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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. AU-rich RNA binding proteins in hematopoiesis and leukemogenesis.

    PubMed

    Baou, Maria; Norton, John D; Murphy, John J

    2011-11-24

    Posttranscriptional mechanisms are now widely acknowledged to play a central role in orchestrating gene-regulatory networks in hematopoietic cell growth, differentiation, and tumorigenesis. Although much attention has focused on microRNAs as regulators of mRNA stability/translation, recent data have highlighted the role of several diverse classes of AU-rich RNA-binding protein in the regulation of mRNA decay/stabilization. AU-rich elements are found in the 3'-untranslated region of many mRNAs that encode regulators of cell growth and survival, such as cytokines and onco/tumor-suppressor proteins. These are targeted by a burgeoning number of different RNA-binding proteins. Three distinct types of AU-rich RNA binding protein (ARE poly-U-binding degradation factor-1/AUF1, Hu antigen/HuR/HuA/ELAVL1, and the tristetraprolin/ZFP36 family of proteins) are essential for normal hematopoiesis. Together with 2 further AU-rich RNA-binding proteins, nucleolin and KHSRP/KSRP, the functions of these proteins are intimately associated with pathways that are dysregulated in various hematopoietic malignancies. Significantly, all of these AU-rich RNA-binding proteins function via an interconnected network that is integrated with microRNA functions. Studies of these diverse types of RNA binding protein are providing novel insight into gene-regulatory mechanisms in hematopoiesis in addition to offering new opportunities for developing mechanism-based targeted therapeutics in leukemia and lymphoma. PMID:21917750

  3. The rad50 signature motif: essential to ATP binding and biological function.

    PubMed

    Moncalian, Gabriel; Lengsfeld, Bettina; Bhaskara, Venugopal; Hopfner, Karl-Peter; Karcher, Annette; Alden, Erinn; Tainer, John A; Paull, Tanya T

    2004-01-23

    The repair of double-strand breaks in DNA is an essential process in all organisms, and requires the coordinated activities of evolutionarily conserved protein assemblies. One of the most critical of these is the Mre11/Rad50 (M/R) complex, which is present in all three biological kingdoms, but is not well-understood at the biochemical level. Previous structural analysis of a Rad50 homolog from archaebacteria illuminated the catalytic core of the enzyme, an ATP-binding domain related to the ABC transporter family of ATPases. Here, we present the crystallographic structure of the Rad50 mutant S793R. This missense signature motif mutation changes the key serine residue in the signature motif that is conserved among Rad50 homologs and ABC ATPases. The S793R mutation is analogous to the mutation S549R in the cystic fibrosis transmembrane conductance regulator (CFTR) that results in cystic fibrosis. We show here that the serine to arginine change in the Rad50 protein prevents ATP binding and disrupts the communication among the other ATP-binding loops. This structural change, in turn, alters the communication between Rad50 monomers and thus prevents Rad50 dimerization. The equivalent mutation was made in the human Rad50 gene, and the resulting mutant protein did form a complex with Mre11 and Nbs1, but was specifically deficient in all ATP-dependent enzymatic activities. This signature motif structure-function homology extends to yeast, because the same mutation introduced into the Saccharomyces cerevisiae RAD50 gene generated an allele that failed to complement a rad50 deletion strain in DNA repair assays in vivo. These structural and biochemical results extend our understanding of the Rad50 catalytic domain and validate the use of the signature motif mutant to test the role of Rad50 ATP binding in diverse organisms. PMID:14698290

  4. Signature motif-guided identification of receptors for peptide hormones essential for root meristem growth.

    PubMed

    Song, Wen; Liu, Li; Wang, Jizong; Wu, Zhen; Zhang, Heqiao; Tang, Jiao; Lin, Guangzhong; Wang, Yichuan; Wen, Xing; Li, Wenyang; Han, Zhifu; Guo, Hongwei; Chai, Jijie

    2016-06-01

    Peptide-mediated cell-to-cell signaling has crucial roles in coordination and definition of cellular functions in plants. Peptide-receptor matching is important for understanding the mechanisms underlying peptide-mediated signaling. Here we report the structure-guided identification of root meristem growth factor (RGF) receptors important for plant development. An assay based on a signature ligand recognition motif (Arg-x-Arg) conserved in a subfamily of leucine-rich repeat receptor kinases (LRR-RKs) identified the functionally uncharacterized LRR-RK At4g26540 as a receptor of RGF1 (RGFR1). We further solved the crystal structure of RGF1 in complex with the LRR domain of RGFR1 at a resolution of 2.6 Å, which reveals that the Arg-x-Gly-Gly (RxGG) motif is responsible for specific recognition of the sulfate group of RGF1 by RGFR1. Based on the RxGG motif, we identified additional four RGFRs. Participation of the five RGFRs in RGF-induced signaling is supported by biochemical and genetic data. We also offer evidence showing that SERKs function as co-receptors for RGFs. Taken together, our study identifies RGF receptors and co-receptors that can link RGF signals with their downstream components and provides a proof of principle for structure-based matching of LRR-RKs with their peptide ligands. PMID:27229311

  5. 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

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

    PubMed

    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

    2016-01-01

    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. PMID:26983597

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26983597

  8. Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1.

    PubMed Central

    Zhang, W; Wagner, B J; Ehrenman, K; Schaefer, A W; DeMaria, C T; Crater, D; DeHaven, K; Long, L; Brewer, G

    1993-01-01

    The degradation of some proto-oncogene and lymphokine mRNAs is controlled in part by an AU-rich element (ARE) in the 3' untranslated region. It was shown previously (G. Brewer, Mol. Cell. Biol. 11:2460-2466, 1991) that two polypeptides (37 and 40 kDa) copurified with fractions of a 130,000 x g postribosomal supernatant (S130) from K562 cells that selectively accelerated degradation of c-myc mRNA in a cell-free decay system. These polypeptides bound specifically to the c-myc and granulocyte-macrophage colony-stimulating factor 3' UTRs, suggesting they are in part responsible for selective mRNA degradation. In the present work, we have purified the RNA-binding component of this mRNA degradation activity, which we refer to as AUF1. Using antisera specific for these polypeptides, we demonstrate that the 37- and 40-kDa polypeptides are immunologically cross-reactive and that both polypeptides are phosphorylated and can be found in a complex(s) with other polypeptides. Immunologically related polypeptides are found in both the nucleus and the cytoplasm. The antibodies were also used to clone a cDNA for the 37-kDa polypeptide. This cDNA contains an open reading frame predicted to produce a protein with several features, including two RNA recognition motifs and domains that potentially mediate protein-protein interactions. These results provide further support for a role of this protein in mediating ARE-directed mRNA degradation. Images PMID:8246982

  9. Signature amino acids enable the archaeal L7Ae box C/D RNP core protein to recognize and bind the K-loop RNA motif

    PubMed Central

    Gagnon, Keith T.; Zhang, Xinxin; Qu, Guosheng; Biswas, Shyamasri; Suryadi, Jimmy; Brown, Bernard A.; Maxwell, E. Stuart

    2010-01-01

    The archaeal L7Ae and eukaryotic 15.5kD protein homologs are members of the L7Ae/15.5kD protein family that characteristically recognize K-turn motifs found in both archaeal and eukaryotic RNAs. In Archaea, the L7Ae protein uniquely binds the K-loop motif found in box C/D and H/ACA sRNAs, whereas the eukaryotic 15.5kD homolog is unable to recognize this variant K-turn RNA. Comparative sequence and structural analyses, coupled with amino acid replacement experiments, have demonstrated that five amino acids enable the archaeal L7Ae core protein to recognize and bind the K-loop motif. These signature residues are highly conserved in the archaeal L7Ae and eukaryotic 15.5kD homologs, but differ between the two domains of life. Interestingly, loss of K-loop binding by archaeal L7Ae does not disrupt C′/D′ RNP formation or RNA-guided nucleotide modification. L7Ae is still incorporated into the C′/D′ RNP despite its inability to bind the K-loop, thus indicating the importance of protein–protein interactions for RNP assembly and function. Finally, these five signature amino acids are distinct for each of the L7Ae/L30 family members, suggesting an evolutionary continuum of these RNA-binding proteins for recognition of the various K-turn motifs contained in their cognate RNAs. PMID:19926724

  10. HIV-1 Gag shares a signature motif with annexin (Anx7), which is required for virus replication

    PubMed Central

    Srivastava, M.; Cartas, M.; Rizvi, T. A.; Singh, S. P.; Serio, D.; Kalyanaraman, V. S.; Pollard, H. B.; Srinivasan, A.

    1999-01-01

    Genetic and biochemical analyses of the Gag protein of HIV-1 indicate a crucial role for this protein in several functions related to viral replication, including viral assembly. It has been suggested that Gag may fulfill some of the functions by recruiting host cellular protein(s). In our effort to identify structural and functional homologies between Gag and cellular cytoskeletal and secretory proteins involved in transport, we observed that HIV-1 Gag contains a unique PGQM motif in the capsid region. This motif was initially noted in the regulatory domain of synexin the membrane fusion protein of Xenopus laevis. To evaluate the functional significance of the highly conserved PGQM motif, we introduced alanine (A) in place of individual residues of the PGQM and deleted the motif altogether in a Gag expression plasmid and in an HIV-1 proviral DNA. The proviral DNA containing mutations in the PGQM motif showed altered expression, assembly, and release of viral particles in comparison to parental (NL4-3) DNA. When tested in multiple- and single-round replication assays, the mutant viruses exhibited distinct replication phenotypes; the viruses containing the A for the G and Q residues failed to replicate, whereas A in place of the P and M residues did not inhibit viral replication. Deletion of the tetrapeptide also resulted in the inhibition of replication. These results suggest that the PGQM motif may play an important role in the infection process of HIV-1 by facilitating protein–protein interactions between viral and/or viral and cellular proteins. PMID:10077575

  11. Mutations in the nucleotide binding domain 1 signature motif region rescue processing and functional defects of cystic fibrosis transmembrane conductance regulator delta f508.

    PubMed

    DeCarvalho, Ana C V; Gansheroff, Lisa J; Teem, John L

    2002-09-27

    The gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), an ATP binding cassette (ABC) transporter that functions as a phosphorylation- and nucleotide-regulated chloride channel, is mutated in cystic fibrosis (CF) patients. Deletion of a phenylalanine at amino acid position 508 (DeltaF508) in the first nucleotide binding domain (NBD1) is the most prevalent CF-causing mutation and results in defective protein processing and reduced CFTR function, leading to chloride impermeability in CF epithelia and heterologous systems. Using a STE6/CFTRDeltaF508 chimera system in yeast, we isolated two novel DeltaF508 revertant mutations, I539T and G550E, proximal to and within the conserved ABC signature motif of NBD1, respectively. Western blot and functional analysis in mammalian cells indicate that mutations I539T and G550E each partially rescue the CFTRDeltaF508 defect. Furthermore, a combination of both revertant mutations resulted in a 38-fold increase in CFTRDeltaF508-mediated chloride current, representing 29% of wild type channel activity. The G550E mutation increased the sensitivity of CFTRDeltaF508 and wild type CFTR to activation by cAMP agonists and blocked the enhancement of CFTRDeltaF508 channel activity by 2 mm 3-isobutyl-1-methylxanthine. The data show that the DeltaF508 defect can be significantly rescued by second-site mutations in the nucleotide binding domain 1 region, that includes the LSGGQ consensus motif. PMID:12110684

  12. 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

  13. 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

    Rodriguez, Yacidzohara; Gonzalez-Mendez, Ricardo R; Cadilla, Carmen L

    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 within

  14. Identification of a novel AU-rich-element-binding protein which is related to AUF1.

    PubMed Central

    Dean, Jonathan L E; Sully, Gareth; Wait, Robin; Rawlinson, Lesley; Clark, Andrew R; Saklatvala, Jeremy

    2002-01-01

    The AU-rich element (ARE) is an important instability determinant for a large number of early-response-gene mRNAs. AREs also mediate the stabilization of certain pro-inflammatory mRNAs, such as tumour necrosis factor (TNF)-alpha and cyclo-oxygenase-2 (COX-2), in response to inflammatory stimuli. To understand how AREs control mRNA stability, it is necessary to identify trans-acting factors. We have purified a new ARE-binding protein and identified it as CArG box-binding factor-A (CBF-A). The amino acid sequence of CBF-A is highly similar to that of the ARE-binding protein AUF1. Recombinant CBF-A bound the COX-2 and TNF-alpha AREs, but not a non-specific control RNA. In contrast, in an electrophoretic-mobility-shift assay (EMSA) of crude RAW 264.7 macrophage-like cell extracts, an antiserum that recognizes both AUF1 and CBF-A failed to supershift complexes formed on the TNF-alpha ARE, but did supershift a complex specific for the COX-2 ARE. CBF-A exists as two isoforms, p37 and p42, that differ by a 47-amino-acid insertion close to the C-terminus. By expressing epitope-tagged isoforms of CBF-A it was shown that the p42 isoform binds the COX-2 ARE in EMSA of crude cell extracts. In a HeLa-cell tetracycline-regulated reporter system, overexpression of the p42 CBF-A isoform resulted in stabilization of a COX-2 ARE reporter mRNA. Epitope-tagged p42 CBF-A expressed in HeLa cells co-immunoprecipitated with endogenous COX-2 mRNA, but not glyceraldehyde-3-phosphate dehydrogenase mRNA, as shown by reverse-transcription PCR. The similarity between CBF-A and AUF1 suggests that CBF-A could be re-named AUF2. PMID:12086581

  15. Tristetraprolin Recruits the Herpes Simplex Virion Host Shutoff RNase to AU-Rich Elements in Stress Response mRNAs To Enable Their Cleavage

    PubMed Central

    Shu, Minfeng; Taddeo, Brunella

    2015-01-01

    ABSTRACT Herpes simplex viruses (HSV) package and bring into cells an RNase designated virion host shutoff (VHS) RNase. In infected cells, the VHS RNase targets primarily stress response mRNAs characterized by the presence of AU-rich elements in their 3′ untranslated regions (UTRs). In uninfected cells, these RNAs are sequestered in exosomes or P bodies by host proteins that bind to the AU-rich elements. In infected cells, the AU-rich RNAs are deadenylated and cleaved close to the AU-rich elements, leading to long-term persistence of nontranslatable RNAs consisting of the 5′ portions of the cleavage products. The host proteins that bind to the AU-rich elements are either resident in cells (e.g., TIA-1) or induced (e.g., tristetraprolin). Earlier, this laboratory reported that tristetraprolin binds VHS RNase. To test the hypothesis that tristetraprolin directs VHS RNase to the AU-rich elements, we mapped the domains of VHS and tristetraprolin required for their interactions. We report that VHS binds to the domain of tristetraprolin that enables its interaction with RNA. A single amino acid substitution in that domain abolished the interaction with RNA but did not block the binding to VHS RNase. In transfected cells, the mutant but not the wild-type tristetraprolin precluded the degradation of the AU-rich RNAs by VHS RNase. We conclude that TTP mediates the cleavage of the 3′ UTRs of stress response mRNAs by recruiting the VHS RNase to the AU-rich elements. IMPORTANCE The primary host response to HSV infection is the synthesis of stress response mRNAs characterized by the presence of AU-rich elements in their 3′ UTRs. These mRNAs are the targets of the virion host shutoff (VHS) RNase. The VHS RNase binds both to mRNA cap structure and to tristetraprolin, an inducible host protein that sequesters AU-rich mRNAs in exosomes or P bodies. Here we show that tristetraprolin recruits VHS RNase to the AU-rich elements and enables the degradation of the stress response

  16. Regulation of AU-Rich Element RNA Binding Proteins by Phosphorylation and the Prolyl Isomerase Pin1

    PubMed Central

    Shen, Zhong-Jian; Malter, James S.

    2015-01-01

    The accumulation of 3' untranslated region (3'-UTR), AU-rich element (ARE) containing mRNAs, are predominantly controlled at the post-transcriptional level. Regulation appears to rely on a variable and dynamic interaction between mRNA target and ARE-specific binding proteins (AUBPs). The AUBP-ARE mRNA recognition is directed by multiple intracellular signals that are predominantly targeted at the AUBPs. These include (but are unlikely limited to) methylation, acetylation, phosphorylation, ubiquitination and isomerization. These regulatory events ultimately affect ARE mRNA location, abundance, translation and stability. In this review, we describe recent advances in our understanding of phosphorylation and its impact on conformation of the AUBPs, interaction with ARE mRNAs and highlight the role of Pin1 mediated prolyl cis-trans isomerization in these biological process. PMID:25874604

  17. The p53 target Wig-1 regulates p53 mRNA stability through an AU-rich element

    PubMed Central

    Vilborg, Anna; Glahder, Jacob A.; Wilhelm, Margareta T.; Bersani, Cinzia; Corcoran, Martin; Mahmoudi, Salah; Rosenstierne, Maiken; Grandér, Dan; Farnebo, Marianne; Norrild, Bodil; Wiman, Klas G.

    2009-01-01

    The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that Wig-1 binds to p53 mRNA and stabilizes it through an AU-rich element (ARE) in the 3′ UTR of the p53 mRNA. This effect is mirrored by enhanced p53 protein levels in both unstressed cells and cells exposed to p53-activating stress agents. Thus, the p53 target Wig-1 is a previously undescribed ARE-regulating protein that acts as a positive feedback regulator of p53, with implications both for the steady-state levels of p53 and for the p53 stress response. Our data reveal a previously undescribed link between the tumor suppressor p53 and posttranscriptional gene regulation via AREs in mRNA. PMID:19805223

  18. Interplay of two functionally and structurally distinct domains of the c-fos AU-rich element specifies its mRNA-destabilizing function.

    PubMed Central

    Chen, C Y; Chen, T M; Shyu, A B

    1994-01-01

    AU-rich elements (ARE) in the 3' untranslated region of many highly labile mRNAs for proto-oncogenes, lymphokines, and cytokines can act as an RNA-destabilizing element. The absence of a clear understanding of the key sequence and structural features of the ARE that are required for its destabilizing function has precluded the further elucidation of its mode of action and the basis of its specificity. Combining extensive mutagenesis of the c-fos ARE with in vivo analysis of mRNA stability, we were able to identify mutations that exhibited kinetic phenotypes consistent with the biphasic decay characteristic of a two-step mechanism: accelerated poly(A) shortening and subsequent decay of the transcribed portion of the mRNA. These mutations, which affected either an individual step or both steps, all changed the mRNA stability. Our experiments further revealed the existence of two structurally distinct and functionally interdependent domains that constitute the c-fos ARE. Domain I, which is located within the 5' 49-nucleotide segment of the ARE and contains the three AUUUA motifs, can function as an RNA destabilizer by itself. It forms the essential core unit necessary for the ARE-destabilizing function. Domain II is a 20-nucleotide U-rich sequence which is located within the 3' part of the c-fos ARE. Although it alone can not act as an RNA destabilizer, this domain serves two critical roles: (i) its presence enhances the destabilizing ability of domain I by accelerating the deadenylation step, and (ii) it has a novel capacity of buffering decay-impeding effects exerted by mutations introduced within domain I. A model is proposed to explain how these critical structural features may be involved in the c-fos ARE-directed mRNA decay pathway. These findings have important implications for furthering our understanding of the molecular basis of differential mRNA decay mediated by different AREs. Images PMID:7903419

  19. Assembly of Functional Ribonucleoprotein Complexes by AU-rich Element RNA-binding Protein 1 (AUF1) Requires Base-dependent and -independent RNA Contacts*

    PubMed Central

    Zucconi, Beth E.; Wilson, Gerald M.

    2013-01-01

    AU-rich element RNA-binding protein 1 (AUF1) regulates the stability and/or translational efficiency of diverse mRNA targets, including many encoding products controlling the cell cycle, apoptosis, and inflammation by associating with AU-rich elements residing in their 3′-untranslated regions. Previous biochemical studies showed that optimal AUF1 binding requires 33–34 nucleotides with a strong preference for U-rich RNA despite observations that few AUF1-associated cellular mRNAs contain such extended U-rich domains. Using the smallest AUF1 isoform (p37AUF1) as a model, we employed fluorescence anisotropy-based approaches to define thermodynamic parameters describing AUF1 ribonucleoprotein (RNP) complex formation across a panel of RNA substrates. These data demonstrated that 15 nucleotides of AU-rich sequence were sufficient to nucleate high affinity p37AUF1 RNP complexes within a larger RNA context. In particular, p37AUF1 binding to short AU-rich RNA targets was significantly stabilized by interactions with a 3′-purine residue and largely base-independent but non-ionic contacts 5′ of the AU-rich site. RNP stabilization by the upstream RNA domain was associated with an enhanced negative change in heat capacity consistent with conformational changes in protein and/or RNA components, and fluorescence resonance energy transfer-based assays demonstrated that these contacts were required for p37AUF1 to remodel local RNA structure. Finally, reporter mRNAs containing minimal high affinity p37AUF1 target sequences associated with AUF1 and were destabilized in a p37AUF1-dependent manner in cells. These findings provide a mechanistic explanation for the diverse population of AUF1 target mRNAs but also suggest how AUF1 binding could regulate protein and/or microRNA binding events at adjacent sites. PMID:23940053

  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. Binding of a protein to an AU-rich domain of tumour necrosis factor alpha mRNA as a 35 kDa complex and its regulation in primary rat astrocytes.

    PubMed

    Kim, Y U; Rus, H G; Fisher, S N; Pitha, P M; Shin, M L

    1996-06-01

    Newcastle disease virus (NDV) induces tumour necrosis factor alpha (TNF alpha) gene transcription and increases the mRNA stability. NDV stabilizes TNF alpha mRNA by preventing poly(A) shortening in a protein kinase C-dependent manner. TNF alpha 3'-untranslated region (UTR) contains an AU-rich domain (ARD) with seven AUUUA pentamers, a motif implicated in poly(A) removal and mRNA degradation. In this report, protein binding to TNF alpha ARD and the effects of NDV and kinases on ARD-binding activity were investigated in primary rat astrocytes. Both nuclear and cytoplasmic extracts contained proteins binding to centrally located 27 nt AUUUAUUAUUUAUUUAUUAUUUAUUUA, within TNF alpha ARD. Portions of ARD with a single AUUUA did not show ARD-binding activity. The ARD-protein complexes migrated as two bands on electrophoretic mobility-shift assay. The slower moving complexes appeared either as a broader band or doublets. The UV cross-linked ARD-protein complexes, however, migrated as a single 35 kDa band on SDS/PAGE. In cytoplasmic extracts treated with alkaline phosphatase there was a decrease in the faster moving complex and an increase in the slower moving complex, whereas NDV infection produced the reverse effect. In addition, the faster moving complex was decreased when cytoplasmic extracts from NDV-infected cells were treated with protein phosphatase 1 or 2A. Neither NDV infection nor phosphatase treatment affected the mobility pattern of nuclear extracts. The data indicate that a protein of molecular mass less than 35 kDa binds to a segment of TNF alpha ARD containing primarily UUAUUUAUU motifs, and the ARD-binding activity in cytoplasmic compartment is post-transcriptionally modified. PMID:8687387

  2. Binding of a protein to an AU-rich domain of tumour necrosis factor alpha mRNA as a 35 kDa complex and its regulation in primary rat astrocytes.

    PubMed Central

    Kim, Y U; Rus, H G; Fisher, S N; Pitha, P M; Shin, M L

    1996-01-01

    Newcastle disease virus (NDV) induces tumour necrosis factor alpha (TNF alpha) gene transcription and increases the mRNA stability. NDV stabilizes TNF alpha mRNA by preventing poly(A) shortening in a protein kinase C-dependent manner. TNF alpha 3'-untranslated region (UTR) contains an AU-rich domain (ARD) with seven AUUUA pentamers, a motif implicated in poly(A) removal and mRNA degradation. In this report, protein binding to TNF alpha ARD and the effects of NDV and kinases on ARD-binding activity were investigated in primary rat astrocytes. Both nuclear and cytoplasmic extracts contained proteins binding to centrally located 27 nt AUUUAUUAUUUAUUUAUUAUUUAUUUA, within TNF alpha ARD. Portions of ARD with a single AUUUA did not show ARD-binding activity. The ARD-protein complexes migrated as two bands on electrophoretic mobility-shift assay. The slower moving complexes appeared either as a broader band or doublets. The UV cross-linked ARD-protein complexes, however, migrated as a single 35 kDa band on SDS/PAGE. In cytoplasmic extracts treated with alkaline phosphatase there was a decrease in the faster moving complex and an increase in the slower moving complex, whereas NDV infection produced the reverse effect. In addition, the faster moving complex was decreased when cytoplasmic extracts from NDV-infected cells were treated with protein phosphatase 1 or 2A. Neither NDV infection nor phosphatase treatment affected the mobility pattern of nuclear extracts. The data indicate that a protein of molecular mass less than 35 kDa binds to a segment of TNF alpha ARD containing primarily UUAUUUAUU motifs, and the ARD-binding activity in cytoplasmic compartment is post-transcriptionally modified. PMID:8687387

  3. 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

  4. RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3′ UTRs

    PubMed Central

    Di Giammartino, Dafne Campigli; Li, Wencheng; Ogami, Koichi; Yashinskie, Jossie J.; Hoque, Mainul; Tian, Bin

    2014-01-01

    Polyadenylation of mRNA precursors is mediated by a large multisubunit protein complex. Here we show that RBBP6 (retinoblastoma-binding protein 6), identified initially as an Rb- and p53-binding protein, is a component of this complex and functions in 3′ processing in vitro and in vivo. RBBP6 associates with other core factors, and this interaction is mediated by an unusual ubiquitin-like domain, DWNN (“domain with no name”), that is required for 3′ processing activity. The DWNN is also expressed, via alternative RNA processing, as a small single-domain protein (isoform 3 [iso3]). Importantly, we show that iso3, known to be down-regulated in several cancers, competes with RBBP6 for binding to the core machinery, thereby inhibiting 3′ processing. Genome-wide analyses following RBBP6 knockdown revealed decreased transcript levels, especially of mRNAs with AU-rich 3′ untranslated regions (UTRs) such as c-Fos and c-Jun, and increased usage of distal poly(A) sites. Our results implicate RBBP6 and iso3 as novel regulators of 3′ processing, especially of RNAs with AU-rich 3′ UTRs. PMID:25319826

  5. 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

  6. 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

    2016-01-01

    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

  7. 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

  8. 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. PMID:26001795

  9. Transcriptional repression by the orphan steroid receptor RVR/Rev-erb beta is dependent on the signature motif and helix 5 in the E region: functional evidence for a biological role of RVR in myogenesis.

    PubMed Central

    Burke, L; Downes, M; Carozzi, A; Giguère, V; Muscat, G E

    1996-01-01

    RVR/Rev-erb beta/BD73 is an orphan steroid receptor that has no known ligand in the "classical' sense. RVR binds as a monomer to an element which consists of an A/T-rich sequence upstream of the consensus hexameric half-site. However, RVR does not activate transcription and blocks transactivation of this element by ROR/RZR. The mechanism of RVR action remains obscure, hence we used the GAL4 hybrid system to identify and characterize an active transcriptional silencer in the ligand binding domain (LBD) of RVR. Rigorous deletion and mutational analysis demonstrated that this repressor domain is encoded by amino acids 416-449 of RVR. Furthermore, we demonstrated that efficient repression is dependent on the so-called LBD-specific signature motif, (F/W)AKxxxxFxxLxxxDQxxLL (which spans loop3-4 and helix 4) and helix 5 (H5; identified in the crystal structures of the steroid receptor LBDs). Although RVR is expressed in many adult tissues, including skeletal muscle, and during embryogenesis, its physiological function in differentiation and mammalian development remains unknown. Since other 'orphans', e.g. COUP-TF II and Rev-erbA alpha, have been demonstrated to regulate muscle and adipocyte differentiation, we investigated the expression and functional role of RVR during mouse myogenesis. In C2C12 myogenic cells, RVR mRNA was detected in proliferating myoblasts and was suppressed when the cells were induced to differentiate into post-mitotic, multinucleated myotubes by serum withdrawal. This decrease in RVR mRNA correlated with the appearance of muscle-specific markers (e.g. myogenin mRNA). RVR 'loss of function' studies by constitutive over-expression of a dominant negative RVR delta E resulted in increased levels of p21Cip1/Waf1 and myogenin mRNAs after serum withdrawal. Time course studies indicated that expression of RVR delta E mRNA results in the precocious induction and accumulation of myogenin and p21 mRNAs after serum withdrawal. In addition, we demonstrated

  10. The Protein Zfand5 Binds and Stabilizes mRNAs with AU-rich Elements in Their 3′-Untranslated Regions*

    PubMed Central

    He, Guoan; Sun, Dongxu; Ou, Zhiying; Ding, Aihao

    2012-01-01

    AU-rich elements (AREs) in the 3′-UTR of unstable transcripts play a vital role in the regulation of many inflammatory mediators. To identify novel ARE-dependent gene regulators, we screened a human leukocyte cDNA library for candidates that enhanced the activity of a luciferase reporter bearing the ARE sequence from TNF (ARETNF). Among 171 hits, we focused on Zfand5 (zinc finger, AN1-type domain 5), a 23-kDa protein containing two zinc finger domains. Zfand5 expression was induced in macrophages in response to IFNγ and Toll-like receptor ligands. Knockdown of Zfand5 in macrophages decreased expression of ARE class II transcripts TNF and COX2, whereas overexpression stabilized TNF mRNA by suppressing deadenylation. Zfand5 specifically bound to ARETNF mRNA and competed with tristetraprolin, a protein known to bind and destabilize class II ARE-containing RNAs. Truncation studies indicated that both zinc fingers of Zfand5 contributed to its mRNA-stabilizing function. These findings add Zfand5 to the growing list of RNA-binding proteins and suggest that Zfand5 can enhance ARE-containing mRNA stability by competing with tristetraprolin for mRNA binding. PMID:22665488

  11. Chaperone Hsp27, a Novel Subunit of AUF1 Protein Complexes, Functions in AU-Rich Element-Mediated mRNA Decay▿ †

    PubMed Central

    Sinsimer, Kristina S.; Gratacós, Frances M.; Knapinska, Anna M.; Lu, Jiebo; Krause, Christopher D.; Wierzbowski, Alexandria V.; Maher, Lauren R.; Scrudato, Shannon; Rivera, Yonaira M.; Gupta, Swati; Turrin, Danielle K.; De La Cruz, Mary Pauline; Pestka, Sidney; Brewer, Gary

    2008-01-01

    Controlled, transient cytokine production by monocytes depends heavily upon rapid mRNA degradation, conferred by 3′ untranslated region-localized AU-rich elements (AREs) that associate with RNA-binding proteins. The ARE-binding protein AUF1 forms a complex with cap-dependent translation initiation factors and heat shock proteins to attract the mRNA degradation machinery. We refer to this protein assembly as the AUF1- and signal transduction-regulated complex, ASTRC. Rapid degradation of ARE-bearing mRNAs (ARE-mRNAs) requires ubiquitination of AUF1 and its destruction by proteasomes. Activation of monocytes by adhesion to capillary endothelium at sites of tissue damage and subsequent proinflammatory cytokine induction are prominent features of inflammation, and ARE-mRNA stabilization plays a critical role in the induction process. Here, we demonstrate activation-induced subunit rearrangements within ASTRC and identify chaperone Hsp27 as a novel subunit that is itself an ARE-binding protein essential for rapid ARE-mRNA degradation. As Hsp27 has well-characterized roles in protein ubiquitination as well as in adhesion-induced cytoskeletal remodeling and cell motility, its association with ASTRC may provide a sensing mechanism to couple proinflammatory cytokine induction with monocyte adhesion and motility. PMID:18573886

  12. 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

  13. Mining Conditional Phosphorylation Motifs.

    PubMed

    Liu, Xiaoqing; Wu, Jun; Gong, Haipeng; Deng, Shengchun; He, Zengyou

    2014-01-01

    Phosphorylation motifs represent position-specific amino acid patterns around the phosphorylation sites in the set of phosphopeptides. Several algorithms have been proposed to uncover phosphorylation motifs, whereas the problem of efficiently discovering a set of significant motifs with sufficiently high coverage and non-redundancy still remains unsolved. Here we present a novel notion called conditional phosphorylation motifs. Through this new concept, the motifs whose over-expressiveness mainly benefits from its constituting parts can be filtered out effectively. To discover conditional phosphorylation motifs, we propose an algorithm called C-Motif for a non-redundant identification of significant phosphorylation motifs. C-Motif is implemented under the Apriori framework, and it tests the statistical significance together with the frequency of candidate motifs in a single stage. Experiments demonstrate that C-Motif outperforms some current algorithms such as MMFPh and Motif-All in terms of coverage and non-redundancy of the results and efficiency of the execution. The source code of C-Motif is available at: https://sourceforge. net/projects/cmotif/. PMID:26356863

  14. Tristetraprolin Recruits Eukaryotic Initiation Factor 4E2 To Repress Translation of AU-Rich Element-Containing mRNAs

    PubMed Central

    Tao, Xianzun

    2015-01-01

    Tristetraprolin (TTP) regulates the expression of AU-rich element-containing mRNAs through promoting the degradation and repressing the translation of target mRNA. While the mechanism for promoting target mRNA degradation has been extensively studied, the mechanism underlying translational repression is not well established. Here, we show that TTP recruits eukaryotic initiation factor 4E2 (eIF4E2) to repress target mRNA translation. TTP interacted with eIF4E2 but not with eIF4E. Overexpression of eIF4E2 enhanced TTP-mediated translational repression, and downregulation of endogenous eIF4E2 or overexpression of a truncation mutant of eIF4E2 impaired TTP-mediated translational repression. Overexpression of an eIF4E2 mutant that lost the cap-binding activity also impaired TTP's activity, suggesting that the cap-binding activity of eIF4E2 is important in TTP-mediated translational repression. We further show that TTP promoted eIF4E2 binding to target mRNA. These results imply that TTP recruits eIF4E2 to compete with eIF4E to repress the translation of target mRNA. This notion is supported by the finding that downregulation of endogenous eIF4E2 increased the production of tumor necrosis factor alpha (TNF-α) protein without affecting the mRNA levels in THP-1 cells. Collectively, these results uncover a novel mechanism by which TTP represses target mRNA translation. PMID:26370510

  15. Fast approximate motif statistics.

    PubMed

    Nicodème, P

    2001-01-01

    We present in this article a fast approximate method for computing the statistics of a number of non-self-overlapping matches of motifs in a random text in the nonuniform Bernoulli model. This method is well suited for protein motifs where the probability of self-overlap of motifs is small. For 96% of the PROSITE motifs, the expectations of occurrences of the motifs in a 7-million-amino-acids random database are computed by the approximate method with less than 1% error when compared with the exact method. Processing of the whole PROSITE takes about 30 seconds with the approximate method. We apply this new method to a comparison of the C. elegans and S. cerevisiae proteomes. PMID:11535175

  16. Gold solubility and partitioning between sulfide liquid, monosulfide solid solution and hydrous mantle melts: Implications for the formation of Au-rich magmas and crust-mantle differentiation

    NASA Astrophysics Data System (ADS)

    Li, Yuan; Audétat, Andreas

    2013-10-01

    The solubility of Au in sulfur-free vs. sulfide-saturated melts and its partitioning behavior between sulfide liquid (SL), monosulfide solid solution (MSS) and hydrous basanite melt at variable Au activities was investigated in a fO2 range of FMQ-2 to FMQ+1.6 at 1200 °C/1.5 GPa using piston cylinder apparatus. Gold solubility in sulfur-free (<100 μg/g S) melt is low (0.6-1.6 μg/g) and increases with fO2 in a manner consistent with Au dissolution as AuO1/2, whereas in sulfide-saturated melts it is high (13.6 ± 1.7 μg/g) and independent of fO2. Variations in the chlorine content of sulfide-saturated melts (0.2-1.2 wt% Cl) had no measurable effect on Au solubility. Gold partition coefficients between sulfide liquid and silicate melt (DAuSL/SM) are very high, ∼10,000 ± 3000, which is at the upper end of values reported in previous studies. Gold partition coefficients between MSS and silicate melt (DAuMSS/SM) are much lower, 60 ± 10, which is at the lower end of previous values. Both DAuSL/SM and DAuMSS/SM are independent of fO2. The new Au partition coefficients were used in conjunction with previously published Cu and Ag partition coefficients to investigate the role of MSS versus SL during partial melting in the source region of primitive potassic magmas and during crust-mantle differentiation. The high Au content of ore deposits associated with potassic magmas has commonly been explained by the dissolution of Au-rich sulfide liquid, either during partial melting in the mantle source or during partial re-melting of sulfide-bearing cumulates at the crust-mantle boundary. We argue that MSS is the dominant sulfide phase in the mantle source region of these magmas, and thus that their high Au content is a consequence of low MSS-silicate melt partition coefficients rather than of sulfide exhaustion or partial re-melting of sulfide-bearing cumulates. Continental crust is depleted in Au, Ag and Cu relative to mantle melts, which was thought to be due to removal of

  17. Multidimensional signatures in antimicrobial peptides

    PubMed Central

    Yount, Nannette Y.; Yeaman, Michael R.

    2004-01-01

    Conventional analyses distinguish between antimicrobial peptides by differences in amino acid sequence. Yet structural paradigms common to broader classes of these molecules have not been established. The current analyses examined the potential conservation of structural themes in antimicrobial peptides from evolutionarily diverse organisms. Using proteomics, an antimicrobial peptide signature was discovered to integrate stereospecific sequence patterns and a hallmark three-dimensional motif. This striking multidimensional signature is conserved among disulfide-containing antimicrobial peptides spanning biological kingdoms, and it transcends motifs previously limited to defined peptide subclasses. Experimental data validating this model enabled the identification of previously unrecognized antimicrobial activity in peptides of known identity. The multidimensional signature model provides a unifying structural theme in broad classes of antimicrobial peptides, will facilitate discovery of antimicrobial peptides as yet unknown, and offers insights into the evolution of molecular determinants in these and related host defense effector molecules. PMID:15118082

  18. Efficient exact motif discovery

    PubMed Central

    Marschall, Tobias; Rahmann, Sven

    2009-01-01

    Motivation: The motif discovery problem consists of finding over-represented patterns in a collection of biosequences. It is one of the classical sequence analysis problems, but still has not been satisfactorily solved in an exact and efficient manner. This is partly due to the large number of possibilities of defining the motif search space and the notion of over-representation. Even for well-defined formalizations, the problem is frequently solved in an ad hoc manner with heuristics that do not guarantee to find the best motif. Results: We show how to solve the motif discovery problem (almost) exactly on a practically relevant space of IUPAC generalized string patterns, using the p-value with respect to an i.i.d. model or a Markov model as the measure of over-representation. In particular, (i) we use a highly accurate compound Poisson approximation for the null distribution of the number of motif occurrences. We show how to compute the exact clump size distribution using a recently introduced device called probabilistic arithmetic automaton (PAA). (ii) We define two p-value scores for over-representation, the first one based on the total number of motif occurrences, the second one based on the number of sequences in a collection with at least one occurrence. (iii) We describe an algorithm to discover the optimal pattern with respect to either of the scores. The method exploits monotonicity properties of the compound Poisson approximation and is by orders of magnitude faster than exhaustive enumeration of IUPAC strings (11.8 h compared with an extrapolated runtime of 4.8 years). (iv) We justify the use of the proposed scores for motif discovery by showing our method to outperform other motif discovery algorithms (e.g. MEME, Weeder) on benchmark datasets. We also propose new motifs on Mycobacterium tuberculosis. Availability and Implementation: The method has been implemented in Java. It can be obtained from http://ls11-www

  19. Crystal Structure of the N-Terminal RNA Recognition Motif of mRNA Decay Regulator AUF1.

    PubMed

    Choi, Young Jun; Yoon, Je-Hyun; Chang, Jeong Ho

    2016-01-01

    AU-rich element binding/degradation factor 1 (AUF1) plays a role in destabilizing mRNAs by forming complexes with AU-rich elements (ARE) in the 3'-untranslated regions. Multiple AUF1-ARE complexes regulate the translation of encoded products related to the cell cycle, apoptosis, and inflammation. AUF1 contains two tandem RNA recognition motifs (RRM) and a Gln- (Q-) rich domain in their C-terminal region. To observe how the two RRMs are involved in recognizing ARE, we obtained the AUF1-p37 protein covering the two RRMs. However, only N-terminal RRM (RRM1) was crystallized and its structure was determined at 1.7 Å resolution. It appears that the RRM1 and RRM2 separated before crystallization. To demonstrate which factors affect the separate RRM1-2, we performed limited proteolysis using trypsin. The results indicated that the intact proteins were cleaved by unknown proteases that were associated with them prior to crystallization. In comparison with each of the monomers, the conformations of the β2-β3 loops were highly variable. Furthermore, a comparison with the RRM1-2 structures of HuR and hnRNP A1 revealed that a dimer of RRM1 could be one of the possible conformations of RRM1-2. Our data may provide a guidance for further structural investigations of AUF1 tandem RRM repeat and its mode of ARE binding. PMID:27437398

  20. Crystal Structure of the N-Terminal RNA Recognition Motif of mRNA Decay Regulator AUF1

    PubMed Central

    Choi, Young Jun

    2016-01-01

    AU-rich element binding/degradation factor 1 (AUF1) plays a role in destabilizing mRNAs by forming complexes with AU-rich elements (ARE) in the 3′-untranslated regions. Multiple AUF1-ARE complexes regulate the translation of encoded products related to the cell cycle, apoptosis, and inflammation. AUF1 contains two tandem RNA recognition motifs (RRM) and a Gln- (Q-) rich domain in their C-terminal region. To observe how the two RRMs are involved in recognizing ARE, we obtained the AUF1-p37 protein covering the two RRMs. However, only N-terminal RRM (RRM1) was crystallized and its structure was determined at 1.7 Å resolution. It appears that the RRM1 and RRM2 separated before crystallization. To demonstrate which factors affect the separate RRM1-2, we performed limited proteolysis using trypsin. The results indicated that the intact proteins were cleaved by unknown proteases that were associated with them prior to crystallization. In comparison with each of the monomers, the conformations of the β2-β3 loops were highly variable. Furthermore, a comparison with the RRM1-2 structures of HuR and hnRNP A1 revealed that a dimer of RRM1 could be one of the possible conformations of RRM1-2. Our data may provide a guidance for further structural investigations of AUF1 tandem RRM repeat and its mode of ARE binding. PMID:27437398

  1. [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. PMID:26202617

  2. Novel recognition motifs and biological functions of the RNA-binding protein HuD revealed by genome-wide identification of its targets

    PubMed Central

    Bolognani, Federico; Contente-Cuomo, Tania; Perrone-Bizzozero, Nora I.

    2010-01-01

    HuD is a neuronal ELAV-like RNA-binding protein (RBP) involved in nervous system development, regeneration, and learning and memory. This protein stabilizes mRNAs by binding to AU-rich instability elements (AREs) in their 3′ unstranslated regions (3′ UTR). To isolate its in vivo targets, messenger ribonucleoprotein (mRNP) complexes containing HuD were first immunoprecipitated from brain extracts and directly bound mRNAs identified by subsequent GST-HuD pull downs and microarray assays. Using the 3′ UTR sequences of the most enriched targets and the known sequence restrictions of the HuD ARE-binding site, we discovered three novel recognition motifs. Motifs 2 and 3 are U-rich whereas motif 1 is C-rich. In vitro binding assays indicated that HuD binds motif 3 with the highest affinity, followed by motifs 2 and 1, with less affinity. These motifs were found to be over-represented in brain mRNAs that are upregulated in HuD overexpressor mice, supporting the biological function of these sequences. Gene ontology analyses revealed that HuD targets are enriched in signaling pathways involved in neuronal differentiation and that many of these mRNAs encode other RBPs, translation factors and actin-binding proteins. These findings provide further insights into the post-transcriptional mechanisms by which HuD promotes neural development and synaptic plasticity. PMID:19846595

  3. Mining protein sequences for motifs.

    PubMed

    Narasimhan, Giri; Bu, Changsong; Gao, Yuan; Wang, Xuning; Xu, Ning; Mathee, Kalai

    2002-01-01

    We use methods from Data Mining and Knowledge Discovery to design an algorithm for detecting motifs in protein sequences. The algorithm assumes that a motif is constituted by the presence of a "good" combination of residues in appropriate locations of the motif. The algorithm attempts to compile such good combinations into a "pattern dictionary" by processing an aligned training set of protein sequences. The dictionary is subsequently used to detect motifs in new protein sequences. Statistical significance of the detection results are ensured by statistically determining the various parameters of the algorithm. Based on this approach, we have implemented a program called GYM. The Helix-Turn-Helix motif was used as a model system on which to test our program. The program was also extended to detect Homeodomain motifs. The detection results for the two motifs compare favorably with existing programs. In addition, the GYM program provides a lot of useful information about a given protein sequence. PMID:12487759

  4. 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.

  5. Comparative genomic analysis of upstream miRNA regulatory motifs in Caenorhabditis.

    PubMed

    Jovelin, Richard; Krizus, Aldis; Taghizada, Bakhtiyar; Gray, Jeremy C; Phillips, Patrick C; Claycomb, Julie M; Cutter, Asher D

    2016-07-01

    MicroRNAs (miRNAs) comprise a class of short noncoding RNA molecules that play diverse developmental and physiological roles by controlling mRNA abundance and protein output of the vast majority of transcripts. Despite the importance of miRNAs in regulating gene function, we still lack a complete understanding of how miRNAs themselves are transcriptionally regulated. To fill this gap, we predicted regulatory sequences by searching for abundant short motifs located upstream of miRNAs in eight species of Caenorhabditis nematodes. We identified three conserved motifs across the Caenorhabditis phylogeny that show clear signatures of purifying selection from comparative genomics, patterns of nucleotide changes in motifs of orthologous miRNAs, and correlation between motif incidence and miRNA expression. We then validated our predictions with transgenic green fluorescent protein reporters and site-directed mutagenesis for a subset of motifs located in an enhancer region upstream of let-7 We demonstrate that a CT-dinucleotide motif is sufficient for proper expression of GFP in the seam cells of adult C. elegans, and that two other motifs play incremental roles in combination with the CT-rich motif. Thus, functional tests of sequence motifs identified through analysis of molecular evolutionary signatures provide a powerful path for efficiently characterizing the transcriptional regulation of miRNA genes. PMID:27140965

  6. 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

  7. Activation of p38 signaling increases utrophin A expression in skeletal muscle via the RNA-binding protein KSRP and inhibition of AU-rich element-mediated mRNA decay: implications for novel DMD therapeutics.

    PubMed

    Amirouche, Adel; Tadesse, Helina; Lunde, John A; Bélanger, Guy; Côté, Jocelyn; Jasmin, Bernard J

    2013-08-01

    Several therapeutic approaches are currently being developed for Duchenne muscular dystrophy (DMD) including upregulating the levels of endogenous utrophin A in dystrophic fibers. Here, we examined the role of post-transcriptional mechanisms in controlling utrophin A expression in skeletal muscle. We show that activation of p38 leads to an increase in utrophin A independently of a transcriptional induction. Rather, p38 controls the levels of utrophin A mRNA by extending the half-life of transcripts via AU-rich elements (AREs). This mechanism critically depends on a decrease in the functional availability of KSRP, an RNA-binding protein known to promote decay of ARE-containing transcripts. In vitro and in vivo binding studies revealed that KSRP interacts with specific AREs located within the utrophin A 3' UTR. Electroporation experiments to knockdown KSRP led to an increase in utrophin A in wild-type and mdx mouse muscles. In pre-clinical studies, treatment of mdx mice with heparin, an activator of p38, causes a pronounced increase in utrophin A in diaphragm muscle fibers. Together, these studies identify a pathway that culminates in the post-transcriptional regulation of utrophin A through increases in mRNA stability. Furthermore, our results constitute proof-of-principle showing that pharmacological activation of p38 may prove beneficial as a novel therapeutic approach for DMD. PMID:23575223

  8. Structural alphabet motif discovery and a structural motif database.

    PubMed

    Ku, Shih-Yen; Hu, Yuh-Jyh

    2012-01-01

    This study proposes a general framework for structural motif discovery. The framework is based on a modular design in which the system components can be modified or replaced independently to increase its applicability to various studies. It is a two-stage approach that first converts protein 3D structures into structural alphabet sequences, and then applies a sequence motif-finding tool to these sequences to detect conserved motifs. We named the structural motif database we built the SA-Motifbase, which provides the structural information conserved at different hierarchical levels in SCOP. For each motif, SA-Motifbase presents its 3D view; alphabet letter preference; alphabet letter frequency distribution; and the significance. SA-Motifbase is available at http://bioinfo.cis.nctu.edu.tw/samotifbase/. PMID:22099701

  9. 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

  10. Structural motifs and the stability of fullerenes

    SciTech Connect

    Austin, S.J.; Fowler, P.W.; Manolopoulos, D.E.; Orlandi, G.; Zerbetto, F.

    1995-05-18

    Full geometry optimization has been performed within the semiempirical QCFF/PI model for the 1812 fullerene structural isomers of C{sub 60} formed by 12 pentagons and 20 hexagons. All are local minima on the potential energy hypersurface. Correlations of total energy with many structural motifs yield highly scattered diagrams, but some exhibit linear trends. Penalty and merit functions can be assigned to certain motifs: inclusion of a fused pentagon pair entails an average penalty of 111 kJ mol{sup -1}; a generic hexagon triple costs 23 kJ mol{sup -1}; a triple (open or fused) comprising a pentagon between two hexagonal neighbors gives a stabilization of 19 kJ mol{sup -1}. These results can be understood in terms of the curved nature of fullerene molecules: pentagons should be isolated to avoid sharp local curvature, hexagon triples are costly because they enforce local planarity and hence imply high curvature in another part of the fullerene surface, but hexagon-pentagon-hexagon triples allow the surface to distribute steric strain by warping. The best linear fit is found for H, the second moment of the hexagon-neighbor-index signature, which fits the total energies with a standard deviation of only 53 kJ mol{sup -1} and must be minimized for stability; this index too can be interpreted in terms of curvature. 26 refs., 5 figs.

  11. A novel zinc-binding motif found in two ubiquitous deaminase families.

    PubMed Central

    Reizer, J.; Buskirk, S.; Bairoch, A.; Reizer, A.; Saier, M. H.

    1994-01-01

    Two families of deaminases, one specific for cytidine, the other for deoxycytidylate, are shown to possess a novel zinc-binding motif, here designated ZBS. We have (1) identified the protein members of these 2 families, (2) carried out sequence analyses that allow specification of this zinc-binding motif, and (3) determined signature sequences that will allow identification of additional members of these families as their sequences become available. PMID:8061614

  12. The Annotation of RNA Motifs

    PubMed Central

    2002-01-01

    The recent deluge of new RNA structures, including complete atomic-resolution views of both subunits of the ribosome, has on the one hand literally overwhelmed our individual abilities to comprehend the diversity of RNA structure, and on the other hand presented us with new opportunities for comprehensive use of RNA sequences for comparative genetic, evolutionary and phylogenetic studies. Two concepts are key to understanding RNA structure: hierarchical organization of global structure and isostericity of local interactions. Global structure changes extremely slowly, as it relies on conserved long-range tertiary interactions. Tertiary RNA–RNA and quaternary RNA–protein interactions are mediated by RNA motifs, defined as recurrent and ordered arrays of non-Watson–Crick base-pairs. A single RNA motif comprises a family of sequences, all of which can fold into the same three-dimensional structure and can mediate the same interaction(s). The chemistry and geometry of base pairing constrain the evolution of motifs in such a way that random mutations that occur within motifs are accepted or rejected insofar as they can mediate a similar ordered array of interactions. The steps involved in the analysis and annotation of RNA motifs in 3D structures are: (a) decomposition of each motif into non-Watson–Crick base-pairs; (b) geometric classification of each basepair; (c) identification of isosteric substitutions for each basepair by comparison to isostericity matrices; (d) alignment of homologous sequences using the isostericity matrices to identify corresponding positions in the crystal structure; (e) acceptance or rejection of the null hypothesis that the motif is conserved. PMID:18629252

  13. Redox active motifs in selenoproteins.

    PubMed

    Li, Fei; Lutz, Patricia B; Pepelyayeva, Yuliya; Arnér, Elias S J; Bayse, Craig A; Rozovsky, Sharon

    2014-05-13

    Selenoproteins use the rare amino acid selenocysteine (Sec) to act as the first line of defense against oxidants, which are linked to aging, cancer, and neurodegenerative diseases. Many selenoproteins are oxidoreductases in which the reactive Sec is connected to a neighboring Cys and able to form a ring. These Sec-containing redox motifs govern much of the reactivity of selenoproteins. To study their fundamental properties, we have used (77)Se NMR spectroscopy in concert with theoretical calculations to determine the conformational preferences and mobility of representative motifs. This use of (77)Se as a probe enables the direct recording of the properties of Sec as its environment is systematically changed. We find that all motifs have several ring conformations in their oxidized state. These ring structures are most likely stabilized by weak, nonbonding interactions between the selenium and the amide carbon. To examine how the presence of selenium and ring geometric strain governs the motifs' reactivity, we measured the redox potentials of Sec-containing motifs and their corresponding Cys-only variants. The comparisons reveal that for C-terminal motifs the redox potentials increased between 20-25 mV when the selenenylsulfide bond was changed to a disulfide bond. Changes of similar magnitude arose when we varied ring size or the motifs' flanking residues. This suggests that the presence of Sec is not tied to unusually low redox potentials. The unique roles of selenoproteins in human health and their chemical reactivities may therefore not necessarily be explained by lower redox potentials, as has often been claimed. PMID:24769567

  14. [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. PMID:26524912

  15. 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.

  16. 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.

  17. Searching for protein signatures using a multilevel alphabet.

    PubMed

    Hod, Ronit; Kohen, Refael; Mandel-Gutfreund, Yael

    2013-06-01

    Short motifs are known to play diverse roles in proteins, such as in mediating the interactions with other molecules, binding to membranes, or conducting a specific biological function. Standard approaches currently employed to detect short motifs in proteins search for enrichment of amino acid motifs considering mostly the sequence information. Here, we presented a new approach to search for common motifs (protein signatures) which share both physicochemical and structural properties, looking simultaneously at different features. Our method takes as an input an amino acid sequence and translates it to a new alphabet that reflects its intrinsic structural and chemical properties. Using the MEME search algorithm, we identified the proteins signatures within subsets of protein which encompass common sequence and structural information. We demonstrated that we can detect enriched structural motifs, such as the amphipathic helix, from large datasets of linear sequences, as well as predicting common structural properties (such as disorder, surface accessibility, or secondary structures) of known functional-motifs. Finally, we applied the method to the yeast protein interactome and identified novel putative interacting motifs. We propose that our approach can be applied for de novo protein function prediction given either sequence or structural information. PMID:23386227

  18. Redox active motifs in selenoproteins

    PubMed Central

    Li, Fei; Lutz, Patricia B.; Pepelyayeva, Yuliya; Arnér, Elias S. J.; Bayse, Craig A.; Rozovsky, Sharon

    2014-01-01

    Selenoproteins use the rare amino acid selenocysteine (Sec) to act as the first line of defense against oxidants, which are linked to aging, cancer, and neurodegenerative diseases. Many selenoproteins are oxidoreductases in which the reactive Sec is connected to a neighboring Cys and able to form a ring. These Sec-containing redox motifs govern much of the reactivity of selenoproteins. To study their fundamental properties, we have used 77Se NMR spectroscopy in concert with theoretical calculations to determine the conformational preferences and mobility of representative motifs. This use of 77Se as a probe enables the direct recording of the properties of Sec as its environment is systematically changed. We find that all motifs have several ring conformations in their oxidized state. These ring structures are most likely stabilized by weak, nonbonding interactions between the selenium and the amide carbon. To examine how the presence of selenium and ring geometric strain governs the motifs’ reactivity, we measured the redox potentials of Sec-containing motifs and their corresponding Cys-only variants. The comparisons reveal that for C-terminal motifs the redox potentials increased between 20–25 mV when the selenenylsulfide bond was changed to a disulfide bond. Changes of similar magnitude arose when we varied ring size or the motifs’ flanking residues. This suggests that the presence of Sec is not tied to unusually low redox potentials. The unique roles of selenoproteins in human health and their chemical reactivities may therefore not necessarily be explained by lower redox potentials, as has often been claimed. PMID:24769567

  19. 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.

  20. 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.

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

    PubMed Central

    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/. PMID:25505144

  2. Detecting correlations among functional-sequence motifs

    NASA Astrophysics Data System (ADS)

    Pirino, Davide; Rigosa, Jacopo; Ledda, Alice; Ferretti, Luca

    2012-06-01

    Sequence motifs are words of nucleotides in DNA with biological functions, e.g., gene regulation. Identification of such words proceeds through rejection of Markov models on the expected motif frequency along the genome. Additional biological information can be extracted from the correlation structure among patterns of motif occurrences. In this paper a log-linear multivariate intensity Poisson model is estimated via expectation maximization on a set of motifs along the genome of E. coli K12. The proposed approach allows for excitatory as well as inhibitory interactions among motifs and between motifs and other genomic features like gene occurrences. Our findings confirm previous stylized facts about such types of interactions and shed new light on genome-maintenance functions of some particular motifs. We expect these methods to be applicable to a wider set of genomic features.

  3. Detecting correlations among functional-sequence motifs.

    PubMed

    Pirino, Davide; Rigosa, Jacopo; Ledda, Alice; Ferretti, Luca

    2012-06-01

    Sequence motifs are words of nucleotides in DNA with biological functions, e.g., gene regulation. Identification of such words proceeds through rejection of Markov models on the expected motif frequency along the genome. Additional biological information can be extracted from the correlation structure among patterns of motif occurrences. In this paper a log-linear multivariate intensity Poisson model is estimated via expectation maximization on a set of motifs along the genome of E. coli K12. The proposed approach allows for excitatory as well as inhibitory interactions among motifs and between motifs and other genomic features like gene occurrences. Our findings confirm previous stylized facts about such types of interactions and shed new light on genome-maintenance functions of some particular motifs. We expect these methods to be applicable to a wider set of genomic features. PMID:23005179

  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. Developing composite signatures

    NASA Astrophysics Data System (ADS)

    Hawley, Chadwick T.; Carpenter, Tom; Cappelaere, Patrice G.; Frye, Stu; Lemoigne-Stewart, Jacqueline J.; Mandle, Dan; Montgomery, Sarah; Williams-Bess, Autumn

    2011-06-01

    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 explores the merits of using composite signatures, in lieu of waiting for opportunities for the more elusive diagnostic signatures, to satisfy key essential elements of information Keywords: signature, composite signature, civil disaster (EEI) associated with civil disaster-related problems. It discusses efforts to refine composite signature development methodology and quantify the relative value of composite vs. diagnostic signatures. The objectives are to: 1) investigate and develop innovative composite signatures associated with civil disasters, including physical, chemical and pattern/behavioral; 2) explore the feasibility of collecting representative composite signatures using current and emerging intelligence, surveillance, and reconnaissance (ISR) collection architectures leveraging civilian and commercial architectures; and 3) collaborate extensively with scientists and engineers from U.S. government organizations and laboratories, the defense industry, and academic institutions.

  6. 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.

  7. Synthetic biology with RNA motifs.

    PubMed

    Saito, Hirohide; Inoue, Tan

    2009-02-01

    Structural motifs in naturally occurring RNAs and RNPs can be employed as new molecular parts for synthetic biology to facilitate the development of novel devices and systems that modulate cellular functions. In this review, we focus on the following: (i) experimental evolution techniques of RNA molecules in vitro and (ii) their applications for regulating gene expression systems in vivo. For experimental evolution, new artificial RNA aptamers and RNA enzymes (ribozymes) have been selected in vitro. These functional RNA molecules are likely to be applicable in the reprogramming of existing gene regulatory systems. Furthermore, they may be used for designing hypothetical RNA-based living systems in the so-called RNA world. For the regulation of gene expressions in living cells, the development of new riboswitches allows us to modulate the target gene expression in a tailor-made manner. Moreover, recently RNA-based synthetic genetic circuits have been reported by employing functional RNA molecules, expanding the repertory of synthetic biology with RNA motifs. PMID:18775792

  8. DILIMOT: discovery of linear motifs in proteins.

    PubMed

    Neduva, Victor; Russell, Robert B

    2006-07-01

    Discovery of protein functional motifs is critical in modern biology. Small segments of 3-10 residues play critical roles in protein interactions, post-translational modifications and trafficking. DILIMOT (DIscovery of LInear MOTifs) is a server for the prediction of these short linear motifs within a set of proteins. Given a set of sequences sharing a common functional feature (e.g. interaction partner or localization) the method finds statistically over-represented motifs likely to be responsible for it. The input sequences are first passed through a set of filters to remove regions unlikely to contain instances of linear motifs. Motifs are then found in the remaining sequence and ranked according to a statistic that measure over-representation and conservation across homologues in related species. The results are displayed via a visual interface for easy perusal. The server is available at http://dilimot.embl.de. PMID:16845024

  9. Bridge and brick motifs in complex networks

    NASA Astrophysics Data System (ADS)

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

    2007-04-01

    Acknowledging the expanding role of complex networks in numerous scientific contexts, we examine significant functional and topological differences between bridge and brick motifs for predicting network behaviors and functions. After observing similarities between social networks and their genetic, ecological, and engineering counterparts, we identify a larger number of brick motifs in social networks and bridge motifs in the other three types. We conclude that bridge and brick motif content analysis can assist researchers in understanding the small-world and clustering properties of network structures when investigating network functions and behaviors.

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

    PubMed

    Tran, Ngoc Tam L; Huang, Chun-Hsi

    2014-01-01

    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. PMID:24555784

  11. Anonymous Signatures Revisited

    NASA Astrophysics Data System (ADS)

    Saraswat, Vishal; Yun, Aaram

    We revisit the notion of the anonymous signature, first formalized by Yang, Wong, Deng and Wang [10], and then further developed by Fischlin [4] and Zhang and Imai [11]. We present a new formalism of anonymous signature, where instead of the message, a part of the signature is withheld to maintain anonymity. We introduce the notion unpretendability to guarantee infeasibility for someone other than the correct signer to pretend authorship of the message and signature. Our definition retains applicability for all previous applications of the anonymous signature, provides stronger security, and is conceptually simpler. We give a generic construction from any ordinary signature scheme, and also show that the short signature scheme by Boneh and Boyen [2] can be naturally regarded as such a secure anonymous signature scheme according to our formalism.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Automated Motif Discovery from Glycan Array Data

    PubMed Central

    Cholleti, Sharath R.; Agravat, Sanjay; Morris, Tim; Saltz, Joel H.; Song, Xuezheng

    2012-01-01

    Abstract Assessing interactions of a glycan-binding protein (GBP) or lectin with glycans on a microarray generates large datasets, making it difficult to identify a glycan structural motif or determinant associated with the highest apparent binding strength of the GBP. We have developed a computational method, termed GlycanMotifMiner, that uses the relative binding of a GBP with glycans within a glycan microarray to automatically reveal the glycan structural motifs recognized by a GBP. We implemented the software with a web-based graphical interface for users to explore and visualize the discovered motifs. The utility of GlycanMotifMiner was determined using five plant lectins, SNA, HPA, PNA, Con A, and UEA-I. Data from the analyses of the lectins at different protein concentrations were processed to rank the glycans based on their relative binding strengths. The motifs, defined as glycan substructures that exist in a large number of the bound glycans and few non-bound glycans, were then discovered by our algorithm and displayed in a web-based graphical user interface (http://glycanmotifminer.emory.edu). The information is used in defining the glycan-binding specificity of GBPs. The results were compared to the known glycan specificities of these lectins generated by manual methods. A more complex analysis was also carried out using glycan microarray data obtained for a recombinant form of human galectin-8. Results for all of these lectins show that GlycanMotifMiner identified the major motifs known in the literature along with some unexpected novel binding motifs. PMID:22877213

  17. Automated motif discovery from glycan array data.

    PubMed

    Cholleti, Sharath R; Agravat, Sanjay; Morris, Tim; Saltz, Joel H; Song, Xuezheng; Cummings, Richard D; Smith, David F

    2012-10-01

    Assessing interactions of a glycan-binding protein (GBP) or lectin with glycans on a microarray generates large datasets, making it difficult to identify a glycan structural motif or determinant associated with the highest apparent binding strength of the GBP. We have developed a computational method, termed GlycanMotifMiner, that uses the relative binding of a GBP with glycans within a glycan microarray to automatically reveal the glycan structural motifs recognized by a GBP. We implemented the software with a web-based graphical interface for users to explore and visualize the discovered motifs. The utility of GlycanMotifMiner was determined using five plant lectins, SNA, HPA, PNA, Con A, and UEA-I. Data from the analyses of the lectins at different protein concentrations were processed to rank the glycans based on their relative binding strengths. The motifs, defined as glycan substructures that exist in a large number of the bound glycans and few non-bound glycans, were then discovered by our algorithm and displayed in a web-based graphical user interface ( http://glycanmotifminer.emory.edu ). The information is used in defining the glycan-binding specificity of GBPs. The results were compared to the known glycan specificities of these lectins generated by manual methods. A more complex analysis was also carried out using glycan microarray data obtained for a recombinant form of human galectin-8. Results for all of these lectins show that GlycanMotifMiner identified the major motifs known in the literature along with some unexpected novel binding motifs. PMID:22877213

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

    PubMed Central

    Diwan, Gaurav D; Agashe, Deepa

    2016-01-01

    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. PMID:27189998

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

    PubMed

    Diwan, Gaurav D; Agashe, Deepa

    2016-01-01

    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. PMID:27189998

  20. 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. PMID:22156162

  1. CodingMotif: exact determination of overrepresented nucleotide motifs in coding sequences

    PubMed Central

    2012-01-01

    Background It has been increasingly appreciated that coding sequences harbor regulatory sequence motifs in addition to encoding for protein. These sequence motifs are expected to be overrepresented in nucleotide sequences bound by a common protein or small RNA. However, detecting overrepresented motifs has been difficult because of interference by constraints at the protein level. Sampling-based approaches to solve this problem based on codon-shuffling have been limited to exploring only an infinitesimal fraction of the sequence space and by their use of parametric approximations. Results We present a novel O(N(log N)2)-time algorithm, CodingMotif, to identify nucleotide-level motifs of unusual copy number in protein-coding regions. Using a new dynamic programming algorithm we are able to exhaustively calculate the distribution of the number of occurrences of a motif over all possible coding sequences that encode the same amino acid sequence, given a background model for codon usage and dinucleotide biases. Our method takes advantage of the sparseness of loci where a given motif can occur, greatly speeding up the required convolution calculations. Knowledge of the distribution allows one to assess the exact non-parametric p-value of whether a given motif is over- or under- represented. We demonstrate that our method identifies known functional motifs more accurately than sampling and parametric-based approaches in a variety of coding datasets of various size, including ChIP-seq data for the transcription factors NRSF and GABP. Conclusions CodingMotif provides a theoretically and empirically-demonstrated advance for the detection of motifs overrepresented in coding sequences. We expect CodingMotif to be useful for identifying motifs in functional genomic datasets such as DNA-protein binding, RNA-protein binding, or microRNA-RNA binding within coding regions. A software implementation is available at http://bioinformatics.bc.edu/chuanglab/codingmotif.tar PMID

  2. 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

  3. 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.

  4. Uncertainty in hydrological signatures

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    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, including 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.

  5. MotifMiner: A Table Driven Greedy Algorithm for DNA Motif Mining

    NASA Astrophysics Data System (ADS)

    Seeja, K. R.; Alam, M. A.; Jain, S. K.

    DNA motif discovery is a much explored problem in functional genomics. This paper describes a table driven greedy algorithm for discovering regulatory motifs in the promoter sequences of co-expressed genes. The proposed algorithm searches both DNA strands for the common patterns or motifs. The inputs to the algorithm are set of promoter sequences, the motif length and minimum Information Content. The algorithm generates subsequences of given length from the shortest input promoter sequence. It stores these subsequences and their reverse complements in a table. Then it searches the remaining sequences for good matches of these subsequences. The Information Content score is used to measure the goodness of the motifs. The algorithm has been tested with synthetic data and real data. The results are found promising. The algorithm could discover meaningful motifs from the muscle specific regulatory sequences.

  6. DNA Motif Databases and Their Uses.

    PubMed

    Stormo, Gary D

    2015-01-01

    Transcription factors (TFs) recognize and bind to specific DNA sequences. The specificity of a TF is usually represented as a position weight matrix (PWM). Several databases of DNA motifs exist and are used in biological research to address important biological questions. This overview describes PWMs and some of the most commonly used motif databases, as well as a few of their common applications. PMID:26334922

  7. Sephardic signature in haplogroup T mitochondrial DNA

    PubMed Central

    Bedford, Felice L

    2012-01-01

    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. PMID:22108605

  8. Basic OSF/Motif programming and applications

    SciTech Connect

    Brooks, D. ); Novak, B. )

    1992-09-15

    When users refer to Motif, they are usually talking about mwm, the window manager. However, when programmers mention Motif they are usually discussing the programming toolkit. This toolkit is used to develop new or modify existing applications. In this presentation, the term Motif will refer to the toolkit. Motif comes with a number of features that help users effectively use the applications built with it. The term look and feel may be overused; nonetheless, a consistent and well designed look and feel assists the user in Teaming and using new applications. The term point and click generally refers to using a mouse to select program commands. While Motif supports point and click, the toolkit also supports using the keyboard as a substitute for many operations. This gives a good typist a distinct advantage when using a familiar application. We will give an overview of the toolkit, touching on the user interface features and general programming considerations. Since the source code for many useful Motif programs is readily available, we will explain how to get these sources and touch on derived benefits. We win also point to other sources of on-line help and documentation. Finally, we will present some practical experiences developing applications.

  9. Detecting seeded motifs in DNA sequences.

    PubMed

    Pizzi, Cinzia; Bortoluzzi, Stefania; Bisognin, Andrea; Coppe, Alessandro; Danieli, Gian Antonio

    2005-01-01

    The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, composed by regions with a different extent of variability. The method is based on a multi-step approach, which was implemented in a motif searching web tool (MOST). Overrepresented exact patterns are extracted from input sequences and clustered to produce motifs core regions, which are then extended and scored to generate seeded motifs. The combination of automated pattern discovery algorithms and different display tools for the evaluation and selection of results at several analysis steps can potentially lead to much more meaningful results than complete automation can produce. Experimental results on different yeast and human real datasets proved the methodology to be a promising solution for finding seeded motifs. MOST web tool is freely available at http://telethon.bio.unipd.it/bioinfo/MOST. PMID:16141193

  10. Detecting seeded motifs in DNA sequences

    PubMed Central

    Pizzi, Cinzia; Bortoluzzi, Stefania; Bisognin, Andrea; Coppe, Alessandro; Danieli, Gian Antonio

    2005-01-01

    The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, composed by regions with a different extent of variability. The method is based on a multi-step approach, which was implemented in a motif searching web tool (MOST). Overrepresented exact patterns are extracted from input sequences and clustered to produce motifs core regions, which are then extended and scored to generate seeded motifs. The combination of automated pattern discovery algorithms and different display tools for the evaluation and selection of results at several analysis steps can potentially lead to much more meaningful results than complete automation can produce. Experimental results on different yeast and human real datasets proved the methodology to be a promising solution for finding seeded motifs. MOST web tool is freely available at . PMID:16141193

  11. Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets

    PubMed Central

    2012-01-01

    Background To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. Results We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. Conclusions SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery

  12. 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…

  13. SVM2Motif--Reconstructing Overlapping DNA Sequence Motifs by Mimicking an SVM Predictor.

    PubMed

    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

  14. Traceable Ring Signature

    NASA Astrophysics Data System (ADS)

    Fujisaki, Eiichiro; Suzuki, Koutarou

    The ring signature allows a signer to leak secrets anonymously, without the risk of identity escrow. At the same time, the ring signature provides great flexibility: No group manager, no special setup, and the dynamics of group choice. The ring signature is, however, vulnerable to malicious or irresponsible signers in some applications, because of its anonymity. In this paper, we propose a traceable ring signature scheme. A traceable ring scheme is a ring signature except that it can restrict “excessive” anonymity. The traceable ring signature has a tag that consists of a list of ring members and an issue that refers to, for instance, a social affair or an election. A ring member can make any signed but anonymous opinion regarding the issue, but only once (per tag). If the member submits another signed opinion, possibly pretending to be another person who supports the first opinion, the identity of the member is immediately revealed. If the member submits the same opinion, for instance, voting “yes” regarding the same issue twice, everyone can see that these two are linked. The traceable ring signature can suit to many applications, such as an anonymous voting on a BBS. We formalize the security definitions for this primitive and show an efficient and simple construction in the random oracle model.

  15. 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

  16. 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).

  17. Signature extension studies

    NASA Technical Reports Server (NTRS)

    Vincent, R. K.; Thomas, G. S.; Nalepka, R. F.

    1974-01-01

    The importance of specific spectral regions to signature extension is explored. In the recent past, the signature extension task was focused on the development of new techniques. Tested techniques are now used to investigate this spectral aspect of the large area survey. Sets of channels were sought which, for a given technique, were the least affected by several sources of variation over four data sets and yet provided good object class separation on each individual data set. Using sets of channels determined as part of this study, signature extension was accomplished between data sets collected over a six-day period and over a range of about 400 kilometers.

  18. MEME Suite: tools for motif discovery and searching

    PubMed Central

    Bailey, Timothy L.; Boden, Mikael; Buske, Fabian A.; Frith, Martin; Grant, Charles E.; Clementi, Luca; Ren, Jingyuan; Li, Wilfred W.; Noble, William S.

    2009-01-01

    The MEME Suite web server provides a unified portal for online discovery and analysis of sequence motifs representing features such as DNA binding sites and protein interaction domains. The popular MEME motif discovery algorithm is now complemented by the GLAM2 algorithm which allows discovery of motifs containing gaps. Three sequence scanning algorithms—MAST, FIMO and GLAM2SCAN—allow scanning numerous DNA and protein sequence databases for motifs discovered by MEME and GLAM2. Transcription factor motifs (including those discovered using MEME) can be compared with motifs in many popular motif databases using the motif database scanning algorithm Tomtom. Transcription factor motifs can be further analyzed for putative function by association with Gene Ontology (GO) terms using the motif-GO term association tool GOMO. MEME output now contains sequence LOGOS for each discovered motif, as well as buttons to allow motifs to be conveniently submitted to the sequence and motif database scanning algorithms (MAST, FIMO and Tomtom), or to GOMO, for further analysis. GLAM2 output similarly contains buttons for further analysis using GLAM2SCAN and for rerunning GLAM2 with different parameters. All of the motif-based tools are now implemented as web services via Opal. Source code, binaries and a web server are freely available for noncommercial use at http://meme.nbcr.net. PMID:19458158

  19. 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.

  20. 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…

  1. 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.

  2. Accumulation of extracellular proteins bearing unique proline-rich motifs in intercellular spaces of the legume nodule parenchyma.

    PubMed

    Sherrier, D J; Taylor, G S; Silverstein, K A T; Gonzales, M B; VandenBosch, K A

    2005-04-01

    Nodulins encoding repetitive proline-rich cell wall proteins (PRPs) are induced during early interactions with rhizobia, suggesting a massive restructuring of the plant extracellular matrix during infection and nodulation. However, the proteins corresponding to these gene products have not been isolated or characterized, nor have cell wall localizations been confirmed. Posttranslational modifications, conformation, and interactions with other wall polymers are difficult to predict on the basis of only the deduced amino acid sequence of PRPs. PsENOD2 is expressed in nodule parenchyma tissue during nodule organogenesis and encodes a protein with distinctive PRP motifs that are rich in glutamate and basic amino acids. A database search for the ENOD2 signature motifs indicates that similar proteins may have a limited phylogenetic distribution, as they are presently only known from legumes. To determine the ultrastructural location of the proteins, antibodies were raised against unique motifs from the predicted ENOD2 sequence. The antibodies recognized nodule-specific proteins in pea (Pisum sativum), with a major band detected at 110 kDa, representing a subset of PRPs from nodules. The protein was detected specifically in organelles of the secretory pathway and intercellular spaces in the nodule parenchyma, but it was not abundant in primary walls. Similar proteins with an analogous distribution were detected in soybean (Glycine max). The use of polyclonal antibodies raised against signature motifs of extracellular matrix proteins thus appears to be an effective strategy to identify and isolate specific structural proteins for functional analysis. PMID:15868212

  3. 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

  4. UV signature mutations.

    PubMed

    Brash, Douglas E

    2015-01-01

    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 nontranscribed 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; UV's nonsignature mutations may cause melanoma BRAF mutations; and the mutagen for sunlight-related skin neoplasms may vary between continents. PMID:25354245

  5. DNA motif elucidation using belief propagation.

    PubMed

    Wong, Ka-Chun; Chan, Tak-Ming; Peng, Chengbin; Li, Yue; Zhang, Zhaolei

    2013-09-01

    Protein-binding microarray (PBM) is a high-throughout platform that can measure the DNA-binding preference of a protein in a comprehensive and unbiased manner. A typical PBM experiment can measure binding signal intensities of a protein to all the possible DNA k-mers (k=8∼10); such comprehensive binding affinity data usually need to be reduced and represented as motif models before they can be further analyzed and applied. Since proteins can often bind to DNA in multiple modes, one of the major challenges is to decompose the comprehensive affinity data into multimodal motif representations. Here, we describe a new algorithm that uses Hidden Markov Models (HMMs) and can derive precise and multimodal motifs using belief propagations. We describe an HMM-based approach using belief propagations (kmerHMM), which accepts and preprocesses PBM probe raw data into median-binding intensities of individual k-mers. The k-mers are ranked and aligned for training an HMM as the underlying motif representation. Multiple motifs are then extracted from the HMM using belief propagations. Comparisons of kmerHMM with other leading methods on several data sets demonstrated its effectiveness and uniqueness. Especially, it achieved the best performance on more than half of the data sets. In addition, the multiple binding modes derived by kmerHMM are biologically meaningful and will be useful in interpreting other genome-wide data such as those generated from ChIP-seq. The executables and source codes are available at the authors' websites: e.g. http://www.cs.toronto.edu/∼wkc/kmerHMM. PMID:23814189

  6. The Molecular Evolution of the Qo Motif

    PubMed Central

    Kao, Wei-Chun; Hunte, Carola

    2014-01-01

    Quinol oxidation in the catalytic quinol oxidation site (Qo site) of cytochrome (cyt) bc1 complexes is the key step of the Q cycle mechanism, which laid the ground for Mitchell’s chemiosmotic theory of energy conversion. Bifurcated electron transfer upon quinol oxidation enables proton uptake and release on opposite membrane sides, thus generating a proton gradient that fuels ATP synthesis in cellular respiration and photosynthesis. The Qo site architecture formed by cyt b and Rieske iron–sulfur protein (ISP) impedes harmful bypass reactions. Catalytic importance is assigned to four residues of cyt b formerly described as PEWY motif in the context of mitochondrial complexes, which we now denominate Qo motif as comprehensive evolutionary sequence analysis of cyt b shows substantial natural variance of the motif with phylogenetically specific patterns. In particular, the Qo motif is identified as PEWY in mitochondria, α- and ε-Proteobacteria, Aquificae, Chlorobi, Cyanobacteria, and chloroplasts. PDWY is present in Gram-positive bacteria, Deinococcus–Thermus and haloarchaea, and PVWY in β- and γ-Proteobacteria. PPWF only exists in Archaea. Distinct patterns for acidophilic organisms indicate environment-specific adaptations. Importantly, the presence of PDWY and PEWY is correlated with the redox potential of Rieske ISP and quinone species. We propose that during evolution from low to high potential electron-transfer systems in the emerging oxygenic atmosphere, cyt bc1 complexes with PEWY as Qo motif prevailed to efficiently use high potential ubiquinone as substrate, whereas cyt b with PDWY operate best with low potential Rieske ISP and menaquinone, with the latter being the likely composition of the ancestral cyt bc1 complex. PMID:25115012

  7. 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.

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

    PubMed Central

    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. PMID:25431579

  9. 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. PMID:25431579

  10. 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.

  11. Ab Initio Coordination Chemistry for Nickel Chelation Motifs

    PubMed Central

    Jesu Jaya Sudan, R.; Lesitha Jeeva Kumari, J.; 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. PMID:25985439

  12. Motifs, modules and games in bacteria

    SciTech Connect

    Wolf, Denise M.; Arkin, Adam P.

    2003-04-01

    Global explorations of regulatory network dynamics, organization and evolution have become tractable thanks to high-throughput sequencing and molecular measurement of bacterial physiology. From these, a nascent conceptual framework is developing, that views the principles of regulation in term of motifs, modules and games. Motifs are small, repeated, and conserved biological units ranging from molecular domains to small reaction networks. They are arranged into functional modules, genetically dissectible cellular functions such as the cell cycle, or different stress responses. The dynamical functioning of modules defines the organism's strategy to survive in a game, pitting cell against cell, and cell against environment. Placing pathway structure and dynamics into an evolutionary context begins to allow discrimination between those physical and molecular features that particularize a species to its surroundings, and those that provide core physiological function. This approach promises to generate a higher level understanding of cellular design, pathway evolution and cellular bioengineering.

  13. A Basic Set of Homeostatic Controller Motifs

    PubMed Central

    Drengstig, T.; Jolma, I.W.; Ni, X.Y.; Thorsen, K.; Xu, X.M.; Ruoff, P.

    2012-01-01

    Adaptation and homeostasis are essential properties of all living systems. However, our knowledge about the reaction kinetic mechanisms leading to robust homeostatic behavior in the presence of environmental perturbations is still poor. Here, we describe, and provide physiological examples of, a set of two-component controller motifs that show robust homeostasis. This basic set of controller motifs, which can be considered as complete, divides into two operational work modes, termed as inflow and outflow control. We show how controller combinations within a cell can integrate uptake and metabolization of a homeostatic controlled species and how pathways can be activated and lead to the formation of alternative products, as observed, for example, in the change of fermentation products by microorganisms when the supply of the carbon source is altered. The antagonistic character of hormonal control systems can be understood by a combination of inflow and outflow controllers. PMID:23199928

  14. 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.

  15. 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

  16. Bioinformatics Approaches for Predicting Disordered Protein Motifs.

    PubMed

    Bhowmick, Pallab; Guharoy, Mainak; Tompa, Peter

    2015-01-01

    Short, linear motifs (SLiMs) in proteins are functional microdomains consisting of contiguous residue segments along the protein sequence, typically not more than 10 consecutive amino acids in length with less than 5 defined positions. Many positions are 'degenerate' thus offering flexibility in terms of the amino acid types allowed at those positions. Their short length and degenerate nature confers evolutionary plasticity meaning that SLiMs often evolve convergently. Further, SLiMs have a propensity to occur within intrinsically unstructured protein segments and this confers versatile functionality to unstructured regions of the proteome. SLiMs mediate multiple types of protein interactions based on domain-peptide recognition and guide functions including posttranslational modifications, subcellular localization of proteins, and ligand binding. SLiMs thus behave as modular interaction units that confer versatility to protein function and SLiM-mediated interactions are increasingly being recognized as therapeutic targets. In this chapter we start with a brief description about the properties of SLiMs and their interactions and then move on to discuss algorithms and tools including several web-based methods that enable the discovery of novel SLiMs (de novo motif discovery) as well as the prediction of novel occurrences of known SLiMs. Both individual amino acid sequences as well as sets of protein sequences can be scanned using these methods to obtain statistically overrepresented sequence patterns. Lists of putatively functional SLiMs are then assembled based on parameters such as evolutionary sequence conservation, disorder scores, structural data, gene ontology terms and other contextual information that helps to assess the functional credibility or significance of these motifs. These bioinformatics methods should certainly guide experiments aimed at motif discovery. PMID:26387106

  17. Analyzing network reliability using structural motifs

    NASA Astrophysics Data System (ADS)

    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.

  18. [Conserved motifs in voltage sensing proteins].

    PubMed

    Wang, Chang-He; Xie, Zhen-Li; Lv, Jian-Wei; Yu, Zhi-Dan; Shao, Shu-Li

    2012-08-25

    This paper was aimed to study conserved motifs of voltage sensing proteins (VSPs) and establish a voltage sensing model. All VSPs were collected from the Uniprot database using a comprehensive keyword search followed by manual curation, and the results indicated that there are only two types of known VSPs, voltage gated ion channels and voltage dependent phosphatases. All the VSPs have a common domain of four helical transmembrane segments (TMS, S1-S4), which constitute the voltage sensing module of the VSPs. The S1 segment was shown to be responsible for membrane targeting and insertion of these proteins, while S2-S4 segments, which can sense membrane potential, for protein properties. Conserved motifs/residues and their functional significance of each TMS were identified using profile-to-profile sequence alignments. Conserved motifs in these four segments are strikingly similar for all VSPs, especially, the conserved motif [RK]-X(2)-R-X(2)-R-X(2)-[RK] was presented in all the S4 segments, with positively charged arginine (R) alternating with two hydrophobic or uncharged residues. Movement of these arginines across the membrane electric field is the core mechanism by which the VSPs detect changes in membrane potential. The negatively charged aspartate (D) in the S3 segment is universally conserved in all the VSPs, suggesting that the aspartate residue may be involved in voltage sensing properties of VSPs as well as the electrostatic interactions with the positively charged residues in the S4 segment, which may enhance the thermodynamic stability of the S4 segments in plasma membrane. PMID:22907298

  19. 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.

  20. Uncertainty in hydrological signatures

    NASA Astrophysics Data System (ADS)

    McMillan, Hilary; Westerberg, Ida

    2015-04-01

    Information that summarises the hydrological behaviour or flow regime of a catchment is essential for comparing responses of different catchments to understand catchment organisation and similarity, and for many other modelling and water-management applications. Such information types derived as an index value from observed data are known as hydrological signatures, and can include descriptors of high flows (e.g. mean annual flood), low flows (e.g. mean annual low flow, recession shape), the flow variability, flow duration curve, and runoff ratio. Because the hydrological signatures are calculated from observed data such as rainfall and flow records, they are affected by uncertainty in those data. Subjective choices in the method used to calculate the signatures create a further source of uncertainty. Uncertainties in the signatures may affect our ability to compare different locations, to detect changes, or to compare future water resource management scenarios. The aim of this study was to contribute to the hydrological community's awareness and knowledge of data uncertainty in hydrological signatures, including typical sources, magnitude and methods for its assessment. We proposed a generally applicable method to calculate these uncertainties based on Monte Carlo sampling and demonstrated it for a variety of commonly used signatures. The study was made for two data rich catchments, the 50 km2 Mahurangi catchment in New Zealand and the 135 km2 Brue catchment in the UK. For rainfall data the uncertainty sources included point measurement uncertainty, the number of gauges used in calculation of the catchment spatial average, and uncertainties relating to lack of quality control. For flow data the uncertainty sources included uncertainties in stage/discharge measurement and in the approximation of the true stage-discharge relation by a rating curve. The resulting uncertainties were compared across the different signatures and catchments, to quantify uncertainty

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:12614545

  5. ET-Motif: Solving the Exact (l, d)-Planted Motif Problem Using Error Tree Structure.

    PubMed

    Al-Okaily, Anas; Huang, Chun-Hsi

    2016-07-01

    Motif finding is an important and a challenging problem in many biological applications such as discovering promoters, enhancers, locus control regions, transcription factors, and more. The (l, d)-planted motif search, PMS, is one of several variations of the problem. In this problem, there are n given sequences over alphabets of size [Formula: see text], each of length m, and two given integers l and d. The problem is to find a motif m of length l, where in each sequence there is at least an l-mer at a Hamming distance of [Formula: see text] of m. In this article, we propose ET-Motif, an algorithm that can solve the PMS problem in [Formula: see text] time and [Formula: see text] space. The time bound can be further reduced by a factor of m with [Formula: see text] space. In case the suffix tree that is built for the input sequences is balanced, the problem can be solved in [Formula: see text] time and [Formula: see text] space. Similarly, the time bound can be reduced by a factor of m using [Formula: see text] space. Moreover, the variations of the problem, namely the edit distance PMS and edited PMS (Quorum), can be solved using ET-Motif with simple modifications but upper bands of space and time. For edit distance PMS, the time and space bounds will be increased by [Formula: see text], while for edited PMS the increase will be of [Formula: see text] in the time bound. PMID:27152692

  6. Suppression of TLR9 Immunostimulatory Motifs in the Genome of a Gammaherpesvirus

    PubMed Central

    Pezda, Andrea C.; Penn, Alex; Barton, Gregory M.; Coscoy, Laurent

    2013-01-01

    Multiple receptors within the innate immune system have evolved to recognize nucleic acids as signatures of viral infection. It is believed that this specificity is essential for viral detection, as viruses often lack other invariant features that can serve as suitable targets for innate receptors. One such innate receptor, TLR9, has been implicated in the detection of many dsDNA viruses. In this study, we investigate the detection of murine gammaherpesvirus 68 (MHV68) by TLR9. We find that the genomic DNA of the murine CMV, a very potent inducer of innate responses. Genome-wide analysis of the number of stimulatory versus nonstimulatory CpG motifs present in the genome of each virus reveals that the MHV68 genome contains only a fraction of the number of immunostimulatory motifs present in murine CMV. Notably, MHV68 appears to have selectively suppressed the number of stimulatory motifs through cytosine to thymine conversion. These data suggest that certain viruses may have evolved and modified their genomic content to avoid recognition by nucleic acid-sensing receptors of the innate immune system. PMID:21666062

  7. Motif module map reveals enforcement of aging by continual NF-κB activity

    PubMed Central

    Adler, Adam S.; Sinha, Saurabh; Kawahara, Tiara L.A.; Zhang, Jennifer Y.; Segal, Eran; Chang, Howard Y.

    2007-01-01

    Aging is characterized by specific alterations in gene expression, but their underlying mechanisms and functional consequences are not well understood. Here we develop a systematic approach to identify combinatorial cis-regulatory motifs that drive age-dependent gene expression across different tissues and organisms. Integrated analysis of 365 microarrays spanning nine tissue types predicted fourteen motifs as major regulators of age-dependent gene expression in human and mouse. The motif most strongly associated with aging was that of the transcription factor NF-κB. Inducible genetic blockade of NF-κB for 2 wk in the epidermis of chronologically aged mice reverted the tissue characteristics and global gene expression programs to those of young mice. Age-specific NF-κB blockade and orthogonal cell cycle interventions revealed that NF-κB controls cell cycle exit and gene expression signature of aging in parallel but not sequential pathways. These results identify a conserved network of regulatory pathways underlying mammalian aging and show that NF-κB is continually required to enforce many features of aging in a tissue-specific manner. PMID:18055696

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

    PubMed

    Zhang, Shaoqiang; 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. 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

  11. 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…

  12. The RNA 3D Motif Atlas: Computational methods for extraction, organization and evaluation of RNA motifs.

    PubMed

    Parlea, Lorena G; Sweeney, Blake A; Hosseini-Asanjan, Maryam; Zirbel, Craig L; Leontis, Neocles B

    2016-07-01

    RNA 3D motifs occupy places in structured RNA molecules that correspond to the hairpin, internal and multi-helix junction "loops" of their secondary structure representations. As many as 40% of the nucleotides of an RNA molecule can belong to these structural elements, which are distinct from the regular double helical regions formed by contiguous AU, GC, and GU Watson-Crick basepairs. With the large number of atomic- or near atomic-resolution 3D structures appearing in a steady stream in the PDB/NDB structure databases, the automated identification, extraction, comparison, clustering and visualization of these structural elements presents an opportunity to enhance RNA science. Three broad applications are: (1) identification of modular, autonomous structural units for RNA nanotechnology, nanobiology and synthetic biology applications; (2) bioinformatic analysis to improve RNA 3D structure prediction from sequence; and (3) creation of searchable databases for exploring the binding specificities, structural flexibility, and dynamics of these RNA elements. In this contribution, we review methods developed for computational extraction of hairpin and internal loop motifs from a non-redundant set of high-quality RNA 3D structures. We provide a statistical summary of the extracted hairpin and internal loop motifs in the most recent version of the RNA 3D Motif Atlas. We also explore the reliability and accuracy of the extraction process by examining its performance in clustering recurrent motifs from homologous ribosomal RNA (rRNA) structures. We conclude with a summary of remaining challenges, especially with regard to extraction of multi-helix junction motifs. PMID:27125735

  13. Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain.

    PubMed

    Mo, Alisa; Mukamel, Eran A; Davis, Fred P; Luo, Chongyuan; Henry, Gilbert L; Picard, Serge; Urich, Mark A; Nery, Joseph R; Sejnowski, Terrence J; Lister, Ryan; Eddy, Sean R; Ecker, Joseph R; Nathans, Jeremy

    2015-06-17

    Neuronal diversity is essential for mammalian brain function but poses a challenge to molecular profiling. To address the need for tools that facilitate cell-type-specific epigenomic studies, we developed the first affinity purification approach to isolate nuclei from genetically defined cell types in a mammal. We combine this technique with next-generation sequencing to show that three subtypes of neocortical neurons have highly distinctive epigenomic landscapes. Over 200,000 regions differ in chromatin accessibility and DNA methylation signatures characteristic of gene regulatory regions. By footprinting and motif analyses, these regions are predicted to bind distinct cohorts of neuron subtype-specific transcription factors. Neuronal epigenomes reflect both past and present gene expression, with DNA hyper-methylation at developmentally critical genes appearing as a novel epigenomic signature in mature neurons. Taken together, our findings link the functional and transcriptional complexity of neurons to their underlying epigenomic diversity. PMID:26087164

  14. Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain

    PubMed Central

    Mo, Alisa; Mukamel, Eran A.; Davis, Fred P.; Luo, Chongyuan; Henry, Gilbert L.; Picard, Serge; Urich, Mark A.; Nery, Joseph R.; Sejnowski, Terrence J.; Lister, Ryan; Eddy, Sean R.; Ecker, Joseph R.; Nathans, Jeremy

    2015-01-01

    SUMMARY Neuronal diversity is essential for mammalian brain function but poses a challenge to molecular profiling. To address the need for tools that facilitate cell-type-specific epigenomic studies, we developed the first affinity purification approach to isolate nuclei from genetically defined cell types in a mammal. We combine this technique with next-generation sequencing to show that three subtypes of neocortical neurons have highly distinctive epigenomic landscapes. Over 200,000 regions differ in chromatin accessibility and DNA methylation signatures characteristic of gene regulatory regions. By footprinting and motif analyses, these regions are predicted to bind distinct cohorts of neuron subtype-specific transcription factors. Neuronal epigenomes reflect both past and present gene expression, with DNA hyper-methylation at developmentally critical genes appearing as a novel epigenomic signature in mature neurons. Taken together, our findings link the functional and transcriptional complexity of neurons to their underlying epigenomic diversity. PMID:26087164

  15. 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. PMID:25983553

  16. Cross-Disciplinary Detection and Analysis of Network Motifs

    PubMed Central

    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. PMID:25983553

  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. RMOD: a tool for regulatory motif detection in signaling network.

    PubMed

    Kim, Jinki; Yi, Gwan-Su

    2013-01-01

    Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod. PMID:23874612

  19. 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.

  20. Structural motifs of pre-nucleation clusters.

    PubMed

    Zhang, Y; Türkmen, I R; Wassermann, B; Erko, A; Rühl, E

    2013-10-01

    Structural motifs of pre-nucleation clusters prepared in single, optically levitated supersaturated aqueous aerosol microparticles containing CaBr2 as a model system are reported. Cluster formation is identified by means of X-ray absorption in the Br K-edge regime. The salt concentration beyond the saturation point is varied by controlling the humidity in the ambient atmosphere surrounding the 15-30 μm microdroplets. This leads to the formation of metastable supersaturated liquid particles. Distinct spectral shifts in near-edge spectra as a function of salt concentration are observed, in which the energy position of the Br K-edge is red-shifted by up to 7.1 ± 0.4 eV if the dilute solution is compared to the solid. The K-edge positions of supersaturated solutions are found between these limits. The changes in electronic structure are rationalized in terms of the formation of pre-nucleation clusters. This assumption is verified by spectral simulations using first-principle density functional theory and molecular dynamics calculations, in which structural motifs are considered, explaining the experimental results. These consist of solvated CaBr2 moieties, rather than building blocks forming calcium bromide hexahydrates, the crystal system that is formed by drying aqueous CaBr2 solutions. PMID:24116574

  1. 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.

  2. A Gibbs sampler for motif detection in phylogenetically close sequences

    NASA Astrophysics Data System (ADS)

    Siddharthan, Rahul; van Nimwegen, Erik; Siggia, Eric

    2004-03-01

    Genes are regulated by transcription factors that bind to DNA upstream of genes and recognize short conserved ``motifs'' in a random intergenic ``background''. Motif-finders such as the Gibbs sampler compare the probability of these short sequences being represented by ``weight matrices'' to the probability of their arising from the background ``null model'', and explore this space (analogous to a free-energy landscape). But closely related species may show conservation not because of functional sites but simply because they have not had sufficient time to diverge, so conventional methods will fail. We introduce a new Gibbs sampler algorithm that accounts for common ancestry when searching for motifs, while requiring minimal ``prior'' assumptions on the number and types of motifs, assessing the significance of detected motifs by ``tracking'' clusters that stay together. We apply this scheme to motif detection in sporulation-cycle genes in the yeast S. cerevisiae, using recent sequences of other closely-related Saccharomyces species.

  3. 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.

  4. AptaTRACE Elucidates RNA Sequence-Structure Motifs from Selection Trends in HT-SELEX Experiments.

    PubMed

    Dao, Phuong; Hoinka, Jan; Takahashi, Mayumi; Zhou, Jiehua; Ho, Michelle; Wang, Yijie; Costa, Fabrizio; Rossi, John J; Backofen, Rolf; Burnett, John; Przytycka, Teresa M

    2016-07-01

    Aptamers, short RNA or DNA molecules that bind distinct targets with high affinity and specificity, can be identified using high-throughput systematic evolution of ligands by exponential enrichment (HT-SELEX), but scalable analytic tools for understanding sequence-function relationships from diverse HT-SELEX data are not available. Here we present AptaTRACE, a computational approach that leverages the experimental design of the HT-SELEX protocol, RNA secondary structure, and the potential presence of many secondary motifs to identify sequence-structure motifs that show a signature of selection. We apply AptaTRACE to identify nine motifs in C-C chemokine receptor type 7 targeted by aptamers in an in vitro cell-SELEX experiment. We experimentally validate two aptamers whose binding required both sequence and structural features. AptaTRACE can identify low-abundance motifs, and we show through simulations that, because of this, it could lower HT-SELEX cost and time by reducing the number of selection cycles required. PMID:27467247

  5. Ballast: A Ball-based Algorithm for Structural Motifs

    PubMed Central

    He, Lu; Vandin, Fabio; Pandurangan, Gopal

    2013-01-01

    Abstract Structural motifs encapsulate local sequence-structure-function relationships characteristic of related proteins, enabling the prediction of functional characteristics of new proteins, providing molecular-level insights into how those functions are performed, and supporting the development of variants specifically maintaining or perturbing function in concert with other properties. Numerous computational methods have been developed to search through databases of structures for instances of specified motifs. However, it remains an open problem how best to leverage the local geometric and chemical constraints underlying structural motifs in order to develop motif-finding algorithms that are both theoretically and practically efficient. We present a simple, general, efficient approach, called Ballast (ball-based algorithm for structural motifs), to match given structural motifs to given structures. Ballast combines the best properties of previously developed methods, exploiting the composition and local geometry of a structural motif and its possible instances in order to effectively filter candidate matches. We show that on a wide range of motif-matching problems, Ballast efficiently and effectively finds good matches, and we provide theoretical insights into why it works well. By supporting generic measures of compositional and geometric similarity, Ballast provides a powerful substrate for the development of motif-matching algorithms. PMID:23383999

  6. 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

  7. 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

  8. Invisible RNA state dynamically couples distant motifs

    PubMed Central

    Lee, Janghyun; Dethoff, Elizabeth A.; Al-Hashimi, Hashim M.

    2014-01-01

    Using on- and off-resonance carbon and nitrogen R1ρ NMR relaxation dispersion in concert with mutagenesis and NMR chemical shift fingerprinting, we show that the transactivation response element RNA from the HIV-1 exists in dynamic equilibrium with a transient state that has a lifetime of ∼2 ms and population of ∼0.4%, which simultaneously remodels the structure of a bulge, stem, and apical loop. This is accomplished by a global change in strand register, in which bulge residues pair up with residues in the upper stem, causing a reshuffling of base pairs that propagates to the tip of apical loop, resulting in the creation of three noncanonical base pairs. Our results show that transient states can remodel distant RNA motifs and possibly give rise to mechanisms for rapid long-range communication in RNA that can be harnessed in processes such as cooperative folding and ribonucleoprotein assembly. PMID:24979799

  9. 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.

  10. Signatures of nonthermal melting.

    PubMed

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

    2015-09-01

    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

  11. Signature CERN-URSS

    ScienceCinema

    None

    2011-04-25

    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.

  12. 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

  13. Encoded Expansion: An Efficient Algorithm to Discover Identical String Motifs

    PubMed Central

    Azmi, Aqil M.; Al-Ssulami, Abdulrakeeb

    2014-01-01

    A major task in computational biology is the discovery of short recurring string patterns known as motifs. Most of the schemes to discover motifs are either stochastic or combinatorial in nature. Stochastic approaches do not guarantee finding the correct motifs, while the combinatorial schemes tend to have an exponential time complexity with respect to motif length. To alleviate the cost, the combinatorial approach exploits dynamic data structures such as trees or graphs. Recently (Karci (2009) Efficient automatic exact motif discovery algorithms for biological sequences, Expert Systems with Applications 36:7952–7963) devised a deterministic algorithm that finds all the identical copies of string motifs of all sizes in theoretical time complexity of and a space complexity of where is the length of the input sequence and is the length of the longest possible string motif. In this paper, we present a significant improvement on Karci's original algorithm. The algorithm that we propose reports all identical string motifs of sizes that occur at least times. Our algorithm starts with string motifs of size 2, and at each iteration it expands the candidate string motifs by one symbol throwing out those that occur less than times in the entire input sequence. We use a simple array and data encoding to achieve theoretical worst-case time complexity of and a space complexity of Encoding of the substrings can speed up the process of comparison between string motifs. Experimental results on random and real biological sequences confirm that our algorithm has indeed a linear time complexity and it is more scalable in terms of sequence length than the existing algorithms. PMID:24871320

  14. 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

  15. 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.

  16. Clustering signatures classify directed networks

    NASA Astrophysics Data System (ADS)

    Ahnert, S. E.; Fink, T. M. A.

    2008-09-01

    We use a clustering signature, based on a recently introduced generalization of the clustering coefficient to directed networks, to analyze 16 directed real-world networks of five different types: social networks, genetic transcription networks, word adjacency networks, food webs, and electric circuits. We show that these five classes of networks are cleanly separated in the space of clustering signatures due to the statistical properties of their local neighborhoods, demonstrating the usefulness of clustering signatures as a classifier of directed networks.

  17. Differences in local genomic context of bound and unbound motifs

    PubMed Central

    Hansen, Loren; Mariño-Ramírez, Leonardo; Landsman, David

    2012-01-01

    Understanding gene regulation is a major objective in molecular biology research. Frequently, transcription is driven by transcription factors (TFs) that bind to specific DNA sequences. These motifs are usually short and degenerate, rendering the likelihood of multiple copies occurring throughout the genome due to random chance as high. Despite this, TFs only bind to a small subset of sites, thus prompting our investigation into the differences between motifs that are bound by TFs and those that remain unbound. Here we constructed vectors representing various chromatin- and sequence-based features for a published set of bound and unbound motifs representing nine TFs in the budding yeast Saccharomyces cerevisiae. Using a machine learning approach, we identified a set of features that can be used to discriminate between bound and unbound motifs. We also discovered that some TFs bind most or all of their strong motifs in intergenic regions. Our data demonstrate that local sequence context can be strikingly different around motifs that are bound compared to motifs that are unbound. We concluded that there are multiple combinations of genomic features that characterize bound or unbound motifs. PMID:22692006

  18. ELM: the status of the 2010 eukaryotic linear motif resource

    PubMed Central

    Gould, Cathryn M.; Diella, Francesca; Via, Allegra; Puntervoll, Pål; Gemünd, Christine; Chabanis-Davidson, Sophie; Michael, Sushama; Sayadi, Ahmed; Bryne, Jan Christian; Chica, Claudia; Seiler, Markus; Davey, Norman E.; Haslam, Niall; Weatheritt, Robert J.; Budd, Aidan; Hughes, Tim; Paś, Jakub; Rychlewski, Leszek; Travé, Gilles; Aasland, Rein; Helmer-Citterich, Manuela; Linding, Rune; Gibson, Toby J.

    2010-01-01

    Linear motifs are short segments of multidomain proteins that provide regulatory functions independently of protein tertiary structure. Much of intracellular signalling passes through protein modifications at linear motifs. Many thousands of linear motif instances, most notably phosphorylation sites, have now been reported. Although clearly very abundant, linear motifs are difficult to predict de novo in protein sequences due to the difficulty of obtaining robust statistical assessments. The ELM resource at http://elm.eu.org/ provides an expanding knowledge base, currently covering 146 known motifs, with annotation that includes >1300 experimentally reported instances. ELM is also an exploratory tool for suggesting new candidates of known linear motifs in proteins of interest. Information about protein domains, protein structure and native disorder, cellular and taxonomic contexts is used to reduce or deprecate false positive matches. Results are graphically displayed in a ‘Bar Code’ format, which also displays known instances from homologous proteins through a novel ‘Instance Mapper’ protocol based on PHI-BLAST. ELM server output provides links to the ELM annotation as well as to a number of remote resources. Using the links, researchers can explore the motifs, proteins, complex structures and associated literature to evaluate whether candidate motifs might be worth experimental investigation. PMID:19920119

  19. Aztec, Incan and Mayan Motifs...Lead to Distinctive Designs.

    ERIC Educational Resources Information Center

    Shields, Joanne

    2001-01-01

    Describes an art project for seventh-grade students in which they choose motifs based on Incan, Aztec, and Mayan Indian materials to incorporate into two-dimensional designs. Explains that the activity objective is to create a unified, balanced and pleasing composition using a minimum of three motifs. (CMK)

  20. Identifying novel sequence variants of RNA 3D motifs

    PubMed Central

    Zirbel, Craig L.; Roll, James; Sweeney, Blake A.; Petrov, Anton I.; Pirrung, Meg; Leontis, Neocles B.

    2015-01-01

    Predicting RNA 3D structure from sequence is a major challenge in biophysics. An important sub-goal is accurately identifying recurrent 3D motifs from RNA internal and hairpin loop sequences extracted from secondary structure (2D) diagrams. We have developed and validated new probabilistic models for 3D motif sequences based on hybrid Stochastic Context-Free Grammars and Markov Random Fields (SCFG/MRF). The SCFG/MRF models are constructed using atomic-resolution RNA 3D structures. To parameterize each model, we use all instances of each motif found in the RNA 3D Motif Atlas and annotations of pairwise nucleotide interactions generated by the FR3D software. Isostericity relations between non-Watson–Crick basepairs are used in scoring sequence variants. SCFG techniques model nested pairs and insertions, while MRF ideas handle crossing interactions and base triples. We use test sets of randomly-generated sequences to set acceptance and rejection thresholds for each motif group and thus control the false positive rate. Validation was carried out by comparing results for four motif groups to RMDetect. The software developed for sequence scoring (JAR3D) is structured to automatically incorporate new motifs as they accumulate in the RNA 3D Motif Atlas when new structures are solved and is available free for download. PMID:26130723

  1. Stochastic EM-based TFBS motif discovery with MITSU

    PubMed Central

    Kilpatrick, Alastair M.; Ward, Bruce; Aitken, Stuart

    2014-01-01

    Motivation: The Expectation–Maximization (EM) algorithm has been successfully applied to the problem of transcription factor binding site (TFBS) motif discovery and underlies the most widely used motif discovery algorithms. In the wider field of probabilistic modelling, the stochastic EM (sEM) algorithm has been used to overcome some of the limitations of the EM algorithm; however, the application of sEM to motif discovery has not been fully explored. Results: We present MITSU (Motif discovery by ITerative Sampling and Updating), a novel algorithm for motif discovery, which combines sEM with an improved approximation to the likelihood function, which is unconstrained with regard to the distribution of motif occurrences within the input dataset. The algorithm is evaluated quantitatively on realistic synthetic data and several collections of characterized prokaryotic TFBS motifs and shown to outperform EM and an alternative sEM-based algorithm, particularly in terms of site-level positive predictive value. Availability and implementation: Java executable available for download at http://www.sourceforge.net/p/mitsu-motif/, supported on Linux/OS X. Contact: a.m.kilpatrick@sms.ed.ac.uk PMID:24931999

  2. Identifying novel sequence variants of RNA 3D motifs.

    PubMed

    Zirbel, Craig L; Roll, James; Sweeney, Blake A; Petrov, Anton I; Pirrung, Meg; Leontis, Neocles B

    2015-09-01

    Predicting RNA 3D structure from sequence is a major challenge in biophysics. An important sub-goal is accurately identifying recurrent 3D motifs from RNA internal and hairpin loop sequences extracted from secondary structure (2D) diagrams. We have developed and validated new probabilistic models for 3D motif sequences based on hybrid Stochastic Context-Free Grammars and Markov Random Fields (SCFG/MRF). The SCFG/MRF models are constructed using atomic-resolution RNA 3D structures. To parameterize each model, we use all instances of each motif found in the RNA 3D Motif Atlas and annotations of pairwise nucleotide interactions generated by the FR3D software. Isostericity relations between non-Watson-Crick basepairs are used in scoring sequence variants. SCFG techniques model nested pairs and insertions, while MRF ideas handle crossing interactions and base triples. We use test sets of randomly-generated sequences to set acceptance and rejection thresholds for each motif group and thus control the false positive rate. Validation was carried out by comparing results for four motif groups to RMDetect. The software developed for sequence scoring (JAR3D) is structured to automatically incorporate new motifs as they accumulate in the RNA 3D Motif Atlas when new structures are solved and is available free for download. PMID:26130723

  3. The phenomenon of astral motifs on late mediaeval tombstones

    NASA Astrophysics Data System (ADS)

    Mijatović, V.; Ninković, S.; Vemić, D.

    2003-10-01

    The authors study astral motifs present on some mediaeval tombstones found in present-day Serbia and Montenegro and in the neighbouring countries (especially in Bosnia and Herzegovina). The authors discern some important astral motifs, explain them and present a short review concerning their frequency.

  4. 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

  5. Role of GxxxG Motifs in Transmembrane Domain Interactions.

    PubMed

    Teese, Mark G; Langosch, Dieter

    2015-08-25

    Transmembrane (TM) helices of integral membrane proteins can facilitate strong and specific noncovalent protein-protein interactions. Mutagenesis and structural analyses have revealed numerous examples in which the interaction between TM helices of single-pass membrane proteins is dependent on a GxxxG or (small)xxx(small) motif. It is therefore tempting to use the presence of these simple motifs as an indicator of TM helix interactions. In this Current Topic review, we point out that these motifs are quite common, with more than 50% of single-pass TM domains containing a (small)xxx(small) motif. However, the actual interaction strength of motif-containing helices depends strongly on sequence context and membrane properties. In addition, recent studies have revealed several GxxxG-containing TM domains that interact via alternative interfaces involving hydrophobic, polar, aromatic, or even ionizable residues that do not form recognizable motifs. In multipass membrane proteins, GxxxG motifs can be important for protein folding, and not just oligomerization. Our current knowledge thus suggests that the presence of a GxxxG motif alone is a weak predictor of protein dimerization in the membrane. PMID:26244771

  6. 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.

  7. Guanine nucleotide dissociation inhibitor activity of the triple GoLoco motif protein G18: alanine-to-aspartate mutation restores function to an inactive second GoLoco motif.

    PubMed

    Kimple, Randall J; Willard, Francis S; Hains, Melinda D; Jones, Miller B; Nweke, Gift K; Siderovski, David P

    2004-03-15

    GoLoco ('Galpha(i/o)-Loco' interaction) motif proteins have recently been identified as novel GDIs (guanine nucleotide dissociation inhibitors) for heterotrimeric G-protein alpha subunits. G18 is a member of the mammalian GoLoco-motif gene family and was uncovered by analyses of human and mouse genomes for anonymous open-reading frames. The encoded G18 polypeptide is predicted to contain three 19-amino-acid GoLoco motifs, which have been shown in other proteins to bind Galpha subunits and inhibit spontaneous nucleotide release. However, the G18 protein has thus far not been characterized biochemically. Here, we have cloned and expressed the G18 protein and assessed its ability to act as a GDI. G18 is capable of simultaneously binding more than one Galpha(i1) subunit. In binding assays with the non-hydrolysable GTP analogue guanosine 5'-[gamma-thio]triphosphate, G18 exhibits GDI activity, slowing the exchange of GDP for GTP by Galpha(i1). Only the first and third GoLoco motifs within G18 are capable of interacting with Galpha subunits, and these bind with low micromolar affinity only to Galpha(i1) in the GDP-bound form, and not to Galpha(o), Galpha(q), Galpha(s) or Galpha12. Mutation of Ala-121 to aspartate in the inactive second GoLoco motif of G18, to restore the signature acidic-glutamine-arginine tripeptide that forms critical contacts with Galpha and its bound nucleotide [Kimple, Kimple, Betts, Sondek and Siderovski (2002) Nature (London) 416, 878-881], results in gain-of-function with respect to Galpha binding and GDI activity. PMID:14656218

  8. 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

  9. Signatures of Reputation

    NASA Astrophysics Data System (ADS)

    Bethencourt, John; Shi, Elaine; Song, Dawn

    Reputation systems have become an increasingly important tool for highlighting quality information and filtering spam within online forums. However, the dependence of a user's reputation on their history of activities seems to preclude any possibility of anonymity. We show that useful reputation information can, in fact, coexist with strong privacy guarantees. We introduce and formalize a novel cryptographic primitive we call signatures of reputation which supports monotonic measures of reputation in a completely anonymous setting. In our system, a user can express trust in others by voting for them, collect votes to build up her own reputation, and attach a proof of her reputation to any data she publishes, all while maintaining the unlinkability of her actions.

  10. Neural signatures of autism

    PubMed Central

    Kaiser, Martha D.; Hudac, Caitlin M.; Shultz, Sarah; Lee, Su Mei; Cheung, Celeste; Berken, Allison M.; Deen, Ben; Pitskel, Naomi B.; Sugrue, Daniel R.; Voos, Avery C.; Saulnier, Celine A.; Ventola, Pamela; Wolf, Julie M.; Klin, Ami; Vander Wyk, Brent C.; Pelphrey, Kevin A.

    2010-01-01

    Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system–level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism. PMID:21078973

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Identification and characterization of an hnRNP E1 translational silencing motif

    PubMed Central

    Brown, Andrew S.; Mohanty, Bidyut K.; Howe, Philip H.

    2016-01-01

    Non-canonical transforming growth factor β (TGFβ) signaling through protein kinase B (Akt2) induces phosphorylation of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) at serine-43 (p-hnRNP E1). This post-translational modification (PTM) of hnRNP E1 promotes its dissociation from a 3′ untranslated region (UTR) nucleic acid regulatory motif, driving epithelial to mesenchymal transition (EMT) and metastasis. We have identified an hnRNP E1 consensus-binding motif and genomically resolved a subset of genes in which it is contained. This study characterizes the binding kinetics of the consensus-binding motif and hnRNP E1, its various K-homology (KH) domains and p-hnRNP E1. Levels of p-hnRNP E1 are highly upregulated in metastatic cancer cells and low in normal epithelial tissue. We show a correlation between this PTM and levels of Akt2 and its activated form, phosphorylated serine-474 (p-Akt2). Using cellular progression models of metastasis, we observed a signature high level of Akt2, p-Akt2 and p-hnRNP E1 protein expression, coupled to a significantly reduced level of total hnRNP E1 in metastatic cells. Genes that are translationally silenced by hnRNP E1 and expressed by its dissociation are highly implicated in the progression of EMT and metastasis. This study provides insight into a non-canonical TGFβ signaling cascade that is responsible for inducing EMT by aberrant expression of hnRNP E1 silenced targets. The relevance of this system in metastatic progression is clearly shown in cellular models by the high abundance of p-hnRNP E1 and low levels of hnRNP E1. New insights provided by the resolution of this molecular mechanism provide targets for therapeutic intervention and give further insight into the role of the TGFβ microenvironment. PMID:27067543

  16. 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

  17. 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. PMID:21138970

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

    PubMed Central

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

    2011-01-01

    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. PMID:21138970

  19. Tripartite motif 32 prevents pathological cardiac hypertrophy.

    PubMed

    Chen, Lijuan; Huang, Jia; Ji, Yanxiao; Zhang, Xiaojing; Wang, Pixiao; Deng, Keqiong; Jiang, Xi; Ma, Genshan; Li, Hongliang

    2016-05-01

    TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II)-mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32-deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt-dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. PMID:26884348

  20. Tripartite motif 32 prevents pathological cardiac hypertrophy

    PubMed Central

    Huang, Jia; Ji, Yanxiao; Zhang, Xiaojing; Wang, Pixiao; Deng, Keqiong; Jiang, Xi; Ma, Genshan

    2016-01-01

    TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II)-mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32-deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt-dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. PMID:26884348

  1. New online signature acquisition system

    NASA Astrophysics Data System (ADS)

    Oulefki, Adel; Mostefai, Messaoud; Abbadi, Belkacem; Djebrani, Samira; Bouziane, Abderraouf; Chahir, Youssef

    2013-01-01

    We present a nonconstraining and low-cost online signature acquisition system that has been developed to enhance the performances of an existing multimodal biometric authentication system (based initially on both voice and image modalities). A laboratory prototype has been developed and validated for an online signature acquisition.

  2. BlockLogo: visualization of peptide and sequence motif conservation.

    PubMed

    Olsen, Lars Rønn; Kudahl, Ulrich Johan; Simon, Christian; Sun, Jing; Schönbach, Christian; Reinherz, Ellis L; Zhang, Guang Lan; Brusic, Vladimir

    2013-12-31

    BlockLogo is a web-server application for the visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, selection of motif positions, type of sequence, and output format definition. The output has BlockLogo along with the sequence logo, and a table of motif frequencies. We deployed BlockLogo as an online application and have demonstrated its utility through examples that show visualization of T-cell epitopes and B-cell epitopes (both continuous and discontinuous). Our additional example shows a visualization and analysis of structural motifs that determine the specificity of peptide binding to HLA-DR molecules. The BlockLogo server also employs selected experimentally validated prediction algorithms to enable on-the-fly prediction of MHC binding affinity to 15 common HLA class I and class II alleles as well as visual analysis of discontinuous epitopes from multiple sequence alignments. It enables the visualization and analysis of structural and functional motifs that are usually described as regular expressions. It provides a compact view of discontinuous motifs composed of distant positions within biological sequences. BlockLogo is available at: http://research4.dfci.harvard.edu/cvc/blocklogo/ and http://met-hilab.bu.edu/blocklogo/. PMID:24001880

  3. Recurrent Structural Motifs in Non-Homologous Protein Structures

    PubMed Central

    Johansson, Maria U.; Zoete, Vincent; Guex, Nicolas

    2013-01-01

    We have extracted an extensive collection of recurrent structural motifs (RSMs), which consist of sequentially non-contiguous structural motifs (4–6 residues), each of which appears with very similar conformation in three or more mutually unrelated protein structures. We find that the proteins in our set are covered to a substantial extent by the recurrent non-contiguous structural motifs, especially the helix and strand regions. Computational alanine scanning calculations indicate that the average folding free energy changes upon alanine mutation for most types of non-alanine residues are higher for amino acids that are present in recurrent structural motifs than for amino acids that are not. The non-alanine amino acids that are most common in the recurrent structural motifs, i.e., phenylalanine, isoleucine, leucine, valine and tyrosine and the less abundant methionine and tryptophan, have the largest folding free energy changes. This indicates that the recurrent structural motifs, as we define them, describe recurrent structural patterns that are important for protein stability. In view of their properties, such structural motifs are potentially useful for inter-residue contact prediction and protein structure refinement. PMID:23574940

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

    PubMed

    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

  5. Cell surface lectin array: parameters affecting cell glycan signature.

    PubMed

    Landemarre, Ludovic; Cancellieri, Perrine; Duverger, Eric

    2013-04-01

    Among the "omics", glycomics is one of the most complex fields and needs complementary strategies of analysis to decipher the "glycan dictionary". As an alternative method, which has developed since the beginning of the 21st century, lectin array technology could generate relevant information related to glycan motifs, accessibility and a number of other valuable insights from molecules (purified and non-purified) or cells. Based on a cell line model, this study deals with the key parameters that influence the whole cell surface glycan interaction with lectin arrays and the consequences on the interpretation and reliability of the results. The comparison between the adherent and suspension forms of Chinese Hamster Ovary (CHO) cells, showed respective glycan signatures, which could be inhibited specifically by neoglycoproteins. The modifications of the respective glycan signatures were also revealed according to the detachment modes and cell growth conditions. Finally the power of lectin array technology was highlighted by the possibility of selecting and characterizing a specific clone from the mother cell line, based on the slight difference determination in the respective glycan signatures. PMID:22899543

  6. Multiple Dileucine-like Motifs Direct VGLUT1 Trafficking

    PubMed Central

    Foss, Sarah M.; Li, Haiyan; Santos, Magda S.; Edwards, Robert H.

    2013-01-01

    The vesicular glutamate transporters (VGLUTs) package glutamate into synaptic vesicles, and the two principal isoforms VGLUT1 and VGLUT2 have been suggested to influence the properties of release. To understand how a VGLUT isoform might influence transmitter release, we have studied their trafficking and previously identified a dileucine-like endocytic motif in the C terminus of VGLUT1. Disruption of this motif impairs the activity-dependent recycling of VGLUT1, but does not eliminate its endocytosis. We now report the identification of two additional dileucine-like motifs in the N terminus of VGLUT1 that are not well conserved in the other isoforms. In the absence of all three motifs, rat VGLUT1 shows limited accumulation at synaptic sites and no longer responds to stimulation. In addition, shRNA-mediated knockdown of clathrin adaptor proteins AP-1 and AP-2 shows that the C-terminal motif acts largely via AP-2, whereas the N-terminal motifs use AP-1. Without the C-terminal motif, knockdown of AP-1 reduces the proportion of VGLUT1 that responds to stimulation. VGLUT1 thus contains multiple sorting signals that engage distinct trafficking mechanisms. In contrast to VGLUT1, the trafficking of VGLUT2 depends almost entirely on the conserved C-terminal dileucine-like motif: without this motif, a substantial fraction of VGLUT2 redistributes to the plasma membrane and the transporter's synaptic localization is disrupted. Consistent with these differences in trafficking signals, wild-type VGLUT1 and VGLUT2 differ in their response to stimulation. PMID:23804088

  7. 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.

  8. 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.

  9. On the signature of LINCOS

    NASA Astrophysics Data System (ADS)

    Ollongren, Alexander

    2010-12-01

    Suppose the international SETI effort yields the discovery of some signal of evidently non-natural origin. Could it contain linguistic information formulated in some kind of Lingua Cosmica? One way to get insight into this matter is to consider what specific (bio) linguistic signature( s) could be attached to a cosmic language for interstellar communication—designed by humans or an alien society having reached a level of intelligence (and technology) comparable to or surpassing ours. For this purpose, we consider in the present paper the logico-linguistic system LINCOS for ( A)CETI, developed during a number of years by the author in several papers and a monograph [1]. The system has a two-fold signature, which distinguishes it significantly from natural languages. In fact abstract and concrete signatures can be distinguished. That an abstract kind occurs is due to the manner in which abstractions of reality are represented in LINCOS-texts. They can take compound forms because the system is multi-expressive—partly due to the availability of inductive (recursive) entities. On the other hand, the concrete signature of LINCOS is related to the distribution of delimiters and predefined tokens in texts. Assigning measures to concrete signatures will be discussed elsewhere. The present contribution concentrates on the abstract signature of the language. At the same time, it is realized that an alien Lingua Cosmica might, but not necessarily needs to have this kind of signatures.

  10. Infrasound Rocket Signatures

    NASA Astrophysics Data System (ADS)

    Olson, J.

    2012-09-01

    This presentation reviews the work performed by our research group at the Geophysical Institute as we have applied the tools of infrasound research to rocket studies. This report represents one aspect of the effort associated with work done for the National Consortium for MASINT Research (NCMR) program operated by the National MASINT Office (NMO) of the Defense Intelligence Agency (DIA). Infrasound, the study of acoustic signals and their propagation in a frequency band below 15 Hz, enables an investigator to collect and diagnose acoustic signals from distant sources. Absorption of acoustic energy in the atmosphere decreases as the frequency is reduced. In the infrasound band signals can propagate hundreds and thousands of kilometers with little degradation. We will present an overview of signatures from rockets ranging from small sounding rockets such as the Black Brandt and Orion series to larger rockets such as Delta 2,4 and Atlas V. Analysis of the ignition transients provides information that can uniquely identify the motor type. After the rocket ascends infrasound signals can be used to characterize the rocket and identify the various events that take place along a trajectory such as staging and maneuvering. We have also collected information on atmospheric shocks and sonic booms from the passage of supersonic vehicles such as the shuttle. This review is intended to show the richness of the unique signal set that occurs in the low-frequency infrasound band.

  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. UHECR: Signatures and models

    NASA Astrophysics Data System (ADS)

    Berezinsky, V.

    2013-06-01

    The signatures of Ultra High Energy (E ≳ 1 EeV) proton propagation through CMB radiation are pair-production dip and GZK cutoff. The visible characteristics of these two spectral features are ankle, which is intrinsic part of the dip, beginning of GZK cutoff in the differential spectrum and E1/2 in integral spectrum. Measured by HiRes and Telescope Array (TA) these characteristics agree with theoretical predictions. However, directly measured mass composition remains a puzzle. While HiRes and TA detectors observe the proton-dominated mass composition, the data of Auger detector strongly evidence for nuclei mass composition becoming progressively heavier at energy higher than 4 EeV and reaching Iron at energy about 35 EeV. The models based on the Auger and HiRes/TA data are considered independently and classified using the transition from galactic to extragalactic cosmic rays. The ankle cannot provide this transition. since data of all three detector at energy (1-3) EeV agree with pure proton composition (or at least not heavier than Helium). If produced in Galaxy these particles result in too high anisotropy. This argument excludes or strongly disfavours all ankle models with ankle energy Ea > 3 EeV. The calculation of elongation curves, Xmax(E), for different ankle models strengthens further this conclusion. Status of other models, the dip, mixed composition and Auger based models are discussed.

  13. Statistical clumped isotope signatures.

    PubMed

    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

  14. Network motifs emerge from interconnections that favour stability

    NASA Astrophysics Data System (ADS)

    Angulo, Marco Tulio; Liu, Yang-Yu; Slotine, Jean-Jacques

    2015-10-01

    The microscopic principles organizing dynamic units in complex networks--from proteins to power generators--can be understood in terms of network `motifs’: small interconnection patterns that appear much more frequently in real networks than expected in random networks. When considered as small subgraphs isolated from a large network, these motifs are more robust to parameter variations, easier to synchronize than other possible subgraphs, and can provide specific functionalities. But one can isolate these subgraphs only by assuming, for example, a significant separation of timescales, and the origin of network motifs and their functionalities when embedded in larger networks remain unclear. Here we show that most motifs emerge from interconnection patterns that best exploit the intrinsic stability characteristics at different scales of interconnection, from simple nodes to whole modules. This functionality suggests an efficient mechanism to stably build complex systems by recursively interconnecting nodes and modules as motifs. We present direct evidence of this mechanism in several biological networks.

  15. The building blocks and motifs of RNA architecture

    PubMed Central

    Leontis, Neocles B; Lescoute, Aurelie; Westhof, Eric

    2010-01-01

    RNA motifs can be defined broadly as recurrent structural elements containing multiple intramolecular RNA–RNA interactions, as observed in atomic-resolution RNA structures. They constitute the modular building blocks of RNA architecture, which is organized hierarchically. Recent work has focused on analyzing RNA backbone conformations to identify, define and search for new instances of recurrent motifs in X-ray structures. One current view asserts that recurrent RNA strand segments with characteristic backbone configurations qualify as independent motifs. Other considerations indicate that, to characterize modular motifs, one must take into account the larger structural context of such strand segments. This follows the biologically relevant motivation, which is to identify RNA structural characteristics that are subject to sequence constraints and that thus relate RNA architectures to sequences. PMID:16713707

  16. 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. PMID:25038412

  17. 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

  18. 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

  19. A proposed neutral line signature

    NASA Technical Reports Server (NTRS)

    Doxas, I.; Speiser, T. W.; Dusenbery, P. B.; Horton, W.

    1992-01-01

    An identifying signature is proposed for the existence and location of the neutral line in the magnetotail. The signature, abrupt density, and temperature changes in the Earthtail direction, was first discovered in test particle simulations. Such temperature variations have been observed in ISEE data (Huang et. al. 1992), but their connection to the possible existence of a neutral line in the tail has not yet been established. The proposed signature develops earlier than the ion velocity space ridge of Martin and Speiser (1988), but can only be seen by spacecraft in the vicinity of the neutral line, while the latter can locate a neutral line remotely.

  20. Signature surveillance of nuclear fuel

    SciTech Connect

    Bernatowicz, H.; Schoenig, F.C.

    1982-08-31

    Typical nuclear fuel material contains tramp ferromagnetic particles of random size and distribution. Also, selected amounts of paramagnetic or ferromagnetic material can be added at random or at known positions in the fuel material. The fuel material in its nonmagnetic container can be scanned by magnetic susceptibility change detecting apparatus to provide a unique signal waveform of the container of fuel material as a signature thereof. At subsequent times in its life, the container similarly can be scanned to provide subsequent signatures. Comparison of the signatures reveals any alteration or tampering with the fuel material.

  1. Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I

    PubMed Central

    Xu, Jie; Mercado-López, Xiomara; Grier, Jennifer T.; Kim, Won-keun; Chun, Lauren F.; Irvine, Edward B.; Del Toro Duany, Yoandris; Kell, Alison; Hur, Sun; Gale, Michael; Raj, Arjun

    2015-01-01

    ABSTRACT Stimulation of the antiviral response depends on the sensing of viral pathogen-associated molecular patterns (PAMPs) by specialized cellular proteins. During infection with RNA viruses, 5′-di- or -triphosphates accompanying specific single or double-stranded RNA motifs trigger signaling of intracellular RIG-I-like receptors (RLRs) and initiate the antiviral response. Although these molecular signatures are present during the replication of many viruses, it is unknown whether they are sufficient for strong activation of RLRs during infection. Immunostimulatory defective viral genomes (iDVGs) from Sendai virus (SeV) are among the most potent natural viral triggers of antiviral immunity. Here we describe an RNA motif (DVG70-114) that is essential for the potent immunostimulatory activity of 5′-triphosphate-containing SeV iDVGs. DVG70-114 enhances viral sensing by the host cell independently of the long stretches of complementary RNA flanking the iDVGs, and it retains its stimulatory potential when transferred to otherwise inert viral RNA. In vitro analysis showed that DVG70-114 augments the binding of RIG-I to viral RNA and promotes enhanced RIG-I polymerization, thereby facilitating the onset of the antiviral response. Together, our results define a new natural viral PAMP enhancer motif that promotes viral recognition by RLRs and confers potent immunostimulatory activity to viral RNA. PMID:26443454

  2. Metabolic network motifs can provide novel insights into evolution: The evolutionary origin of Eukaryotic organelles as a case study

    PubMed Central

    Shellman, Erin R.; Chen, Yu; Lin, Xiaoxia; Burant, Charles F.; Schnell, Santiago

    2014-01-01

    Phylogenetic trees are typically constructed using genetic and genomic data, and provide robust evolutionary relationships of species from the genomic point of view. We present an application of network motif mining and analysis of metabolic pathways that when used in combination with phylogenetic trees can provide a more complete picture of evolution. By using distributions of three-node motifs as a proxy for metabolic similarity, we analyze the ancestral origin of Eukaryotic organelles from the metabolic point of view to illustrate the application of our motif mining and analysis network approach. Our analysis suggests that the hypothesis of an early proto-Eukaryote could be valid. It also suggests that a δ- or ε-Proteobacteria may have been the endosymbiotic partner that gave rise to modern mitochondria. Our evolutionary analysis needs to be extended by building metabolic network reconstructions of species from the phylum Crenarchaeota, which is considered to be a possible archaeal ancestor of the eukaryotic cell. In this paper, we also propose a methodology for constructing phylogenetic trees that incorporates metabolic network signatures to identify regions of genomically-estimated phylogenies that may be spurious. We find that results generated from our approach are consistent with a parallel phylogenetic analysis using the method of feature frequency profiles. PMID:25462333

  3. Direct vs 2-stage approaches to structured motif finding

    PubMed Central

    2012-01-01

    Background The notion of DNA motif is a mathematical abstraction used to model regions of the DNA (known as Transcription Factor Binding Sites, or TFBSs) that are bound by a given Transcription Factor to regulate gene expression or repression. In turn, DNA structured motifs are a mathematical counterpart that models sets of TFBSs that work in concert in the gene regulations processes of higher eukaryotic organisms. Typically, a structured motif is composed of an ordered set of isolated (or simple) motifs, separated by a variable, but somewhat constrained number of “irrelevant” base-pairs. Discovering structured motifs in a set of DNA sequences is a computationally hard problem that has been addressed by a number of authors using either a direct approach, or via the preliminary identification and successive combination of simple motifs. Results We describe a computational tool, named SISMA, for the de-novo discovery of structured motifs in a set of DNA sequences. SISMA is an exact, enumerative algorithm, meaning that it finds all the motifs conforming to the specifications. It does so in two stages: first it discovers all the possible component simple motifs, then combines them in a way that respects the given constraints. We developed SISMA mainly with the aim of understanding the potential benefits of such a 2-stage approach w.r.t. direct methods. In fact, no 2-stage software was available for the general problem of structured motif discovery, but only a few tools that solved restricted versions of the problem. We evaluated SISMA against other published tools on a comprehensive benchmark made of both synthetic and real biological datasets. In a significant number of cases, SISMA outperformed the competitors, exhibiting a good performance also in most of the cases in which it was inferior. Conclusions A reflection on the results obtained lead us to conclude that a 2-stage approach can be implemented with many advantages over direct approaches. Some of these

  4. Network motif-based method for identifying coronary artery disease

    PubMed Central

    LI, YIN; CONG, YAN; ZHAO, YUN

    2016-01-01

    The present study aimed to develop a more efficient method for identifying coronary artery disease (CAD) than the conventional method using individual differentially expressed genes (DEGs). GSE42148 gene microarray data were downloaded, preprocessed and screened for DEGs. Additionally, based on transcriptional regulation data obtained from ENCODE database and protein-protein interaction data from the HPRD, the common genes were downloaded and compared with genes annotated from gene microarrays to screen additional common genes in order to construct an integrated regulation network. FANMOD was then used to detect significant three-gene network motifs. Subsequently, GlobalAncova was used to screen differential three-gene network motifs between the CAD group and the normal control data from GSE42148. Genes involved in the differential network motifs were then subjected to functional annotation and pathway enrichment analysis. Finally, clustering analysis of the CAD and control samples was performed based on individual DEGs and the top 20 network motifs identified. In total, 9,008 significant three-node network motifs were detected from the integrated regulation network; these were categorized into 22 interaction modes, each containing a minimum of one transcription factor. Subsequently, 1,132 differential network motifs involving 697 genes were screened between the CAD and control group. The 697 genes were enriched in 154 gene ontology terms, including 119 biological processes, and 14 KEGG pathways. Identifying patients with CAD based on the top 20 network motifs provided increased accuracy compared with the conventional method based on individual DEGs. The results of the present study indicate that the network motif-based method is more efficient and accurate for identifying CAD patients than the conventional method based on individual DEGs. PMID:27347046

  5. Robust and Adaptive MicroRNA-Mediated Incoherent Feedforward Motifs

    NASA Astrophysics Data System (ADS)

    Xu, Feng-Dan; Liu, Zeng-Rong; Zhang, Zhi-Yong; Shen, Jian-Wei

    2009-02-01

    We integrate transcriptional and post-transcriptional regulation into microRNA-mediated incoherent feedforward motifs and analyse their dynamical behaviour and functions. The analysis show that the behaviour of the system is almost uninfluenced by the varying input in certain ranges and by introducing of delay and noise. The results indicate that microRNA-mediated incoherent feedforward motifs greatly enhance the robustness of gene regulation.

  6. Directed network motifs in Alzheimer's disease and mild cognitive impairment.

    PubMed

    Friedman, Eric J; Young, Karl; Tremper, Graham; Liang, Jason; Landsberg, Adam S; Schuff, Norbert

    2015-01-01

    Directed network motifs are the building blocks of complex networks, such as human brain networks, and capture deep connectivity information that is not contained in standard network measures. In this paper we present the first application of directed network motifs in vivo to human brain networks, utilizing recently developed directed progression networks which are built upon rates of cortical thickness changes between brain regions. This is in contrast to previous studies which have relied on simulations and in vitro analysis of non-human brains. We show that frequencies of specific directed network motifs can be used to distinguish between patients with Alzheimer's disease (AD) and normal control (NC) subjects. Especially interesting from a clinical standpoint, these motif frequencies can also distinguish between subjects with mild cognitive impairment who remained stable over three years (MCI) and those who converted to AD (CONV). Furthermore, we find that the entropy of the distribution of directed network motifs increased from MCI to CONV to AD, implying that the distribution of pathology is more structured in MCI but becomes less so as it progresses to CONV and further to AD. Thus, directed network motifs frequencies and distributional properties provide new insights into the progression of Alzheimer's disease as well as new imaging markers for distinguishing between normal controls, stable mild cognitive impairment, MCI converters and Alzheimer's disease. PMID:25879535

  7. Motif for controllable toggle switch in gene regulatory networks

    NASA Astrophysics Data System (ADS)

    Zhao, Chen; Bin, Ao; Ye, Weiming; Fan, Ying; Di, Zengru

    2015-02-01

    Toggle switch as a common phenomenon in gene regulatory networks has been recognized important for biological functions. Despite much effort dedicated to understanding the toggle switch and designing synthetic biology circuit to achieve the biological function, we still lack a comprehensive understanding of the intrinsic dynamics behind such phenomenon and the minimum structure that is imperative for producing toggle switch. In this paper, we discover a minimum structure, a motif that enables a controllable toggle switch. In particular, the motif consists of a transformative double negative feedback loop (DNFL) that is regulated by an additional driver node. By enumerating all possible regulatory configurations from the driver node, we identify two types of motifs associated with the toggle switch that is captured by the existence of bistable states. The toggle switch is controllable in the sense that the gap between the bistable states is adjustable as determined by the regulatory strength from the driver nodes. We test the effect of the motifs in self-oscillating gene regulatory network (SON) with respect to the interplay between the motifs and the other genes, and find that the switching dynamics of the whole network can be successfully controlled insofar as the network contains a single motif. Our findings are important to uncover the underlying nonlinear dynamics of controllable toggle switch and can have implications in devising biology circuit in the field of synthetic biology.

  8. Heparin-Binding Motifs and Biofilm Formation by Candida albicans

    PubMed Central

    Green, Julianne V.; Orsborn, Kris I.; Zhang, Minlu; Tan, Queenie K. G.; Greis, Kenneth D.; Porollo, Alexey; Andes, David R.; Long Lu, Jason; Hostetter, Margaret K.

    2013-01-01

    Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequence-based search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms. PMID:23904295

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

    PubMed Central

    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. PMID:26528473

  10. Discovering Motifs in Biological Sequences Using the Micron Automata Processor.

    PubMed

    Roy, Indranil; Aluru, Srinivas

    2016-01-01

    Finding approximately conserved sequences, called motifs, across multiple DNA or protein sequences is an important problem in computational biology. In this paper, we consider the (l, d) motif search problem of identifying one or more motifs of length l present in at least q of the n given sequences, with each occurrence differing from the motif in at most d substitutions. The problem is known to be NP-complete, and the largest solved instance reported to date is (26,11). We propose a novel algorithm for the (l,d) motif search problem using streaming execution over a large set of non-deterministic finite automata (NFA). This solution is designed to take advantage of the micron automata processor, a new technology close to deployment that can simultaneously execute multiple NFA in parallel. We demonstrate the capability for solving much larger instances of the (l, d) motif search problem using the resources available within a single automata processor board, by estimating run-times for problem instances (39,18) and (40,17). The paper serves as a useful guide to solving problems using this new accelerator technology. PMID:26886735

  11. 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

  12. 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).

  13. 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%.

  14. 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.

  15. Signature-based image identification

    NASA Astrophysics Data System (ADS)

    Abdel-Mottaleb, Mohamed; Vaithilingam, Gandhimathi; Krishnamachari, Santhana

    1999-11-01

    The use of digital images and video is growing on the Internet and on consumer devices. Digital images and video are easy to manipulate, but this ease of manipulation makes tampering with digital content possible. Examples of the misuse of digital content include violating copyrights of the content and tampering with important material such as contents of video surveillance. In this paper we present an algorithm that extracts a binary signature from an image. This approach can be used to search for possible copyright violations by finding images with signatures close to that of a given image. The experimental results show that the algorithm can be very effective in helping users to retrieve sets of almost identical images from large collections of images. The signature can also be used for tamper detection. We will show that the signatures we extract are immune to quantization errors that result from compression and decompression.

  16. 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.

  17. 1 CFR 18.7 - Signature.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Signature. 18.7 Section 18.7 General Provisions... PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.7 Signature. The original and each duplicate original... stamped beneath the signature. Initialed or impressed signatures will not be accepted. Documents...

  18. 1 CFR 18.7 - Signature.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Signature. 18.7 Section 18.7 General Provisions... PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.7 Signature. The original and each duplicate original... stamped beneath the signature. Initialed or impressed signatures will not be accepted. Documents...

  19. A comprehensive analysis of the La-motif protein superfamily

    PubMed Central

    Bousquet-Antonelli, Cécile; Deragon, Jean-Marc

    2009-01-01

    The extremely well-conserved La motif (LAM), in synergy with the immediately following RNA recognition motif (RRM), allows direct binding of the (genuine) La autoantigen to RNA polymerase III primary transcripts. This motif is not only found on La homologs, but also on La-related proteins (LARPs) of unrelated function. LARPs are widely found amongst eukaryotes and, although poorly characterized, appear to be RNA-binding proteins fulfilling crucial cellular functions. We searched the fully sequenced genomes of 83 eukaryotic species scattered along the tree of life for the presence of LAM-containing proteins. We observed that these proteins are absent from archaea and present in all eukaryotes (except protists from the Plasmodium genus), strongly suggesting that the LAM is an ancestral motif that emerged early after the archaea-eukarya radiation. A complete evolutionary and structural analysis of these proteins resulted in their classification into five families: the genuine La homologs and four LARP families. Unexpectedly, in each family a conserved domain representing either a classical RRM or an RRM-like motif immediately follows the LAM of most proteins. An evolutionary analysis of the LAM-RRM/RRM-L regions shows that these motifs co-evolved and should be used as a single entity to define the functional region of interaction of LARPs with their substrates. We also found two extremely well conserved motifs, named LSA and DM15, shared by LARP6 and LARP1 family members, respectively. We suggest that members of the same family are functional homologs and/or share a common molecular mode of action on different RNA baits. PMID:19299548

  20. In vivo analysis of Caenorhabditis elegans noncoding RNA promoter motifs

    PubMed Central

    Li, Tiantian; He, Housheng; Wang, Yunfei; Zheng, Haixia; Skogerbø, Geir; Chen, Runsheng

    2008-01-01

    Background Noncoding RNAs (ncRNAs) play important roles in a variety of cellular processes. Characterizing the transcriptional activity of ncRNA promoters is therefore a critical step toward understanding the complex cellular roles of ncRNAs. Results Here we present an in vivo transcriptional analysis of three C. elegans ncRNA upstream motifs (UM1-3). Transcriptional activity of all three motifs has been demonstrated, and mutational analysis revealed differential contributions of different parts of each motif. We showed that upstream motif 1 (UM1) can drive the expression of green fluorescent protein (GFP), and utilized this for detailed analysis of temporal and spatial expression patterns of 5 SL2 RNAs. Upstream motifs 2 and 3 do not drive GFP expression, and termination at consecutive T runs suggests transcription by RNA polymerase III. The UM2 sequence resembles the tRNA promoter, and is actually embedded within its own short-lived, primary transcript. This is a structure which is also found at a few plant and yeast loci, and may indicate an evolutionarily very old dicistronic transcription pattern in which a tRNA serves as a promoter for an adjacent snoRNA. Conclusion The study has demonstrated that the three upstream motifs UM1-3 have promoter activity. The UM1 sequence can drive expression of GFP, which allows for the use of UM1::GFP fusion constructs to study temporal-spatial expression patterns of UM1 ncRNA loci. The UM1 loci appear to act in concert with other upstream sequences, whereas the transcriptional activities of the UM2 and UM3 are confined to the motifs themselves. PMID:18680611

  1. 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.

  2. 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.

  3. Structural and functional studies of a phosphatidic acid-binding antifungal plant defensin MtDef4: Identification of an RGFRRR motif governing fungal cell entry

    SciTech Connect

    Sagaram, Uma S.; El-Mounadi, Kaoutar; Buchko, Garry W.; Berg, Howard R.; Kaur, Jagdeep; Pandurangi, Raghoottama; Smith, Thomas J.; Shah, Dilip

    2013-12-04

    A highly conserved plant defensin MtDef4 potently inhibits the growth of a filamentous fungus Fusarium graminearum. MtDef4 is internalized by cells of F. graminearum. To determine its mechanism of fungal cell entry and antifungal action, NMR solution structure of MtDef4 has been determined. The analysis of its structure has revealed a positively charged patch on the surface of the protein consisting of arginine residues in its γ-core signature, a major determinant of the antifungal activity of MtDef4. Here, we report functional analysis of the RGFRRR motif of the γ-core signature of MtDef4. The replacement of RGFRRR to AAAARR or to RGFRAA not only abolishes fungal cell entry but also results in loss of the antifungal activity of MtDef4. MtDef4 binds strongly to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Mutations of RGFRRR which abolish fungal cell entry of MtDef4 also impair its binding to PA. Our results suggest that RGFRRR motif is a translocation signal for entry of MtDef4 into fungal cells and that this positively charged motif likely mediates interaction of this defensin with PA as part of its antifungal action.

  4. Discovering Motifs in Ranked Lists of DNA Sequences

    PubMed Central

    Eden, Eran; Lipson, Doron; Yogev, Sivan; Yakhini, Zohar

    2007-01-01

    Computational methods for discovery of sequence elements that are enriched in a target set compared with a background set are fundamental in molecular biology research. One example is the discovery of transcription factor binding motifs that are inferred from ChIP–chip (chromatin immuno-precipitation on a microarray) measurements. Several major challenges in sequence motif discovery still require consideration: (i) the need for a principled approach to partitioning the data into target and background sets; (ii) the lack of rigorous models and of an exact p-value for measuring motif enrichment; (iii) the need for an appropriate framework for accounting for motif multiplicity; (iv) the tendency, in many of the existing methods, to report presumably significant motifs even when applied to randomly generated data. In this paper we present a statistical framework for discovering enriched sequence elements in ranked lists that resolves these four issues. We demonstrate the implementation of this framework in a software application, termed DRIM (discovery of rank imbalanced motifs), which identifies sequence motifs in lists of ranked DNA sequences. We applied DRIM to ChIP–chip and CpG methylation data and obtained the following results. (i) Identification of 50 novel putative transcription factor (TF) binding sites in yeast ChIP–chip data. The biological function of some of them was further investigated to gain new insights on transcription regulation networks in yeast. For example, our discoveries enable the elucidation of the network of the TF ARO80. Another finding concerns a systematic TF binding enhancement to sequences containing CA repeats. (ii) Discovery of novel motifs in human cancer CpG methylation data. Remarkably, most of these motifs are similar to DNA sequence elements bound by the Polycomb complex that promotes histone methylation. Our findings thus support a model in which histone methylation and CpG methylation are mechanistically linked. Overall

  5. MALISAM: a database of structurally analogous motifs in proteins.

    PubMed

    Cheng, Hua; Kim, Bong-Hyun; Grishin, Nick V

    2008-01-01

    MALISAM (manual alignments for structurally analogous motifs) represents the first database containing pairs of structural analogs and their alignments. To find reliable analogs, we developed an approach based on three ideas. First, an insertion together with a part of the evolutionary core of one domain family (a hybrid motif) is analogous to a similar motif contained within the core of another domain family. Second, a motif at an interface, formed by secondary structural elements (SSEs) contributed by two or more domains or subunits contacting along that interface, is analogous to a similar motif present in the core of a single domain. Third, an artificial protein obtained through selection from random peptides or in sequence design experiments not biased by sequences of a particular homologous family, is analogous to a structurally similar natural protein. Each analogous pair is superimposed and aligned manually, as well as by several commonly used programs. Applications of this database may range from protein evolution studies, e.g. development of remote homology inference tools and discriminators between homologs and analogs, to protein-folding research, since in the absence of evolutionary reasons, similarity between proteins is caused by structural and folding constraints. The database is publicly available at http://prodata.swmed.edu/malisam. PMID:17855399

  6. 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

  7. BC1 RNA motifs required for dendritic transport in vivo

    PubMed Central

    Robeck, Thomas; Skryabin, Boris V.; Rozhdestvensky, Timofey S.; Skryabin, Anastasiya B.; Brosius, Jürgen

    2016-01-01

    BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo. PMID:27350115

  8. BC1 RNA motifs required for dendritic transport in vivo.

    PubMed

    Robeck, Thomas; Skryabin, Boris V; Rozhdestvensky, Timofey S; Skryabin, Anastasiya B; Brosius, Jürgen

    2016-01-01

    BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo. PMID:27350115

  9. Mining tertiary structural motifs for assessment of designability.

    PubMed

    Zhang, Jian; Grigoryan, Gevorg

    2013-01-01

    The observation of a limited secondary-structural alphabet in native proteins, with significant sequence preferences, has profoundly influenced the fields of protein design and structure prediction (Simons, Kooperberg, Huang, & Baker, 1997; Verschueren et al., 2011). In the era of structural genomics, as the size of the structural dataset continues to grow rapidly, it is becoming possible to extend this analysis to tertiary structural motifs and their sequences. For a hypothetical tertiary motif, the rate of its utilization in natural proteins may be used to assess its designability-the ease with which the motif can be realized with natural amino acids. This requires a structural similarity search methodology, which rather than looking for global topological agreement (more appropriate for categorization of full proteins or domains), identifies detailed geometric matches. In this chapter, we introduce such a method, called MaDCaT, and demonstrate its use by assessing the designability landscapes of two tertiary structural motifs. We also show that such analysis can establish structure/sequence links by providing the sequence constraints necessary to encode designable motifs. As logical extension of their secondary-structure counterparts, tertiary structural preferences will likely prove extremely useful in de novo protein design and structure prediction. PMID:23422424

  10. DynaMIT: the dynamic motif integration toolkit

    PubMed Central

    Dassi, Erik; Quattrone, Alessandro

    2016-01-01

    De-novo motif search is a frequently applied bioinformatics procedure to identify and prioritize recurrent elements in sequences sets for biological investigation, such as the ones derived from high-throughput differential expression experiments. Several algorithms have been developed to perform motif search, employing widely different approaches and often giving divergent results. In order to maximize the power of these investigations and ultimately be able to draft solid biological hypotheses, there is the need for applying multiple tools on the same sequences and merge the obtained results. However, motif reporting formats and statistical evaluation methods currently make such an integration task difficult to perform and mostly restricted to specific scenarios. We thus introduce here the Dynamic Motif Integration Toolkit (DynaMIT), an extremely flexible platform allowing to identify motifs employing multiple algorithms, integrate them by means of a user-selected strategy and visualize results in several ways; furthermore, the platform is user-extendible in all its aspects. DynaMIT is freely available at http://cibioltg.bitbucket.org. PMID:26253738

  11. 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.

  12. 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

  13. Robustness to noise in synchronization of network motifs: Experimental results

    NASA Astrophysics Data System (ADS)

    Buscarino, Arturo; Fortuna, Luigi; Frasca, Mattia; Iachello, Marco; Pham, Viet-Thanh

    2012-12-01

    In this work, we experimentally investigate the robustness to noise of synchronization in all the four-nodes network motifs. The experimental setup consists of four Chua's circuits diffusively coupled in order to implement the six different undirected network motifs that can be obtained with four nodes. In this experimental setup, synchronization in the presence of noise injected in one of the network nodes is investigated and network motifs are compared in terms of the synchronization error obtained. The analysis has been then extended to some selected case studies of networks with five and six nodes. Numerical simulations have been also performed and results in agreement with experiments have been obtained. A correlation between node degree and robustness to noise has been found also in these networks.

  14. 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.

  15. 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.

  16. Functionally related transcripts have common RNA motifs for specific RNA-binding proteins in trypanosomes

    PubMed Central

    Noé, Griselda; De Gaudenzi, Javier G; Frasch, Alberto C

    2008-01-01

    Background Trypanosomes mostly control gene expression by post-transcriptional events such as modulation of mRNA stability and translational efficiency. These mechanisms involve RNA-binding proteins (RBPs), which associate with transcripts to form messenger ribonucleoprotein (mRNP) complexes. Results In this study, we report the identification of mRNA targets for Trypanosoma cruzi U-rich RBP 1 (TcUBP1) and T. cruzi RBP 3 (TcRBP3), two phylogenetically conserved proteins among Kinetoplastids. Co-immunoprecipitated RBP-associated RNAs were extracted from mRNP complexes and binding of RBPs to several targets was confirmed by independent experimental assays. Analysis of target transcript sequences allowed the identification of different signature RNA motifs for each protein. Cis-elements for RBP binding have a stem-loop structure of 30–35 bases and are more frequently represented in the 3'-untranslated region (UTR) of mRNAs. Insertion of the correctly folded RNA elements to a non-specific mRNA rendered it into a target transcript, whereas substitution of the RNA elements abolished RBP interaction. In addition, RBPs competed for RNA-binding sites in accordance with the distribution of different and overlapping motifs in the 3'-UTRs of common mRNAs. Conclusion Functionally related transcripts were preferentially associated with a given RBP; TcUBP1 targets were enriched in genes encoding proteins involved in metabolism, whereas ribosomal protein-encoding transcripts were the largest group within TcRBP3 targets. Together, these results suggest coordinated control of different mRNA subsets at the post-transcriptional level by specific RBPs. PMID:19063746

  17. Identification of high-molecular-weight proteins with multiple EGF-like motifs by motif-trap screening.

    PubMed

    Nakayama, M; Nakajima, D; Nagase, T; Nomura, N; Seki, N; Ohara, O

    1998-07-01

    To identify large proteins with an EGF-like-motif in a systematic manner, we developed a computer-assisted method called motif-trap screening. The method exploits 5'-end single-pass sequence data obtained from a pool of cDNAs whose sizes exceed 5 kb. Using this screening procedure, we were able to identify five known and nine new genes for proteins with multiple EGF-like-motifs from 8000 redundant human brain cDNA clones. These new genes were found to encode a novel mammalian homologue of Drosophila fat protein, two seven-transmembrane proteins containing multiple cadherin and EGF-like motifs, two mammalian homologues of Drosophila slit protein, an unidentified LDL receptor-like protein, and three totally uncharacterized proteins. The organization of the domains in the proteins, together with their expression profiles and fine chromosomal locations, has indicated their biological significance, demonstrating that motif-trap screening is a powerful tool for the discovery of new genes that have been difficult to identify by conventional methods. PMID:9693030

  18. Analysis of interactions between ribosomal proteins and RNA structural motifs

    PubMed Central

    2010-01-01

    Background One important goal of structural bioinformatics is to recognize and predict the interactions between protein binding sites and RNA. Recently, a comprehensive analysis of ribosomal proteins and their interactions with rRNA has been done. Interesting results emerged from the comparison of r-proteins within the small subunit in T. thermophilus and E. coli, supporting the idea of a core made by both RNA and proteins, conserved by evolution. Recent work showed also that ribosomal RNA is modularly composed. Motifs are generally single-stranded sequences of consecutive nucleotides (ssRNA) with characteristic folding. The role of these motifs in protein-RNA interactions has been so far only sparsely investigated. Results This work explores the role of RNA structural motifs in the interaction of proteins with ribosomal RNA (rRNA). We analyze composition, local geometries and conformation of interface regions involving motifs such as tetraloops, kink turns and single extruded nucleotides. We construct an interaction map of protein binding sites that allows us to identify the common types of shared 3-D physicochemical binding patterns for tetraloops. Furthermore, we investigate the protein binding pockets that accommodate single extruded nucleotides either involved in kink-turns or in arbitrary RNA strands. This analysis reveals a new structural motif, called tripod. It corresponds to small pockets consisting of three aminoacids arranged at the vertices of an almost equilateral triangle. We developed a search procedure for the recognition of tripods, based on an empirical tripod fingerprint. Conclusion A comparative analysis with the overall RNA surface and interfaces shows that contact surfaces involving RNA motifs have distinctive features that may be useful for the recognition and prediction of interactions. PMID:20122215

  19. 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.

  20. Specific RNA self-assembly with minimal paranemic motifs

    PubMed Central

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

    2016-01-01

    The paranemic crossover (PX) is a motif for assembling two nucleic acid molecules using Watson-Crick (WC) basepairing without unfolding pre-formed secondary structure in the individual molecules. Once formed, the paranemic assembly motif comprises adjacent parallel double helices that cross over 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 cross-over 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 cross-overs spanning the major groove to form paranemic motifs with a length of three half-turns (3HT). Dissociation constants (Kds) were measured for series of molecules in which the number of basepairs between the cross-over 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 = 1×10−8 M. The half-time for kinetic exchange of the 3HT_6M complex was determined to be ~100 minutes, from which we calculated association and dissociation rate constants ka = 5.11×103 M−1sec−1 and kd = 5.11×10−5 sec−1. RNA paranemic assembly of 3HT and 5HT complexes is blocked by single-base substitutions that disrupt individual inter-molecular 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. PMID:18072767

  1. SPIC: A novel similarity metric for comparing transcription factor binding site motifs based on information contents

    PubMed Central

    2013-01-01

    Background Discovering transcription factor binding sites (TFBS) is one of primary challenges to decipher complex gene regulatory networks encrypted in a genome. A set of short DNA sequences identified by a transcription factor (TF) is known as a motif, which can be expressed accurately in matrix form such as a position-specific scoring matrix (PSSM) and a position frequency matrix. Very frequently, we need to query a motif in a database of motifs by seeking its similar motifs, merge similar TFBS motifs possibly identified by the same TF, separate irrelevant motifs, or filter out spurious motifs. Therefore, a novel metric is required to seize slight differences between irrelevant motifs and highlight the similarity between motifs of the same group in all these applications. While there are already several metrics for motif similarity proposed before, their performance is still far from satisfactory for these applications. Methods A novel metric has been proposed in this paper with name as SPIC (Similarity with Position Information Contents) for measuring the similarity between a column of a motif and a column of another motif. When defining this similarity score, we consider the likelihood that the column of the first motif's PFM can be produced by the column of the second motif's PSSM, and multiply the likelihood by the information content of the column of the second motif's PSSM, and vise versa. We evaluated the performance of SPIC combined with a local or a global alignment method having a function for affine gap penalty, for computing the similarity between two motifs. We also compared SPIC with seven existing state-of-the-arts metrics for their capability of clustering motifs from the same group and retrieving motifs from a database on three datasets. Results When used jointly with the Smith-Waterman local alignment method with an affine gap penalty function (gap open penalty is equal to1, gap extension penalty is equal to 0.5), SPIC outperforms the seven

  2. 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

  3. 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.

  4. Using the Gibbs Motif Sampler for Phylogenetic Footprinting

    SciTech Connect

    Thompson, William; Conlan, Sean; McCue, Lee Ann; Lawrence, Charles

    2007-07-01

    The Gibbs Motif Sampler (Gibbs) (1) is a software package used to predict conserved elements in biopolymer sequences. While the software can be used to locate conserved motifs in protein sequences, its most common use is the prediction of transcription factor binding sites (TFBSs) in promoters upstream of gene sequences. We will describe approaches that use Gibbs to locate TFBSs in a collection of orthologous nucleotide sequences, i.e. phylogenetic footprinting. To illustrate this technique, we present examples that use Gibbs to detect binding sites for the transcription factor LexA in orthologous sequence data from representative species belonging to two different proteobacterial divisions.

  5. 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. PMID:23646825

  6. 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...

  7. Invisibly Sanitizable Digital Signature Scheme

    NASA Astrophysics Data System (ADS)

    Miyazaki, Kunihiko; Hanaoka, Goichiro; Imai, Hideki

    A digital signature does not allow any alteration of the document to which it is attached. Appropriate alteration of some signed documents, however, should be allowed because there are security requirements other than the integrity of the document. In the disclosure of official information, for example, sensitive information such as personal information or national secrets is masked when an official document is sanitized so that its nonsensitive information can be disclosed when it is requested by a citizen. If this disclosure is done digitally by using the current digital signature schemes, the citizen cannot verify the disclosed information because it has been altered to prevent the leakage of sensitive information. The confidentiality of official information is thus incompatible with the integrity of that information, and this is called the digital document sanitizing problem. Conventional solutions such as content extraction signatures and digitally signed document sanitizing schemes with disclosure condition control can either let the sanitizer assign disclosure conditions or hide the number of sanitized portions. The digitally signed document sanitizing scheme we propose here is based on the aggregate signature derived from bilinear maps and can do both. Moreover, the proposed scheme can sanitize a signed document invisibly, that is, no one can distinguish whether the signed document has been sanitized or not.

  8. 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.

  9. 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. PMID:19114635

  10. Mutations at the Signature Sequence of CFTR Create a Cd2+-gated Chloride Channel

    PubMed Central

    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 [Cd2+] can dramatically increase the activity of G551D-CFTR in the absence of ATP. This effect of Cd2+ 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 Cd2+ activation, suggesting an involvement of endogenous cysteine residue(s) in mediating this effect of Cd2+. The mutants G551C, L548C, and S549C, all in the signature sequence of CFTR's NBD1, show robust response to Cd2+. On the other hand, negligible effects of Cd2+ were seen with T547C, Q552C, and R553C, indicating that a specific region of the signature sequence is involved in transmitting the signal of Cd2+ binding to the gate. Collectively, these results suggest that the effect of Cd2+ 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. PMID:19114635