W. Korjeff; Yentsch, C. S.

    1990-01-01

    The feasibility of distinguishing macroalgal classes by their fluorescence signatures was investigated using narrow-waveband light to excite groups of accessory pigments in brown, red, and green macroalgae and measuring fluorescence emission at 685 nm. Results obtained on 20 marine macroalgae field-collected samples showed that fluorescence excitation signatures were relatively uniform within phylogenetic classes but were substantially different for different classes. It is suggested that it may be possible to characterize the type and the abundance of subtidal macroalgae from low-flying aircraft using existing laser-induced fluorescence methodology.

  1. Enhanced Cancelable Biometrics for Online Signature Verification

    NASA Astrophysics Data System (ADS)

    Muramatsu, Daigo; Inuma, Manabu; Shikata, Junji; Otsuka, Akira

    Cancelable approaches for biometric person authentication have been studied to protect enrolled biometric data, and several algorithms have been proposed. One drawback of cancelable approaches is that the performance is inferior to that of non-cancelable approaches. In this paper, we propose a scheme to improve the performance of a cancelable approach for online signature verification. Our scheme generates two cancelable dataset from one raw dataset and uses them for verification. Preliminary experiments were performed using a distance-based online signature verification algorithm. The experimental results show that our proposed scheme is promising.

  2. Techni-Dilaton Signatures at LHC

    NASA Astrophysics Data System (ADS)

    Matsuzaki, Shinya; Yamawaki, Koichi

    2013-03-01

    We explore LHC discovery signatures of techni-dilaton (TD) arising as a composite pseudo Nambu-Goldstone boson (pNGB), associated with the spontaneous breaking of the approximate scale symmetry in the walking technicolor (WTC). We explicitly evaluate the TD 7 TeV LHC production cross sections times the branching ratios in terms of the TD mass MTD as an input parameter for the region 200 GeV < MTD < 1000 GeV in the typical WTC models. It turns out that the TD signatures are quite different from those of the standard model (SM) Higgs.

  3. Security problem on arbitrated quantum signature schemes

    SciTech Connect

    Choi, Jeong Woon; Chang, Ku-Young; Hong, Dowon

    2011-12-15

    Many arbitrated quantum signature schemes implemented with the help of a trusted third party have been developed up to now. In order to guarantee unconditional security, most of them take advantage of the optimal quantum one-time encryption based on Pauli operators. However, in this paper we point out that the previous schemes provide security only against a total break attack and show in fact that there exists an existential forgery attack that can validly modify the transmitted pair of message and signature. In addition, we also provide a simple method to recover security against the proposed attack.

  4. Covariant change of signature in classical relativity

    NASA Astrophysics Data System (ADS)

    Ellis, G. F. R.

    1992-10-01

    This paper gives a covariant formalism enabling investigation of the possibility of change of signature in classical General Relativity, when the geometry is that of a Robertson-Walker universe. It is shown that such changes are compatible with the Einstein field equations, both in the case of a barotropic fluid and of a scalar field. A criterion is given for when such a change of signature should take place in the scalar field case. Some examples show the kind of resulting exact solutions of the field equations.

  5. Bayesian Separation of Lamb Wave Signatures

    SciTech Connect

    Kercel, SW

    2001-07-19

    A persistent problem in the analysis of Lamb wave signatures in experimental data is the fact that several different modes appear simultaneously in the signal. The modes overlap in both the frequency and time domains. Attempts to separate the overlapping Lamb wave signatures by conventional signal processing methods have been unsatisfactory. This paper reports an exciting alternative to conventional methods. Severely overlapping Lamb waves are found to be readily separable by Bayesian parameter estimation. The authors have used linear-chirped Gaussian-windowed sinusoids as models of each Lamb wave mode. The separation algorithm allows each mode to be examined individually.

  6. Transient aspects of stream interface signatures

    SciTech Connect

    Crooker, N.U.; Shodhan, S.; Forsyth, R.J.; Burton, M.E.; Gosling, J.T.; Fitzenreiter, R.J.; Lepping, R.P.

    1999-06-01

    Although stream interfaces are steady-state, corotating boundaries between slow and fast solar wind, their signatures are sometimes associated with transient features. Here the authors illustrate two modes of association: interfaces trailing interplanetary coronal mass ejections (ICMEs) at 1 AU and interfaces within ICMEs in the range 4--5 AU. The former are readily understood as boundaries between transient slow wind and steady-state fast wind, where the ICMEs add variability to the interface signatures. The latter are puzzling and may be related to evolution of interfaces.

  7. Attack and improvements of fair quantum blind signature schemes

    NASA Astrophysics Data System (ADS)

    Zou, Xiangfu; Qiu, Daowen

    2013-06-01

    Blind signature schemes allow users to obtain the signature of a message while the signer learns neither the message nor the resulting signature. Therefore, blind signatures have been used to realize cryptographic protocols providing the anonymity of some participants, such as: secure electronic payment systems and electronic voting systems. A fair blind signature is a form of blind signature which the anonymity could be removed with the help of a trusted entity, when this is required for legal reasons. Recently, a fair quantum blind signature scheme was proposed and thought to be safe. In this paper, we first point out that there exists a new attack on fair quantum blind signature schemes. The attack shows that, if any sender has intercepted any valid signature, he (she) can counterfeit a valid signature for any message and can not be traced by the counterfeited blind signature. Then, we construct a fair quantum blind signature scheme by improved the existed one. The proposed fair quantum blind signature scheme can resist the preceding attack. Furthermore, we demonstrate the security of the proposed fair quantum blind signature scheme and compare it with the other one.

  8. Trafficking of ODV-E66 is mediated via a sorting motif and other viral proteins: facilitated trafficking to the inner nuclear membrane.

    PubMed

    Braunagel, Sharon C; Williamson, Shawn T; Saksena, Suraj; Zhong, Zhenping; Russell, William K; Russell, David H; Summers, Max D

    2004-06-01

    The N-terminal 33 aa of the envelope protein ODV-E66 are sufficient to traffic fusion proteins to intranuclear membranes and the ODV envelope during infection with Autographa californica nucleopolyhedrovirus. This sequence has two distinct features: (i) an extremely hydrophobic sequence of 18 aa and (ii) positively charged amino acids close to the C-terminal end of the hydrophobic sequence. In the absence of infection, this sequence is sufficient to promote protein accumulation at the inner nuclear membrane. Covalent cross-linking results show that the lysines of the motif are proximal to FP25K and/or BV/ODV-E26 during transit from the endoplasmic reticulum to the nuclear envelope. We propose that the 33 aa comprise a signature for sorting proteins to the inner nuclear membrane (sorting motif) and that, unlike other resident proteins of the inner nuclear membrane, ODV-E66 and sortingmotif fusions do not randomly diffuse from their site of insertion at the endoplasmic reticulum to the nuclear envelope and viral-induced intranuclear membranes. Rather, during infection, trafficking is mediated by protein-protein interactions.

  9. Patient-derived C-terminal mutation of FANCI causes protein mislocalization and reveals putative EDGE motif function in DNA repair.

    PubMed

    Colnaghi, Luca; Jones, Mathew J K; Cotto-Rios, Xiomaris M; Schindler, Detlev; Hanenberg, Helmut; Huang, Tony T

    2011-02-17

    Fanconi anemia (FA) is a rare familial genome instability syndrome caused by mutations in FA genes that results in defective DNA crosslink repair. Activation of the FA pathway requires the FA core ubiquitin ligase complex-dependent monoubiquitination of 2 interacting FA proteins, FANCI and FANCD2. Although loss of either FANCI or FANCD2 is known to prevent monoubiquitination of its respective partner, it is unclear whether FANCI has any additional domains that may be important in promoting DNA repair, independent of its monoubiquitination. Here, we focus on an FA-I patient-derived FANCI mutant protein, R1299X (deletion of 30 residues from its C-terminus), to characterize important structural region(s) in FANCI that is required to activate the FA pathway. We show that, within this short 30 amino acid stretch contains 2 separable functional signatures, a nuclear localization signal and a putative EDGE motif, that is critical for the ability of FANCI to properly monoubiquitinate FANCD2 and promote DNA crosslink resistance. Our study enable us to conclude that, although proper nuclear localization of FANCI is crucial for robust FANCD2 monoubiquitination, the putative FANCI EDGE motif is important for DNA crosslink repair.

  10. One motif to bind them: A small-XXX-small motif affects transmembrane domain 1 oligomerization, function, localization, and cross-talk between two yeast GPCRs.

    PubMed

    Lock, Antonia; Forfar, Rachel; Weston, Cathryn; Bowsher, Leo; Upton, Graham J G; Reynolds, Christopher A; Ladds, Graham; Dixon, Ann M

    2014-12-01

    G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors in mammals and facilitate a range of physiological responses triggered by a variety of ligands. GPCRs were thought to function as monomers, however it is now accepted that GPCR homo- and hetero-oligomers also exist and influence receptor properties. The Schizosaccharomyces pombe GPCR Mam2 is a pheromone-sensing receptor involved in mating and has previously been shown to form oligomers in vivo. The first transmembrane domain (TMD) of Mam2 contains a small-XXX-small motif, overrepresented in membrane proteins and well-known for promoting helix-helix interactions. An ortholog of Mam2 in Saccharomyces cerevisiae, Ste2, contains an analogous small-XXX-small motif which has been shown to contribute to receptor homo-oligomerization, localization and function. Here we have used experimental and computational techniques to characterize the role of the small-XXX-small motif in function and assembly of Mam2 for the first time. We find that disruption of the motif via mutagenesis leads to reduction of Mam2 TMD1 homo-oligomerization and pheromone-responsive cellular signaling of the full-length protein. It also impairs correct targeting to the plasma membrane. Mutation of the analogous motif in Ste2 yielded similar results, suggesting a conserved mechanism for assembly. Using co-expression of the two fungal receptors in conjunction with computational models, we demonstrate a functional change in G protein specificity and propose that this is brought about through hetero-dimeric interactions of Mam2 with Ste2 via the complementary small-XXX-small motifs. This highlights the potential of these motifs to affect a range of properties that can be investigated in other GPCRs.

  11. Identification of single C motif-1/lymphotactin receptor XCR1.

    PubMed

    Yoshida, T; Imai, T; Kakizaki, M; Nishimura, M; Takagi, S; Yoshie, O

    1998-06-26

    Single C motif-1 (SCM-1)/lymphotactin is a member of the chemokine superfamily, but retains only the 2nd and 4th of the four cysteine residues conserved in other chemokines. In humans, there are two highly homologous SCM-1 genes encoding SCM-1alpha and SCM-1beta with two amino acid substitutions. To identify a specific receptor for SCM-1 proteins, we produced recombinant SCM-1alpha and SCM-1beta by the baculovirus expression system and tested them on murine L1.2 cells stably expressing eight known chemokine receptors and three orphan receptors. Both proteins specifically induced migration in cells expressing an orphan receptor, GPR5. The migration was chemotactic and suppressed by pertussis toxin, indicating coupling to a Galpha type of G protein. Both proteins also induced intracellular calcium mobilization in GPR5-expressing L1.2 cells with efficient mutual cross desensitization. SCM-1alpha bound specifically to GPR5-expressing L1.2 cells with a Kd of 10 nM. By Northern blot analysis, GPR5 mRNA of about 5 kilobases was detected strongly in placenta and weakly in spleen and thymus among various human tissues. Identification of a specific receptor for SCM-1 would facilitate our investigation on its biological function. Following the set rule for the chemokine receptor nomenclature, we propose to designate GPR5 as XCR1 from XC chemokine receptor-1.

  12. Peptide motif analysis predicts alphaviruses as triggers for rheumatoid arthritis.

    PubMed

    Hogeboom, Charissa

    2015-12-01

    Rheumatoid arthritis (RA) develops in response to both genetic and environmental factors. The strongest genetic determinant is HLA-DR, where polymorphisms within the P4 and P6 binding pockets confer elevated risk. However, low disease concordance across monozygotic twin pairs underscores the importance of an environmental factor, probably infectious. The goal of this investigation was to predict the microorganism most likely to interact with HLA-DR to trigger RA under the molecular mimicry hypothesis. A set of 185 structural proteins from viruses or intracellular bacteria was scanned for regions of sequence homology with a collagen peptide that binds preferentially to DR4; candidates were then evaluated against a motif required for T cell cross-reactivity. The plausibility of the predicted agent was evaluated by comparison of microbial prevalence patterns to epidemiological characteristics of RA. Peptides from alphavirus capsid proteins provided the closest fit. Variations in the P6 position suggest that the HLA binding preference may vary by species, with Ross River virus, Chikungunya virus, and Mayaro virus peptides binding preferentially to DR4, and peptides from Sindbis/Ockelbo virus showing stronger affinity to DR1. The predicted HLA preference is supported by epidemiological studies of post-infection chronic arthralgia. Parallels between the cytokine profiles of RA and chronic alphavirus infection are discussed.

  13. Network motifs that stabilize the hybrid epithelial/mesenchymal phenotype

    NASA Astrophysics Data System (ADS)

    Jolly, Mohit Kumar; Jia, Dongya; Tripathi, Satyendra; Hanash, Samir; Mani, Sendurai; Ben-Jacob, Eshel; Levine, Herbert

    Epithelial to Mesenchymal Transition (EMT) and its reverse - MET - are hallmarks of cancer metastasis. While transitioning between E and M phenotypes, cells can also attain a hybrid epithelial/mesenchymal (E/M) phenotype that enables collective cell migration as a cluster of Circulating Tumor Cells (CTCs). These clusters can form 50-times more tumors than individually migrating CTCs, underlining their importance in metastasis. However, this hybrid E/M phenotype has been hypothesized to be only a transient one that is attained en route EMT. Here, via mathematically modeling, we identify certain `phenotypic stability factors' that couple with the core three-way decision-making circuit (miR-200/ZEB) and can maintain or stabilize the hybrid E/M phenotype. Further, we show experimentally that this phenotype can be maintained stably at a single-cell level, and knockdown of these factors impairs collective cell migration. We also show that these factors enable the association of hybrid E/M with high stemness or tumor-initiating potential. Finally, based on these factors, we deduce specific network motifs that can maintain the E/M phenotype. Our framework can be used to elucidate the effect of other players in regulating cellular plasticity during metastasis. This work was supported by NSF PHY-1427654 (Center for Theoretical Biological Physics) and the CPRIT Scholar in Cancer Research of the State of Texas at Rice University.

  14. Crossover among structural motifs in Pd-Au nanoalloys.

    PubMed

    Zhu, Beien; Guesmi, Hazar; Creuze, Jérôme; Legrand, Bernard; Mottet, Christine

    2015-11-14

    The crossovers among the most abundant structural motifs (icosahedra, decahedra and truncated octahedra) of Pd-Au nanoalloys have been determined theoretically in a size range between 2 and 7 nm and for three compositions equivalent to Pd3Au, PdAu and PdAu3. The chemical ordering and segregation optimisation are performed via Monte Carlo simulations using semi-empirical tight-binding potentials fitted to ab initio calculations. The chemical configurations are then quenched via molecular dynamic simulations in order to compare their energy and characterize the equilibrium structures as a function of the cluster size. For the smaller sizes (of around 300 atoms and fewer) the structures are also optimized at the electronic level within ab initio calculations in order to validate the semi-empirical potential. The predictions of the crossover sizes for the nanoalloys cannot be simply extrapolated from the crossover of the pure nanoparticles but imply stress release phenomena related to the size misfit between the two metals. Indeed, alloying extends the range of stability of the icosahedron beyond that of the pure systems and the energy differences between decahedra and truncated octahedra become asymptotic, around the sizes of 5-6 nm. Nevertheless, such equilibrium results should be modulated regarding kinetic considerations or possible gas adsorption under experimental conditions.

  15. Evidence for a gamma-turn motif in antifreeze glycopeptides.

    PubMed Central

    Drewes, J A; Rowlen, K L

    1993-01-01

    Knowledge of the secondary structure of antifreeze peptides (AFPs) and glycopeptides (AFGPs) is crucial to understanding the mechanism by which these molecules inhibit ice crystal growth. A polyproline type II helix is perhaps the most widely accepted conformation for active AFGPs; however, random coil and alpha-helix conformations have also been proposed. In this report we present vibrational spectroscopic evidence that the conformation of AFGPs in solution is not random, not alpha-helical, and not polyproline type II. Comparison of AFGP amide vibrational frequencies with those observed and calculated for beta and gamma-turns in other peptides strongly suggests that AFGPs contain substantial turn structure. Computer-generated molecular models were utilized to compare gamma-turn, beta-turn, and polyproline II structures. The gamma-turn motif is consistent with observed amide frequencies and results in a molecule with planar symmetry with respect to the disaccharides. This intriguing conformation may provide new insight into the unusual properties of AFGPs. Images FIGURE 6 PMID:8241413

  16. Eukaryotic Penelope-Like Retroelements Encode Hammerhead Ribozyme Motifs

    PubMed Central

    Cervera, Amelia; De la Peña, Marcos

    2014-01-01

    Small self-cleaving RNAs, such as the paradigmatic Hammerhead ribozyme (HHR), have been recently found widespread in DNA genomes across all kingdoms of life. In this work, we found that new HHR variants are preserved in the ancient family of Penelope-like elements (PLEs), a group of eukaryotic retrotransposons regarded as exceptional for encoding telomerase-like retrotranscriptases and spliceosomal introns. Our bioinformatic analysis revealed not only the presence of minimalist HHRs in the two flanking repeats of PLEs but also their massive and widespread occurrence in metazoan genomes. The architecture of these ribozymes indicates that they may work as dimers, although their low self-cleavage activity in vitro suggests the requirement of other factors in vivo. In plants, however, PLEs show canonical HHRs, whereas fungi and protist PLEs encode ribozyme variants with a stable active conformation as monomers. Overall, our data confirm the connection of self-cleaving RNAs with eukaryotic retroelements and unveil these motifs as a significant fraction of the encoded information in eukaryotic genomes. PMID:25135949

  17. Motif mimetic of epsin perturbs tumor growth and metastasis

    PubMed Central

    Dong, Yunzhou; Wu, Hao; Rahman, H.N. Ashiqur; Liu, Yanjun; Pasula, Satish; Tessneer, Kandice L.; Cai, Xiaofeng; Liu, Xiaolei; Chang, Baojun; McManus, John; Hahn, Scott; Dong, Jiali; Brophy, Megan L.; Yu, Lili; Song, Kai; Silasi-Mansat, Robert; Saunders, Debra; Njoku, Charity; Song, Hoogeun; Mehta-D’Souza, Padmaja; Towner, Rheal; Lupu, Florea; McEver, Rodger P.; Xia, Lijun; Boerboom, Derek; Srinivasan, R. Sathish; Chen, Hong

    2015-01-01

    Tumor angiogenesis is critical for cancer progression. In multiple murine models, endothelium-specific epsin deficiency abrogates tumor progression by shifting the balance of VEGFR2 signaling toward uncontrolled tumor angiogenesis, resulting in dysfunctional tumor vasculature. Here, we designed a tumor endothelium–targeting chimeric peptide (UPI) for the purpose of inhibiting endogenous tumor endothelial epsins by competitively binding activated VEGFR2. We determined that the UPI peptide specifically targets tumor endothelial VEGFR2 through an unconventional binding mechanism that is driven by unique residues present only in the epsin ubiquitin–interacting motif (UIM) and the VEGFR2 kinase domain. In murine models of neoangiogenesis, UPI peptide increased VEGF-driven angiogenesis and neovascularization but spared quiescent vascular beds. Further, in tumor-bearing mice, UPI peptide markedly impaired functional tumor angiogenesis, tumor growth, and metastasis, resulting in a notable increase in survival. Coadministration of UPI peptide with cytotoxic chemotherapeutics further sustained tumor inhibition. Equipped with localized tumor endothelium–specific targeting, our UPI peptide provides potential for an effective and alternative cancer therapy. PMID:26571402

  18. Crammed signaling motifs in the T-cell receptor.

    PubMed

    Borroto, Aldo; Abia, David; Alarcón, Balbino

    2014-09-01

    Although the T cell antigen receptor (TCR) is long known to contain multiple signaling subunits (CD3γ, CD3δ, CD3ɛ and CD3ζ), their role in signal transduction is still not well understood. The presence of at least one immunoreceptor tyrosine-based activation motif (ITAM) in each CD3 subunit has led to the idea that the multiplication of such elements essentially serves to amplify signals. However, the evolutionary conservation of non-ITAM sequences suggests that each CD3 subunit is likely to have specific non-redundant roles at some stage of development or in mature T cell function. The CD3ɛ subunit is paradigmatic because in a relatively short cytoplasmic sequence (∼55 amino acids) it contains several docking sites for proteins involved in intracellular trafficking and signaling, proteins whose relevance in T cell activation is slowly starting to be revealed. In this review we will summarize our current knowledge on the signaling effectors that bind directly to the TCR and we will propose a hierarchy in their response to TCR triggering.

  19. Organizational motifs for ground squirrel cone bipolar cells.

    PubMed

    Light, Adam C; Zhu, Yongling; Shi, Jun; Saszik, Shannon; Lindstrom, Sarah; Davidson, Laura; Li, Xiaoyu; Chiodo, Vince A; Hauswirth, William W; Li, Wei; DeVries, Steven H

    2012-09-01

    In daylight vision, parallel processing starts at the cone synapse. Cone signals flow to On and Off bipolar cells, which are further divided into types according to morphology, immunocytochemistry, and function. The axons of the bipolar cell types stratify at different levels in the inner plexiform layer (IPL) and can interact with costratifying amacrine and ganglion cells. These interactions endow the ganglion cell types with unique functional properties. The wiring that underlies the interactions among bipolar, amacrine, and ganglion cells is poorly understood. It may be easier to elucidate this wiring if organizational rules can be established. We identify 13 types of cone bipolar cells in the ground squirrel, 11 of which contact contiguous cones, with the possible exception of short-wavelength-sensitive cones. Cells were identified by antibody labeling, tracer filling, and Golgi-like filling following transduction with an adeno-associated virus encoding for green fluorescent protein. The 11 bipolar cell types displayed two organizational patterns. In the first pattern, eight to 10 of the 11 types came in pairs with partially overlapping axonal stratification. Pairs shared morphological, immunocytochemical, and functional properties. The existence of similar pairs is a new motif that might have implications for how signals first diverge from a cone to bipolar cells and then reconverge onto a costratifying ganglion cell. The second pattern is a mirror symmetric organization about the middle of the IPL involving at least seven bipolar cell types. This anatomical symmetry may be associated with a functional symmetry in On and Off ganglion cell responses.

  20. Information processing by simple molecular motifs and susceptibility to noise.

    PubMed

    Mc Mahon, Siobhan S; Lenive, Oleg; Filippi, Sarah; Stumpf, Michael P H

    2015-09-06

    Biological organisms rely on their ability to sense and respond appropriately to their environment. The molecular mechanisms that facilitate these essential processes are however subject to a range of random effects and stochastic processes, which jointly affect the reliability of information transmission between receptors and, for example, the physiological downstream response. Information is mathematically defined in terms of the entropy; and the extent of information flowing across an information channel or signalling system is typically measured by the 'mutual information', or the reduction in the uncertainty about the output once the input signal is known. Here, we quantify how extrinsic and intrinsic noise affects the transmission of simple signals along simple motifs of molecular interaction networks. Even for very simple systems, the effects of the different sources of variability alone and in combination can give rise to bewildering complexity. In particular, extrinsic variability is apt to generate 'apparent' information that can, in extreme cases, mask the actual information that for a single system would flow between the different molecular components making up cellular signalling pathways. We show how this artificial inflation in apparent information arises and how the effects of different types of noise alone and in combination can be understood.

  1. Plasticity of the RNA Kink Turn Structural Motif

    SciTech Connect

    Antonioli, A.; Cochrane, J; Lipchock, S; Strobel, S

    2010-01-01

    The kink turn (K-turn) is an RNA structural motif found in many biologically significant RNAs. While most examples of the K-turn have a similar fold, the crystal structure of the Azoarcus group I intron revealed a novel RNA conformation, a reverse kink turn bent in the direction opposite that of a consensus K-turn. The reverse K-turn is bent toward the major grooves rather than the minor grooves of the flanking helices, yet the sequence differs from the K-turn consensus by only a single nucleotide. Here we demonstrate that the reverse bend direction is not solely defined by internal sequence elements, but is instead affected by structural elements external to the K-turn. It bends toward the major groove under the direction of a tetraloop-tetraloop receptor. The ability of one sequence to form two distinct structures demonstrates the inherent plasticity of the K-turn sequence. Such plasticity suggests that the K-turn is not a primary element in RNA folding, but instead is shaped by other structural elements within the RNA or ribonucleoprotein assembly.

  2. LibME-automatic extraction of 3D ligand-binding motifs for mechanistic analysis of protein-ligand recognition.

    PubMed

    He, Wei; Liang, Zhi; Teng, MaiKun; Niu, LiWen

    2016-12-01

    Identifying conserved binding motifs is an efficient way to study protein-ligand recognition. Most 3D binding motifs only contain information from the protein side, and so motifs that combine information from both protein and ligand sides are desired. Here, we propose an algorithm called LibME (Ligand-binding Motif Extractor), which automatically extracts 3D binding motifs composed of the target ligand and surrounding conserved residues. We show that the motifs extracted by LibME for ATP and its analogs are highly similar to well-known motifs reported by previous studies. The superiority of our method to handle flexible ligands was also demonstrated using isocitric acid as an example. Finally, we show that these motifs, together with their visual exhibition, permit better investigating and understanding of protein-ligand recognition process.

  3. Hyperspectral signature analysis of skin parameters

    NASA Astrophysics Data System (ADS)

    Vyas, Saurabh; Banerjee, Amit; Garza, Luis; Kang, Sewon; Burlina, Philippe

    2013-02-01

    The temporal analysis of changes in biological skin parameters, including melanosome concentration, collagen concentration and blood oxygenation, may serve as a valuable tool in diagnosing the progression of malignant skin cancers and in understanding the pathophysiology of cancerous tumors. Quantitative knowledge of these parameters can also be useful in applications such as wound assessment, and point-of-care diagnostics, amongst others. We propose an approach to estimate in vivo skin parameters using a forward computational model based on Kubelka-Munk theory and the Fresnel Equations. We use this model to map the skin parameters to their corresponding hyperspectral signature. We then use machine learning based regression to develop an inverse map from hyperspectral signatures to skin parameters. In particular, we employ support vector machine based regression to estimate the in vivo skin parameters given their corresponding hyperspectral signature. We build on our work from SPIE 2012, and validate our methodology on an in vivo dataset. This dataset consists of 241 signatures collected from in vivo hyperspectral imaging of patients of both genders and Caucasian, Asian and African American ethnicities. In addition, we also extend our methodology past the visible region and through the short-wave infrared region of the electromagnetic spectrum. We find promising results when comparing the estimated skin parameters to the ground truth, demonstrating good agreement with well-established physiological precepts. This methodology can have potential use in non-invasive skin anomaly detection and for developing minimally invasive pre-screening tools.

  4. 42 CFR 424.36 - Signature requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... personal contact between the provider, hospital, or supplier and the beneficiary (for example, a physician sent a blood sample to the provider for diagnostic tests), a representative of the provider, hospital... Part B may be signed by the entity on the beneficiary's behalf. (e) Acceptance of other signatures...

  5. The Face Signature of Fibrodysplasia Ossificans Progressiva

    PubMed Central

    Hammond, Peter; Suttie, Michael; Hennekam, Raoul C.; Allanson, Judith; Shore, Eileen M.; Kaplan, Frederick S.

    2012-01-01

    Fibrodysplasia Ossificans Progressiva (FOP) causes extensive heterotopic bone formation due to heterozygous mutations in the glycine-serine activation domain of ACVR1 (ALK2), a bone morphogenetic protein type I receptor. Anecdotal observations of facial similarity have been made by clinicians and parents, but no objective quantitative analysis of the faces of FOP patients has ever been undertaken. We delineated the common facial characteristics of 55 individuals with molecularly confirmed FOP by analysing their face signature (face shape difference normalized against age and sex matched controls) and associated face signature graphs (with face signatures as vertices and adjacency corresponding to greatest similarity). Our analysis identified 10 affected individuals whose face signature is more homogeneous than others with FOP. This distinct subgroup showed the previously identified reduced mandible as well as newly identified features: underdevelopment of the upper orbit/supra-orbital ridge; infra-orbital prominence; and, low-set ears. These findings strongly suggest that the canonical FOP mutation variably affects the postnatal morphogenesis of the normotopic cranial skeleton in the upper midface and mandible and may have important diagnostic and functional implications. PMID:22581580

  6. Tagging a monotop signature in natural SUSY

    NASA Astrophysics Data System (ADS)

    Gonçalves, Dorival; Sakurai, Kazuki; Takeuchi, Michihisa

    2017-01-01

    We study the feasibility of probing a region of natural supersymmetry where the stop and Higgsino masses are compressed. Although this region is most effectively searched for in the monojet channel, this signature is present in many other nonsupersymmetric frameworks. Therefore, another channel that carries orthogonal information is required to confirm the existence of the light stop and Higgsinos. We show that a supersymmetric version of the t t ¯H process, p p →t t˜ 1χ˜1 (2 ) 0 , can have an observably large rate when both the stop and Higgsinos are significantly light, and it leads to a distinctive monotop signature in the compressed mass region. We demonstrate that the hadronic channel of the monotop signature can effectively discriminate the signal from backgrounds by tagging a hadronic top jet. We show that the hadronic channel of the monotop signature offers a significant improvement over the leptonic channel and the sensitivity reaches mt˜1≃420 GeV at the 13 TeV LHC with 3 ab-1 luminosity.

  7. Exploring Signature Pedagogies in Undergraduate Leadership Education

    ERIC Educational Resources Information Center

    Jenkins, Daniel M.

    2012-01-01

    This research explores the instructional strategies most frequently used by leadership educators who teach academic credit-bearing undergraduate leadership studies courses through a national survey and identifies signature pedagogies within the leadership discipline. Findings from this study suggest that class discussion--whether in the form of…

  8. The Pedagogic Signature of Special Needs Education

    ERIC Educational Resources Information Center

    Weiß, Sabine; Kollmannsberger, Markus; Lerche, Thomas; Oubaid, Viktor; Kiel, Ewald

    2014-01-01

    The goal of the following study is to identify a pedagogic signature, according to LS Shulman, for working with students who have special educational needs. Special educational needs are defined as significant limitations in personal development and learning which require particular educational measures beyond regular education. The development of…

  9. 5 CFR 850.106 - Electronic signatures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be... signature of an electronic communication may be deemed to satisfy any statutory or regulatory requirement... communication, including an application, claim, or notice, designation of beneficiary, or assignment that—...

  10. Signatures of black holes at the LHC

    NASA Astrophysics Data System (ADS)

    Cavaglià, Marco; Godang, Romulus; Cremaldi, Lucien M.; Summers, Donald J.

    2007-06-01

    Signatures of black hole events at CERN's Large Hadron Collider are discussed. Event simulations are carried out with the Fortran Monte Carlo generator CATFISH. Inelasticity effects, exact field emissivities, color and charge conservation, corrections to semiclassical black hole evaporation, gravitational energy loss at formation and possibility of a black hole remnant are included in the analysis.

  11. Negative obstacle detection by thermal signature

    NASA Technical Reports Server (NTRS)

    Matthies, Larry; Rankin, A.

    2003-01-01

    Detecting negative obstacles (ditches, potholes, and other depressions) is one of the most difficult problems in perception for autonomous, off-road navigation. Past work has largely relied on range imagery, because that is based on the geometry of the obstacle, is largely insensitive to illumination variables, and because there have not been other reliable alternatives. However, the visible aspect of negative obstacles shrinks rapidly with range, making them impossible to detect in time to avoid them at high speed. To relive this problem, we show that the interiors of negative obstacles generally remain warmer than the surrounding terrain throughout the night, making thermal signature a stable property for night-time negative obstacle detection. Experimental results to date have achieved detection distances 45% greater by using thermal signature than by using range data alone. Thermal signature is the first known observable with potential to reveal a deep negative obstacle without actually seeing far into it. Modeling solar illumination has potential to extend the usefulness of thermal signature through daylight hours.

  12. Digital gene expression signatures for maize development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome-wide expression signatures detect specific perturbations in developmental programs and contribute to functional resolution of key regulatory networks. In maize (Zea mays) inflorescences, mutations in the RAMOSA (RA) genes affect determinacy of axillary meristems and thus alter branching patt...

  13. Developing a Predictive Capability for Bioluminescence Signatures

    DTIC Science & Technology

    2011-09-30

    naval nighttime operations because the flow field associated with their motion stimulates naturally occurring plankton . In the littoral, the primary...sources of bioluminescence are dinoflagellates, common unicellular plankton that are also known to form red tides. Dinoflagellate bioluminescence is...bioluminescent signatures of some swimming fish are distinct enough to differentiate species; nocturnally foraging predators may use bioluminescent

  14. Cosmological perturbations and classical change of signature

    NASA Astrophysics Data System (ADS)

    Martin, Jérôme

    1995-12-01

    Cosmological perturbations on a manifold admitting signature change are studied. The background solution consists in a Friedmann-Lemaître-Robertson-Walker universe filled by a constant scalar field playing the role of a cosmological constant. It is shown that no regular solution exists satisfying the junction conditions at the surface of change. The comparison with similar studies in quantum cosmology is made.

  15. 5 CFR 850.106 - Electronic signatures.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be... signature of an electronic communication may be deemed to satisfy any statutory or regulatory requirement... communication, including an application, claim, or notice, designation of beneficiary, or assignment that—...

  16. 5 CFR 850.106 - Electronic signatures.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be... signature of an electronic communication may be deemed to satisfy any statutory or regulatory requirement... communication, including an application, claim, or notice, designation of beneficiary, or assignment that—...

  17. 5 CFR 850.106 - Electronic signatures.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... to any provisions prescribed by the Director under § 850.104— (1) An electronic communication may be... signature of an electronic communication may be deemed to satisfy any statutory or regulatory requirement... communication, including an application, claim, or notice, designation of beneficiary, or assignment that—...

  18. Observational signatures of self-destructive civilizations

    NASA Astrophysics Data System (ADS)

    Stevens, Adam; Forgan, Duncan; James, Jack O'malley

    2016-10-01

    We address the possibility that intelligent civilizations that destroy themselves could present signatures observable by humanity. Placing limits on the number of self-destroyed civilizations in the Milky Way has strong implications for the final three terms in Drake's Equation, and would allow us to identify which classes of solution to Fermi's Paradox fit with the evidence (or lack thereof). Using the Earth as an example, we consider a variety of scenarios in which humans could extinguish their own technological civilization. Each scenario presents some form of observable signature that could be probed by astronomical campaigns to detect and characterize extrasolar planetary systems. Some observables are unlikely to be detected at interstellar distances, but some scenarios are likely to produce significant changes in atmospheric composition that could be detected serendipitously with next-generation telescopes. In some cases, the timing of the observation would prove crucial to detection, as the decay of signatures is rapid compared with humanity's communication lifetime. In others, the signatures persist on far longer timescales.

  19. Peptide-based identification of functional motifs and their binding partners.

    PubMed

    Shelton, Martin N; Huang, Ming Bo; Ali, Syed; Johnson, Kateena; Roth, William; Powell, Michael; Bond, Vincent

    2013-06-30

    Specific short peptides derived from motifs found in full-length proteins, in our case HIV-1 Nef, not only retain their biological function, but can also competitively inhibit the function of the full-length protein. A set of 20 Nef scanning peptides, 20 amino acids in length with each overlapping 10 amino acids of its neighbor, were used to identify motifs in Nef responsible for its induction of apoptosis. Peptides containing these apoptotic motifs induced apoptosis at levels comparable to the full-length Nef protein. A second peptide, derived from the Secretion Modification Region (SMR) of Nef, retained the ability to interact with cellular proteins involved in Nef's secretion in exosomes (exNef). This SMRwt peptide was used as the "bait" protein in co-immunoprecipitation experiments to isolate cellular proteins that bind specifically to Nef's SMR motif. Protein transfection and antibody inhibition was used to physically disrupt the interaction between Nef and mortalin, one of the isolated SMR-binding proteins, and the effect was measured with a fluorescent-based exNef secretion assay. The SMRwt peptide's ability to outcompete full-length Nef for cellular proteins that bind the SMR motif, make it the first inhibitor of exNef secretion. Thus, by employing the techniques described here, which utilize the unique properties of specific short peptides derived from motifs found in full-length proteins, one may accelerate the identification of functional motifs in proteins and the development of peptide-based inhibitors of pathogenic functions.

  20. Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction

    NASA Astrophysics Data System (ADS)

    Yeger-Lotem, Esti; Sattath, Shmuel; Kashtan, Nadav; Itzkovitz, Shalev; Milo, Ron; Pinter, Ron Y.; Alon, Uri; Margalit, Hanah

    2004-04-01

    Genes and proteins generate molecular circuitry that enables the cell to process information and respond to stimuli. A major challenge is to identify characteristic patterns in this network of interactions that may shed light on basic cellular mechanisms. Previous studies have analyzed aspects of this network, concentrating on either transcription-regulation or protein-protein interactions. Here we search for composite network motifs: characteristic network patterns consisting of both transcription-regulation and protein-protein interactions that recur significantly more often than in random networks. To this end we developed algorithms for detecting motifs in networks with two or more types of interactions and applied them to an integrated data set of protein-protein interactions and transcription regulation in Saccharomyces cerevisiae. We found a two-protein mixed-feedback loop motif, five types of three-protein motifs exhibiting coregulation and complex formation, and many motifs involving four proteins. Virtually all four-protein motifs consisted of combinations of smaller motifs. This study presents a basic framework for detecting the building blocks of networks with multiple types of interactions.

  1. A novel motif in telomerase reverse transcriptase regulates telomere repeat addition rate and processivity

    PubMed Central

    Xie, Mingyi; Podlevsky, Joshua D.; Qi, Xiaodong; Bley, Christopher J.; Chen, Julian J.-L.

    2010-01-01

    Telomerase is a specialized reverse transcriptase that adds telomeric DNA repeats onto chromosome termini. Here, we characterize a new telomerase-specific motif, called motif 3, in the catalytic domain of telomerase reverse transcriptase, that is crucial for telomerase function and evolutionally conserved between vertebrates and ciliates. Comprehensive mutagenesis of motif 3 identified mutations that remarkably increase the rate or alter the processivity of telomere repeat addition. Notably, the rate and processivity of repeat addition are affected independently by separate motif 3 mutations. The processive telomerase action relies upon a template translocation mechanism whereby the RNA template and the telomeric DNA strand separate and realign between each repeat synthesis. By analyzing the mutant telomerases reconstituted in vitro and in cells, we show that the hyperactive mutants exhibit higher repeat addition rates and faster enzyme turnovers, suggesting higher rates of strand-separation during template translocation. In addition, the strong correlation between the processivity of the motif 3 mutants and their ability to use an 8 nt DNA primer, suggests that motif 3 facilitates realignment between the telomeric DNA and the template RNA following strand-separation. These findings support motif 3 as a key determinant for telomerase activity and processivity. PMID:20044353

  2. Trend Motif: A Graph Mining Approach for Analysis of Dynamic Complex Networks

    SciTech Connect

    Jin, R; McCallen, S; Almaas, E

    2007-05-28

    Complex networks have been used successfully in scientific disciplines ranging from sociology to microbiology to describe systems of interacting units. Until recently, studies of complex networks have mainly focused on their network topology. However, in many real world applications, the edges and vertices have associated attributes that are frequently represented as vertex or edge weights. Furthermore, these weights are often not static, instead changing with time and forming a time series. Hence, to fully understand the dynamics of the complex network, we have to consider both network topology and related time series data. In this work, we propose a motif mining approach to identify trend motifs for such purposes. Simply stated, a trend motif describes a recurring subgraph where each of its vertices or edges displays similar dynamics over a userdefined period. Given this, each trend motif occurrence can help reveal significant events in a complex system; frequent trend motifs may aid in uncovering dynamic rules of change for the system, and the distribution of trend motifs may characterize the global dynamics of the system. Here, we have developed efficient mining algorithms to extract trend motifs. Our experimental validation using three disparate empirical datasets, ranging from the stock market, world trade, to a protein interaction network, has demonstrated the efficiency and effectiveness of our approach.

  3. Recurrent motifs as resonant attractor states in the narrative field: a testable model of archetype.

    PubMed

    Goodwyn, Erik

    2013-06-01

    At the most basic level, archetypes represented Jung's attempt to explain the phenomenon of recurrent myths and folktale motifs (Jung 1956, 1959, para. 99). But the archetype remains controversial as an explanation of recurrent motifs, as the existence of recurrent motifs does not prove that archetypes exist. Thus, the challenge for contemporary archetype theory is not merely to demonstrate that recurrent motifs exist, since that is not disputed, but to demonstrate that archetypes exist and cause recurrent motifs. The present paper proposes a new model which is unlike others in that it postulates how the archetype creates resonant motifs. This model necessarily clarifies and adapts some of Jung's seminal ideas on archetype in order to provide a working framework grounded in contemporary practice and methodologies. For the first time, a model of archetype is proposed that can be validated on empirical, rather than theoretical grounds. This is achieved by linking the archetype to the hard data of recurrent motifs rather than academic trends in other fields.

  4. SVM2Motif—Reconstructing Overlapping DNA Sequence Motifs by Mimicking an SVM Predictor

    PubMed Central

    Vidovic, Marina M. -C.; Görnitz, Nico; Müller, Klaus-Robert; Rätsch, Gunnar; Kloft, Marius

    2015-01-01

    Identifying discriminative motifs underlying the functionality and evolution of organisms is a major challenge in computational biology. Machine learning approaches such as support vector machines (SVMs) achieve state-of-the-art performances in genomic discrimination tasks, but—due to its black-box character—motifs underlying its decision function are largely unknown. As a remedy, positional oligomer importance matrices (POIMs) allow us to visualize the significance of position-specific subsequences. Although being a major step towards the explanation of trained SVM models, they suffer from the fact that their size grows exponentially in the length of the motif, which renders their manual inspection feasible only for comparably small motif sizes, typically k ≤ 5. In this work, we extend the work on positional oligomer importance matrices, by presenting a new machine-learning methodology, entitled motifPOIM, to extract the truly relevant motifs—regardless of their length and complexity—underlying the predictions of a trained SVM model. Our framework thereby considers the motifs as free parameters in a probabilistic model, a task which can be phrased as a non-convex optimization problem. The exponential dependence of the POIM size on the oligomer length poses a major numerical challenge, which we address by an efficient optimization framework that allows us to find possibly overlapping motifs consisting of up to hundreds of nucleotides. We demonstrate the efficacy of our approach on a synthetic data set as well as a real-world human splice site data set. PMID:26690911

  5. MODA: an efficient algorithm for network motif discovery in biological networks.

    PubMed

    Omidi, Saeed; Schreiber, Falk; Masoudi-Nejad, Ali

    2009-10-01

    In recent years, interest has been growing in the study of complex networks. Since Erdös and Rényi (1960) proposed their random graph model about 50 years ago, many researchers have investigated and shaped this field. Many indicators have been proposed to assess the global features of networks. Recently, an active research area has developed in studying local features named motifs as the building blocks of networks. Unfortunately, network motif discovery is a computationally hard problem and finding rather large motifs (larger than 8 nodes) by means of current algorithms is impractical as it demands too much computational effort. In this paper, we present a new algorithm (MODA) that incorporates techniques such as a pattern growth approach for extracting larger motifs efficiently. We have tested our algorithm and found it able to identify larger motifs with more than 8 nodes more efficiently than most of the current state-of-the-art motif discovery algorithms. While most of the algorithms rely on induced subgraphs as motifs of the networks, MODA is able to extract both induced and non-induced subgraphs simultaneously. The MODA source code is freely available at: http://LBB.ut.ac.ir/Download/LBBsoft/MODA/

  6. Repression domains of class II ERF transcriptional repressors share an essential motif for active repression.

    PubMed

    Ohta, M; Matsui, K; Hiratsu, K; Shinshi, H; Ohme-Takagi, M

    2001-08-01

    We reported previously that three ERF transcription factors, tobacco ERF3 (NtERF3) and Arabidopsis AtERF3 and AtERF4, which are categorized as class II ERFs, are active repressors of transcription. To clarify the roles of these repressors in transcriptional regulation in plants, we attempted to identify the functional domains of the ERF repressor that mediates the repression of transcription. Analysis of the results of a series of deletions revealed that the C-terminal 35 amino acids of NtERF3 are sufficient to confer the capacity for repression of transcription on a heterologous DNA binding domain. This repression domain suppressed the intermolecular activities of other transcriptional activators. In addition, fusion of this repression domain to the VP16 activation domain completely inhibited the transactivation function of VP16. Comparison of amino acid sequences of class II ERF repressors revealed the conservation of the sequence motif (L)/(F)DLN(L)/(F)(x)P. This motif was essential for repression because mutations within the motif eliminated the capacity for repression. We designated this motif the ERF-associated amphiphilic repression (EAR) motif, and we identified this motif in a number of zinc-finger proteins from wheat, Arabidopsis, and petunia plants. These zinc finger proteins functioned as repressors, and their repression domains were identified as regions that contained an EAR motif.

  7. Minimal motif peptide structure of metzincin clan zinc peptidases in micelles.

    PubMed

    Onoda, Akira; Suzuki, Takako; Ishizuka, Hiroaki; Sugiyama, Rumiko; Ariyasu, Shinya; Yamamura, Takeshi

    2009-12-01

    It is well known that the functions of metalloproteins generally originate from their metal-binding motifs. However, the intrinsic nature of individual motifs remains unknown, particularly the details about metal-binding effects on the folding of motifs; the converse is also unknown, although there is no doubt that the motif is the core of the reactivity for each metalloprotein. In this study, we focused our attention on the zinc-binding motif of the metzincin clan family, HEXXHXXGXXH; this family contains the general zinc-binding sequence His-Glu-Xaa-Xaa-His (HEXXH) and the extended GXXH region. We adopted the motif sequence of stromelysin-1 and investigated the folding properties of the Trp-labeled peptides WAHEIAHSLGLFHA (STR-W1), AWHEIAHSLGLFHA (STR-W2), AHEIAHSLGWFHA (STR-W11), and AHEIAHSLGLFHWA (STR-W14) in the presence and absence of zinc ions in hydrophobic micellar environments by circular dichroism (CD) measurements. We accessed successful incorporation of these zinc peptides into micelles using quenching of Trp fluorescence. Results of CD studies indicated that two of the Trp-incorporated peptides, STR-W1 and STR-W14, exhibited helical folding in the hydrophobic region of cetyltrimethylammonium chloride micelle. The NMR structural analysis of the apo STR-W14 revealed that the conformation in the C-terminus GXXH region significantly differred between the apo state in the micelle and the reported Zn-bound state of stromelysin-1 in crystal structures. The structural analyses of the qualitative Zn-binding properties of this motif peptide provide an interesting Zn-binding mechanism: the minimum consensus motif in the metzincin clan, a basic zinc-binding motif with an extended GXXH region, has the potential to serve as a preorganized Zn binding scaffold in a hydrophobic environment.

  8. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    SciTech Connect

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum; Uhm, Sang-Jun; Song, Hyuk; Kim, Nam-Hyung; Kim, Jae-Hwan

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer We found the putative nuclear export signal motif within human NANOG homeodomain. Black-Right-Pointing-Pointer Leucine-rich residues are important for human NANOG homeodomain nuclear export. Black-Right-Pointing-Pointer CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ({sup 125}MQELSNILNL{sup 134}) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-{Delta}NLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  9. Dispom: a discriminative de-novo motif discovery tool based on the jstacs library.

    PubMed

    Grau, Jan; Keilwagen, Jens; Gohr, André; Paponov, Ivan A; Posch, Stefan; Seifert, Michael; Strickert, Marc; Grosse, Ivo

    2013-02-01

    DNA-binding proteins are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in target regions of genomic DNA. However, de-novo discovery of these binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology, which has not yet been solved satisfactorily. Here, we present a detailed description and analysis of the de-novo motif discovery tool Dispom, which has been developed for finding binding sites of DNA-binding proteins that are differentially abundant in a set of target regions compared to a set of control regions. Two additional features of Dispom are its capability of modeling positional preferences of binding sites and adjusting the length of the motif in the learning process. Dispom yields an increased prediction accuracy compared to existing tools for de-novo motif discovery, suggesting that the combination of searching for differentially abundant motifs, inferring their positional distributions, and adjusting the motif lengths is beneficial for de-novo motif discovery. When applying Dispom to promoters of auxin-responsive genes and those of ABI3 target genes from Arabidopsis thaliana, we identify relevant binding motifs with pronounced positional distributions. These results suggest that learning motifs, their positional distributions, and their lengths by a discriminative learning principle may aid motif discovery from ChIP-chip and gene expression data. We make Dispom freely available as part of Jstacs, an open-source Java library that is tailored to statistical sequence analysis. To facilitate extensions of Dispom, we describe its implementation using Jstacs in this manuscript. In addition, we provide a stand-alone application of Dispom at http://www.jstacs.de/index.php/Dispom for instant use.

  10. Regulatory motifs are present in the ITS1 of some flatworm species.

    PubMed

    Van Herwerden, Lynne; Caley, M Julian; Blair, David

    2003-04-15

    Particular sequence motifs can act as transcription regulators. Because the total regulatory effects of such motifs can be related to their abundance, their presence might be expected at locations within the genome where sequences are repeated. Multiple repeats that vary in number among individuals occur within the ribosomal first internal transcribed spacer (ITS1) in some species in three trematode genera: Paragonimus, Schistosoma and Dolichosaccus. In all of these genera we found in ITS1, sequences identical to known enhancer motifs. We also searched for, and identified, known regulatory motifs in published ITS1 sequences of other parasitic flatworms including Echinostoma spp. (Trematoda) and Echinococcus spp. (Cestoda) which lack multiple repeats in ITS1. We present three lines of evidence that this widespread occurrence of such motifs within the ITS1 of parasitic flatworms may indicate a functional role in regulating tissue- or stage-specific transcription of ribosomal genes. First, these motifs are identical to ones whose functional roles have been established using in vitro assays of transcriptional rates. Second, in all 18 species investigated here, between one and three different regulatory motifs were identified. In 14 of these 18 species, the probability that at least one of these motifs occurred because of the random assortment of bases within the regions investigated was 10% or less. In 12 of these 14 species, the probability was 5% or less. Third, the evolutionary divergence of flatworm species investigated is quite ancient. Therefore, the interspecific distribution of motifs observed here, in a rapidly evolving region such as ITS1, is unlikely to be attributable solely to shared evolutionary histories. These results, therefore, suggest a broader functional role for the ITS1 than previously thought.

  11. Infrared Signature Masking by Air Plasma Radiation

    NASA Technical Reports Server (NTRS)

    Kruger, C. H.; Laux, C. O.

    1998-01-01

    This report describes progress during the second year of our research program on Infrared Signature Masking by Air Plasmas at Stanford University. This program is intended to investigate the masking of infrared signatures by the air plasma formed behind the bow shock of high velocity missiles. Our previous annual report described spectral measurements and modeling of the radiation emitted between 3.2 and 5.5 microns by an atmospheric pressure air plasma in chemical and thermal equilibrium at a temperature of approximately 3100 K. One of our goals was to examine the spectral emission of secondary species such as water vapor or carbon dioxide. The cold air stream injected in the plasma torch contained approximately 330 parts per million Of CO2, which is the natural CO2 concentration in atmospheric air at room temperature, and a small amount of water vapor with an estimated mole fraction of 3.8 x 10(exp -4). As can be seen from Figure 1, it was found that the measured spectrum exhibited intense spectral features due to the fundamental rovibrational bands of NO at 4.9 - 5.5 microns and the V(3) band of CO2 (antisymmetric stretch) at 4.2-4.8 microns. These observations confirmed the well-known fact that infrared signatures between 4.15 - 5.5 microns can be masked by radiative emission in the interceptor's bow-shock. Figure I also suggested that the range 3.2 - 4.15 microns did not contain any significant emission features (lines or continuum) that could mask IR signatures. However, the signal-to-noise level, close to one in that range, precluded definite conclusions. Thus, in an effort to further investigate the spectral emission in the range of interest to signature masking problem, new measurements were made with a higher signal-to-noise ratio and an extended wavelength range.

  12. Observational signatures of binary supermassive black holes

    SciTech Connect

    Roedig, Constanze; Krolik, Julian H.; Miller, M. Coleman

    2014-04-20

    Observations indicate that most massive galaxies contain a supermassive black hole, and theoretical studies suggest that when such galaxies have a major merger, the central black holes will form a binary and eventually coalesce. Here we discuss two spectral signatures of such binaries that may help distinguish them from ordinary active galactic nuclei. These signatures are expected when the mass ratio between the holes is not extreme and the system is fed by a circumbinary disk. One such signature is a notch in the thermal continuum that has been predicted by other authors; we point out that it should be accompanied by a spectral revival at shorter wavelengths and also discuss its dependence on binary properties such as mass, mass ratio, and separation. In particular, we note that the wavelength λ {sub n} at which the notch occurs depends on these three parameters in such a way as to make the number of systems displaying these notches ∝λ{sub n}{sup 16/3}; longer wavelength searches are therefore strongly favored. A second signature, first discussed here, is hard X-ray emission with a Wien-like spectrum at a characteristic temperature ∼100 keV produced by Compton cooling of the shock generated when streams from the circumbinary disk hit the accretion disks around the individual black holes. We investigate the observability of both signatures. The hard X-ray signal may be particularly valuable as it can provide an indicator of black hole merger a few decades in advance of the event.

  13. ELM 2016—data update and new functionality of the eukaryotic linear motif resource

    PubMed Central

    Dinkel, Holger; Van Roey, Kim; Michael, Sushama; Kumar, Manjeet; Uyar, Bora; Altenberg, Brigitte; Milchevskaya, Vladislava; Schneider, Melanie; Kühn, Helen; Behrendt, Annika; Dahl, Sophie Luise; Damerell, Victoria; Diebel, Sandra; Kalman, Sara; Klein, Steffen; Knudsen, Arne C.; Mäder, Christina; Merrill, Sabina; Staudt, Angelina; Thiel, Vera; Welti, Lukas; Davey, Norman E.; Diella, Francesca; Gibson, Toby J.

    2016-01-01

    The Eukaryotic Linear Motif (ELM) resource (http://elm.eu.org) is a manually curated database of short linear motifs (SLiMs). In this update, we present the latest additions to this resource, along with more improvements to the web interface. ELM 2016 contains more than 240 different motif classes with over 2700 experimentally validated instances, manually curated from more than 2400 scientific publications. In addition, more data have been made available as individually searchable pages and are downloadable in various formats. PMID:26615199

  14. Phosphopeptide interactions with BRCA1 BRCT domains: More than just a motif.

    PubMed

    Wu, Qian; Jubb, Harry; Blundell, Tom L

    2015-03-01

    BRCA1 BRCT domains function as phosphoprotein-binding modules for recognition of the phosphorylated protein-sequence motif pSXXF. While the motif interaction interface provides strong anchor points for binding, protein regions outside the motif have recently been found to be important for binding affinity. In this review, we compare the available structural data for BRCA1 BRCT domains in complex with phosphopeptides in order to gain a more complete understanding of the interaction between phosphopeptides and BRCA1-BRCT domains.

  15. The coxsackievirus A9 RGD motif is not essential for virus viability.

    PubMed Central

    Hughes, P J; Horsnell, C; Hyypiä, T; Stanway, G

    1995-01-01

    An RGD (arginine-glycine-aspartic acid) motif in coxsackievirus A9 has been implicated in internalization through an interaction with the integrin alpha v beta 3. We have produced a number of virus mutants, lacking the motif, which have a small-plaque phenotype in LLC-Mk2 and A-Vero cells and are phenotypically normal in RD cells. Substitution of flanking amino acids also affected plaque size. The results suggest that interaction between the RGD motif and alpha v beta 3 is not critical for virus viability in the cell lines tested and therefore that alternative regions of the CAV-9 capsid are involved in internalization. PMID:7494317

  16. Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators

    PubMed Central

    Yaklichkin, Sergey; Vekker, Alexander; Stayrook, Steven; Lewis, Mitchell; Kessler, Daniel S

    2007-01-01

    Background The Fox gene family comprises a large and functionally diverse group of forkhead-related transcriptional regulators, many of which are essential for metazoan embryogenesis and physiology. Defining conserved functional domains that mediate the transcriptional activity of Fox proteins will contribute to a comprehensive understanding of the biological function of Fox family genes. Results Systematic analysis of 458 protein sequences of the metazoan Fox family was performed to identify the presence of the engrailed homology-1 motif (eh1), a motif known to mediate physical interaction with transcriptional corepressors of the TLE/Groucho family. Greater than 50% of Fox proteins contain sequences with high similarity to the eh1 motif, including ten of the nineteen Fox subclasses (A, B, C, D, E, G, H, I, L, and Q) and Fox proteins of early divergent species such as marine sponge. The eh1 motif is not detected in Fox proteins of the F, J, K, M, N, O, P, R and S subclasses, or in yeast Fox proteins. The eh1-like motifs are positioned C-terminal to the winged helix DNA-binding domain in all subclasses except for FoxG proteins, which have an N-terminal motif. Two similar eh1-like motifs are found in the zebrafish FoxQ1 and in FoxG proteins of sea urchin and amphioxus. The identification of eh1-like motifs by manual sequence alignment was validated by statistical analyses of the Swiss protein database, confirming a high frequency of occurrence of eh1-like sequences in Fox family proteins. Structural predictions suggest that the majority of identified eh1-like motifs are short α-helices, and wheel modeling revealed an amphipathicity that supports this secondary structure prediction. Conclusion A search for eh1 Groucho interaction motifs in the Fox gene family has identified eh1-like sequences in greater than 50% of Fox proteins. The results predict a physical and functional interaction of TLE/Groucho corepressors with many members of the Fox family of transcriptional

  17. Specific regulatory motifs predict glucocorticoid responsiveness of hippocampal gene expression.

    PubMed

    Datson, N A; Polman, J A E; de Jonge, R T; van Boheemen, P T M; van Maanen, E M T; Welten, J; McEwen, B S; Meiland, H C; Meijer, O C

    2011-10-01

    The glucocorticoid receptor (GR) is an ubiquitously expressed ligand-activated transcription factor that mediates effects of cortisol in relation to adaptation to stress. In the brain, GR affects the hippocampus to modulate memory processes through direct binding to glucocorticoid response elements (GREs) in the DNA. However, its effects are to a high degree cell specific, and its target genes in different cell types as well as the mechanisms conferring this specificity are largely unknown. To gain insight in hippocampal GR signaling, we characterized to which GRE GR binds in the rat hippocampus. Using a position-specific scoring matrix, we identified evolutionary-conserved putative GREs from a microarray based set of hippocampal target genes. Using chromatin immunoprecipitation, we were able to confirm GR binding to 15 out of a selection of 32 predicted sites (47%). The majority of these 15 GREs are previously undescribed and thus represent novel GREs that bind GR and therefore may be functional in the rat hippocampus. GRE nucleotide composition was not predictive for binding of GR to a GRE. A search for conserved flanking sequences that may predict GR-GRE interaction resulted in the identification of GC-box associated motifs, such as Myc-associated zinc finger protein 1, within 2 kb of GREs with GR binding in the hippocampus. This enrichment was not present around nonbinding GRE sequences nor around proven GR-binding sites from a mesenchymal stem-like cell dataset that we analyzed. GC-binding transcription factors therefore may be unique partners for DNA-bound GR and may in part explain cell-specific transcriptional regulation by glucocorticoids in the context of the hippocampus.

  18. Elongated polyproline motifs facilitate enamel evolution through matrix subunit compaction.

    PubMed

    Jin, Tianquan; Ito, Yoshihiro; Luan, Xianghong; Dangaria, Smit; Walker, Cameron; Allen, Michael; Kulkarni, Ashok; Gibson, Carolyn; Braatz, Richard; Liao, Xiubei; Diekwisch, Thomas G H

    2009-12-01

    Vertebrate body designs rely on hydroxyapatite as the principal mineral component of relatively light-weight, articulated endoskeletons and sophisticated tooth-bearing jaws, facilitating rapid movement and efficient predation. Biological mineralization and skeletal growth are frequently accomplished through proteins containing polyproline repeat elements. Through their well-defined yet mobile and flexible structure polyproline-rich proteins control mineral shape and contribute many other biological functions including Alzheimer's amyloid aggregation and prolamine plant storage. In the present study we have hypothesized that polyproline repeat proteins exert their control over biological events such as mineral growth, plaque aggregation, or viscous adhesion by altering the length of their central repeat domain, resulting in dramatic changes in supramolecular assembly dimensions. In order to test our hypothesis, we have used the vertebrate mineralization protein amelogenin as an exemplar and determined the biological effect of the four-fold increased polyproline tandem repeat length in the amphibian/mammalian transition. To study the effect of polyproline repeat length on matrix assembly, protein structure, and apatite crystal growth, we have measured supramolecular assembly dimensions in various vertebrates using atomic force microscopy, tested the effect of protein assemblies on crystal growth by electron microscopy, generated a transgenic mouse model to examine the effect of an abbreviated polyproline sequence on crystal growth, and determined the structure of polyproline repeat elements using 3D NMR. Our study shows that an increase in PXX/PXQ tandem repeat motif length results (i) in a compaction of protein matrix subunit dimensions, (ii) reduced conformational variability, (iii) an increase in polyproline II helices, and (iv) promotion of apatite crystal length. Together, these findings establish a direct relationship between polyproline tandem repeat fragment

  19. Peptoid nanosheets exhibit a new secondary-structure motif

    NASA Astrophysics Data System (ADS)

    Mannige, Ranjan V.; Haxton, Thomas K.; Proulx, Caroline; Robertson, Ellen J.; Battigelli, Alessia; Butterfoss, Glenn L.; Zuckermann, Ronald N.; Whitelam, Stephen

    2015-10-01

    A promising route to the synthesis of protein-mimetic materials that are capable of complex functions, such as molecular recognition and catalysis, is provided by sequence-defined peptoid polymers--structural relatives of biologically occurring polypeptides. Peptoids, which are relatively non-toxic and resistant to degradation, can fold into defined structures through a combination of sequence-dependent interactions. However, the range of possible structures that are accessible to peptoids and other biological mimetics is unknown, and our ability to design protein-like architectures from these polymer classes is limited. Here we use molecular-dynamics simulations, together with scattering and microscopy data, to determine the atomic-resolution structure of the recently discovered peptoid nanosheet, an ordered supramolecular assembly that extends macroscopically in only two dimensions. Our simulations show that nanosheets are structurally and dynamically heterogeneous, can be formed only from peptoids of certain lengths, and are potentially porous to water and ions. Moreover, their formation is enabled by the peptoids' adoption of a secondary structure that is not seen in the natural world. This structure, a zigzag pattern that we call a Σ(`sigma')-strand, results from the ability of adjacent backbone monomers to adopt opposed rotational states, thereby allowing the backbone to remain linear and untwisted. Linear backbones tiled in a brick-like way form an extended two-dimensional nanostructure, the Σ-sheet. The binary rotational-state motif of the Σ-strand is not seen in regular protein structures, which are usually built from one type of rotational state. We also show that the concept of building regular structures from multiple rotational states can be generalized beyond the peptoid nanosheet system.

  20. Elongated Polyproline Motifs Facilitate Enamel Evolution through Matrix Subunit Compaction

    PubMed Central

    Luan, Xianghong; Dangaria, Smit; Walker, Cameron; Allen, Michael; Kulkarni, Ashok; Gibson, Carolyn; Braatz, Richard; Liao, Xiubei; Diekwisch, Thomas G. H.

    2009-01-01

    Vertebrate body designs rely on hydroxyapatite as the principal mineral component of relatively light-weight, articulated endoskeletons and sophisticated tooth-bearing jaws, facilitating rapid movement and efficient predation. Biological mineralization and skeletal growth are frequently accomplished through proteins containing polyproline repeat elements. Through their well-defined yet mobile and flexible structure polyproline-rich proteins control mineral shape and contribute many other biological functions including Alzheimer's amyloid aggregation and prolamine plant storage. In the present study we have hypothesized that polyproline repeat proteins exert their control over biological events such as mineral growth, plaque aggregation, or viscous adhesion by altering the length of their central repeat domain, resulting in dramatic changes in supramolecular assembly dimensions. In order to test our hypothesis, we have used the vertebrate mineralization protein amelogenin as an exemplar and determined the biological effect of the four-fold increased polyproline tandem repeat length in the amphibian/mammalian transition. To study the effect of polyproline repeat length on matrix assembly, protein structure, and apatite crystal growth, we have measured supramolecular assembly dimensions in various vertebrates using atomic force microscopy, tested the effect of protein assemblies on crystal growth by electron microscopy, generated a transgenic mouse model to examine the effect of an abbreviated polyproline sequence on crystal growth, and determined the structure of polyproline repeat elements using 3D NMR. Our study shows that an increase in PXX/PXQ tandem repeat motif length results (i) in a compaction of protein matrix subunit dimensions, (ii) reduced conformational variability, (iii) an increase in polyproline II helices, and (iv) promotion of apatite crystal length. Together, these findings establish a direct relationship between polyproline tandem repeat fragment