WorldWideScience

Sample records for trinucleotide bulged rna

  1. Role of the CCA bulge of prohead RNA of bacteriophage ø29 in DNA packaging.

    Science.gov (United States)

    Zhao, Wei; Morais, Marc C; Anderson, Dwight L; Jardine, Paul J; Grimes, Shelley

    2008-11-14

    The oligomeric ring of prohead RNA (pRNA) is an essential component of the ATP-driven DNA packaging motor of bacteriophage ø29. The A-helix of pRNA binds the DNA translocating ATPase gp16 (gene product 16) and the CCA bulge in this helix is essential for DNA packaging in vitro. Mutation of the bulge by base substitution or deletion showed that the size of the bulge, rather than its sequence, is primary in DNA packaging activity. Proheads reconstituted with CCA bulge mutant pRNAs bound the packaging ATPase gp16 and the packaging substrate DNA-gp3, although DNA translocation was not detected with several mutants. Prohead/bulge-mutant pRNA complexes with low packaging activity had a higher rate of ATP hydrolysis per base pair of DNA packaged than proheads with wild-type pRNA. Cryoelectron microscopy three-dimensional reconstruction of proheads reconstituted with a CCA deletion pRNA showed that the protruding pRNA spokes of the motor occupy a different position relative to the head when compared to particles with wild-type pRNA. Therefore, the CCA bulge seems to dictate the orientation of the pRNA spokes. The conformational changes observed for this mutant pRNA may affect gp16 conformation and/or subsequent ATPase-DNA interaction and, consequently, explain the decreased packaging activity observed for CCA mutants.

  2. A "bulged" double helix in a RNA-protein contact site

    DEFF Research Database (Denmark)

    Peattie, D A; Douthwaite, S; Garrett, R A

    1981-01-01

    as a singly bulged nucleotide extending the Fox and Woese central helix by two base pairs in the E. coli sequence (to positions 16-23/60-68) as well as in each of 61 (prokaryotic and eukaryotic) aligned 5S RNA sequences. In each case, the single bulged nucleotide is at the relative position of adenosine-66...... in the RNA sequences. The presence of this putative bulged nucleotide appears to have been conserved in 5S RNA sequences throughout evolution, and its identity varies with major phylogenetic divisions. This residue is likely involved in specific 5S RNA-protein recognition or interaction in prokaryotic...... and eukaryotic ribosomes. The uridine-65 to adenosine-66 internucleotide bond is protected from RNase A digestion in the complex, and carbethoxylation of E. coli adenosine-66 prior to L18 binding affects formation of a stable RNA-protein complex. Thus, we identify a region of E. coli 5S RNA protected...

  3. Improved Model for Predicting the Free Energy Contribution of Dinucleotide Bulges to RNA Duplex Stability.

    Science.gov (United States)

    Tomcho, Jeremy C; Tillman, Magdalena R; Znosko, Brent M

    2015-09-01

    Predicting the secondary structure of RNA is an intermediate in predicting RNA three-dimensional structure. Commonly, determining RNA secondary structure from sequence uses free energy minimization and nearest neighbor parameters. Current algorithms utilize a sequence-independent model to predict free energy contributions of dinucleotide bulges. To determine if a sequence-dependent model would be more accurate, short RNA duplexes containing dinucleotide bulges with different sequences and nearest neighbor combinations were optically melted to derive thermodynamic parameters. These data suggested energy contributions of dinucleotide bulges were sequence-dependent, and a sequence-dependent model was derived. This model assigns free energy penalties based on the identity of nucleotides in the bulge (3.06 kcal/mol for two purines, 2.93 kcal/mol for two pyrimidines, 2.71 kcal/mol for 5'-purine-pyrimidine-3', and 2.41 kcal/mol for 5'-pyrimidine-purine-3'). The predictive model also includes a 0.45 kcal/mol penalty for an A-U pair adjacent to the bulge and a -0.28 kcal/mol bonus for a G-U pair adjacent to the bulge. The new sequence-dependent model results in predicted values within, on average, 0.17 kcal/mol of experimental values, a significant improvement over the sequence-independent model. This model and new experimental values can be incorporated into algorithms that predict RNA stability and secondary structure from sequence.

  4. Ubiquitous expression of CUG or CAG trinucleotide repeat RNA causes common morphological defects in a Drosophila model of RNA-mediated pathology.

    Directory of Open Access Journals (Sweden)

    Kynan T Lawlor

    Full Text Available Expanded DNA repeat sequences are known to cause over 20 diseases, including Huntington's disease, several types of spinocerebellar ataxia and myotonic dystrophy type 1 and 2. A shared genetic basis, and overlapping clinical features for some of these diseases, indicate that common pathways may contribute to pathology. Multiple mechanisms, mediated by both expanded homopolymeric proteins and expanded repeat RNA, have been identified by the use of model systems, that may account for shared pathology. The use of such animal models enables identification of distinct pathways and their 'molecular hallmarks' that can be used to determine the contribution of each pathway in human pathology. Here we characterise a tergite disruption phenotype in adult flies, caused by ubiquitous expression of either untranslated CUG or CAG expanded repeat RNA. Using the tergite phenotype as a quantitative trait we define a new genetic system in which to examine 'hairpin' repeat RNA-mediated cellular perturbation. Further experiments use this system to examine whether pathways involving Muscleblind sequestration or Dicer processing, which have been shown to mediate repeat RNA-mediated pathology in other model systems, contribute to cellular perturbation in this model.

  5. Recognition of DNA/RNA bulges by antimicrobial and antitumor metallohelices

    Czech Academy of Sciences Publication Activity Database

    Malina, Jaroslav; Scott, P.; Brabec, Viktor

    2015-01-01

    Roč. 44, č. 33 (2015), s. 14656-14665 ISSN 1477-9226 R&D Projects: GA ČR(CZ) GAP205/11/0856 Institutional support: RVO:68081707 Keywords : CONTAINING DEOXYTRIDECANUCLEOTIDE DUPLEXES * HIV -1 TAR RNA * METALLOSUPRAMOLECULAR CYLINDERS Subject RIV: BO - Biophysics Impact factor: 4.177, year: 2015

  6. Galactic bulges

    CERN Document Server

    Peletier, Reynier; Gadotti, Dimitri

    2016-01-01

    This book consists of invited reviews on Galactic Bulges written by experts in the field. A central point of the book is that, while in the standard picture of galaxy formation a significant amount of the baryonic mass is expected to reside in classical bulges, the question what is the fraction of galaxies with no classical bulges in the local Universe has remained open. The most spectacular example of a galaxy with no significant classical bulge is the Milky Way. The reviews of this book attempt to clarify the role of the various types of bulges during the mass build-up of galaxies, based on morphology, kinematics, and stellar populations, and connecting their properties at low and high redshifts. The observed properties are compared with the predictions of the theoretical models, accounting for the many physical processes leading to the central mass concentration and their destruction in galaxies. This book serves as an entry point for PhD students and non-specialists and as a reference work for researchers...

  7. Eyes, Bulging (Proptosis)

    Science.gov (United States)

    ... Early Breast Cancer to Avoid Chemo Could a Blood Test Spot Lung Cancer Early? Experimental Drug Shows 'Modest' Benefit ... often done when bulging affects only one eye. Blood tests to measure how well the thyroid is working are done when ... When bulging leads to severe dry eyes, lubrication with artificial tears is needed to ...

  8. MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review of the literature.

    Science.gov (United States)

    Dumitrescu, Laura; Popescu, Bogdan O

    2015-01-01

    MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.

  9. Abundances in the Galactic bulge

    Energy Technology Data Exchange (ETDEWEB)

    Barbuy, B; Alves-Brito, A [Universidade de Sao Paulo, IAG, Rua do Matao 1226, Sao Paulo 05508-900 (Brazil); Ortolani, S; Zoccali, M [Dipartimento di Astronomia, Universita di Padova, Vicolo dell' Osservatorio 2, I-35122 Padova (Italy); Hill, V; Gomez, A [Observatoire de Paris-Meudon, 92195 Meudon Cedex (France); Melendez, J [Centro de AstrofIsica da Universidade de Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Asplund, M [Max Planck Institute for Astrophysics, Postfach 1317, 85741 Garching (Germany); Bica, E [Departamento de Astronomia, Universidade Federal do Rio Grande do Sul, CP 15051, Porto Alegre 91501-970 (Brazil); Renzini, A [Osservatorio Astronomico di Padova, Vicolo dell' Osservatorio 5, I-35122 Padova (Italy); Minniti, D [Department of Astronomy and Astrophysics, Universidad Catolica de Chile, Casilla 306, Santiago 22 (Chile)], E-mail: barbuy@astro.iag.usp.br

    2008-12-15

    The metallicity distribution and abundance ratios of the Galactic bulge are reviewed. Issues raised by recent work of different groups, in particular the high metallicity end, the overabundance of {alpha}-elements in the bulge relative to the thick disc and the measurement of giants versus dwarfs, are discussed. Abundances in the old moderately metal-poor bulge globular clusters are described.

  10. The effect of pre-mutation of X chromosome CGG trinucleotide repeats on brain anatomy.

    Science.gov (United States)

    Moore, Caroline J; Daly, Eileen M; Tassone, Flora; Tysoe, Carolyn; Schmitz, Nicole; Ng, Virginia; Chitnis, Xavier; McGuire, Philip; Suckling, John; Davies, Kay E; Hagerman, Randi J; Hagerman, Paul J; Murphy, Kieran C; Murphy, Declan G M

    2004-12-01

    Expanded trinucleotide repeats are associated with several neuropsychiatric disorders, including fragile X syndrome (FraX) which is the most common inherited form of mental retardation. It is currently thought that FraX results from having >200 CGG trinucleotide repeats, with consequent methylation of the fragile X mental retardation gene (FMR1) and loss of FMR1 protein (FMRP). Pre-mutation carriers of FraX (with 55-200 CGG trinucleotide repeats) were originally considered unaffected, although recent studies challenge this view. However, there are few studies on the effect of pre-mutation trinucleotide repeat expansion on the male human brain using quantitative MRI. Also the results of prior investigations may be confounded because people were selected on the basis of clinical and neurological features, and not genetic phenotype. We compared the brain anatomy of 20 adult male pre-mutation members of known FraX families with 20 healthy male controls. The two groups did not differ significantly in age, intelligence quotient (IQ) or handedness. We also investigated whether any observed effects were associated with: (i) ageing; (ii) expansion of pre-mutation CGG trinucleotide repeats; (iii) reduction in the percentage of lymphocytes staining with anti-FMRP antibodies [%FMRP(+) lymphocytes]; and (iv) elevation of FMR1 mRNA levels. Male pre-mutation carriers of FraX, compared with matched controls, had significantly less voxel density in several brain regions, including the cerebellum, amygdalo-hippocampal complex and thalamus. Within pre-mutation carriers of FraX, ageing, increases in the number of CGG trinucleotide repeats and decreases in %FMRP(+) lymphocytes were associated with decreasing voxel density of regions previously identified as decreased relative to controls. Regional grey and white matter density is significantly affected in male pre-mutation carriers of FraX recruited on the basis of genetic, not clinical, phenotype. The association of voxel density

  11. Solving the Mystery of Galaxy Bulges and Bulge Substructure

    Science.gov (United States)

    Erwin, Peter

    2017-08-01

    Understanding galaxy bulges is crucial for understanding galaxy evolution and the growth of supermassive black holes (SMBHs). Recent studies have shown that at least some - perhaps most - disk-galaxy bulges are actually composite structures, with both classical-bulge (spheroid) and pseudobulge (disky) components; this calls into question the standard practice of using simple, low-resolution bulge/disk decompositions to determine spheroid and SMBH mass functions. We propose WFC3 optical and near-IR imaging of a volume- and mass-limited sample of local disk galaxies to determine the full range of pure-classical, pure-pseudobulge, and composite-bulge frequencies and parameters, including stellar masses for classical bulges, disky pseudobulges, and boxy/peanut-shaped bulges. We will combine this with ground-based spectroscopy to determine the stellar-kinematic and population characteristics of the different substructures revealed by our WFC3 imaging. This will help resolve growing uncertainties about the status and nature of bulges and their relation to SMBH masses, and will provide an essential local-universe reference for understanding bulge (and SMBH) formation and evolution.

  12. Velocity Dispersions Across Bulge Types

    International Nuclear Information System (INIS)

    Fabricius, Maximilian; Bender, Ralf; Hopp, Ulrich; Saglia, Roberto; Drory, Niv; Fisher, David

    2010-01-01

    We present first results from a long-slit spectroscopic survey of bulge kinematics in local spiral galaxies. Our optical spectra were obtained at the Hobby-Eberly Telescope with the LRS spectrograph and have a velocity resolution of 45 km/s (σ*), which allows us to resolve the velocity dispersions in the bulge regions of most objects in our sample. We find that the velocity dispersion profiles in morphological classical bulge galaxies are always centrally peaked while the velocity dispersion of morphologically disk-like bulges stays relatively flat towards the center--once strongly barred galaxies are discarded.

  13. ATXN2 trinucleotide repeat length correlates with risk of ALS.

    Science.gov (United States)

    Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar

    2017-03-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2  = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Grid sleeve bulge tool

    International Nuclear Information System (INIS)

    Phillips, W.D.; Vaill, R.E.

    1980-01-01

    An improved grid sleeve bulge tool is designed for securing control rod guide tubes to sleeves brazed in a fuel assembly grid. The tool includes a cylinder having an outer diameter less than the internal diameter of the control rod guide tubes. The walls of the cylinder are cut in an axial direction along its length to provide several flexible tines or ligaments. These tines are similar to a fork except they are spaced in a circumferential direction. The end of each alternate tine is equipped with a semispherical projection which extends radially outwardly from the tine surface. A ram or plunger of generally cylindrical configuration and about the same length as the cylinder is designed to fit in and move axially of the cylinder and thereby force the tined projections outwardly when the ram is pulled into the cylinder. The ram surface includes axially extending grooves and plane surfaces which are complimentary to the inner surfaces formed on the tines on the cylinder. As the cylinder is inserted into a control rod guide tube, and the projections on the cylinder placed in a position just below or above a grid strap, the ram is pulled into the cylinder, thus moving the tines and the projections thereon outwardly into contact with the sleeve, to plastically deform both the sleeve and the control rod guide tube, and thereby form four bulges which extend outwardly from the sleeve surface and beyond the outer periphery of the grid peripheral strap. This process is then repeated at the points above the grid to also provide for outwardly projecting surfaces, the result being that the grid is accurately positioned on and mechanically secured to the control rod guide tubes which extend the length of a fuel assembly

  15. ATXN2 trinucleotide repeat length correlates with risk of ALS

    NARCIS (Netherlands)

    Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M.; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard W; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy A.; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H.; van den Berg, Leonard H.; Shaw, Christopher E; Powell, John F.; Al-Chalabi, Ammar

    2017-01-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we

  16. Trinucleotide repeat microsatellite markers for Black Poplar (Populus nigra L.)

    NARCIS (Netherlands)

    Smulders, M.J.M.; Schoot, van der J.; Arens, P.; Vosman, B.

    2001-01-01

    Using an enrichment procedure, we have cloned microsatellite repeats from black poplar (Populus nigra L.) and developed primers for microsatellite marker analysis. Ten primer pairs, mostly for trinucleotide repeats, produced polymorphic fragments in P. nigra. Some of them also showed amplification

  17. Living with a parastomal bulge

    DEFF Research Database (Denmark)

    Krogsgaard, Marianne; Thomsen, Thordis; Vinther, Anders

    2017-01-01

    was performed using a phenomenological-hermeneutic approach. FINDINGS: The bulge caused different unfamiliar bodily sensations that interacted with patients' everyday lives. Some but not all of these sensations were modifiable. As the bulge and the ostomy changed size and shape, patients had to adjust...... and readjust stoma care continuously. The physical change called for patients' awareness and posed a threat to patients' control of the ostomy and challenged stoma self-care. The bulge caused a bodily asymmetry that deformed the patients' bodies in a way that exceeded the perceived alteration already caused...... is limited and highly warranted to improve clinical outcome. RELEVANCE TO CLINICAL PRACTICE: The ever-changing bulge posed a threat to patients' control of the ostomy and required specific care from the stoma therapist. Needs-based access to counselling, advice and supplementary materials is important....

  18. Conformational properties of trinucleotide repeats associated with human neurodegenerative diseases

    Czech Academy of Sciences Publication Activity Database

    Vorlíčková, Michaela; Renčiuk, Daniel; Fojtík, Petr; Zemánek, Michal; Kejnovská, Iva

    2007-01-01

    Roč. 24, č. 6 (2007), s. 745 ISSN 0739-1102. [The 15th Conversation . 19.06.2007-23.06.2007, Albany] R&D Projects: GA AV ČR(CZ) IAA100040701; GA ČR(CZ) GA204/07/0057 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : DNA conformational properties * trinucleotide repeats * fragile X chromosome Subject RIV: BO - Biophysics

  19. RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

    OpenAIRE

    Aisling Frizzell; Jennifer H.G. Nguyen; Mark I.R. Petalcorin; Katherine D. Turner; Simon J. Boulton; Catherine H. Freudenreich; Robert S. Lahue

    2014-01-01

    SUMMARY Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG·CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vi...

  20. Improved guide tube bulge tool

    International Nuclear Information System (INIS)

    Vaill, R.E.; Phillips, W.D.

    1979-01-01

    A guide tube bulge tool for securing control rod guide tubes to a fuel assembly grid, includes a cylinder having several flexible tines each of which is equipped with a semispherical radially outwardly extending projection. A tapered ram fits into the cylinder so as to force the tines outwardly when the ram is pulled into the cylinder while supporting the other tines. (UK)

  1. Non-radioactive detection of trinucleotide repeat size variability.

    Science.gov (United States)

    Tomé, Stéphanie; Nicole, Annie; Gomes-Pereira, Mario; Gourdon, Genevieve

    2014-03-06

    Many human diseases are associated with the abnormal expansion of unstable trinucleotide repeat sequences. The mechanisms of trinucleotide repeat size mutation have not been fully dissected, and their understanding must be grounded on the detailed analysis of repeat size distributions in human tissues and animal models. Small-pool PCR (SP-PCR) is a robust, highly sensitive and efficient PCR-based approach to assess the levels of repeat size variation, providing both quantitative and qualitative data. The method relies on the amplification of a very low number of DNA molecules, through sucessive dilution of a stock genomic DNA solution. Radioactive Southern blot hybridization is sensitive enough to detect SP-PCR products derived from single template molecules, separated by agarose gel electrophoresis and transferred onto DNA membranes. We describe a variation of the detection method that uses digoxigenin-labelled locked nucleic acid probes. This protocol keeps the sensitivity of the original method, while eliminating the health risks associated with the manipulation of radiolabelled probes, and the burden associated with their regulation, manipulation and waste disposal.

  2. Molecular analysis of the eTG trinucleotide repeat in South African ...

    African Journals Online (AJOL)

    -4 When amplified, this trinucleotide repeat is responsible for DNA instability and molecular pathology. A similar mechanism of trinucleotide repeat expansion has been described in fragile X mental retardation syndrome. (CGG):·· spinobulbar muscular atrophy (CAG)' and, more. MRC Human Ecogenetics Research Unit, ...

  3. Ancient conservation of trinucleotide microsatellite loci in polistine wasps

    DEFF Research Database (Denmark)

    Ezenwa, V O; Peters, J M; Zhu, Y

    1998-01-01

    Microsatellites have proven to be very useful genetic markers for studies of kinship, parentage, and gene mapping. If microsatellites are conserved among species, then those developed for one species can be used on related species, which would save the time and effort of developing new loci. We...... evaluated conservation of 27 trinucleotide loci that were derived from 2 species of Polistes wasps in cross-species applications on 27 species chosen from the major lineages of the Vespidae, which diverged as much as 144 million years ago. We further investigated cross-species polymorphism levels for 18...... of the loci. There was a clear relationship between cladistic distance and both conservation of the priming sites and heterozygosity. However the loci derived from P. bellicosus were much more widely conserved and polymorphic than were those derived from P. annularis. The disparity in cross-species utility...

  4. Instability of (CTGn•(CAGn trinucleotide repeats and DNA synthesis

    Directory of Open Access Journals (Sweden)

    Liu Guoqi

    2012-02-01

    Full Text Available Abstract Expansion of (CTGn•(CAGn trinucleotide repeat (TNR microsatellite sequences is the cause of more than a dozen human neurodegenerative diseases. (CTGn and (CAGn repeats form imperfectly base paired hairpins that tend to expand in vivo in a length-dependent manner. Yeast, mouse and human models confirm that (CTGn•(CAGn instability increases with repeat number, and implicate both DNA replication and DNA damage response mechanisms in (CTGn•(CAGn TNR expansion and contraction. Mutation and knockdown models that abrogate the expression of individual genes might also mask more subtle, cumulative effects of multiple additional pathways on (CTGn•(CAGn instability in whole animals. The identification of second site genetic modifiers may help to explain the variability of (CTGn•(CAGn TNR instability patterns between tissues and individuals, and offer opportunities for prognosis and treatment.

  5. Ultrasonographic findings in patients with peristomal bulging

    DEFF Research Database (Denmark)

    Sjödahl, Rune I; Thorelius, Lars; Hallböök, Olof J

    2011-01-01

    The aim of this study was to obtain a classification of peristomal bulging based on findings at ultrasonography in patients with a sigmoid colostomy.......The aim of this study was to obtain a classification of peristomal bulging based on findings at ultrasonography in patients with a sigmoid colostomy....

  6. Environmental stress induces trinucleotide repeat mutagenesis in human cells.

    Science.gov (United States)

    Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

    2015-03-24

    The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

  7. RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

    Directory of Open Access Journals (Sweden)

    Aisling Frizzell

    2014-03-01

    Full Text Available Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG repeat expansions and fragility, likely by unwinding problematic hairpins.

  8. RTEL1 inhibits trinucleotide repeat expansions and fragility.

    Science.gov (United States)

    Frizzell, Aisling; Nguyen, Jennifer H G; Petalcorin, Mark I R; Turner, Katherine D; Boulton, Simon J; Freudenreich, Catherine H; Lahue, Robert S

    2014-03-13

    Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG) repeat expansions and fragility, likely by unwinding problematic hairpins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Regional intercostal bulging of the parietal pleura

    International Nuclear Information System (INIS)

    Jantsch, H.; Greene, R.; Lechner, G.; Mavritz, W.; Pichler, W.; Winkler, M.; Zadrobilek, E.

    1989-01-01

    This paper describes bedside radiographs with localized intercostal bulging as the sole indication of tension pneumothorax in six patients with acute deterioration in gas exchange. Relief of the pneumothorax was followed by a rush of gas from the tension space and a prompt improvement in gas exchange. The authors concluded the regional intercostal bulging of the parietal pleura may be the sole indicator of life-threatening tension pneumothorax in patients on mechanical ventilation

  10. Phylogenetic tree construction using trinucleotide usage profile (TUP).

    Science.gov (United States)

    Chen, Si; Deng, Lih-Yuan; Bowman, Dale; Shiau, Jyh-Jen Horng; Wong, Tit-Yee; Madahian, Behrouz; Lu, Henry Horng-Shing

    2016-10-06

    It has been a challenging task to build a genome-wide phylogenetic tree for a large group of species containing a large number of genes with long nucleotides sequences. The most popular method, called feature frequency profile (FFP-k), finds the frequency distribution for all words of certain length k over the whole genome sequence using (overlapping) windows of the same length. For a satisfactory result, the recommended word length (k) ranges from 6 to 15 and it may not be a multiple of 3 (codon length). The total number of possible words needed for FFP-k can range from 4 6 =4096 to 4 15 . We propose a simple improvement over the popular FFP method using only a typical word length of 3. A new method, called Trinucleotide Usage Profile (TUP), is proposed based only on the (relative) frequency distribution using non-overlapping windows of length 3. The total number of possible words needed for TUP is 4 3 =64, which is much less than the total count for the recommended optimal "resolution" for FFP. To build a phylogenetic tree, we propose first representing each of the species by a TUP vector and then using an appropriate distance measure between pairs of the TUP vectors for the tree construction. In particular, we propose summarizing a DNA sequence by a matrix of three rows corresponding to three reading frames, recording the frequency distribution of the non-overlapping words of length 3 in each of the reading frame. We also provide a numerical measure for comparing trees constructed with various methods. Compared to the FFP method, our empirical study showed that the proposed TUP method is more capable of building phylogenetic trees with a stronger biological support. We further provide some justifications on this from the information theory viewpoint. Unlike the FFP method, the TUP method takes the advantage that the starting of the first reading frame is (usually) known. Without this information, the FFP method could only rely on the frequency distribution of

  11. KINEMATIC SIGNATURES OF BULGES CORRELATE WITH BULGE MORPHOLOGIES AND SÉRSIC INDEX

    International Nuclear Information System (INIS)

    Fabricius, Maximilian H.; Saglia, Roberto P.; Bender, Ralf; Hopp, Ulrich; Fisher, David B.; Drory, Niv

    2012-01-01

    We use the Marcario Low Resolution Spectrograph at the Hobby-Eberly Telescope to study the kinematics of pseudobulges and classical bulges in the nearby universe. We present major axis rotational velocities, velocity dispersions, and h 3 and h 4 moments derived from high-resolution (σ inst ≈ 39 km s –1 ) spectra for 45 S0 to Sc galaxies; for 27 of the galaxies we also present minor axis data. We combine our kinematics with bulge-to-disk decompositions. We demonstrate for the first time that purely kinematic diagnostics of the bulge dichotomy agree systematically with those based on Sérsic index. Low Sérsic index bulges have both increased rotational support (higher v/σ values) and on average lower central velocity dispersions. Furthermore, we confirm that the same correlation also holds when visual morphologies are used to diagnose bulge type. The previously noted trend of photometrically flattened bulges to have shallower velocity dispersion profiles turns out to be significant and systematic if the Sérsic index is used to distinguish between pseudobulges and classical bulges. The anti-correlation between h 3 and v/σ observed in elliptical galaxies is also observed in intermediate-type galaxies, irrespective of bulge type. Finally, we present evidence for formerly undetected counter-rotation in the two systems NGC 3945 and NGC 4736.

  12. Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

    Directory of Open Access Journals (Sweden)

    Agathi-Vasiliki Goula

    2013-07-01

    Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

  13. Does the Galactic Bulge Have Fewer Planets?

    Science.gov (United States)

    Kohler, Susanna

    2016-12-01

    The Milky Ways dense central bulge is a very different environment than the surrounding galactic disk in which we live. Do the differences affect the ability of planets to form in the bulge?Exploring Galactic PlanetsSchematic illustrating how gravitational microlensing by an extrasolar planet works. [NASA]Planet formation is a complex process with many aspects that we dont yet understand. Do environmental properties like host star metallicity, the density of nearby stars, or the intensity of the ambient radiation field affect the ability of planets to form? To answer these questions, we will ultimately need to search for planets around stars in a large variety of different environments in our galaxy.One way to detect recently formed, distant planets is by gravitational microlensing. In this process, light from a distant source star is bent by a lens star that is briefly located between us and the source. As the Earth moves, this momentary alignment causes a blip in the sources light curve that we can detect and planets hosted by the lens star can cause an additional observable bump.Artists impression of the Milky Way galaxy. The central bulge is much denserthan the surroundingdisk. [ESO/NASA/JPL-Caltech/M. Kornmesser/R. Hurt]Relative AbundancesMost source stars reside in the galactic bulge, so microlensing events can probe planetary systems at any distance between the Earth and the galactic bulge. This means that planet detections from microlensing could potentially be used to measure the relative abundances of exoplanets in different parts of our galaxy.A team of scientists led by Matthew Penny, a Sagan postdoctoral fellow at Ohio State University, set out to do just that. The group considered a sample of 31 exoplanetary systems detected by microlensing and asked the following question: are the planet abundances in the galactic bulge and the galactic disk the same?A Paucity of PlanetsTo answer this question, Penny and collaborators derived the expected

  14. Isolation and characterization of trinucleotide repeat microsatellite markers for Plutella xylostella L.

    NARCIS (Netherlands)

    Esselink, G.D.; Belder, den E.; Elderson, J.; Smulders, M.J.M.

    2006-01-01

    Thirteen microsatellite markers generating high quality patterns have been developed and characterized for diamondback moth (Plutella xylostella L.), of which 11 are based on trinucleotide repeats. These markers are polymorphic, generating up to 15 alleles in a test set of 12 caterpillars. The

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

    KAUST Repository

    Viterbo, David

    2016-03-16

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

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

    KAUST Repository

    Viterbo, David; Michoud, Gregoire; Mosbach, Valentine; Dujon, Bernard; Richard, Guy-Franck

    2016-01-01

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

  17. Functional myelographic differentiation of lumbar bulging annulus

    Energy Technology Data Exchange (ETDEWEB)

    Park, Choong Ki; Kim, Hong Kil; Park, Sang Gyu; Lee, Young Jung; Yoon, Jong Sup [Hallym University College of Medicine, Seoul (Korea, Republic of)

    1988-08-15

    Herniated disk and bulging annulus are the major causes of lower back pain. It is necessary to differentiate bulging annulus from herniated disk because of their different methods of treatment. Myelography is one of the useful diagnostic methods for disk diseases even though advanced diagnostic modalities such as CT and MRI are more accurate. Functional myelography is not a new technology expect for two additional views, flexion and extension, are obtained with conventional myelography. Differentiation between bulging annulus and herniated disk by conventional myelography is based on the extent and multiplicity of extradural deformity of the contrast filled dural sac and neural sleeve as well as the changes of nerve root. There is no previous report about differential points between bulging annulus and herniated disk according to functional myelography. It is the purpose of this study to find any additional differential points on functional myelography between bulging annulus and herniated disk over convectional myelography. Authors analysed functional myelographic findings of 152 cases from July 1986 to July 1987. Among them, 22 cases who had been suffered from cervical abnormality or vague lower back pain were diagnosed as normal by myelography, and 30 cases of L4-5 herniated disk and 21 cases of L4-5 bulging annulus which had been finally diagnosed by operation were studied. The results were as follows. 1. In normal group, anterior epidural space was gradually widened from the upper lumbar vertebra downward. And anterior epidural space was more sidened at the disk level in extension view than in flexion except for L5-S1 lever. 2. In bulging annulus group, the shape of anterior epidural space in flexion state was as similar as normal. Anoterior epidural space in extension state was more sidened at the buldging annulus than normal, but lesser than herniated disk. 3. In herniated disk group, widening of anterior epidural space at the herniated disk level was

  18. RNA.

    Science.gov (United States)

    Darnell, James E., Jr.

    1985-01-01

    Ribonucleic acid (RNA) converts genetic information into protein and usually must be processed to serve its function. RNA types, chemical structure, protein synthesis, translation, manufacture, and processing are discussed. Concludes that the first genes might have been spliced RNA and that humans might be closer than bacteria to primitive…

  19. The intrinsic shape of bulges in the CALIFA survey

    Science.gov (United States)

    Costantin, L.; Méndez-Abreu, J.; Corsini, E. M.; Eliche-Moral, M. C.; Tapia, T.; Morelli, L.; Dalla Bontà, E.; Pizzella, A.

    2018-02-01

    Context. The intrinsic shape of galactic bulges in nearby galaxies provides crucial information to separate bulge types. Aims: We aim to derive accurate constraints to the intrinsic shape of bulges to provide new clues on their formation mechanisms and set new limitations for future simulations. Methods: We retrieved the intrinsic shape of a sample of CALIFA bulges using a statistical approach. Taking advantage of GalMer numerical simulations of binary mergers we estimated the reliability of the procedure. Analyzing the i-band mock images of resulting lenticular remnants, we studied the intrinsic shape of their bulges at different galaxy inclinations. Finally, we introduced a new (B/A, C/A) diagram to analyze possible correlations between the intrinsic shape and the properties of bulges. Results: We tested the method on simulated lenticular remnants, finding that for galaxies with inclinations of 25° ≤ θ ≤ 65° we can safely derive the intrinsic shape of their bulges. We found that our CALIFA bulges tend to be nearly oblate systems (66%), with a smaller fraction of prolate spheroids (19%), and triaxial ellipsoids (15%). The majority of triaxial bulges are in barred galaxies (75%). Moreover, we found that bulges with low Sérsic indices or in galaxies with low bulge-to-total luminosity ratios form a heterogeneous class of objects; additionally, bulges in late-type galaxies or in less massive galaxies have no preference for being oblate, prolate, or triaxial. On the contrary, bulges with high Sérsic index, in early-type galaxies, or in more massive galaxies are mostly oblate systems. Conclusions: We concluded that various evolutionary pathways may coexist in galaxies, with merging events and dissipative collapse being the main mechanisms driving the formation of the most massive oblate bulges and bar evolution reshaping the less massive triaxial bulges.

  20. Effect of massive disks on bulge isophotes

    International Nuclear Information System (INIS)

    Monet, D.G.; Richstone, D.O.; Schechter, P.L.

    1981-01-01

    Massive disks produce flattened equipotentials. Unless the stars in a galaxy bulge are preferentially hotter in the z direction than in the plane, the isophotes will be at least as flat as the equipotentials. The comparison of two galaxy models having flat rotation curves with the available surface photometry for five external galaxies does not restrict the mass fraction which might reside in the disk. However, star counts in our own Galaxy indicate that unless the disk terminates close to the solar circle, no more than half the mass within that circle lies in the disk. The remaining half must lie either in the bulge or, more probably, in a third dark, round, dynamically distinct component

  1. Rotation of the bulge components of barred galaxies

    International Nuclear Information System (INIS)

    Kormendy, J.

    1982-01-01

    Stellar rotation and velocity-dispersion measurements are presented for the bulge components of the SBO galaxies NGC 1023, 2859, 2950, 4340, 4371, and 7743. The kinematics of nine SB bulges with data available are compared with bulges of unbarred galaxies studied by Kormendy and Illingworth. All of the SB bulges are found to rotate at least as rapidly as oblate-spheroid dynamical models which are flattened by rotation. This result confirms the conclusion of Kormendy and Illingworth that bulges rotate very rapidly. Six SB bulges found by Kormendy and Koo to be triaxial rotate even more rapidly than the oblate models. In this respect, they resemble published n-body models of bars. That is, triaxial bulges are dynamically like bars and unlike elliptical galaxies, which are also believed to be triaxial, but which rotate slowly. Measured velocity anisotropies are found to be consistent with these conclusions. Two ordinary bulges whose rotation is well described by isotropic modes have a ratio of radial to azimuthal velocity dispersion of sigma/sub r//sigma/sub theta/ = 0.96 +- 0.03. In contrast, the triaxial bulge of NGC 3945, which rotates much faster than the isotropic models, has sigma/sub r//sigma/sub theta/ approx.1.31 +- 0.06. This is similar to the degree of anisotropy, sigma/sub r//sigma/sub theta/approx.1.21 +- 0.03, found in a recent n-body bar model by Hohl and Zang. Altogether the kinematic observations imply the triaxial bulges are more disklike than SA bulges. They appear to have been formed with more dissipation than ordinary bulges. These results are consistent with the hypothesis that part of the bulge in many SB galaxies consists of disk material (i.e., gas) which has been transported to the center by the bar. The resulting star formation may produce a very centrally concentrated light distribution which resembles a bulge but which has dislike dynamics

  2. Spatial analyses of mono, di and trinucleotide trends in plant genes.

    Directory of Open Access Journals (Sweden)

    Andrea Porceddu

    Full Text Available Genomic DNA sequences display compositional heterogeneity on many scales. In this paper we analyzed tendencies and anomalies in the occurence of mono, di and trinucleotides in structural regions of plant genes. Representation of these trends as a function of position along genic sequences highlighted compositional features peculiar of either monocots or eudicots that were remarkably uniform within these two evolutionary clades. The most evident of these features appeared in the form of gradient of base content along the direction of transcription. The robustness of such a representation was validated in sequences sub-datasets generated considering structural and compositional features such as total length of cds, overall GC content and genic orientation in the genome. Piecewise regression analyses indicated that the gradients could be conveniently approximated to a two segmented model where a first region featuring a steep slope is followed by a second segment fitting a milder variation. In general, monocots species showed steeper segments than eudicots. The guanine gradient was the most distinctive feature between the two evolutionary clades, being moderately increasing in eudicots and firmly decreasing in monocots. Single gene investigation revealed that a high proportion of genes show compositional trends compatible with a segmented model suggesting that these features are essential attributes of gene organization. Dinucleotide and trinucleotide biases were referred to expectation based on a random union of the component elements. The average bias at dinucleotide level identified a significant undererpresentation of some dinucleotide and the overrepresention of others. The bias at trinucleotide level was on average low. Finally, the analysis of bryophyte coding sequences showed mononucleotide, dinucleotide and trinucleotide compositional trends resembling those of higher plants. This finding suggested that the emergenge of compositional bias

  3. Structure Based Sequence Dependent Stiffness Scale for Trinucleotides: A Direct Method

    OpenAIRE

    Gromiha, M. Michael

    2000-01-01

    A new set of stiffness parameters for all the 32trinucleotide units has been set up directly from thethree dimensional structures of DNA molecules. It wasobserved that GAC/GTC is the stiffest trinucleotideand ACC/GGT is the most flexible one. The averagestiffness values computed for a set of operatorsequences using the new parameters correlate very wellwith the protein-DNA binding specificity and bindingfree energy change of 434 repressor and Cro repressor,respectively. The new structure base...

  4. Nuclear starburst activity induced by elongated bulges in spiral galaxies

    Science.gov (United States)

    Kim, Eunbin; Kim, Sungsoo S.; Choi, Yun-Young; Lee, Gwang-Ho; de Grijs, Richard; Lee, Myung Gyoon; Hwang, Ho Seong

    2018-06-01

    We study the effects of bulge elongation on the star formation activity in the centres of spiral galaxies using the data from the Sloan Digital Sky Survey Data Release 7. We construct a volume-limited sample of face-on spiral galaxies with Mr nuclear starbursts using the fibre specific star formation rates derived from the SDSS spectra. We find a statistically significant correlation between bulge elongation and nuclear starbursts in the sense that the fraction of nuclear starbursts increases with bulge elongation. This correlation is more prominent for fainter and redder galaxies, which exhibit higher ratios of elongated bulges. We find no significant environmental dependence of the correlation between bulge elongation and nuclear starbursts. These results suggest that non-axisymmetric bulges can efficiently feed the gas into the centre of galaxies to trigger nuclear starburst activity.

  5. Monitoring and Mapping the Galactic Bulge

    Science.gov (United States)

    Markwardt, Craig

    Both neutron star and black hole binary transients are providing some of the most exciting RXTE science, and fortunately many are concentrated in the galactic bulge region. We propose to continue our twice weekly PCA scans of the region, which cover about 500 sq deg. The observations will be sensitive to new sources at the ~1 mCrab level (a factor of 10-60 more sensitive than the ASM in the region). We have had success finding new sources and new types of variability, including three millisecond pulsars, and new increased solid angle will improve the chances of finding more in the final RXTE years. We will continue efforts to search for variability in new and known sources. Companion follow-up proposals would be triggered by the results.

  6. BULGE n AND B/T IN HIGH-MASS GALAXIES: CONSTRAINTS ON THE ORIGIN OF BULGES IN HIERARCHICAL MODELS

    International Nuclear Information System (INIS)

    Weinzirl, Tim; Jogee, Shardha; Kormendy, John; Khochfar, Sadegh; Burkert, Andreas

    2009-01-01

    We use the bulge Sersic index n and bulge-to-total mass ratio (B/T) to explore the fundamental question of how bulges form. We perform two-dimensional bulge-disk-bar decomposition on H-band images of 143 bright, high-mass (M * ≥ 1.0 x 10 10 M sun ) low-to-moderately inclined (i 0 ) spirals. Our results are as follows. (1) Our H-band bar fraction (∼58%) is consistent with that from ellipse fits. (2) 70% of the stellar mass is in disks, 10% in bars, and 20% in bulges. (3) A large fraction (∼69%) of bright spirals have B/T≤ 0.2, and ∼76% have low n ≤ 2 bulges. These bulges exist in barred and unbarred galaxies across a wide range of Hubble types. (4) About 65% (68%) of bright spirals with n ≤ 2 (B/T ≤ 0.2) bulges host bars, suggesting a possible link between bars and bulges. (5) We compare the results with predictions from a set of ΛCDM models. In the models, a high-mass spiral can have a bulge with a present-day low B/T≤ 0.2 only if it did not undergo a major merger since z ≤ 2. The predicted fraction (∼ 1.6%) of high-mass spirals, which have undergone a major merger since z ≤ 4 and host a bulge with a present-day low B/T ≤ 0.2, is a factor of over 30 smaller than the observed fraction (∼66%) of high-mass spirals with B/T ≤ 0.2. Thus, contrary to common perception, bulges built via major mergers since z ≤ 4 seriously fail to account for the bulges present in ∼66% of high mass spirals. Most of these present-day low B/T ≤ 0.2 bulges are likely to have been built by a combination of minor mergers and/or secular processes since z ≤ 4.

  7. The formation of the Galactic bulge of the Milky Way

    Directory of Open Access Journals (Sweden)

    Freeman K.

    2012-02-01

    Full Text Available We aim to determine if the bulge formed via mergers as predicted by Cold Dark Matter (CDM theory, or from disk instabilities, as suggested by its boxy shape, or both processes. We are observing about 28,000 bulge stars in fields that span longitudes of − 31 to + 26° and latitudes of − 5° to − 10°, targeting mostly red clump giants and we are measuring stellar velocities and chemical abundances. We have almost concluded our observations and have analysed data of 23,000 stars. We find a cylindrical rotation profile for the bulge which blends smoothly out into the disk and from the [Fe/H] results we find the bulge to be comprised of separate components, with an underlying slowly rotating metal poor subsample which we believe to be the inner halo stars and metal weak thick disk. We find only a small [Fe/H] gradient with latitude in the bulge, of − 0.07dex/kpc. This weak gradient does not necessarily support a merger origin for our bulge and the composite nature of the bulge is consistent with formation out of the thin disk as per instability formation models.

  8. Tube Bulge Process : Theoretical Analysis and Finite Element Simulations

    International Nuclear Information System (INIS)

    Velasco, Raphael; Boudeau, Nathalie

    2007-01-01

    This paper is focused on the determination of mechanics characteristics for tubular materials, using tube bulge process. A comparative study is made between two different models: theoretical model and finite element analysis. The theoretical model is completely developed, based first on a geometrical analysis of the tube profile during bulging, which is assumed to strain in arc of circles. Strain and stress analysis complete the theoretical model, which allows to evaluate tube thickness and state of stress, at any point of the free bulge region. Free bulging of a 304L stainless steel is simulated using Ls-Dyna 970. To validate FE simulations approach, a comparison between theoretical and finite elements models is led on several parameters such as: thickness variation at the free bulge region pole with bulge height, tube thickness variation with z axial coordinate, and von Mises stress variation with plastic strain. Finally, the influence of geometrical parameters deviations on flow stress curve is observed using analytical model: deviations of the tube outer diameter, its initial thickness and the bulge height measurement are taken into account to obtain a resulting error on plastic strain and von Mises stress

  9. The gravitational self-interaction of the Earth's tidal bulge

    Science.gov (United States)

    Norsen, Travis; Dreese, Mackenzie; West, Christopher

    2017-09-01

    According to a standard, idealized analysis, the Moon would produce a 54 cm equilibrium tidal bulge in the Earth's oceans. This analysis omits many factors (beyond the scope of the simple idealized model) that dramatically influence the actual height and timing of the tides at different locations, but it is nevertheless an important foundation for more detailed studies. Here, we show that the standard analysis also omits another factor—the gravitational interaction of the tidal bulge with itself—which is entirely compatible with the simple, idealized equilibrium model and which produces a surprisingly non-trivial correction to the predicted size of the tidal bulge. Our analysis uses ideas and techniques that are familiar from electrostatics, and should thus be of interest to teachers and students of undergraduate E&M, Classical Mechanics (and/or other courses that cover the tides), and geophysics courses that cover the closely related topic of Earth's equatorial bulge.

  10. COBE diffuse infrared background experiment observations of the galactic bulge

    Science.gov (United States)

    Weiland, J. L.; Arendt, R. G.; Berriman, G. B.; Dwek, E.; Freudenreich, H. T.; Hauser, M. G.; Kelsall, T.; Lisse, C. M.; Mitra, M.; Moseley, S. H.

    1994-01-01

    Low angular resolution maps of the Galactic bulge at 1.25, 2.2, 3.5, and 4.9 micrometers obtained by the Diffuse Infrared Background Experiment (DIRBE) onboard NASA's Cosmic Background Explorer (COBE) are presented. After correction for extinction and subtraction of an empirical model for the Galactic disk, the surface brightness distribution of the bulge resembles a flattened ellipse with a minor-to-major axis ratio of approximately 0.6. The bulge minor axis scale height is found to be 2.1 deg +/- 0.2 deg for all four near-infrared wavelengths. Asymmetries in the longitudinal distribution of bulge brightness contours are qualitatively consistent with those expected for a triaxial bar with its near end in the first Galactic quadrant (0 deg less than l less than 90 deg). There is no evidence for an out-of-plane tilt of such a bar.

  11. Analysis of Terminal Metallic Armor Plate Free-Surface Bulging

    National Research Council Canada - National Science Library

    Rapacki, Jr, E. J

    2008-01-01

    An analysis of the bulge formed on the free-surface of the terminal metallic plate of an armor array is shown to lead to reasonable estimates of the armor array's remaining penetration/perforation resistance...

  12. Environmental Stress Induces Trinucleotide Repeat Mutagenesis in Human Cells by Alt-Nonhomologous End Joining Repair.

    Science.gov (United States)

    Chatterjee, Nimrat; Lin, Yunfu; Yotnda, Patricia; Wilson, John H

    2016-07-31

    Multiple pathways modulate the dynamic mutability of trinucleotide repeats (TNRs), which are implicated in neurodegenerative disease and evolution. Recently, we reported that environmental stresses induce TNR mutagenesis via stress responses and rereplication, with more than 50% of mutants carrying deletions or insertions-molecular signatures of DNA double-strand break repair. We now show that knockdown of alt-nonhomologous end joining (alt-NHEJ) components-XRCC1, LIG3, and PARP1-suppresses stress-induced TNR mutagenesis, in contrast to the components of homologous recombination and NHEJ, which have no effect. Thus, alt-NHEJ, which contributes to genetic mutability in cancer cells, also plays a novel role in environmental stress-induced TNR mutagenesis. Published by Elsevier Ltd.

  13. Galaxies Grow Their Bulges and Black Holes in Diverse Ways

    Energy Technology Data Exchange (ETDEWEB)

    Bell, Eric F.; Harmsen, Benjamin; D’Souza, Richard [Department of Astronomy, University of Michigan, 1085 South University Avenue, Ann Arbor, MI 48109-1107 (United States); Monachesi, Antonela [Max Planck Institut für Astrophysik, Karl-Schwarzschild-Str. 1, Postfach 1317, D-85741 Garching (Germany); Jong, Roelof S. de [Leibniz-Institut für Astrophysik Potsdam (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Bailin, Jeremy [Department of Physics and Astronomy, University of Alabama, Box 870324, Tuscaloosa, AL 35487-0324 (United States); Radburn-Smith, David J. [Department of Astronomy, University of Washington, 3910 15th Avenue NE, Seattle, WA 98195 (United States); Holwerda, Benne W., E-mail: ericbell@umich.edu [Department of Physics and Astronomy, University of Louisville, 102 Natural Science Building, Louisville, KY 40292 (United States)

    2017-03-01

    Galaxies with Milky Way–like stellar masses have a wide range of bulge and black hole masses; in turn, these correlate with other properties such as star formation history. While many processes may drive bulge formation, major and minor mergers are expected to play a crucial role. Stellar halos offer a novel and robust measurement of galactic merger history; cosmologically motivated models predict that mergers with larger satellites produce more massive, higher-metallicity stellar halos, reproducing the recently observed stellar halo metallicity–mass relation. We quantify the relationship between stellar halo mass and bulge or black hole prominence using a sample of 18 Milky Way-mass galaxies with newly available measurements of (or limits on) stellar halo properties. There is an order of magnitude range in bulge mass, and two orders of magnitude in black hole mass, at a given stellar halo mass (or, equivalently, merger history). Galaxies with low-mass bulges show a wide range of quiet merger histories, implying formation mechanisms that do not require intense merging activity. Galaxies with massive “classical” bulges and central black holes also show a wide range of merger histories. While three of these galaxies have massive stellar halos consistent with a merger origin, two do not—merging appears to have had little impact on making these two massive “classical” bulges. Such galaxies may be ideal laboratories to study massive bulge formation through pathways such as early gas-rich accretion, violent disk instabilities, or misaligned infall of gas throughout cosmic time.

  14. Proton nuclear magnetic resonance studies on bulge-containing DNA oligonucleotides from a mutational hot-spot sequence

    International Nuclear Information System (INIS)

    Woodson, S.A.; Crothers, D.M.

    1987-01-01

    A series of bulge-containing and normal double-helical synthetic oligodeoxyribonucleotides, of sequence corresponding to a frame-shift mutational hot spot in the λ C/sub I/ gene, are compared by proton magnetic resonance spectroscopy at 500 MHz. The imino proton resonances are assigned by one-dimensional nuclear Overhauser effect spectroscopy. Nonselective T 1 inversion-recovery experiments are used to determine exchangeable proton lifetimes and to compare helix stability and dynamics of the three duplexes. An extra adenosine flanking the internal G-C base pairs has a strongly localized effect on helix stability, but the destabilizing effect of an extra cytidine in a C tract is delocalized over the entire G-C run. These data lead to the conclusion that the position of the bulge migrates along the run in the fast-exchange limit on the NMR time scale. Rapid migration of the bulge defect in homopolymeric sequences may help rationalize both frame-shift mutagenesis and translational frame shifting. The authors estimate that the unfavorable free energy of a localized bulge defect is 2.9-3.2 kcal/mol, in good agreement with earlier estimates for RNA helices

  15. The continuous rise of bulges out of galactic disks

    Science.gov (United States)

    Breda, Iris; Papaderos, Polychronis

    2018-06-01

    Context. A key subject in extragalactic astronomy concerns the chronology and driving mechanisms of bulge formation in late-type galaxies (LTGs). The standard scenario distinguishes between classical bulges and pseudo-bulges (CBs and PBs, respectively), the first thought to form monolithically prior to disks and the second gradually out of disks. These two bulge formation routes obviously yield antipodal predictions on the bulge age and bulge-to-disk age contrast, both expected to be high (low) in CBs (PBs). Aims: Our main goal is to explore whether bulges in present-day LTGs segregate into two evolutionary distinct classes, as expected from the standard scenario. Other questions motivating this study center on evolutionary relations between LTG bulges and their hosting disks, and the occurrence of accretion-powered nuclear activity as a function of bulge stellar mass ℳ⋆ and stellar surface density Σ⋆. Methods: In this study, we have combined three techniques - surface photometry, spectral modeling of integral field spectroscopy data and suppression of stellar populations younger than an adjustable age cutoff with the code REMOVEYOUNG (ℛ𝒴) - toward a systematic analysis of the physical and evolutionary properties (e.g., ℳ⋆, Σ⋆ and mass-weighted stellar age ℳ and metallicity ℳ, respectively) of a representative sample of 135 nearby (≤ 130 Mpc) LTGs from the CALIFA survey that cover a range between 108.9 M⊙ and 1011.5 M⊙ in total stellar mass ℳ⋆,T. In particular, the analysis here revolves around ⟨δμ9G⟩, a new distance- and formally extinction-independent measure of the contribution by stellar populations of age ≥ 9 Gyr to the mean r-band surface brightness of the bulge. We argue that ⟨δμ9G⟩ offers a handy semi-empirical tracer of the physical and evolutionary properties of LTG bulges and a promising means for their characterization. Results: The essential insight from this study is that LTG bulges form over 3 dex

  16. Bulge Growth Through Disc Instabilities in High-Redshift Galaxies

    Science.gov (United States)

    Bournaud, Frédéric

    The role of disc instabilities, such as bars and spiral arms, and the associated resonances, in growing bulges in the inner regions of disc galaxies have long been studied in the low-redshift nearby Universe. There it has long been probed observationally, in particular through peanut-shaped bulges (Chap. 14 10.1007/978-3-319-19378-6_14"). This secular growth of bulges in modern disc galaxies is driven by weak, non-axisymmetric instabilities: it mostly produces pseudobulges at slow rates and with long star-formation timescales. Disc instabilities at high redshift (z > 1) in moderate-mass to massive galaxies (1010 to a few 1011 M⊙ of stars) are very different from those found in modern spiral galaxies. High-redshift discs are globally unstable and fragment into giant clumps containing 108-9 M⊙ of gas and stars each, which results in highly irregular galaxy morphologies. The clumps and other features associated to the violent instability drive disc evolution and bulge growth through various mechanisms on short timescales. The giant clumps can migrate inward and coalesce into the bulge in a few 108 years. The instability in the very turbulent media drives intense gas inflows toward the bulge and nuclear region. Thick discs and supermassive black holes can grow concurrently as a result of the violent instability. This chapter reviews the properties of high-redshift disc instabilities, the evolution of giant clumps and other features associated to the instability, and the resulting growth of bulges and associated sub-galactic components.

  17. Searching for fossil fragments of the Galactic bulge formation process

    Science.gov (United States)

    Ferraro, Francesco

    2017-08-01

    We have discovered that the stellar system Terzan5 (Ter5) in the Galactic bulge harbors stellar populations with very different IRON content (delta[Fe/H] 1 dex, Ferraro+09, Nature 462, 483) and AGES (12 Gyr and 4.5 Gyr for the sub-solar and super-solar metallicity populations, respectively, Ferraro+16, ApJ,828,75). This evidence demonstrates that Ter5 is not a globular cluster, and identifies it as (1) a site in the Galactic bulge where recent star formation occurred, and (2) the remnant of a massive system able to retain the iron-enriched gas ejected by violent supernova explosions. The striking chemical similarity between Ter5 and the bulge opens the fascinating possibility that we discovered the fossil remnant of a pristine massive structure that could have contributed to the Galactic bulge assembly.Prompted by this finding, here we propose to secure deep HST optical observations for the bulge stellar system Liller1, that shows a similar complexity as Ter5, with evidence of two stellar populations with different iron content. The immediate goal is to properly explore the main sequence turnoff region of the system for unveiling possible splits due to stellar populations of different ages. As demonstrated by our experience with Ter5, the requested HST observations, in combination with the K-band diffraction limited images that we already secured with GeMS-Gemini, are essential to achieve this goal.The project will allow us to establish if other fossil remnants of the bulge formation epoch do exist, thus probing that the merging of pre-evolved massive structures has been an important channel for the formation of the Galactic bulge.

  18. Investigation into the factors that influence inverse bulging effect during sheet hydro-mechanical deep drawing

    Directory of Open Access Journals (Sweden)

    Lang Lihui

    2015-01-01

    Full Text Available The factors that influence inverse bulging effect during sheet hydro-mechanical deep drawing are especially researched in this paper. According to the different inverse bulging process, two modes can be singled: the initial inverse bulging (IIB and the local inverse bulging (LIB. IIB includes two parameters: inverse bulging height ratio (HIb/t and inverse bulging pressure ratio (PIb/t. LIB is influenced by IIB and has a direct relationship with liquid chamber pressure in the forming process. The optimal inverse bulging parameters of hemispherical bottom cylindrical part and flat bottom cylindrical part are obtained by numerical simulation. Process parameters including the clearance between the punch and the blank holder and the blank holder entrance radius that have a large influence on inverse bulging effect are optimized, so as to make inverse bulging effect behave better in hydroforming process. Finally, the accuracy of the numerical simulation results was verified by experiments.

  19. THE INNER GALACTIC BULGE: EVIDENCE FOR A NUCLEAR BAR?

    International Nuclear Information System (INIS)

    Gerhard, Ortwin; Martinez-Valpuesta, Inma

    2012-01-01

    Recent data from the VVV survey have strengthened evidence for a structural change in the Galactic bulge inward of |l| ≤ 4°. Here we show with an N-body barred galaxy simulation that a boxy bulge formed through the bar and buckling instabilities effortlessly matches measured bulge longitude profiles for red clump stars. The same simulation snapshot was earlier used to clarify the apparent boxy bulge—long bar dichotomy, for the same orientation and scaling. The change in the slope of the model longitude profiles in the inner few degrees is caused by a transition from highly elongated to more nearly axisymmetric isodensity contours in the inner boxy bulge. This transition is confined to a few degrees from the Galactic plane; thus the change of slope is predicted to disappear at higher Galactic latitudes. We also show that the nuclear star count map derived from this simulation snapshot displays a longitudinal asymmetry similar to that observed in the Two Micron All Sky Survey (2MASS) data, but is less flattened to the Galactic plane than the 2MASS map. These results support the interpretation that the Galactic bulge originated from disk evolution and question the evidence advanced from star count data for the existence of a secondary nuclear bar in the Milky Way.

  20. The Star Formation History in the M31 Bulge

    Science.gov (United States)

    Dong, Hui; Olsen, Knut; Lauer, Tod; Saha, Abhijit; Li, Zhiyuan; García-Benito, Ruben; Schödel, Rainer

    2018-05-01

    We present the study of stellar populations in the central 5.5' (˜1.2 kpc) of the M31 bulge by using the optical color magnitude diagram derived from HST ACS WFC/HRC observations. In order to enhance image quality and then obtain deeper photometry, we construct Nyquist-sampled images and use a deconvolution method to detect sources and measure their photometry. We demonstrate that our method performs better than DOLPHOT in the extremely crowded region. The resolved stars in the M31 bulge have been divided into nine annuli and the color magnitude diagram fitting is performed for each of them. We confirm that the majority of stars (>70%) in the M31 bulge are indeed very old (> 5 Gyr) and metal-rich ([Fe/H]˜0.3). At later times, the star formation rate decreased and then experienced a significant rise around 1 Gyr ago, which pervaded the entire M31 bulge. After that, stars formed at less than 500 Myr ago in the central 130" . Through simulation, we find that these intermediate-age stars cannot be the artifacts introduced by the blending effect. Our results suggest that although the majority of the M31 bulge are very old, the secular evolutionary process still continuously builds up the M31 bulge slowly. We compare our star formation history with an older analysis derived from the spectral energy distribution fitting, which suggests that the latter one is still a reasonable tool for the study of stellar populations in remote galaxies.

  1. Modulation of trinucleotide repeat instability by DNA polymerase β polymorphic variant R137Q.

    Directory of Open Access Journals (Sweden)

    Yaou Ren

    Full Text Available Trinucleotide repeat (TNR instability is associated with human neurodegenerative diseases and cancer. Recent studies have pointed out that DNA base excision repair (BER mediated by DNA polymerase β (pol β plays a crucial role in governing somatic TNR instability in a damage-location dependent manner. It has been shown that the activities and function of BER enzymes and cofactors can be modulated by their polymorphic variations. This could alter the function of BER in regulating TNR instability. However, the roles of BER polymorphism in modulating TNR instability remain to be elucidated. A previous study has shown that a pol β polymorphic variant, polβR137Q is associated with cancer due to its impaired polymerase activity and its deficiency in interacting with a BER cofactor, proliferating cell nuclear antigen (PCNA. In this study, we have studied the effect of the pol βR137Q variant on TNR instability. We showed that pol βR137Q exhibited weak DNA synthesis activity to cause TNR deletion during BER. We demonstrated that similar to wild-type pol β, the weak DNA synthesis activity of pol βR137Q allowed it to skip over a small loop formed on the template strand, thereby facilitating TNR deletion during BER. Our results further suggest that carriers with pol βR137Q polymorphic variant may not exhibit an elevated risk of developing human diseases that are associated with TNR instability.

  2. ANALYSIS OF STABILITY OF TRINUCLEOTIDE TTC MOTIFS IN COMMON FLAX PLANTED IN THE CHERNOBYL AREA

    Directory of Open Access Journals (Sweden)

    Veronika Lancíková

    2015-02-01

    Full Text Available Flax (Linum usitatissimum L. is one of the oldest domesticated plants — it was cultivated as early as in ancient Egypt and Samaria 10,000 years ago to serve as a source of fiber and oil, whence it later spread around the world. Compared with other plants, the flax genome consists of a high number of repetitive sequences, middle repetitive sequences and small repetitive sequences of nucleotides. The aim of the study was to analyze the stability of the existing trinucleotides motifs of microsatellite DNA of the flax genome (genotype Kyivskyi, growing in the Chernobyl conditions. The Chernobyl area is the most extensive “natural” laboratory suitable for the study of radiation effects. Over the last 20 years, the researches collected important knowledge about the effects of low and high radiation doses on the DNA isolated from the plant material growing on the remediated fields near Chernobyl and the plant material from fields contaminated by radioactive cesium 137Cs and strontium 90Sr. Using eight pairs of microsatellite primers, we successfully amplified the samples from the remediated fields. For each primer in the control samples and remediated samples, we detected 1 to 3 fragments per locus, each in size up to 120 to 250 base pairs. The applied microsatellite primers confirmed the monomorphic condition of microsatellite loci.

  3. Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

    Science.gov (United States)

    Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

    2015-06-01

    Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Myotonin protein-kinase [AGC]n trinucleotide repeat in seven nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Novelli, G.; Sineo, L.; Pontieri, E. [Catholic Univ. of Rome (Italy)]|[Univ. of Milan (Italy)]|[Univ. Florence (Italy)] [and others

    1994-09-01

    Myotonic dystrophy (DM) is due to a genomic instability of a trinucleotide [AGC]n motif, located at the 3{prime} UTR region of a protein-kinase gene (myotonin protein kinase, MT-PK). The [AGC] repeat is meiotically and mitotically unstable, and it is directly related to the manifestations of the disorder. Although a gene dosage effect of the MT-PK has been demonstrated n DM muscle, the mechanism(s) by which the intragenic repeat expansion leads to disease is largely unknown. This non-standard mutational event could reflect an evolutionary mechanism widespread among animal genomes. We have isolated and sequenced the complete 3{prime}UTR region of the MT-PK gene in seven primates (macaque, orangutan, gorilla, chimpanzee, gibbon, owl monkey, saimiri), and examined by comparative sequence nucleotide analysis the [AGC]n intragenic repeat and the surrounding nucleotides. The genomic organization, including the [AGC]n repeat structure, was conserved in all examined species, excluding the gibbon (Hylobates agilis), in which the [AGC]n upstream sequence (GGAA) is replaced by a GA dinucleotide. The number of [AGC]n in the examined species ranged between 7 (gorilla) and 13 repeats (owl monkeys), with a polymorphism informative content (PIC) similar to that observed in humans. These results indicate that the 3{prime}UTR [AGC] repeat within the MT-PK gene is evolutionarily conserved, supporting that this region has important regulatory functions.

  5. TALEN-Induced Double-Strand Break Repair of CTG Trinucleotide Repeats

    Directory of Open Access Journals (Sweden)

    Valentine Mosbach

    2018-02-01

    Full Text Available Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for several neurodegenerative disorders, including myotonic dystrophy and Huntington’s disease. Because expansions trigger the disease, contracting repeat length could be a possible approach to gene therapy for these disorders. Here, we show that a TALEN-induced double-strand break was very efficient at contracting expanded CTG repeats in yeast. We show that RAD51, POL32, and DNL4 are dispensable for double-strand break repair within CTG repeats, the only required genes being RAD50, SAE2, and RAD52. Resection was totally abolished in the absence of RAD50 on both sides of the break, whereas it was reduced in a sae2Δ mutant on the side of the break containing the longest repeat tract, suggesting that secondary structures at double-strand break ends must be removed by the Mre11-Rad50 complex and Sae2. Following the TALEN double-strand break, single-strand annealing occurred between both sides of the repeat tract, leading to repeat contraction.

  6. THE X-SHAPED BULGE OF THE MILKY WAY REVEALED BY WISE

    International Nuclear Information System (INIS)

    Ness, Melissa; Lang, Dustin

    2016-01-01

    The Milky Way bulge has a boxy/peanut morphology and an X-shaped structure. This X-shape has been revealed by the “split in the red clump” from star counts along the line of sight toward the bulge, measured from photometric surveys. This boxy, X-shaped bulge morphology is not unique to the Milky Way and such bulges are observed in other barred spiral galaxies. N -body simulations show that boxy and X-shaped bulges are formed from the disk via dynamical instabilities. It has also been proposed that the Milky Way bulge is not X-shaped, but rather, the apparent split in the red clump stars is a consequence of different stellar populations, in an old classical spheroidal bulge. We present a Wide-Field Infrared Survey Explorer ( WISE ) image of the Milky Way bulge, produced by downsampling the publicly available “unWISE” coadds. The WISE image of the Milky Way bulge shows that the X-shaped nature of the Milky Way bulge is self-evident and irrefutable. The X-shape morphology of the bulge in itself and the fraction of bulge stars that comprise orbits within this structure has important implications for the formation history of the Milky Way, and, given the ubiquity of boxy X-shaped bulges, spiral galaxies in general.

  7. Elemental abundances in the Galactic bulge from microlensed dwarf stars

    NARCIS (Netherlands)

    Bensby, T.; Feltzing, S.; Johnson, J.A.; Gould, A.; Sana, H.; Gal-Yam, A.; Asplund, M.; Lucatello, S.; Melendez, J.; Udalski, A.; Kubas, D.; James, G.; Adén, D.; Simmerer, J.

    2010-01-01

    We present elemental abundances of 13 microlensed dwarf and subgiant stars in the Galactic bulge, which constitute the largest sample to date. We show that these stars span the full range of metallicity from Fe/H= −0.8 to +0.4, and that they follow well-defined abundance trends, coincident with

  8. Mapping the X-shaped Milky Way Bulge

    Science.gov (United States)

    Saito, R. K.; Zoccali, M.; McWilliam, A.; Minniti, D.; Gonzalez, O. A.; Hill, V.

    2011-09-01

    We analyzed the distribution of the red clump (RC) stars throughout the Galactic bulge using Two Micron All Sky Survey data. We mapped the position of the RC in 1 deg2 fields within the area |l| RC seen in the central area splits into two components at high Galactic longitudes in both hemispheres, produced by two structures at different distances along the same line of sight. The X-shape is clearly visible in the Z-X plane for longitudes close to the l = 0° axis. Crude measurements of the space densities of RC stars in the bright and faint RC populations are consistent with the adopted RC distances, providing further supporting evidence that the X-structure is real, and that there is approximate front-back symmetry in our bulge fields. We conclude that the Milky Way bulge has an X-shaped structure within |l| <~ 2°, seen almost edge-on with respect to the line of sight. Additional deep near-infrared photometry extending into the innermost bulge regions combined with spectroscopic data is needed in order to discriminate among the different possibilities that can cause the observed X-shaped structure.

  9. Disk Model with Central Bulge for Galaxy M94

    International Nuclear Information System (INIS)

    Jalocha, J.; Bratek, L.; Kutschera, M.

    2010-01-01

    A global disk model for spiral galaxies is modified by adding a spherical component to the galactic center to account for the presence of a central spherical bulge. It is verified whether such modification could be substantial for predictions of total mass and of its distribution in spiral galaxy M94. (authors)

  10. COLORS AND COLOR GRADIENTS IN BULGES OF GALAXIES

    NARCIS (Netherlands)

    BALCELLS, M; PELETIER, RF

    We have obtained surface photometry in U, B, R, and I for a complete optically selected sample of 45 early-type spiral galaxies, to investigate the colors and color gradients of spiral bulges. Color profiles in U-R, B-R, U-B, and R-I have been determined in wedges opening on the semiminor axes.

  11. THE BULGE OF M-104 - STELLAR CONTENT AND KINEMATICS

    NARCIS (Netherlands)

    HES, R; PELETIER, RF

    Optical and near-infrared surface photometry of the bulge of M 104, the Sombrero Galaxy, is presented. From these data we have determined the radial variations of colours along the minor axis. We also present absorption line strength gradients of a number of metal lines and molecular bands. The

  12. Recognition of thymine in DNA bulges by a Zn(II) macrocyclic complex.

    Science.gov (United States)

    del Mundo, Imee Marie A; Fountain, Matthew A; Morrow, Janet R

    2011-08-14

    A Zn(II) macrocyclic complex with appended quinoline is a bifunctional recognition agent that uses both the Zn(II) center and the pendent aromatic group to bind to thymine in bulges with good selectivity over DNA containing G, C or A bulges. Spectroscopic studies show that the stem containing the bulge stays largely intact in a DNA hairpin with the Zn(II) complex bound to the thymine bulge. This journal is © The Royal Society of Chemistry 2011

  13. Age bimodality in the central region of pseudo-bulges in S0 galaxies

    Science.gov (United States)

    Mishra, Preetish K.; Barway, Sudhanshu; Wadadekar, Yogesh

    2017-11-01

    We present evidence for bimodal stellar age distribution of pseudo-bulges of S0 galaxies as probed by the Dn(4000) index. We do not observe any bimodality in age distribution for pseudo-bulges in spiral galaxies. Our sample is flux limited and contains 2067 S0 and 2630 spiral galaxies drawn from the Sloan Digital Sky Survey. We identify pseudo-bulges in S0 and spiral galaxies, based on the position of the bulge on the Kormendy diagram and their central velocity dispersion. Dividing the pseudo-bulges of S0 galaxies into those containing old and young stellar populations, we study the connection between global star formation and pseudo-bulge age on the u - r colour-mass diagram. We find that most old pseudo-bulges are hosted by passive galaxies while majority of young bulges are hosted by galaxies that are star forming. Dividing our sample of S0 galaxies into early-type S0s and S0/a galaxies, we find that old pseudo-bulges are mainly hosted by early-type S0 galaxies while most of the pseudo-bulges in S0/a galaxies are young. We speculate that morphology plays a strong role in quenching of star formation in the disc of these S0 galaxies, which stops the growth of pseudo-bulges, giving rise to old pseudo-bulges and the observed age bimodality.

  14. Micro-Bulges Investigation on Laser Modified Tool Steel Surface

    Directory of Open Access Journals (Sweden)

    Fauzun Fazliana

    2017-01-01

    Full Text Available This paper presents micro-bulges investigation on laser modified tool steel. The aim of this study is to understand the effect of laser irradiance and interaction time on surface morphology configuration. An Nd:YAG laser system with TEM00 pulse processing mode was used to modify the samples. Metallographic study shows samples were analyzed for focal position effect on melted pool size, angle of peaks geometry and laser modified layer depth. Surface morphology were analyzed for surface roughness. Laser modified layer shows depth ranged between 42.22 and 420.12 μm. Angle of peak bulge was found to be increase with increasing peak power. The maximum roughness, Ra, achieved in modified H13 was 21.10 μm. These findings are significant to enhance surface properties of laser modified steel and cast iron for dies and high wear resistance applications.

  15. Bulging of cans containing plutonium residues. Summary report

    International Nuclear Information System (INIS)

    Van Konynenburg, R.A.; Wood, D.H.; Condit, R.H.; Shikany, S.D.

    1996-03-01

    In 1994, two cans in the Lawrence Livermore National Laboratory Plutonium Facility were found to be bulging as a result of the generation of gases form the plutonium ash residues contained in the cans. This report describes the chronology of this discovery, the response actions that revealed other pressurized cans, the analysis of the causes, the short-term remedial action, a followup inspection of the short-term storage packages, and a review of proposed long-term remedial options

  16. Spiral Galaxy Central Bulge Tangential Speed of Revolution Curves

    Science.gov (United States)

    Taff, Laurence

    2013-03-01

    The objective was to, for the first time in a century, scientifically analyze the ``rotation curves'' (sic) of the central bulges of scores of spiral galaxies. I commenced with a methodological, rational, geometrical, arithmetic, and statistical examination--none of them carried through before--of the radial velocity data. The requirement for such a thorough treatment is the paucity of data typically available for the central bulge: fewer than 10 observations and frequently only five. The most must be made of these. A consequence of this logical handling is the discovery of a unique model for the central bulge volume mass density resting on the positive slope, linear, rise of its tangential speed of revolution curve and hence--for the first time--a reliable mass estimate. The deduction comes from a known physics-based, mathematically valid, derivation (not assertion). It rests on the full (not partial) equations of motion plus Poisson's equation. Following that is a prediction for the gravitational potential energy and thence the gravitational force. From this comes a forecast for the tangential speed of revolution curve. It was analyzed in a fashion identical to that of the data thereby closing the circle and demonstrating internal self-consistency. This is a hallmark of a scientific method-informed approach to an experimental problem. Multiple plots of the relevant quantities and measures of goodness of fit will be shown. Astronomy related

  17. The Metallicity Gradient of the Old Galactic Bulge Population

    Science.gov (United States)

    Sans Fuentes, Sara Alejandra; De Ridder, Joris

    Understanding the structure, formation and evolution of the Galactic Bulge requires the proper determination of spatial metallicity gradients in both the radial and vertical directions. RR Lyrae pulsators, known to be excellent distance indicators, may hold the key to determining these gradients. Jurcsik and Kovacs (A&A 312:111, 1996) has shown that RR Lyrae light curves and the phase difference of their Fourier decomposition, ϕ 31, can be used to estimate photometric metallicities. The existence of galactic bulge metallicity gradients is a currently debated topic that would help pinpoint the Galaxy's formation and evolution. A recent study of the OGLE-III Galactic Bulge RR Lyrae Population by Pietrukowicz et al. (ApJ 750:169, 2012) suggests that the spatial distribution is uniform. We investigate how small a gradient would be detectable within the current S/N levels of the present data set, given the random and systematic errors associated with the derivation of a photometric metallicity versus spatial position relationship.

  18. a Study of the AGB in Local Group Bulge Populations

    Science.gov (United States)

    Rich, R.

    1994-01-01

    We propose to survey the bolometric luminosities, colors, and space distribution of the most luminous asymptotic giant branch (AGB) stars in the bulges of M31, M32, and M33. We seek to discover whether the bulges of these galaxies are relatively young, of order 10 Gyr rather than 15 Gyr. We will use WFPC2 and the R, I, and F1042M (1 micron) filters. Knowing that F1042M falls on the first continuum point of M giants, we have shown that we can use 1.04 micron fluxes to reliably calculate bolometric magnitudes for these very red stars. Color information from R and I will permit (1) comparison with Galactic bulge M giants, (2) an estimate of the spread of abundance and (3) increase the accuracy of the bolometric magnitudes. Frames with the damaged HST show signs of resolution to within 3" of the M31 nucleus; Red images with the aberrated HST show a red star cluster associated with the nucleus. Ground-based studies of M32 find an intermediate-age population from spectroscopy and infrared photometry. The repaired HST should resolve stars close to the nuclei of these galaxies. We will measure bolometric luminosity functions to determine if the populations are intermediate age, and attempt to measure the abundance range for stars near the nuclei of these galaxies. If metals have been lost due to winds, theory predicts that we should see a substantial spread of abundances even near the nucleus.

  19. The Age of the Young Bulge-like Population in the Stellar System Terzan 5: Linking the Galactic Bulge to the High-z Universe

    NARCIS (Netherlands)

    Ferraro, F. R.; Massari, D.; Dalessandro, E.; Lanzoni, B.; Origlia, L.; Rich, R. M.; Mucciarelli, A.

    2016-01-01

    The Galactic bulge is dominated by an old, metal-rich stellar population. The possible presence and the amount of a young (a few gigayears old) minor component is one of the major issues debated in the literature. Recently, the bulge stellar system Terzan 5 was found to harbor three sub-populations

  20. YOUNG STARS IN AN OLD BULGE: A NATURAL OUTCOME OF INTERNAL EVOLUTION IN THE MILKY WAY

    International Nuclear Information System (INIS)

    Ness, M.; Debattista, Victor P.; Cole, D. R.; Bensby, T.; Feltzing, S.; Roškar, R.; Johnson, J. A.; Freeman, K.

    2014-01-01

    The center of our disk galaxy, the Milky Way, is dominated by a boxy/peanut-shaped bulge. Numerous studies of the bulge based on stellar photometry have concluded that the bulge stars are exclusively old. The perceived lack of young stars in the bulge strongly constrains its likely formation scenarios, providing evidence that the bulge is a unique population that formed early and separately from the disk. However, recent studies of individual bulge stars using the microlensing technique have reported that they span a range of ages, emphasizing that the bulge may not be a monolithic structure. In this Letter we demonstrate that the presence of young stars that are located predominantly nearer to the plane is expected for a bulge that has formed from the disk via dynamical instabilities. Using an N-body+ smoothed particle hydrodynamics simulation of a disk galaxy forming out of gas cooling inside a dark matter halo and forming stars, we find a qualitative agreement between our model and the observations of younger metal-rich stars in the bulge. We are also able to partially resolve the apparent contradiction in the literature between results that argue for a purely old bulge population and those that show a population comprised of a range in ages; the key is where to look

  1. Bulging of pressure tubes at hot spots under LOCA conditions

    International Nuclear Information System (INIS)

    Manu, C.; Shewfelt, R.S.W.; Wright, A.C.D.; Aboud, R.; Lau, J.H.K.; Sanderson, D.B.

    1996-01-01

    During certain postulated loss-of-coolant accidents (LOCA) in a CANDU reactor, some fuel channels can become highly voided within a very short time. Although the pressure tubes are heated mainly by convection and thermal radiation during the LOCA transient, additional heat flow occurs through the bearing pads that are in contact with the pressure tribe. This contact can lead to local hot spots and associated thermal stresses in the pressure tube wall. The two factors that affects the behavior of the pressure tubes during LOCA conditions are the internal pressure and the local heating. Although the effect of internal pressure and of axially uniform temperature has been studied elsewhere, the effect of the local heating on the pressure tube behavior has not been modelled before. This paper shows that the bulging of a pressure tube at a hot spot is the result of the thermal stresses that are developed in a pressure tube during a LOCA transient. To isolate the local heating effect from the internal pressure, a series of single-effect experiments was performed. In these experiments, sections of a CANDU pressure tube were subjected to local heating only. The thermal profile and the local deformation were measured function of time. To quantify the effect of the thermal stresses on the bulging of pressure tubes at hot spots and to develop numerical tools that can predict such bulging, finite element analyses were performed rising the ABAQUS finite element computer code. Use of the measured thermal profiles in the ABAQUS finite element analysis, resulted in very good agreement between the predicted and measured displacements. (author)

  2. The hair follicle bulge: a niche for adult stem cells.

    Science.gov (United States)

    Pasolli, Hilda Amalia

    2011-08-01

    Adult stem cells (SCs) are essential for tissue homeostasis and wound repair. They have the ability to both self-renew and differentiate into multiple cell types. They often reside in specialized microenvironments or niches that preserve their proliferative and tissue regenerative capacity. The murine hair follicle (HF) has a specialized and permanent compartment--the bulge, which safely lodges SCs and provides the necessary molecular cues to regulate their function. The HF undergoes cyclic periods of destruction, regeneration, and rest, making it an excellent system to study SC biology.

  3. Sequence-dependent separation of trinucleotides by ion-interaction reversed-phase liquid chromatography A structure-retention study assisted by soft-modelling and molecular dynamics

    Czech Academy of Sciences Publication Activity Database

    Mikulášek, K.; Jaroň, Kamil S.; Kulhánek, P.; Bittová, M.; Havliš, J.

    2016-01-01

    Roč. 1469, October (2016), s. 88-95 ISSN 0021-9673 Institutional support: RVO:68081766 Keywords : Sequence-dependent separation * Ion-interaction reversed-phase liquid chromatography * Trinucleotides * Oligonucleotide sequence isomers * QSRR * Molecular dynamics Subject RIV: CE - Biochemistry Impact factor: 3.981, year: 2016

  4. Incidence and Risk Factors for Parastomal Bulging in Patients with Ileostomy or Colostomy

    DEFF Research Database (Denmark)

    Andersen, Rune M; Klausen, Tobias W; Danielsen, Anne K

    2018-01-01

    AIM: To investigate incidence and risk factors for parastomal bulging, a clinically important complication, in patients with an ileostomy or colostomy. METHOD: The Danish Stoma Database Capital Region prospectively collects data on patients with a stoma up to a year after surgery. Stoma care nurses...... an exploratory approach. RESULTS: In a study population of 5019, the cumulative incidence (with competing risks) of parastomal bulging was 36.2% at 400 days after surgery. Age, colostomy, male gender, alcohol consumption, and laparoscopy were associated with an increased risk of parastomal bulging. Compared...... for age and colostomy as being risk factors for parastomal bulging. This article is protected by copyright. All rights reserved....

  5. A Comparison of Galaxy Bulge+Disk Decomposition Between Pan-STARRS and SDSS

    Science.gov (United States)

    Lokken, Martine Elena; McPartland, Conor; Sanders, David B.

    2018-01-01

    Measurements of the size and shape of bulges in galaxies provide key constraints for models of galaxy evolution. A comprehensive catalog of bulge measurements for Sloan Digital Sky Survey (SDSS) DR7 galaxies is currently available to the public. However, the Pan-STARRS1 (PS1) 3π survey now covers the same region with ~1-2 mag deeper photometry, a ~10-30% smaller PSF, and additional coverage in y-band. To test how much improvement in galaxy parameter measurements (e.g. bulge + disk) can be achieved using the new PS1 data, we make use of ultra-deep imaging data from the Hyper Suprime-Cam (HSC) Subaru Strategic Program (SSP). We fit bulge+disk models to images of 372 bright (mi SSP images shows a tighter correlation between PS1 and SSP measurements for both bulge and disk parameters. Bulge parameters, such as bulge-to-total fraction and bulge radius, show the strongest improvement. However, measurements of all parameters degrade for galaxies with total r-band magnitude below the SDSS spectroscopic limit, mr = 17.7. We plan to use the PS1 3π survey data to produce an updated catalog of bulge+disk decomposition measurements for the entire SDSS DR7 spectroscopic galaxy sample.

  6. Human mismatch repair protein hMutLα is required to repair short slipped-DNAs of trinucleotide repeats.

    Science.gov (United States)

    Panigrahi, Gagan B; Slean, Meghan M; Simard, Jodie P; Pearson, Christopher E

    2012-12-07

    Mismatch repair (MMR) is required for proper maintenance of the genome by protecting against mutations. The mismatch repair system has also been implicated as a driver of certain mutations, including disease-associated trinucleotide repeat instability. We recently revealed a requirement of hMutSβ in the repair of short slip-outs containing a single CTG repeat unit (1). The involvement of other MMR proteins in short trinucleotide repeat slip-out repair is unknown. Here we show that hMutLα is required for the highly efficient in vitro repair of single CTG repeat slip-outs, to the same degree as hMutSβ. HEK293T cell extracts, deficient in hMLH1, are unable to process single-repeat slip-outs, but are functional when complemented with hMutLα. The MMR-deficient hMLH1 mutant, T117M, which has a point mutation proximal to the ATP-binding domain, is defective in slip-out repair, further supporting a requirement for hMLH1 in the processing of short slip-outs and possibly the involvement of hMHL1 ATPase activity. Extracts of hPMS2-deficient HEC-1-A cells, which express hMLH1, hMLH3, and hPMS1, are only functional when complemented with hMutLα, indicating that neither hMutLβ nor hMutLγ is sufficient to repair short slip-outs. The resolution of clustered short slip-outs, which are poorly repaired, was partially dependent upon a functional hMutLα. The joint involvement of hMutSβ and hMutLα suggests that repeat instability may be the result of aberrant outcomes of repair attempts.

  7. A Specific Hepatic Transfer RNA for Phosphoserine*

    Science.gov (United States)

    Mäenpää, Pekka H.; Bernfield, Merton R.

    1970-01-01

    Radioactive O-phosphoryl-L-serine was detected after alkaline deacylation of rat and rooster liver [3H]seryl-tRNA acylated in vitro with homologous synthetases. Ribonuclease treatment of this tRNA yielded a compound with the properties of phosphoseryl-adenosine. Benzoylated DEAE-cellulose chromatography of seryl-tRNA yielded four distinct peaks, only one of which contained phosphoserine. A unique fraction for phosphoserine was also found on chromatography of nonacylated tRNA. In ribosome binding studies, this fraction responded very slightly with poly(U,C), but not with any of the known serine trinucleotide codons. Substantial incorporation of [3H]-serine into protein from this tRNA species was observed in an aminoacyl-tRNA dependent polysomal system derived from chick oviducts. No phosphoserine was found in Escherichia coli or yeast seryl-tRNA acylated with homologous enzymes, nor in E. coli seryl-tRNA acylated with liver synthetase. In the absence of tRNA, free phosphoserine was not formed in reaction mixtures, which suggests that phosphoseryl-tRNA arises by phosphorylation of the unique seryl-tRNA species. These results demonstrate a discrete tRNASer species in rat and rooster liver containing phosphoserine and suggest that this tRNA is involved in ribosomal polypeptide synthesis. PMID:4943179

  8. Observational constraints to boxy/peanut bulge formation time

    Science.gov (United States)

    Pérez, I.; Martínez-Valpuesta, I.; Ruiz-Lara, T.; de Lorenzo-Caceres, A.; Falcón-Barroso, J.; Florido, E.; González Delgado, R. M.; Lyubenova, M.; Marino, R. A.; Sánchez, S. F.; Sánchez-Blázquez, P.; van de Ven, G.; Zurita, A.

    2017-09-01

    Boxy/peanut bulges are considered to be part of the same stellar structure as bars and both could be linked through the buckling instability. The Milky Way is our closest example. The goal of this Letter is to determine if the mass assembly of the different components leaves an imprint in their stellar populations allowing the estimation the time of bar formation and its evolution. To this aim, we use integral field spectroscopy to derive the stellar age distributions, SADs, along the bar and disc of NGC 6032. The analysis clearly shows different SADs for the different bar areas. There is an underlying old (≥12 Gyr) stellar population for the whole galaxy. The bulge shows star formation happening at all times. The inner bar structure shows stars of ages older than 6 Gyr with a deficit of younger populations. The outer bar region presents an SAD similar to that of the disc. To interpret our results, we use a generic numerical simulation of a barred galaxy. Thus, we constrain, for the first time, the epoch of bar formation, the buckling instability period and the posterior growth from disc material. We establish that the bar of NGC 6032 is old, formed around 10 Gyr ago while the buckling phase possibly happened around 8 Gyr ago. All these results point towards bars being long-lasting even in the presence of gas.

  9. Fragment-based modelling of single stranded RNA bound to RNA recognition motif containing proteins

    Science.gov (United States)

    de Beauchene, Isaure Chauvot; de Vries, Sjoerd J.; Zacharias, Martin

    2016-01-01

    Abstract Protein-RNA complexes are important for many biological processes. However, structural modeling of such complexes is hampered by the high flexibility of RNA. Particularly challenging is the docking of single-stranded RNA (ssRNA). We have developed a fragment-based approach to model the structure of ssRNA bound to a protein, based on only the protein structure, the RNA sequence and conserved contacts. The conformational diversity of each RNA fragment is sampled by an exhaustive library of trinucleotides extracted from all known experimental protein–RNA complexes. The method was applied to ssRNA with up to 12 nucleotides which bind to dimers of the RNA recognition motifs (RRMs), a highly abundant eukaryotic RNA-binding domain. The fragment based docking allows a precise de novo atomic modeling of protein-bound ssRNA chains. On a benchmark of seven experimental ssRNA–RRM complexes, near-native models (with a mean heavy-atom deviation of <3 Å from experiment) were generated for six out of seven bound RNA chains, and even more precise models (deviation < 2 Å) were obtained for five out of seven cases, a significant improvement compared to the state of the art. The method is not restricted to RRMs but was also successfully applied to Pumilio RNA binding proteins. PMID:27131381

  10. Why are classical bulges more common in S0 galaxies than in spiral galaxies?

    Science.gov (United States)

    Mishra, Preetish K.; Wadadekar, Yogesh; Barway, Sudhanshu

    2018-05-01

    In this paper, we try to understand why the classical bulge fraction observed in S0 galaxies is significantly higher than that in spiral galaxies. We carry out a comparative study of the bulge and global properties of a sample of spiral and S0 galaxies in a fixed environment. Our sample is flux limited and contains 262 spiral and 155 S0 galaxies drawn from the Sloan Digital Sky Survey. We have classified bulges into classical and pseudobulge categories based on their position on the Kormendy diagram. Dividing our sample into bins of galaxy stellar mass, we find that the fraction of S0 galaxies hosting a classical bulge is significantly higher than the classical bulge fraction seen in spirals even at fixed stellar mass. We have compared the bulge and the global properties of spirals and S0 galaxies in our sample and find indications that spiral galaxies which host a classical bulge, preferentially get converted into S0 population as compared to pseudobulge hosting spirals. By studying the star formation properties of our galaxies in the NUV - r color-mass diagram, we find that the pseudobulge hosting spirals are mostly star forming while the majority of classical bulge host spirals are in the green valley or in the passive sequence. We suggest that some internal process, such as AGN feedback or morphological quenching due to the massive bulge, quenches these classical bulge hosting spirals and transforms them into S0 galaxies, thus resulting in the observed predominance of the classical bulge in S0 galaxies.

  11. X-ray bursters and the X-ray sources of the galactic bulge

    International Nuclear Information System (INIS)

    Lewin, W.H.G.; Joss, P.C.; Massachusetts Inst. of Tech., Cambridge; Massachusetts Inst. of Tech., Cambridge

    1981-01-01

    In this article we shall discuss the observed X-ray, optical, infrared and radio properties of the galactic bulge sources, with an emphasis on those that produce type I X-ray bursts. There is persuasive evidence that these burst sources and many other galactic bulge sources are neutron stars in low-mass, close-binary stellar systems. (orig./WL)

  12. The INTEGRAL Galactic bulge monitoring program: the first 1.5 years

    NARCIS (Netherlands)

    Kuulkers, E.; Shaw, S.E.; Paizis, A.; Chenevez, J.; Brandt, S.; Courvoisier, T.J.L.; Domingo, A.; Ebisawa, K.; Kretschmar, P.; Markwardt, C.B.; Mowlavi, N.; Oosterbroek, T.; Orr, A.; Rísquez, D.; Sanchez-Fernandez, C.; Wijnands, R.

    2007-01-01

    Aims.The Galactic bulge region is a rich host of variable high-energy point sources. Since 2005, February 17 we are monitoring the source activity in the Galactic bulge region regularly and frequently, i.e., about every three days, with the instruments onboard INTEGRAL. Thanks to the large field of

  13. Chemical abundances and dust in planetary nebulae in the Galactic bulge

    NARCIS (Netherlands)

    Gutenkunst, S.; Bernard-Salas, J.; Pottasch, S. R.; Sloan, G. C.; Houck, J. R.

    2008-01-01

    We present mid-infrared Spitzer spectra of 11 planetary nebulae in the Galactic bulge. We derive argon, neon, sulfur, and oxygen abundances for them using mainly infrared line fluxes combined with some optical line fluxes from the literature. Due to the high extinction toward the bulge, the infrared

  14. No bulging of floor heating pipes to be expected in case of incomplete floor plastering

    Energy Technology Data Exchange (ETDEWEB)

    Radtke, U

    1983-02-01

    According to advertising slogans floor heating pipes are said to be damaged prematurely by bulges if they are not completely surrounded by flooring plaster. The author has thoroughly dealt with this problem and made the respective measurements. He found out that there are so few bulges occurring that they cannot lead to damages.

  15. The chemical evolution of the Galactic Bulge seen through micro-lensing events

    Directory of Open Access Journals (Sweden)

    Lucatello S.

    2012-02-01

    Full Text Available Galactic bulges are central to understanding galaxy formation and evolution. Here we report on recent studies using micro-lensing events to obtain spectra of high resolution and moderately high signal-to-noise ratios of dwarf stars in the Galactic bulge. Normally this is not feasible for the faint turn-off stars in the Galactic bulge, but micro-lensing offers this possibility. Elemental abundance trends in the Galactic bulge as traced by dwarf stars are very similar to those seen for dwarf stars in the solar neighbourhood. We discuss the implications of the ages and metallicity distribution function derived for the micro-lensed dwarf stars in the Galactic bulge.

  16. Numerical Simulation of Bulging Deformation for Wide-Thick Slab Under Uneven Cooling Conditions

    Science.gov (United States)

    Wu, Chenhui; Ji, Cheng; Zhu, Miaoyong

    2018-02-01

    In the present work, the bulging deformation of a wide-thick slab under uneven cooling conditions was studied using finite element method. The non-uniform solidification was first calculated using a 2D heat transfer model. The thermal material properties were derived based on a microsegregation model, and the water flux distribution was measured and applied to calculate the cooling boundary conditions. Based on the solidification results, a 3D bulging model was established. The 2D heat transfer model was verified by the measured shell thickness and the slab surface temperature, and the 3D bulging model was verified by the calculated maximum bulging deflections using formulas. The bulging deformation behavior of the wide-thick slab under uneven cooling condition was then determined, and the effect of uneven solidification, casting speed, and roll misalignment were investigated.

  17. Formation of the Lunar Fossil Bulges and Its Implication for the Early Earth and Moon

    Science.gov (United States)

    Qin, Chuan; Zhong, Shijie; Phillips, Roger

    2018-02-01

    First recognized by Laplace over two centuries ago, the Moon's present tidal-rotational bulges are significantly larger than hydrostatic predictions. They are likely relics of a former hydrostatic state when the Moon was closer to the Earth and had larger bulges, and they were established when stresses in a thickening lunar lithosphere could maintain the bulges against hydrostatic adjustment. We formulate the first dynamically self-consistent model of this process and show that bulge formation is controlled by the relative timing of lithosphere thickening and lunar orbit recession. Viable solutions indicate that lunar bulge formation was a geologically slow process lasting several hundred million years, that the process was complete about 4 Ga when the Moon-Earth distance was less than 32 Earth radii, and that the Earth in Hadean was significantly less dissipative to lunar tides than during the last 4 Gyr, possibly implying a frozen hydrosphere due to the fainter young Sun.

  18. Numerical Simulation of Bulging Deformation for Wide-Thick Slab Under Uneven Cooling Conditions

    Science.gov (United States)

    Wu, Chenhui; Ji, Cheng; Zhu, Miaoyong

    2018-06-01

    In the present work, the bulging deformation of a wide-thick slab under uneven cooling conditions was studied using finite element method. The non-uniform solidification was first calculated using a 2D heat transfer model. The thermal material properties were derived based on a microsegregation model, and the water flux distribution was measured and applied to calculate the cooling boundary conditions. Based on the solidification results, a 3D bulging model was established. The 2D heat transfer model was verified by the measured shell thickness and the slab surface temperature, and the 3D bulging model was verified by the calculated maximum bulging deflections using formulas. The bulging deformation behavior of the wide-thick slab under uneven cooling condition was then determined, and the effect of uneven solidification, casting speed, and roll misalignment were investigated.

  19. A TWO-PHASE SCENARIO FOR BULGE ASSEMBLY IN {Lambda}CDM COSMOLOGIES

    Energy Technology Data Exchange (ETDEWEB)

    Obreja, A.; Dominguez-Tenreiro, R.; Brook, C. [Departamento de Fisica Teorica, Universidad Autonoma de Madrid, E-28049 Cantoblanco Madrid (Spain); Martinez-Serrano, F. J.; Domenech-Moral, M.; Serna, A. [Departamento de Fisica y Arquitectura de Computadores, Universidad Miguel Hernandez, E-03202 Elche (Spain); Molla, M. [Departamento de Investigacion Basica, CIEMAT, E-28040 Madrid (Spain); Stinson, G., E-mail: aura.obreja@uam.es [Max-Planck-Institut fuer Astronomie, Koenigstuhl 17, D-69117, Heidelberg (Germany)

    2013-01-20

    We analyze and compare the bulges of a sample of L {sub *} spiral galaxies in hydrodynamical simulations in a cosmological context, using two different codes, P-DEVA and GASOLINE. The codes regulate star formation in very different ways, with P-DEVA simulations inputting low star formation efficiency under the assumption that feedback occurs on subgrid scales, while the GASOLINE simulations have feedback that drives large-scale outflows. In all cases, the marked knee shape in mass aggregation tracks, corresponding to the transition from an early phase of rapid mass assembly to a later slower one, separates the properties of two populations within the simulated bulges. The bulges analyzed show an important early starburst resulting from the collapse-like fast phase of mass assembly, followed by a second phase with lower star formation, driven by a variety of processes such as disk instabilities and/or mergers. Classifying bulge stellar particles identified at z = 0 into old and young according to these two phases, we found bulge stellar sub-populations with distinct kinematics, shapes, stellar ages, and metal contents. The young components are more oblate, generally smaller, more rotationally supported, with higher metallicity and less alpha-element enhanced than the old ones. These results are consistent with the current observational status of bulges, and provide an explanation for some apparently paradoxical observations, such as bulge rejuvenation and metal-content gradients observed. Our results suggest that bulges of L {sub *} galaxies will generically have two bulge populations that can be likened to classical and pseudo-bulges, with differences being in the relative proportions of the two, which may vary due to galaxy mass and specific mass accretion and merger histories.

  20. Monitoring and Mapping the Galactic Bulge (core Program)

    Science.gov (United States)

    Both neutron star and black hole binary transients are providing some of the most exciting RXTE science, and fortunately many are concentrated in the galactic bulge region. We propose to continue our twice weekly PCA scans of the region, which cover about 500 sq deg. The observations will be sensitive to new sources at the ~1 mCrab level (a factor of 10-60 more sensitive than the ASM in the region). We have had success finding new sources and new types of variability, including three millisecond pulsars, and new increased solid angle will improve the chances of finding more in the final RXTE years. We will continue efforts to search for variability in new and known sources. Companion follow-up proposals would be triggered by the results.

  1. Comparative Analysis of Bulge Deformation between 2D and 3D Finite Element Models

    Directory of Open Access Journals (Sweden)

    Qin Qin

    2014-02-01

    Full Text Available Bulge deformation of the slab is one of the main factors that affect slab quality in continuous casting. This paper describes an investigation into bulge deformation using ABAQUS to model the solidification process. A three-dimensional finite element analysis model of the slab solidification process has been first established because the bulge deformation is closely related to slab temperature distributions. Based on slab temperature distributions, a three-dimensional thermomechanical coupling model including the slab, the rollers, and the dynamic contact between them has also been constructed and applied to a case study. The thermomechanical coupling model produces outputs such as the rules of bulge deformation. Moreover, the three-dimensional model has been compared with a two-dimensional model to discuss the differences between the two models in calculating the bulge deformation. The results show that the platform zone exists in the wide side of the slab and the bulge deformation is affected strongly by the ratio of width-to-thickness. The indications are also that the difference of the bulge deformation for the two modeling ways is little when the ratio of width-to-thickness is larger than six.

  2. Effect of an upstream bulge configuration on film cooling with and without mist injection.

    Science.gov (United States)

    Wang, Jin; Li, Qianqian; Sundén, Bengt; Ma, Ting; Cui, Pei

    2017-12-01

    To meet the economic requirements of power output, the increased inlet temperature of modern gas turbines is above the melting point of the material. Therefore, high-efficient cooling technology is needed to protect the blades from the hot mainstream. In this study, film cooling was investigated in a simplified channel. A bulge located upstream of the film hole was numerically investigated by analysis of the film cooling effectiveness distribution downstream of the wall. The flow distribution in the plate channel is first presented. Comparing with a case without bulge, different cases with bulge heights of 0.1d, 0.3d and 0.5d were examined with blowing ratios of 0.5 and 1.0. Cases with 1% mist injection were also included in order to obtain better cooling performance. Results show that the bulge configuration located upstream the film hole makes the cooling film more uniform, and enhanceslateral cooling effectiveness. Unlike other cases, the configuration with a 0.3d-height bulge shows a good balance in improving the downstream and lateral cooling effectiveness. Compared with the case without mist at M = 0.5, the 0.3d-height bulge with 1% mist injection increases lateral average effectiveness by 559% at x/d = 55. In addition, a reduction of the thermal stress concentration can be obtained by increasing the height of the bulge configuration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Bulge testing of copper and niobium tubes for hydroformed RF cavities

    Energy Technology Data Exchange (ETDEWEB)

    Kim, H.S., E-mail: kim.3237@osu.edu [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH (United States); Sumption, M.D. [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH (United States); Susner, M.A. [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH (United States); Oak Ridge National Laboratory, Oak Ridge, TN (United States); Lim, H. [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH (United States); Sandia National Laboratories, Albuquerque, NM (United States); Collings, E.W. [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH (United States)

    2016-01-27

    The heat treatment, tensile testing, and bulge testing of Cu and Nb tubes has been carried out to gain experience for the subsequent hydroforming of Nb tube into seamless superconducting radio frequency (SRF) cavities for high energy particle acceleration. In the experimental part of the study samples removed from representative tubes were prepared for heat treatment, tensile testing, residual resistance ratio measurement, and orientation imaging electron microscopy (OIM). After being optimally heat treated Cu and Nb tubes were subjected to hydraulic bulge testing and the results analyzed. In the final part of the study finite-element models (FEM) incorporating constitutive (stress–strain) relationships analytically derived from the tensile and bulge tests, respectively, were used to replicate the bulge test. As expected, agreement was obtained between the experimental bulge parameters and the FEM model based on the bulge-derived constitutive relationship. Not so for the FEM model based on tensile-test data. It is concluded that a constitutive relationship based on bulge testing is necessary to predict a material's performance under hydraulic deformation.

  4. Bulge testing of copper and niobium tubes for hydroformed RF cavities

    International Nuclear Information System (INIS)

    Kim, H.S.; Sumption, M.D.; Susner, M.A.; Lim, H.; Collings, E.W.

    2016-01-01

    The heat treatment, tensile testing, and bulge testing of Cu and Nb tubes has been carried out to gain experience for the subsequent hydroforming of Nb tube into seamless superconducting radio frequency (SRF) cavities for high energy particle acceleration. In the experimental part of the study samples removed from representative tubes were prepared for heat treatment, tensile testing, residual resistance ratio measurement, and orientation imaging electron microscopy (OIM). After being optimally heat treated Cu and Nb tubes were subjected to hydraulic bulge testing and the results analyzed. In the final part of the study finite-element models (FEM) incorporating constitutive (stress–strain) relationships analytically derived from the tensile and bulge tests, respectively, were used to replicate the bulge test. As expected, agreement was obtained between the experimental bulge parameters and the FEM model based on the bulge-derived constitutive relationship. Not so for the FEM model based on tensile-test data. It is concluded that a constitutive relationship based on bulge testing is necessary to predict a material's performance under hydraulic deformation.

  5. Morpho-kinematic properties of field S0 bulges in the CALIFA survey

    Science.gov (United States)

    Méndez-Abreu, J.; Aguerri, J. A. L.; Falcón-Barroso, J.; Ruiz-Lara, T.; Sánchez-Menguiano, L.; de Lorenzo-Cáceres, A.; Costantin, L.; Catalán-Torrecilla, C.; Zhu, L.; Sánchez-Blazquez, P.; Florido, E.; Corsini, E. M.; Wild, V.; Lyubenova, M.; van de Ven, G.; Sánchez, S. F.; Bland-Hawthorn, J.; Galbany, L.; García-Benito, R.; García-Lorenzo, B.; González Delgado, R. M.; López-Sánchez, A. R.; Marino, R. A.; Márquez, I.; Ziegler, B.; Califa Collaboration

    2018-02-01

    We study a sample of 28 S0 galaxies extracted from the integral field spectroscopic (IFS) survey Calar Alto Legacy Integral Field Area. We combine an accurate two-dimensional (2D) multicomponent photometric decomposition with the IFS kinematic properties of their bulges to understand their formation scenario. Our final sample is representative of S0s with high stellar masses (M⋆/M⊙ > 1010). They lay mainly on the red sequence and live in relatively isolated environments similar to that of the field and loose groups. We use our 2D photometric decomposition to define the size and photometric properties of the bulges, as well as their location within the galaxies. We perform mock spectroscopic simulations mimicking our observed galaxies to quantify the impact of the underlying disc on our bulge kinematic measurements (λ and v/σ). We compare our bulge corrected kinematic measurements with the results from Schwarzschild dynamical modelling. The good agreement confirms the robustness of our results and allows us to use bulge deprojected values of λ and v/σ. We find that the photometric (n and B/T) and kinematic (v/σ and λ) properties of our field S0 bulges are not correlated. We demonstrate that this morpho-kinematic decoupling is intrinsic to the bulges and it is not due to projection effects. We conclude that photometric diagnostics to separate different types of bulges (disc-like versus classical) might not be useful for S0 galaxies. The morpho-kinematics properties of S0 bulges derived in this paper suggest that they are mainly formed by dissipational processes happening at high redshift, but dedicated high-resolution simulations are necessary to better identify their origin.

  6. Stellar populations of bulges in galaxies with a low surface-brightness disc

    Science.gov (United States)

    Morelli, L.; Corsini, E. M.; Pizzella, A.; Dalla Bontà, E.; Coccato, L.; Méndez-Abreu, J.

    2015-03-01

    The radial profiles of the Hβ, Mg, and Fe line-strength indices are presented for a sample of eight spiral galaxies with a low surface-brightness stellar disc and a bulge. The correlations between the central values of the line-strength indices and velocity dispersion are consistent to those known for early-type galaxies and bulges of high surface-brightness galaxies. The age, metallicity, and α/Fe enhancement of the stellar populations in the bulge-dominated region are obtained using stellar population models with variable element abundance ratios. Almost all the sample bulges are characterized by a young stellar population, on-going star formation, and a solar α/Fe enhancement. Their metallicity spans from high to sub-solar values. No significant gradient in age and α/Fe enhancement is measured, whereas only in a few cases a negative metallicity gradient is found. These properties suggest that a pure dissipative collapse is not able to explain formation of all the sample bulges and that other phenomena, like mergers or acquisition events, need to be invoked. Such a picture is also supported by the lack of a correlation between the central value and gradient of the metallicity in bulges with very low metallicity. The stellar populations of the bulges hosted by low surface-brightness discs share many properties with those of high surface-brightness galaxies. Therefore, they are likely to have common formation scenarios and evolution histories. A strong interplay between bulges and discs is ruled out by the fact that in spite of being hosted by discs with extremely different properties, the bulges of low and high surface-brightness discs are remarkably similar.

  7. Validation of a screening tool for the rapid and reliable detection of CGG trinucleotide repeat expansions in FMR1.

    Science.gov (United States)

    Basehore, Monica J; Marlowe, Natalia M; Jones, Julie R; Behlendorf, Deborah E; Laver, Thomas A; Friez, Michael J

    2012-06-01

    Most individuals with intellectual disability and/or autism are tested for Fragile X syndrome at some point in their lifetime. Greater than 99% of individuals with Fragile X have an expanded CGG trinucleotide repeat motif in the promoter region of the FMR1 gene, and diagnostic testing involves determining the size of the CGG repeat as well as methylation status when an expansion is present. Using a previously described triplet repeat-primed polymerase chain reaction, we have performed additional validation studies using two cohorts with previous diagnostic testing results available for comparison purposes. The first cohort (n=88) consisted of both males and females and had a high percentage of abnormal samples, while the second cohort (n=624) consisted of only females and was not enriched for expansion mutations. Data from each cohort were completely concordant with the results previously obtained during the course of diagnostic testing. This study further demonstrates the utility of using laboratory-developed triplet repeat-primed FMR1 testing in a clinical setting.

  8. ALMA observations of molecular absorption in four directions toward the Galactic bulge

    Science.gov (United States)

    Liszt, H.; Gerin, M.

    2018-02-01

    Context. Alma Cycle 3 observations serendipitously showed strong absorption from diffuse molecular gas in the Galactic bulge at -200 km s-1 51(3σ) for the bulge gas toward J1744 and 58 ± 9 and 64 ± 4 for the disk gas toward J1717 and J1744, respectively, all well above the value of 20-25 typical of the central molecular zone. Conclusions: The kinematics and chemistry of the bulge gas observed toward J1744 more nearly resemble that of gas in the Milky Way disk than in the central molecular zone.

  9. Diffraction and Smith-Purcell radiation on the hemispherical bulges in a metal plate

    Science.gov (United States)

    Syshchenko, V. V.; Larikova, E. A.; Gladkih, Yu. P.

    2017-12-01

    The radiation resulting from the uniform motion of a charged particle near a hemispheric bulge on a metal plane is considered. The description of the radiation process based on the method of images is developed for the case of non-relativistic particle and a perfectly conducting target. The spectral-angular and spectral densities of the diffraction radiation on the single bulge (as well as the Smith-Purcell radiation on the periodic string of bulges) are computed. The possibility of application of the developed approach to the case of relativistic incident particle is discussed.

  10. A catalog of polychromatic bulge-disc decompositions of ˜17.600 galaxies in CANDELS

    Science.gov (United States)

    Dimauro, Paola; Huertas-Company, Marc; Daddi, Emanuele; Pérez-González, Pablo G.; Bernardi, Mariangela; Barro, Guillermo; Buitrago, Fernando; Caro, Fernando; Cattaneo, Andrea; Dominguez-Sánchez, Helena; Faber, Sandra M.; Häußler, Boris; Kocevski, Dale D.; Koekemoer, Anton M.; Koo, David C.; Lee, Christoph T.; Mei, Simona; Margalef-Bentabol, Berta; Primack, Joel; Rodriguez-Puebla, Aldo; Salvato, Mara; Shankar, Francesco; Tuccillo, Diego

    2018-05-01

    Understanding how bulges grow in galaxies is critical step towards unveiling the link between galaxy morphology and star-formation. To do so, it is necessary to decompose large sample of galaxies at different epochs into their main components (bulges and discs). This is particularly challenging, especially at high redshifts, where galaxies are poorly resolved. This work presents a catalog of bulge-disc decompositions of the surface brightness profiles of ˜17.600 H-band selected galaxies in the CANDELS fields (F160W https://lerma.obspm.fr/huertas/form_CANDELS and will be used for scientific analysis in forthcoming works.

  11. Small molecule alteration of RNA sequence in cells and animals.

    Science.gov (United States)

    Guan, Lirui; Luo, Yiling; Ja, William W; Disney, Matthew D

    2017-10-18

    RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat causative of myotonic muscular dystrophy type 1 (DM1), r(CUG) exp . The small molecule, 2H-4-Ru, binds to r(CUG) exp and converts guanosine residues to 8-oxo-7,8-dihydroguanosine upon photochemical irradiation. We demonstrate targeted modification upon irradiation in cell culture and in Drosophila larvae provided a diet containing 2H-4-Ru. Our results highlight a general chemical biology approach for altering RNA sequence in vivo by using small molecules and photochemistry. Furthermore, these studies show that addition of 8-oxo-G lesions into RNA 3' untranslated regions does not affect its steady state levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Dynamical manifestations of quantum chaos: correlation hole and bulge

    Science.gov (United States)

    Torres-Herrera, E. J.; Santos, Lea F.

    2017-10-01

    A main feature of a chaotic quantum system is a rigid spectrum where the levels do not cross. We discuss how the presence of level repulsion in lattice many-body quantum systems can be detected from the analysis of their time evolution instead of their energy spectra. This approach is advantageous to experiments that deal with dynamics, but have limited or no direct access to spectroscopy. Dynamical manifestations of avoided crossings occur at long times. They correspond to a drop, referred to as correlation hole, below the asymptotic value of the survival probability and to a bulge above the saturation point of the von Neumann entanglement entropy and the Shannon information entropy. By contrast, the evolution of these quantities at shorter times reflects the level of delocalization of the initial state, but not necessarily a rigid spectrum. The correlation hole is a general indicator of the integrable-chaos transition in disordered and clean models and as such can be used to detect the transition to the many-body localized phase in disordered interacting systems. This article is part of the themed issue 'Breakdown of ergodicity in quantum systems: from solids to synthetic matter'.

  13. VARIABILITY OF OPTICAL COUNTERPARTS IN THE CHANDRA GALACTIC BULGE SURVEY

    Energy Technology Data Exchange (ETDEWEB)

    Britt, C. T.; Hynes, R. I.; Johnson, C. B.; Baldwin, A.; Collazzi, A.; Gossen, L. [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA 70803-4001 (United States); Jonker, P. G.; Torres, M. A. P. [SRON, Netherlands Institute for Space Research, Sorbonnelaan 2, 3584 CA Utrecht (Netherlands); Nelemans, G. [Department of Astrophysics, IMAPP, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen (Netherlands); Maccarone, T. [Department of Physics, Texas Tech University, Box 41051, Science Building, Lubbock, TX 79409-1051 (United States); Steeghs, D.; Greiss, S. [Astronomy and Astrophysics, Department of Physics, University of Warwick, Coventry, CV4 7AL (United Kingdom); Heinke, C. [Department of Physics, University of Alberta, CCIS 4-183, Edmonton, AB T6G 2E1 (Canada); Bassa, C. G. [Jodrell Bank Centre for Astrophysics, School of Physics and Astronomy, University of Manchester, Manchester M13 9PL (United Kingdom); Villar, A. [Department of Physics, Massachussettes Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4307 (United States); Gabb, M. [Department of Physics, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431-0991 (United States)

    2014-09-01

    We present optical light curves of variable stars consistent with the positions of X-ray sources identified with the Chandra X-ray Observatory for the Chandra Galactic Bulge Survey (GBS). Using data from the Mosaic-II instrument on the Blanco 4 m Telescope at CTIO, we gathered time-resolved photometric data on timescales from ∼2 hr to 8 days over the 3/4 of the X-ray survey containing sources from the initial GBS catalog. Among the light curve morphologies we identify are flickering in interacting binaries, eclipsing sources, dwarf nova outbursts, ellipsoidal variations, long period variables, spotted stars, and flare stars. Eighty-seven percent of X-ray sources have at least one potential optical counterpart. Twenty-seven percent of these candidate counterparts are detectably variable; a much greater fraction than expected for randomly selected field stars, which suggests that most of these variables are real counterparts. We discuss individual sources of interest, provide variability information on candidate counterparts, and discuss the characteristics of the variable population.

  14. Positron Transport and Annihilation in the Galactic Bulge

    Directory of Open Access Journals (Sweden)

    Fiona Helen Panther

    2018-03-01

    Full Text Available The annihilation of positrons in the Milky Way Galaxy has been observed for ∼50 years; however, the production sites of these positrons remains hard to identify. The observed morphology of positron annihilation gamma-rays provides information on the annihilation sites of these Galactic positrons. It is understood that the positrons responsible for the annihilation signal originate at MeV energies. The majority of sources of MeV positrons occupy the star-forming thin disk of the Milky Way. If positrons propagate far from their sources, we must develop accurate models of positron propagation through all interstellar medium (ISM phases in order to reveal the currently uncertain origin of these Galactic positrons. On the other hand, if positrons annihilate close to their sources, an alternative source of MeV positrons with a distribution that matches the annihilation morphology must be identified. In this work, I discuss the various models that have been developed to understand the origin of the 511 keV line from the direction of the Galactic bulge, and the propagation of positrons in the ISM.

  15. EXPLORING THE UNUSUALLY HIGH BLACK-HOLE-TO-BULGE MASS RATIOS IN NGC 4342 AND NGC 4291: THE ASYNCHRONOUS GROWTH OF BULGES AND BLACK HOLES

    International Nuclear Information System (INIS)

    Bogdán, Ákos; Forman, William R.; Kraft, Ralph P.; Li, Zhiyuan; Vikhlinin, Alexey; Nulsen, Paul E. J.; Jones, Christine; Zhuravleva, Irina; Churazov, Eugene; Mihos, J. Christopher; Harding, Paul; Guo, Qi; Schindler, Sabine

    2012-01-01

    We study two nearby early-type galaxies, NGC 4342 and NGC 4291, that host unusually massive black holes relative to their low stellar mass. The observed black-hole-to-bulge mass ratios of NGC 4342 and NGC 4291 are 6.9 +3.8 –2.3 % and 1.9% ± 0.6%, respectively, which significantly exceed the typical observed ratio of ∼0.2%. As a consequence of the exceedingly large black-hole-to-bulge mass ratios, NGC 4342 and NGC 4291 are ≈5.1σ and ≈3.4σ outliers from the M . -M bulge scaling relation, respectively. In this paper, we explore the origin of the unusually high black-hole-to-bulge mass ratio. Based on Chandra X-ray observations of the hot gas content of NGC 4342 and NGC 4291, we compute gravitating mass profiles, and conclude that both galaxies reside in massive dark matter halos, which extend well beyond the stellar light. The presence of dark matter halos around NGC 4342 and NGC 4291 and a deep optical image of the environment of NGC 4342 indicate that tidal stripping, in which ∼> 90% of the stellar mass was lost, cannot explain the observed high black-hole-to-bulge mass ratios. Therefore, we conclude that these galaxies formed with low stellar masses, implying that the bulge and black hole did not grow in tandem. We also find that the black hole mass correlates well with the properties of the dark matter halo, suggesting that dark matter halos may play a major role in regulating the growth of the supermassive black holes.

  16. Material characterization of Inconel 718 from free bulging test at high temperature

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Joon Tae; Yoon, Jong Hoon; Lee, Ho Sung [Korea Aerospace Research Institute, Daejeon (Korea, Republic of); Youn, Sung Kie [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2012-07-15

    Macroscopic superplastic behavior of metallic or non metallic materials is usually represented by the strain rate sensitivity, and it can be determined by tensile tests in uniaxial stress state and bulging tests in multi axial stress state, which is the actual hot forming process. And macroscopic behavior of Non SPF grade materials could be described in a similar way as that of superplastic materials, including strain hardening, cavity and so on. In this study, the material characterization of non SPF grade Inconel 718 has been carried out to determine the material parameters for flow stress throughout free bulging test under constant temperature. The measured height of bulged plate during the test was used for estimation of strain rate sensitivity, strain hardening index and cavity volume fraction with the help of numerical analysis. The bulged height obtained from the simulation showed good agreement with the experimental findings. The effects of strain hardening and cavity volume fraction factor for flow stress were also compared.

  17. Galactic bulge preferred over dark matter for the Galactic centre gamma-ray excess

    Science.gov (United States)

    Macias, Oscar; Gordon, Chris; Crocker, Roland M.; Coleman, Brendan; Paterson, Dylan; Horiuchi, Shunsaku; Pohl, Martin

    2018-05-01

    An anomalous gamma-ray excess emission has been found in the Fermi Large Area Telescope data1 covering the centre of the Galaxy2,3. Several theories have been proposed for this `Galactic centre excess'. They include self-annihilation of dark-matter particles4, an unresolved population of millisecond pulsars5, an unresolved population of young pulsars6, or a series of burst events7. Here, we report on an analysis that exploits hydrodynamical modelling to register the position of interstellar gas associated with diffuse Galactic gamma-ray emission. We find evidence that the Galactic centre excess gamma rays are statistically better described by the stellar over-density in the Galactic bulge and the nuclear stellar bulge, rather than a spherical excess. Given its non-spherical nature, we argue that the Galactic centre excess is not a dark-matter phenomenon but rather associated with the stellar population of the Galactic bulge and the nuclear bulge.

  18. Bulge growth and quenching since z = 2.5 in CANDELS/3D-HST

    International Nuclear Information System (INIS)

    Lang, Philipp; Wuyts, Stijn; Schreiber, Natascha M. Förster; Genzel, Reinhard; Lutz, Dieter; Rosario, David J.; Somerville, Rachel S.; Bell, Eric F.; Brammer, Gabe; Dekel, Avishai; Faber, Sandra M.; Momcheva, Ivelina; Ferguson, Henry C.; Grogin, Norman A.; Koekemoer, Anton M.; Kocevski, Dale D.; McGrath, Elizabeth J.; Nelson, Erica J.; Primack, Joel R.; Skelton, Rosalind E.

    2014-01-01

    Exploiting the deep high-resolution imaging of all five CANDELS fields, and accurate redshift information provided by 3D-HST, we investigate the relation between structure and stellar populations for a mass-selected sample of 6764 galaxies above 10 10 M ☉ , spanning the redshift range 0.5 < z < 2.5. For the first time, we fit two-dimensional models comprising a single Sérsic fit and two-component (i.e., bulge + disk) decompositions not only to the H-band light distributions, but also to the stellar mass maps reconstructed from resolved stellar population modeling. We confirm that the increased bulge prominence among quiescent galaxies, as reported previously based on rest-optical observations, remains in place when considering the distributions of stellar mass. Moreover, we observe an increase of the typical Sérsic index and bulge-to-total ratio (with median B/T reaching 40%-50%) among star-forming galaxies above 10 11 M ☉ . Given that quenching for these most massive systems is likely to be imminent, our findings suggest that significant bulge growth precedes a departure from the star-forming main sequence. We demonstrate that the bulge mass (and ideally knowledge of the bulge and total mass) is a more reliable predictor of the star-forming versus quiescent state of a galaxy than the total stellar mass. The same trends are predicted by the state-of-the-art, semi-analytic model by Somerville et al. In this model, bulges and black holes grow hand in hand through merging and/or disk instabilities, and feedback from active galactic nuclei shuts off star formation. Further observations will be required to pin down star formation quenching mechanisms, but our results imply that they must be internal to the galaxies and closely associated with bulge growth.

  19. VERY METAL-POOR STARS IN THE OUTER GALACTIC BULGE FOUND BY THE APOGEE SURVEY

    International Nuclear Information System (INIS)

    García Pérez, Ana E.; Majewski, Steven R.; Hearty, Fred R.; Cunha, Katia; Shetrone, Matthew; Johnson, Jennifer A.; Zasowski, Gail; Smith, Verne V.; Beers, Timothy C.; Schiavon, Ricardo P.; Holtzman, Jon; Nidever, David; Allende Prieto, Carlos; Bizyaev, Dmitry; Ebelke, Garrett; Malanushenko, Elena; Malanushenko, Viktor; Eisenstein, Daniel J.; Frinchaboy, Peter M.; Girardi, Léo

    2013-01-01

    Despite its importance for understanding the nature of early stellar generations and for constraining Galactic bulge formation models, at present little is known about the metal-poor stellar content of the central Milky Way. This is a consequence of the great distances involved and intervening dust obscuration, which challenge optical studies. However, the Apache Point Observatory Galactic Evolution Experiment (APOGEE), a wide-area, multifiber, high-resolution spectroscopic survey within Sloan Digital Sky Survey III, is exploring the chemistry of all Galactic stellar populations at infrared wavelengths, with particular emphasis on the disk and the bulge. An automated spectral analysis of data on 2403 giant stars in 12 fields in the bulge obtained during APOGEE commissioning yielded five stars with low metallicity ([Fe/H] ≤ –1.7), including two that are very metal-poor [Fe/H] ∼ –2.1 by bulge standards. Luminosity-based distance estimates place the 5 stars within the outer bulge, where 1246 of the other analyzed stars may reside. A manual reanalysis of the spectra verifies the low metallicities, and finds these stars to be enhanced in the α-elements O, Mg, and Si without significant α-pattern differences with other local halo or metal-weak thick-disk stars of similar metallicity, or even with other more metal-rich bulge stars. While neither the kinematics nor chemistry of these stars can yet definitively determine which, if any, are truly bulge members, rather than denizens of other populations co-located with the bulge, the newly identified stars reveal that the chemistry of metal-poor stars in the central Galaxy resembles that of metal-weak thick-disk stars at similar metallicity.

  20. VERY METAL-POOR STARS IN THE OUTER GALACTIC BULGE FOUND BY THE APOGEE SURVEY

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Perez, Ana E.; Majewski, Steven R.; Hearty, Fred R. [Department of Astronomy, University of Virginia, Charlottesville, VA 22904-4325 (United States); Cunha, Katia [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Shetrone, Matthew [McDonald Observatory, University of Texas at Austin, Fort Davis, TX 79734 (United States); Johnson, Jennifer A.; Zasowski, Gail [Department of Astronomy, The Ohio State University, Columbus, OH 43210 (United States); Smith, Verne V.; Beers, Timothy C. [National Optical Astronomy Observatories, Tucson, AZ 85719 (United States); Schiavon, Ricardo P. [Gemini Observatory, 670 N. A' Ohoku Place, Hilo, HI 96720 (United States); Holtzman, Jon [Department of Astronomy, MSC 4500, New Mexico State University, P.O. Box 30001, Las Cruces, NM 88003 (United States); Nidever, David [Department of Astronomy, University of Michigan, Ann Arbor, MI 48109 (United States); Allende Prieto, Carlos [Departamento de Astrofisica, Universidad de La Laguna, E-38206 La Laguna, Tenerife (Spain); Bizyaev, Dmitry; Ebelke, Garrett; Malanushenko, Elena; Malanushenko, Viktor [Apache Point Observatory, P.O. Box 59, Sunspot, NM 88349-0059 (United States); Eisenstein, Daniel J. [Harvard Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Frinchaboy, Peter M. [Department of Physics and Astronomy, Texas Christian University, 2800 South University Drive, Fort Worth, TX 76129 (United States); Girardi, Leo [Laboratorio Interinstitucional de e-Astronomia - LIneA, Rua Gal. Jose Cristino 77, Rio de Janeiro, RJ - 20921-400 (Brazil); and others

    2013-04-10

    Despite its importance for understanding the nature of early stellar generations and for constraining Galactic bulge formation models, at present little is known about the metal-poor stellar content of the central Milky Way. This is a consequence of the great distances involved and intervening dust obscuration, which challenge optical studies. However, the Apache Point Observatory Galactic Evolution Experiment (APOGEE), a wide-area, multifiber, high-resolution spectroscopic survey within Sloan Digital Sky Survey III, is exploring the chemistry of all Galactic stellar populations at infrared wavelengths, with particular emphasis on the disk and the bulge. An automated spectral analysis of data on 2403 giant stars in 12 fields in the bulge obtained during APOGEE commissioning yielded five stars with low metallicity ([Fe/H] {<=} -1.7), including two that are very metal-poor [Fe/H] {approx} -2.1 by bulge standards. Luminosity-based distance estimates place the 5 stars within the outer bulge, where 1246 of the other analyzed stars may reside. A manual reanalysis of the spectra verifies the low metallicities, and finds these stars to be enhanced in the {alpha}-elements O, Mg, and Si without significant {alpha}-pattern differences with other local halo or metal-weak thick-disk stars of similar metallicity, or even with other more metal-rich bulge stars. While neither the kinematics nor chemistry of these stars can yet definitively determine which, if any, are truly bulge members, rather than denizens of other populations co-located with the bulge, the newly identified stars reveal that the chemistry of metal-poor stars in the central Galaxy resembles that of metal-weak thick-disk stars at similar metallicity.

  1. Bulge Growth and Quenching since z = 2.5 in CANDELS/3D-HST

    Science.gov (United States)

    Lang, Philipp; Wuyts, Stijn; Somerville, Rachel S.; Förster Schreiber, Natascha M.; Genzel, Reinhard; Bell, Eric F.; Brammer, Gabe; Dekel, Avishai; Faber, Sandra M.; Ferguson, Henry C.; Grogin, Norman A.; Kocevski, Dale D.; Koekemoer, Anton M.; Lutz, Dieter; McGrath, Elizabeth J.; Momcheva, Ivelina; Nelson, Erica J.; Primack, Joel R.; Rosario, David J.; Skelton, Rosalind E.; Tacconi, Linda J.; van Dokkum, Pieter G.; Whitaker, Katherine E.

    2014-06-01

    Exploiting the deep high-resolution imaging of all five CANDELS fields, and accurate redshift information provided by 3D-HST, we investigate the relation between structure and stellar populations for a mass-selected sample of 6764 galaxies above 1010 M ⊙, spanning the redshift range 0.5 < z < 2.5. For the first time, we fit two-dimensional models comprising a single Sérsic fit and two-component (i.e., bulge + disk) decompositions not only to the H-band light distributions, but also to the stellar mass maps reconstructed from resolved stellar population modeling. We confirm that the increased bulge prominence among quiescent galaxies, as reported previously based on rest-optical observations, remains in place when considering the distributions of stellar mass. Moreover, we observe an increase of the typical Sérsic index and bulge-to-total ratio (with median B/T reaching 40%-50%) among star-forming galaxies above 1011 M ⊙. Given that quenching for these most massive systems is likely to be imminent, our findings suggest that significant bulge growth precedes a departure from the star-forming main sequence. We demonstrate that the bulge mass (and ideally knowledge of the bulge and total mass) is a more reliable predictor of the star-forming versus quiescent state of a galaxy than the total stellar mass. The same trends are predicted by the state-of-the-art, semi-analytic model by Somerville et al. In this model, bulges and black holes grow hand in hand through merging and/or disk instabilities, and feedback from active galactic nuclei shuts off star formation. Further observations will be required to pin down star formation quenching mechanisms, but our results imply that they must be internal to the galaxies and closely associated with bulge growth.

  2. The Chemical Composition of the Galactic Bulge and Implications for its Evolution

    Science.gov (United States)

    McWilliam, Andrew

    2016-08-01

    At a bulge latitude of b = -4°, the average [Fe/H] and [Mg/H] values are +0.06 and +0.17 dex, roughly 0.2 and 0.7 dex higher than the local thin and thick disk values, respectively, suggesting a large bulge effective yield, perhaps due to efficient retention of supernova ejecta. The bulge vertical [Fe/H] gradient, at ∼0.5 dex/kpc, appears to be due to a changing mixture of sub-populations (near +0.3 dex and -0.3 dex and one possibly near -0.7 dex) with latitude. At solar [Fe/H], the bulge [Al/Fe] and [α/Fe] ratios are ∼ +0.15 dex. Below [Fe/H] ∼ -0.5 dex, the bulge and local thick disk compositions are very similar; but the measured [Mg/Fe], [/Fe], [La/Eu] and dramatic [Cu/Fe] ratios suggest higher SFR in the bulge. However, these composition differences with the thick disk could be due to measurement errors and non-LTE effects. Unusual zig-zag trends of [Cu/Fe] and [Na/Fe] suggest metallicity-dependent nucleosynthesis by core-collapse supernovae in the Type Ia supernova time-delay scenario. The bulge sub-population compositions resemble the local thin and thick disks, but at higher [Fe/H], suggesting a radial [Fe/H] gradient of -0.04 to -0.05 dex/kpc for both the thin and thick disks. If the bulge formed through accretion of inner thin and thick disk stars, it appears that these stars retained vertical scale heights characteristic of their kinematic origin, resulting in the vertical [Fe/H] gradient and [α/Fe] trends seen today.

  3. THE NUMBER OF TIDAL DWARF SATELLITE GALAXIES IN DEPENDENCE OF BULGE INDEX

    International Nuclear Information System (INIS)

    López-Corredoira, Martín; Kroupa, Pavel

    2016-01-01

    We show that a significant correlation (up to 5σ) emerges between the bulge index, defined to be larger for a larger bulge/disk ratio, in spiral galaxies with similar luminosities in the Galaxy Zoo 2 of the Sloan Digital Sky Survey and the number of tidal-dwarf galaxies in the catalog by Kaviraj et al. In the standard cold or warm dark matter cosmological models, the number of satellite galaxies correlates with the circular velocity of the dark matter host halo. In generalized gravity models without cold or warm dark matter, such a correlation does not exist, because host galaxies cannot capture infalling dwarf galaxies due to the absence of dark-matter-induced dynamical friction. However, in such models, a correlation is expected to exist between the bulge mass and the number of satellite galaxies because bulges and tidal-dwarf satellite galaxies form in encounters between host galaxies. This is not predicted by dark matter models in which bulge mass and the number of satellites are a priori uncorrelated because higher bulge/disk ratios do not imply higher dark/luminous ratios. Hence, our correlation reproduces the prediction of scenarios without dark matter, whereas an explanation is not found readily from the a priori predictions of the standard scenario with dark matter. Further research is needed to explore whether some application of the standard theory may explain this correlation

  4. A HIGH-VELOCITY BULGE RR LYRAE VARIABLE ON A HALO-LIKE ORBIT

    International Nuclear Information System (INIS)

    Kunder, Andrea; Storm, J.; Rich, R. M.; Hawkins, K.; Poleski, R.; Johnson, C. I.; Shen, J.; Li, Z.-Y.; Cordero, M. J.; Nataf, D. M.; Bono, G.; Walker, A. R.; Koch, A.; De Propris, R.; Udalski, A.; Szymanski, M. K.; Soszynski, I.; Pietrzynski, G.; Ulaczyk, K.; Wyrzykowski, Ł.

    2015-01-01

    We report on the RR Lyrae variable star, MACHO 176.18833.411, located toward the Galactic bulge and observed within the data from the ongoing Bulge RR Lyrae Radial Velocity Assay, which has the unusual radial velocity of −372 ± 8 km s −1 and true space velocity of −482 ± 22 km s −1 relative to the Galactic rest frame. Located less than 1 kpc from the Galactic center and toward a field at (l, b) = (3, −2.5), this pulsating star has properties suggesting it belongs to the bulge RR Lyrae star population, yet a velocity indicating it is abnormal, at least with respect to bulge giants and red clump stars. We show that this star is most likely a halo interloper and therefore suggest that halo contamination is not insignificant when studying metal-poor stars found within the bulge area, even for stars within 1 kpc of the Galactic center. We discuss the possibility that MACHO 176.18833.411 is on the extreme edge of the bulge RR Lyrae radial velocity distribution, and also consider a more exotic scenario in which it is a runaway star moving through the Galaxy

  5. A HIGH-VELOCITY BULGE RR LYRAE VARIABLE ON A HALO-LIKE ORBIT

    Energy Technology Data Exchange (ETDEWEB)

    Kunder, Andrea; Storm, J. [Leibniz-Institut für Astrophysik Potsdam (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Rich, R. M. [Department of Physics and Astronomy, University of California at Los Angeles, Los Angeles, CA 90095-1562 (United States); Hawkins, K. [Institute of Astronomy, Madingley Road, Cambridge CB3 0HA (United Kingdom); Poleski, R. [Department of Astronomy, Ohio State University, 140 W. 18th Avenue, Columbus, OH 43210 (United States); Johnson, C. I. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Shen, J.; Li, Z.-Y. [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Chinese Academy of Sciences, 80 Nandan Road, Shanghai 200030 (China); Cordero, M. J. [Astronomisches Rechen-Institut: Zentrum für Astronomie, Mönchhofstr. 12-14, D-69120 Heidelberg (Germany); Nataf, D. M. [Research School of Astronomy and Astrophysics, The Australian National University, Canberra, ACT 2611 (Australia); Bono, G. [Dipartimento di Fisica, Universita di Roma Tor Vergata, Via della Ricerca Scientifica 1, I-00133 Roma (Italy); Walker, A. R. [Cerro Tololo Inter-American Observatory, National Optical Astronomy Observatory, Casilla 603, La Serena (Chile); Koch, A. [Landessternwarte, Zentrum für Astronomie der Universität Heidelberg, Königstuhl 12, D-69117 Heidelberg (Germany); De Propris, R. [Finnish Centre for Astronomy with ESO (FINCA), University of Turku, Turku (Finland); Udalski, A.; Szymanski, M. K.; Soszynski, I.; Pietrzynski, G.; Ulaczyk, K.; Wyrzykowski, Ł. [Warsaw University Observatory, Al. Ujazdowskie 4, 00-478 Warszawa (Poland); and others

    2015-07-20

    We report on the RR Lyrae variable star, MACHO 176.18833.411, located toward the Galactic bulge and observed within the data from the ongoing Bulge RR Lyrae Radial Velocity Assay, which has the unusual radial velocity of −372 ± 8 km s{sup −1} and true space velocity of −482 ± 22 km s{sup −1} relative to the Galactic rest frame. Located less than 1 kpc from the Galactic center and toward a field at (l, b) = (3, −2.5), this pulsating star has properties suggesting it belongs to the bulge RR Lyrae star population, yet a velocity indicating it is abnormal, at least with respect to bulge giants and red clump stars. We show that this star is most likely a halo interloper and therefore suggest that halo contamination is not insignificant when studying metal-poor stars found within the bulge area, even for stars within 1 kpc of the Galactic center. We discuss the possibility that MACHO 176.18833.411 is on the extreme edge of the bulge RR Lyrae radial velocity distribution, and also consider a more exotic scenario in which it is a runaway star moving through the Galaxy.

  6. Salivary testosterone and a trinucleotide (CAG) length polymorphism in the androgen receptor gene predict amygdala reactivity in men.

    Science.gov (United States)

    Manuck, Stephen B; Marsland, Anna L; Flory, Janine D; Gorka, Adam; Ferrell, Robert E; Hariri, Ahmad R

    2010-01-01

    In studies employing functional magnetic resonance imaging (fMRI), reactivity of the amygdala to threat-related sensory cues (viz., facial displays of negative emotion) has been found to correlate positively with interindividual variability in testosterone levels of women and young men and to increase on acute administration of exogenous testosterone. Many of the biological actions of testosterone are mediated by intracellular androgen receptors (ARs), which exert transcriptional control of androgen-dependent genes and are expressed in various regions of the brain, including the amygdala. Transactivation potential of the AR decreases (yielding relative androgen insensitivity) with expansion a polyglutamine stretch in the N-terminal domain of the AR protein, as encoded by a trinucleotide (CAG) repeat polymorphism in exon 1 of the X-chromosome AR gene. Here we examined whether amygdala reactivity to threat-related facial expressions (fear, anger) differs as a function of AR CAG length variation and endogenous (salivary) testosterone in a mid-life sample of 41 healthy men (mean age=45.6 years, range: 34-54 years; CAG repeats, range: 19-29). Testosterone correlated inversely with participant age (r=-0.39, p=0.012) and positively with number of CAG repeats (r=0.45, p=0.003). In partial correlations adjusted for testosterone level, reactivity in the ventral amygdala was lowest among men with largest number of CAG repeats. This inverse association was seen in both the right (r(p)=-0.34, pleft (r(p)=-0.32, pdifferences in salivary testosterone, also in right (r=0.40, pleft (r=0.32, pdifferences in salivary testosterone also predicted dorsal amygdala reactivity and did so independently of CAG repeats, it is suggested that androgenic influences within this anatomically distinct region may be mediated, in part, by non-genomic or AR-independent mechanisms.

  7. Polycyclic Aromatic Hydrocarbon Emission Toward the Galactic Bulge

    Science.gov (United States)

    Shannon, M. J.; Peeters, E.; Cami, J.; Blommaert, J. A. D. L.

    2018-03-01

    We examine polycyclic aromatic hydrocarbon (PAH), dust, and atomic/molecular emission toward the Galactic bulge using Spitzer Space Telescope observations of four fields: C32, C35, OGLE, and NGC 6522. These fields are approximately centered on (l, b) = (0.°0, 1.°0), (0.°0, ‑1.°0), (0.°4, ‑2.°4), and (1.°0, ‑3.°8), respectively. Far-infrared photometric observations complement the Spitzer/IRS spectroscopic data and are used to construct spectral energy distributions. We find that the dust and PAH emission are exceptionally similar between C32 and C35 overall, in part explained due to their locations—they reside on or near boundaries of a 7 Myr old Galactic outflow event and are partly shock-heated. Within the C32 and C35 fields, we identify a region of elevated Hα emission that is coincident with elevated fine-structure and [O IV] line emission and weak PAH feature strengths. We are likely tracing a transition zone of the outflow into the nascent environment. PAH abundances in these fields are slightly depressed relative to typical ISM values. In the OGLE and NGC 6522 fields, we observe weak features on a continuum dominated by zodiacal dust. SED fitting indicates that thermal dust grains in C32 and C35 have temperatures comparable to those of diffuse, high-latitude cirrus clouds. Little variability is detected in the PAH properties between C32 and C35, indicating that a stable population of PAHs dominates the overall spectral appearance. In fact, their PAH features are exceptionally similar to that of the M82 superwind, emphasizing that we are probing a local Galactic wind environment.

  8. MERGERS AND BULGE FORMATION IN ΛCDM: WHICH MERGERS MATTER?

    International Nuclear Information System (INIS)

    Hopkins, Philip F.; Bundy, Kevin; Wetzel, Andrew; Croton, Darren; Hernquist, Lars; Keres, Dusan; Younger, Joshua D.; Khochfar, Sadegh; Stewart, Kyle

    2010-01-01

    We use a suite of semi-empirical models to predict the galaxy-galaxy merger rate and relative contributions to bulge growth as a function of mass (both halo and stellar), redshift, and mass ratio. The models use empirical constraints on the halo occupation distribution, evolved forward in time, to robustly identify where and when galaxy mergers occur. Together with the results of high-resolution merger simulations, this allows us to quantify the relative contributions of mergers with different properties (e.g., mass ratios, gas fractions, redshifts) to the bulge population. We compare with observational constraints, and find good agreement. We also provide useful fitting functions and make public a code to reproduce the predicted merger rates and contributions to bulge mass growth. We identify several robust conclusions. (1) Major mergers dominate the formation and assembly of ∼L * bulges and the total spheroid mass density, but minor mergers contribute a non-negligible ∼30%. (2) This is mass dependent: bulge formation and assembly is dominated by more minor mergers in lower-mass systems. In higher-mass systems, most bulges originally form in major mergers near ∼L * , but assemble in increasingly minor mergers. (3) The minor/major contribution is also morphology dependent: higher B/T systems preferentially form in more major mergers, with B/T roughly tracing the mass ratio of the largest recent merger; lower B/T systems preferentially form in situ from minor mergers. (4) Low-mass galaxies, being gas-rich, require more mergers to reach the same B/T as high-mass systems. Gas-richness dramatically suppresses the absolute efficiency of bulge formation, but does not strongly influence the relative contribution of major versus minor mergers. (5) Absolute merger rates at fixed mass ratio increase with galaxy mass. (6) Predicted merger rates agree well with those observed in pair and morphology-selected samples, but there is evidence that some morphology

  9. THE AGE OF THE YOUNG BULGE-LIKE POPULATION IN THE STELLAR SYSTEM TERZAN 5: LINKING THE GALACTIC BULGE TO THE HIGH- Z UNIVERSE

    Energy Technology Data Exchange (ETDEWEB)

    Ferraro, F. R.; Dalessandro, E.; Lanzoni, B.; Mucciarelli, A. [Dipartimento di Fisica e Astronomia, Università degli Studi di Bologna, Viale Berti Pichat 6/2, I–40127 Bologna (Italy); Massari, D. [INAF-Osservatorio Astronomico di Bologna, Via Ranzani, 1, I-40127 Bologna (Italy); Origlia, L. [Kapteyn Astronomical Institute, University of Gröningen, Kapteyn Astron Institute, NL-9747 AD Gröningen (Netherlands); Rich, R. M. [Department of Physics and Astronomy, 430 Portola Plaza, Box 951547, Los Angeles, CA 90095-1547 (United States)

    2016-09-10

    The Galactic bulge is dominated by an old, metal-rich stellar population. The possible presence and the amount of a young (a few gigayears old) minor component is one of the major issues debated in the literature. Recently, the bulge stellar system Terzan 5 was found to harbor three sub-populations with iron content varying by more than one order of magnitude (from 0.2 up to two times the solar value), with chemical abundance patterns strikingly similar to those observed in bulge field stars. Here we report on the detection of two distinct main-sequence turnoff points in Terzan 5, providing the age of the two main stellar populations: 12 Gyr for the (dominant) sub-solar component and 4.5 Gyr for the component at super-solar metallicity. This discovery classifies Terzan 5 as a site in the Galactic bulge where multiple bursts of star formation occurred, thus suggesting a quite massive progenitor possibly resembling the giant clumps observed in star-forming galaxies at high redshifts. This connection opens a new route of investigation into the formation process and evolution of spheroids and their stellar content.

  10. The Gaia-ESO Survey: Exploring the complex nature and origins of the Galactic bulge populations

    Science.gov (United States)

    Rojas-Arriagada, A.; Recio-Blanco, A.; de Laverny, P.; Mikolaitis, Š.; Matteucci, F.; Spitoni, E.; Schultheis, M.; Hayden, M.; Hill, V.; Zoccali, M.; Minniti, D.; Gonzalez, O. A.; Gilmore, G.; Randich, S.; Feltzing, S.; Alfaro, E. J.; Babusiaux, C.; Bensby, T.; Bragaglia, A.; Flaccomio, E.; Koposov, S. E.; Pancino, E.; Bayo, A.; Carraro, G.; Casey, A. R.; Costado, M. T.; Damiani, F.; Donati, P.; Franciosini, E.; Hourihane, A.; Jofré, P.; Lardo, C.; Lewis, J.; Lind, K.; Magrini, L.; Morbidelli, L.; Sacco, G. G.; Worley, C. C.; Zaggia, S.

    2017-05-01

    Context. As observational evidence steadily accumulates, the nature of the Galactic bulge has proven to be rather complex: the structural, kinematic, and chemical analyses often lead to contradictory conclusions. The nature of the metal-rich bulge - and especially of the metal-poor bulge - and their relation with other Galactic components, still need to be firmly defined on the basis of statistically significant high-quality data samples. Aims: We used the fourth internal data release of the Gaia-ESO survey to characterize the bulge metallicity distribution function (MDF), magnesium abundance, spatial distribution, and correlation of these properties with kinematics. Moreover, the homogeneous sampling of the different Galactic populations provided by the Gaia-ESO survey allowed us to perform a comparison between the bulge, thin disk, and thick disk sequences in the [Mg/Fe] vs. [Fe/H] plane in order to constrain the extent of their eventual chemical similarities. Methods: We obtained spectroscopic data for 2500 red clump stars in 11 bulge fields, sampling the area -10° ≤ l ≤ + 8° and -10° ≤ b ≤ -4° from the fourth internal data release of the Gaia-ESO survey. A sample of 6300 disk stars was also selected for comparison. Spectrophotometric distances computed via isochrone fitting allowed us to define a sample of stars likely located in the bulge region. Results: From a Gaussian mixture models (GMM) analysis, the bulge MDF is confirmed to be bimodal across the whole sampled area. The relative ratio between the two modes of the MDF changes as a function of b, with metal-poor stars dominating at high latitudes. The metal-rich stars exhibit bar-like kinematics and display a bimodality in their magnitude distribution, a feature which is tightly associated with the X-shape bulge. They overlap with the metal-rich end of the thin disk sequence in the [Mg/Fe] vs. [Fe/H] plane. On the other hand, metal-poor bulge stars have a more isotropic hot kinematics and do

  11. In situ optical sequencing and structure analysis of a trinucleotide repeat genome region by localization microscopy after specific COMBO-FISH nano-probing

    Science.gov (United States)

    Stuhlmüller, M.; Schwarz-Finsterle, J.; Fey, E.; Lux, J.; Bach, M.; Cremer, C.; Hinderhofer, K.; Hausmann, M.; Hildenbrand, G.

    2015-10-01

    Trinucleotide repeat expansions (like (CGG)n) of chromatin in the genome of cell nuclei can cause neurological disorders such as for example the Fragile-X syndrome. Until now the mechanisms are not clearly understood as to how these expansions develop during cell proliferation. Therefore in situ investigations of chromatin structures on the nanoscale are required to better understand supra-molecular mechanisms on the single cell level. By super-resolution localization microscopy (Spectral Position Determination Microscopy; SPDM) in combination with nano-probing using COMBO-FISH (COMBinatorial Oligonucleotide FISH), novel insights into the nano-architecture of the genome will become possible. The native spatial structure of trinucleotide repeat expansion genome regions was analysed and optical sequencing of repetitive units was performed within 3D-conserved nuclei using SPDM after COMBO-FISH. We analysed a (CGG)n-expansion region inside the 5' untranslated region of the FMR1 gene. The number of CGG repeats for a full mutation causing the Fragile-X syndrome was found and also verified by Southern blot. The FMR1 promotor region was similarly condensed like a centromeric region whereas the arrangement of the probes labelling the expansion region seemed to indicate a loop-like nano-structure. These results for the first time demonstrate that in situ chromatin structure measurements on the nanoscale are feasible. Due to further methodological progress it will become possible to estimate the state of trinucleotide repeat mutations in detail and to determine the associated chromatin strand structural changes on the single cell level. In general, the application of the described approach to any genome region will lead to new insights into genome nano-architecture and open new avenues for understanding mechanisms and their relevance in the development of heredity diseases.

  12. Nuclear fuel assembly grid sleeve/guide thimble bulge orientation gage and inspection method

    International Nuclear Information System (INIS)

    Widener, W.H.

    1988-01-01

    This patent describes a method of inspecting a fuel assembly to determine the orientation of externally-projecting mated bulges connecting a grid sleeve to a guide thimble of the assembly, the method comprising the steps of: (a) inserting a radially-expandable tubular member within the guide thimble, the tubular member having externally-projecting embossments thereon spaced circumferentially from one another about the tubular member, the embossments being the same in number as the bulges of the guide thimble and configured to fit therewithin; (b) axially moving an elongated expansion member, which extends through and rotatably mounts the tubular member, relative to the tubular member from a first position in which the expansion member permits inward contraction of the tubular member and displacement of embossments thereon away from the interior of the guide thimble bulges for removing the embossments from registry therewith and a second position in which the expansion member produces radial expansion of the tubular member and displacement of the embossments thereon toward the interior of the guide thimble bulges for placing the embossments in registry therewith; (c) rotating the tubular member relative to the expansion member so as to bring the embossments on the tubular member into alignment with the guide thimble bulges as the embossments on the tubular member are being displaced toward and into registry with the interior of the bulges; and (d) responsive to rotation of the tubular member away from a reference position, providing an indication of the orientation of the guide thimble bulges relative to a reference point upon displacement of the embossments into registry therewith

  13. Supermassive Black Holes and Their Host Galaxies. I. Bulge Luminosities from Dedicated Near-infrared Data

    Science.gov (United States)

    Läsker, Ronald; Ferrarese, Laura; van de Ven, Glenn

    2014-01-01

    In an effort to secure, refine, and supplement the relation between central supermassive black hole masses, M •, and the bulge luminosities of their host galaxies, L bul, we obtained deep, high spatial resolution K-band images of 35 nearby galaxies with securely measured M •, using the wide-field WIRCam imager at the Canada-France-Hawaii-Telescope. A dedicated data reduction and sky subtraction strategy was adopted to estimate the brightness and structure of the sky, a critical step when tracing the light distribution of extended objects in the near-infrared. From the final image product, bulge and total magnitudes were extracted via two-dimensional profile fitting. As a first order approximation, all galaxies were modeled using a simple Sérsic-bulge+exponential-disk decomposition. However, we found that such models did not adequately describe the structure that we observed in a large fraction of our sample galaxies which often include cores, bars, nuclei, inner disks, spiral arms, rings, and envelopes. In such cases, we adopted profile modifications and/or more complex models with additional components. The derived bulge magnitudes are very sensitive to the details and number of components used in the models, although total magnitudes remain almost unaffected. Usually, but not always, the luminosities and sizes of the bulges are overestimated when a simple bulge+disk decomposition is adopted in lieu of a more complex model. Furthermore, we found that some spheroids are not well fit when the ellipticity of the Sérsic model is held fixed. This paper presents the details of the image processing and analysis, while we discuss how model-induced biases and systematics in bulge magnitudes impact the M •-L bul relation in a companion paper.

  14. The influence of changes in cervical lordosis on bulging disk and spinal stenosis: functional MR imaging

    International Nuclear Information System (INIS)

    Lee, Young Joon; Eun, Choong Ki

    2001-01-01

    To assess the effect of lordotic curve change of the cervical spine on disk bulging and spinal stenosis by means of functional cervical MR imaging at the flexion and extension position. Using a 1.5T imager, kinematic MR examinations of 25 patients with degenerative spondylosis (average age, 41 years) were performed at the neutral, flexed and extended position of the cervical spine. Sagittal T2-weighted turbo spin-echo images were obtained during each of the three phases. Lordotic angle, bulging thickness of the disk, AP diameter of the spinal canal, and distance between the disk and spinal cord were measured on the workstation at each disk level. After qualitative independent observation of disk bulging, one of four grades(0, normal; 1, mild; 2, moderate; 3, marked) was assigned at each phase, and after further comparative observation, one of five scores (-2, prominent decrease; -1, mild decrease; 0, no change; 1, notable increase; 2 prominent increase) was also assigned. In addition, bulging thickness of the disk was measured and compared at the neutral, flexed, and extended positions. Average angles of the cervical spine were 160.5±5.9 deg (neutral position, lordotic angle); 185.4±8.5 deg (flexion, kyphotic angle); and 143.7±6.7 deg (extension, lordotic angle). Average grades of disk bulging were 0.55 at the neutral position. 0.16 at flexion, and 0.7 at extension. Comparative observation showed that average scores of disk bulging were -0.39 at flexion and 0.31 at extension. The bulging thickness of the disk decreased by 24.2% at flexion and increased by 30.3% at extension, while the diameter of the spinal canal increased by 4.5% at flexion and decreased by 3.6% at extension. The distance from the posterior margin of the disk to the anterior margin of the spinal cord decreased at both flexion(6.6%) and extension(19.1%). Functional MRI showed that compared with the neutral position, disk bulging and spinal stenosis are less prominent at flexion and accentuated

  15. The influence of changes in cervical lordosis on bulging disk and spinal stenosis: functional MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Joon; Eun, Choong Ki [Pusan Paik Hospital, Inje Univ. College of Medicine, Pusan (Korea, Republic of)

    2001-05-01

    To assess the effect of lordotic curve change of the cervical spine on disk bulging and spinal stenosis by means of functional cervical MR imaging at the flexion and extension position. Using a 1.5T imager, kinematic MR examinations of 25 patients with degenerative spondylosis (average age, 41 years) were performed at the neutral, flexed and extended position of the cervical spine. Sagittal T2-weighted turbo spin-echo images were obtained during each of the three phases. Lordotic angle, bulging thickness of the disk, AP diameter of the spinal canal, and distance between the disk and spinal cord were measured on the workstation at each disk level. After qualitative independent observation of disk bulging, one of four grades(0, normal; 1, mild; 2, moderate; 3, marked) was assigned at each phase, and after further comparative observation, one of five scores (-2, prominent decrease; -1, mild decrease; 0, no change; 1, notable increase; 2 prominent increase) was also assigned. In addition, bulging thickness of the disk was measured and compared at the neutral, flexed, and extended positions. Average angles of the cervical spine were 160.5{+-}5.9 deg (neutral position, lordotic angle); 185.4{+-}8.5 deg (flexion, kyphotic angle); and 143.7{+-}6.7 deg (extension, lordotic angle). Average grades of disk bulging were 0.55 at the neutral position. 0.16 at flexion, and 0.7 at extension. Comparative observation showed that average scores of disk bulging were -0.39 at flexion and 0.31 at extension. The bulging thickness of the disk decreased by 24.2% at flexion and increased by 30.3% at extension, while the diameter of the spinal canal increased by 4.5% at flexion and decreased by 3.6% at extension. The distance from the posterior margin of the disk to the anterior margin of the spinal cord decreased at both flexion(6.6%) and extension(19.1%). Functional MRI showed that compared with the neutral position, disk bulging and spinal stenosis are less prominent at flexion and

  16. Twisting right to left: A…A mismatch in a CAG trinucleotide repeat overexpansion provokes left-handed Z-DNA conformation.

    Directory of Open Access Journals (Sweden)

    Noorain Khan

    2015-04-01

    Full Text Available Conformational polymorphism of DNA is a major causative factor behind several incurable trinucleotide repeat expansion disorders that arise from overexpansion of trinucleotide repeats located in coding/non-coding regions of specific genes. Hairpin DNA structures that are formed due to overexpansion of CAG repeat lead to Huntington's disorder and spinocerebellar ataxias. Nonetheless, DNA hairpin stem structure that generally embraces B-form with canonical base pairs is poorly understood in the context of periodic noncanonical A…A mismatch as found in CAG repeat overexpansion. Molecular dynamics simulations on DNA hairpin stems containing A…A mismatches in a CAG repeat overexpansion show that A…A dictates local Z-form irrespective of starting glycosyl conformation, in sharp contrast to canonical DNA duplex. Transition from B-to-Z is due to the mechanistic effect that originates from its pronounced nonisostericity with flanking canonical base pairs facilitated by base extrusion, backbone and/or base flipping. Based on these structural insights we envisage that such an unusual DNA structure of the CAG hairpin stem may have a role in disease pathogenesis. As this is the first study that delineates the influence of a single A…A mismatch in reversing DNA helicity, it would further have an impact on understanding DNA mismatch repair.

  17. Application of FTA sample collection and DNA purification system on the determination of CTG trinucleotide repeat size by PCR-based Southern blotting.

    Science.gov (United States)

    Hsiao, K M; Lin, H M; Pan, H; Li, T C; Chen, S S; Jou, S B; Chiu, Y L; Wu, M F; Lin, C C; Li, S Y

    1999-01-01

    Myotonic dystrophy (DM) is caused by a CTG trinucleotide expansion mutation at exon 15 of the myotonic dystrophy protein kinase gene. The clinical severity of this disease correlates with the length of the CTG trinucleotide repeats. Determination of the CTG repeat length has been primarily relied on by Southern blot analysis of restriction enzyme-digested genomic DNA. The development of PCR-based Southern blotting methodology provides a much more sensitive and simpler protocol for DM diagnosis. However, the quality of the template and the high (G+C) ratio of the amplified region hamper the use of PCR on the diagnosis of DM. A modified PCR protocol to amplify different lengths of CTG repeat region using various concentrations of 7deaza-dGTP has been reported (1). Here we describe a procedure including sample collection, DNA purification, and PCR analysis of CTG repeat length without using 7-deaza-dGTP. This protocol is very sensitive and convenient because only a small number of nucleate cells are needed for detection of CTG expansion. Therefore, it could be very useful in clinical and prenatal diagnosis as well as in prevalence study of DM.

  18. Tracing the Chemical Evolution of Metal-rich Galactic Bulge Globular Clusters

    Science.gov (United States)

    Munoz Gonzalez, Cesar; Saviane, Ivo; Geisler, Doug; Villanova, Sandro

    2018-01-01

    We present in this poster the metallicity characterization of the four metal rich Bulge Galactic Gobular Clusters, which have controversial metallicities. We analyzed our high-resolution spectra (using UVES-580nm and GIRAFFE-HR13 setups) for a large sample of RGB/AGB targets in each cluster in order to measure their metallicity and prove or discard the iron spread hypothesis. We have also characterized chemically stars with potentially different iron content by measuring light (O, Na, Mg, Al), alpha (Si, Ca, Ti), iron–peak (V, Cr, Ni, Mn) and s and r process (Y, Zr, Ba, Eu) elements. We have identified possible channels responsible for the chemical heterogeneity of the cluster populations, like AGB or massive fast-rotating stars contamination, or SN explosion. Also, we have analyzed the origin and evolution of these bulge GCs and their connection with the bulge itself.

  19. The Globular Clusters of the Galactic Bulge: Results from Multiwavelength Follow-up Imaging

    Science.gov (United States)

    Cohen, Roger; Geisler, Doug; Mauro, Francesco; Alonso Garcia, Javier; Hempel, Maren; Sarajedini, Ata

    2018-01-01

    The Galactic globular clusters (GGCs) located towards the bulge of the Milky Way suffer from severe total and differential extinction and high field star densities. They have therefore been systematically excluded from deep, large-scale homogenous GGC surveys, and will present a challenge for Gaia. Meanwhile, existing observations of bulge GGCs have revealed tantalizing hints that they hold clues to Galactic formation and evolution not found elsewhere. Therefore, in order to better characterize these poorly studied stellar systems and place them in the context of their optically well-studied counterparts, we have undertaken imaging programs at optical and near-infrared wavelengths. We describe these programs and present a variety of results, including self-consistent measurement of bulge GGC ages and structural parameters. The limitations imposed by spatially variable extinction and extinction law are highlighted, along with the complimentary nature of forthcoming facilities, allowing us to finally complete our picture of the Milky Way GGC system.

  20. THE SPLIT RED CLUMP OF THE GALACTIC BULGE FROM OGLE-III

    International Nuclear Information System (INIS)

    Nataf, D. M.; Gould, A.; Stanek, K. Z.; Udalski, A.; Fouque, P.

    2010-01-01

    The red clump (RC) is found to be split into two components along several sightlines toward the Galactic bulge. This split is detected with high significance toward the areas (-3.5 < l < 1, b < -5) and (l, b) = (0, + 5.2), i.e., along the bulge minor axis and at least 5 deg off the plane. The fainter (hereafter 'main') component is the one that more closely follows the distance-longitude relation of the bulge RC. The main component is ∼0.5 mag fainter than the secondary component and with an overall approximately equal population. For sightlines further from the plane, the difference in brightness increases, and more stars are found in the secondary component than in the main component. The two components have very nearly equal (V - I) color.

  1. Pyrite footprinting of RNA

    International Nuclear Information System (INIS)

    Schlatterer, Jörg C.; Wieder, Matthew S.; Jones, Christopher D.; Pollack, Lois; Brenowitz, Michael

    2012-01-01

    Highlights: ► RNA structure is mapped by pyrite mediated · OH footprinting. ► Repetitive experiments can be done in a powdered pyrite filled cartridge. ► High · OH reactivity of nucleotides imply dynamic role in Diels–Alderase catalysis. -- Abstract: In RNA, function follows form. Mapping the surface of RNA molecules with chemical and enzymatic probes has revealed invaluable information about structure and folding. Hydroxyl radicals ( · OH) map the surface of nucleic acids by cutting the backbone where it is accessible to solvent. Recent studies showed that a microfluidic chip containing pyrite (FeS 2 ) can produce sufficient · OH to footprint DNA. The 49-nt Diels–Alder RNA enzyme catalyzes the C–C bond formation between a diene and a dienophile. A crystal structure, molecular dynamics simulation and atomic mutagenesis studies suggest that nucleotides of an asymmetric bulge participate in the dynamic architecture of the ribozyme’s active center. Of note is that residue U42 directly interacts with the product in the crystallized RNA/product complex. Here, we use powdered pyrite held in a commercially available cartridge to footprint the Diels–Alderase ribozyme with single nucleotide resolution. Residues C39 to U42 are more reactive to · OH than predicted by the solvent accessibility calculated from the crystal structure suggesting that this loop is dynamic in solution. The loop’s flexibility may contribute to substrate recruitment and product release. Our implementation of pyrite-mediated · OH footprinting is a readily accessible approach to gleaning information about the architecture of small RNA molecules.

  2. The Split Red Clump of the Galactic Bulge from OGLE-III

    Science.gov (United States)

    Nataf, D. M.; Udalski, A.; Gould, A.; Fouqué, P.; Stanek, K. Z.

    2010-09-01

    The red clump (RC) is found to be split into two components along several sightlines toward the Galactic bulge. This split is detected with high significance toward the areas (-3.5 plane. The fainter (hereafter "main") component is the one that more closely follows the distance-longitude relation of the bulge RC. The main component is ~0.5 mag fainter than the secondary component and with an overall approximately equal population. For sightlines further from the plane, the difference in brightness increases, and more stars are found in the secondary component than in the main component. The two components have very nearly equal (V - I) color.

  3. X-ray spectral models of Galactic bulge sources - the emission-line factor

    International Nuclear Information System (INIS)

    Vrtilek, S.D.; Swank, J.H.; Kallman, T.R.

    1988-01-01

    Current difficulties in finding unique and physically meaningful models for the X-ray spectra of Galactic bulge sources are exacerbated by the presence of strong, variable emission and absorption features that are not resolved by the instruments observing them. Nine Einstein solid state spectrometer (SSS) observations of five Galactic bulge sources are presented for which relatively high resolution objective grating spectrometer (OGS) data have been published. It is found that in every case the goodness of fit of simple models to SSS data is greatly improved by adding line features identified in the OGS that cannot be resolved by the SSS but nevertheless strongly influence the spectra observed by SSS. 32 references

  4. Identifying modifications in RNA by MALDI mass spectrometry

    DEFF Research Database (Denmark)

    Douthwaite, Stephen; Kirpekar, Finn

    2007-01-01

    as RNA modifications added in cell-free in vitro systems. MALDI-MS is particularly useful in cases in which other techniques such as those involving primer extension or chromatographic analyses are not practicable. To date, MALDI-MS has been used to localize rRNA modifications that are involved......Posttranscriptional modifications on the base or sugar of ribonucleosides generally result in mass increases that can be measured by mass spectrometry. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a direct and accurate means of determining the masses of RNAs. Mass...... spectra produced by MALDI are relatively straightforward to interpret, because they are dominated by singly charged ions, making it possible to analyze complex mixtures of RNA oligonucleotides ranging from trinucleotides up to 20-mers. Analysis of modifications within much longer RNAs, such as ribosomal...

  5. The zCOSMOS redshift survey : evolution of the light in bulges and discs since z ~ 0.8

    NARCIS (Netherlands)

    Tasca, L. A. M.; Tresse, L.; Le Fevre, O.; Ilbert, O.; Lilly, S. J.; Zamorani, G.; Lopez-Sanjuan, C.; Ho, L. C.; Bardelli, S.; Cattaneo, A.; Cucciati, O.; Farrah, D.; Iovino, A.; Koekemoer, A. M.; Liu, C. T.; Massey, R.; Renzini, A.; Taniguchi, Y.; Welikala, N.; Zucca, E.; Carollo, C. M.; Contini, T.; Kneib, J. -P.; Mainieri, V.; Scodeggio, M.; Bolzonella, M.; Bongiorno, A.; Caputi, K.; de la Torre, S.; Franzetti, P.; Garilli, B.; Guzzo, L.; Kampczyk, P.; Knobel, C.; Kovac, K.; Lamareille, F.; Le Borgne, J. -F.; Le Brun, V.; Maier, C.; Mignoli, M.; Pello, R.; Peng, Y.; Perez Montero, E.; Rich, R. M.; Tanaka, M.; Vergani, D.; Bordoloi, R.; Cappi, A.; Cimatti, A.; Coppa, G.; McCracken, H. J.; Moresco, M.; Pozzetti, L.; Sanders, D.; Sheth, K.

    We studied the chronology of galactic bulge and disc formation by analysing the relative contributions of these components to the B-band rest-frame luminosity density at different epochs. We present the first estimate of the evolution of the fraction of rest-frame B-band light in galactic bulges and

  6. The zCOSMOS redshift survey: evolution of the light in bulges and discs since z ~ 0.8

    NARCIS (Netherlands)

    Tasca, L. A. M.; Tresse, L.; Le Fèvre, O.; Ilbert, O.; Lilly, S. J.; Zamorani, G.; López-Sanjuan, C.; Ho, L. C.; Bardelli, S.; Cattaneo, A.; Cucciati, O.; Farrah, D.; Iovino, A.; Koekemoer, A. M.; Liu, C. T.; Massey, R.; Renzini, A.; Taniguchi, Y.; Welikala, N.; Zucca, E.; Carollo, C. M.; Contini, T.; Kneib, J.-P.; Mainieri, V.; Scodeggio, M.; Bolzonella, M.; Bongiorno, A.; Caputi, K.; de la Torre, S.; Franzetti, P.; Garilli, B.; Guzzo, L.; Kampczyk, P.; Knobel, C.; Kovač, K.; Lamareille, F.; Le Borgne, J.-F.; Le Brun, V.; Maier, C.; Mignoli, M.; Pello, R.; Peng, Y.; Perez Montero, E.; Rich, R. M.; Tanaka, M.; Vergani, D.; Bordoloi, R.; Cappi, A.; Cimatti, A.; Coppa, G.; McCracken, H. J.; Moresco, M.; Pozzetti, L.; Sanders, D.; Sheth, K.

    We studied the chronology of galactic bulge and disc formation by analysing the relative contributions of these components to the B-band rest-frame luminosity density at different epochs. We present the first estimate of the evolution of the fraction of rest-frame B-band light in galactic bulges and

  7. Ages of galaxy bulges and disks from optical and near-infrared colours

    NARCIS (Netherlands)

    Peletier, RF; Balcells, M; Bender, R; Davies, RL

    1996-01-01

    For a sample of bright nearby early-type galaxies we have obtained surface photometry in bands ranging from U to K. Since the galaxies have inclinations larger than 50 degrees it is easy to separate bulges and disks. By measuring the colours in special regions, we minimize the effects of extinction,

  8. Photoionization modelling of planetary nebulae - II. Galactic bulge nebulae, a comparison with literature results

    NARCIS (Netherlands)

    van Hoof, PAM; Van de Steene, GC

    1999-01-01

    We have constructed photoionization models of five galactic bulge planetary nebulae using our automatic method, which enables a fully self-consistent determination of the physical parameters of a planetary nebula. The models are constrained using the spectrum, the IRAS and radio fluxes and the

  9. Planetary nebula velocities in the disc and bulge of M31

    NARCIS (Netherlands)

    Halliday, C.; Carter, D.; Bridges, T. J.; Jackson, Z. C.; Wilkinson, M. I.; Quinn, D. P.; Evans, N. W.; Douglas, N. G.; Merrett, H. R.; Merrifield, M. R.; Romanowsky, A. J.; Kuijken, K.; Irwin, M. J.

    2006-01-01

    We present radial velocities for a sample of 723 planetary nebulae in the disc and bulge of M31, measured using the WYFFOS fibre spectrograph on the William Herschel Telescope. Velocities are determined using the [OIII] lambda 5007 emission line. Rotation and velocity dispersion are measured to a

  10. Finite Element Analysis of Bulge Forming of Laser Welding Dimple Jacket

    Directory of Open Access Journals (Sweden)

    Peisi ZHONG

    2015-11-01

    Full Text Available The stress-strain states of the model of laser welded dimple jacket is analyzed using ANSYS/LS-DYNA in order to determine the relation between bulging height and pressure and to achieve the controllability of pressure distension of the jacket. It is shown that in the same conditions, the bulging height increases with the increasing of the bulging pressure and the space of honeycomb. And it will decrease when the thickness of jacket plate changing larger. A table showing the relation between bulging height and pressure is obtained. An experiment using a test panel is conducted to certify the reliability of finite element analysis. It turns out that the data of finite element analysis is coincident with experimental data, which support finite element method based ANSYS/LS-DYNA can be an efficient way to research the laser welded dimple jacket. The relation table is useful as guidance for the fabrication process.DOI: http://dx.doi.org/10.5755/j01.ms.21.4.9704

  11. Stellar Sources in the ISOGAL Inner Galactic Bulge Field D. Κ. Ojha1 ...

    Indian Academy of Sciences (India)

    tribpo

    to study the stellar populations and the structure of the bulge. Multicolor mid infrared data ... Section 3 describes the cross identification of ISOGAL and ... observations for this field with a gap of 2 years (Table 1), which were used to check the.

  12. SDSS-IV MaNGA: bulge-disc decomposition of IFU data cubes (BUDDI)

    Science.gov (United States)

    Johnston, Evelyn J.; Häußler, Boris; Aragón-Salamanca, Alfonso; Merrifield, Michael R.; Bamford, Steven; Bershady, Matthew A.; Bundy, Kevin; Drory, Niv; Fu, Hai; Law, David; Nitschelm, Christian; Thomas, Daniel; Roman Lopes, Alexandre; Wake, David; Yan, Renbin

    2017-02-01

    With the availability of large integral field unit (IFU) spectral surveys of nearby galaxies, there is now the potential to extract spectral information from across the bulges and discs of galaxies in a systematic way. This information can address questions such as how these components built up with time, how galaxies evolve and whether their evolution depends on other properties of the galaxy such as its mass or environment. We present bulge-disc decomposition of IFU data cubes (BUDDI), a new approach to fit the two-dimensional light profiles of galaxies as a function of wavelength to extract the spectral properties of these galaxies' discs and bulges. The fitting is carried out using GALFITM, a modified form of GALFIT which can fit multiwaveband images simultaneously. The benefit of this technique over traditional multiwaveband fits is that the stellar populations of each component can be constrained using knowledge over the whole image and spectrum available. The decomposition has been developed using commissioning data from the Sloan Digital Sky Survey-IV Mapping Nearby Galaxies at APO (MaNGA) survey with redshifts z 22 arcsec, but can be applied to any IFU data of a nearby galaxy with similar or better spatial resolution and coverage. We present an overview of the fitting process, the results from our tests, and we finish with example stellar population analyses of early-type galaxies from the MaNGA survey to give an indication of the scientific potential of applying bulge-disc decomposition to IFU data.

  13. Ages of galaxy bulges and disks from optical and near-infrared colors

    NARCIS (Netherlands)

    Peletier, RF; Balcells, M

    We compare optical and near-infrared colors of disks and bulges in a diameter-limited sample of inclined, bright, nearby, early-type spirals. Color profiles along wedge apertures at 15 degrees from the major axis and on the minor axis on the side of the galaxy opposite to the dust lane are used to

  14. Black Holes and Galactic Density Cusps I Radial Orbit Cusps and Bulges

    CERN Document Server

    Henriksen, Richard N; Macmillan, Joseph D

    2011-01-01

    Aims. In this paper we study density cusps made from radial orbits that may contain central black holes. The actual co-eval self-similar growth would not distinguish between the central object and the surroundings. Methods. To study the environment of an existing black hole we seek distribution functions that may contain a black hole and that retain at least a memory of self-similarity. We refer to the environment in brief as the 'bulge' or sometimes the 'halo'. This depends on whether the black hole is a true singularity dominating its halo or rather a core mass concentration that dominates a larger bulge. The hierarchy might extend to include galactic bulge and halo. Results.We find simple descriptions of simulated collisionless matter in the process of examining the presence of central masses. The Fridmann & Polyachenko distribution function describes co-eval growth of a bulge and black hole that might explain the observed mass correlation. Conclusions. We derive our results from first principles assum...

  15. Genetically induced cell death in bulge stem cells reveals their redundancy for hair and epidermal regeneration.

    Science.gov (United States)

    Driskell, Iwona; Oeztuerk-Winder, Feride; Humphreys, Peter; Frye, Michaela

    2015-03-01

    Adult mammalian epidermis contains multiple stem cell populations in which quiescent and more proliferative stem and progenitor populations coexist. However, the precise interrelation of these populations in homeostasis remains unclear. Here, we blocked the contribution of quiescent keratin 19 (K19)-expressing bulge stem cells to hair follicle formation through genetic ablation of the essential histone methyltransferase Setd8 that is required for the maintenance of adult skin. Deletion of Setd8 eliminated the contribution of bulge cells to hair follicle regeneration through inhibition of cell division and induction of cell death, but the growth and morphology of hair follicles were unaffected. Furthermore, ablation of Setd8 in the hair follicle bulge blocked the contribution of K19-postive stem cells to wounded epidermis, but the wound healing process was unaltered. Our data indicate that quiescent bulge stem cells are dispensable for hair follicle regeneration and epidermal injury in the short term and support the hypothesis that quiescent and cycling stem cell populations are equipotent. © 2014 AlphaMed Press.

  16. Light, Alpha, and Fe-peak Element Abundances in the Galactic Bulge

    Science.gov (United States)

    Johnson, Christian I.; Rich, R. Michael; Kobayashi, Chiaki; Kunder, Andrea; Koch, Andreas

    2014-10-01

    We present radial velocities and chemical abundances of O, Na, Mg, Al, Si, Ca, Cr, Fe, Co, Ni, and Cu for a sample of 156 red giant branch stars in two Galactic bulge fields centered near (l, b) = (+5.25,-3.02) and (0,-12). The (+5.25,-3.02) field also includes observations of the bulge globular cluster NGC 6553. The results are based on high-resolution (R ~ 20,000), high signal-to-noise ration (S/N >~ 70) FLAMES-GIRAFFE spectra obtained through the European Southern Observatory archive. However, we only selected a subset of the original observations that included spectra with both high S/N and that did not show strong TiO absorption bands. This work extends previous analyses of this data set beyond Fe and the α-elements Mg, Si, Ca, and Ti. While we find reasonable agreement with past work, the data presented here indicate that the bulge may exhibit a different chemical composition than the local thick disk, especially at [Fe/H] >~ -0.5. In particular, the bulge [α/Fe] ratios may remain enhanced to a slightly higher [Fe/H] than the thick disk, and the Fe-peak elements Co, Ni, and Cu appear enhanced compared to the disk. There is also some evidence that the [Na/Fe] (but not [Al/Fe]) trends between the bulge and local disk may be different at low and high metallicity. We also find that the velocity dispersion decreases as a function of increasing [Fe/H] for both fields, and do not detect any significant cold, high-velocity populations. A comparison with chemical enrichment models indicates that a significant fraction of hypernovae may be required to explain the bulge abundance trends, and that initial mass functions that are steep, top-heavy (and do not include strong outflow), or truncated to avoid including contributions from stars >40 M ⊙ are ruled out, in particular because of disagreement with the Fe-peak abundance data. For most elements, the NGC 6553 stars exhibit abundance trends nearly identical to comparable metallicity bulge field stars. However, the

  17. Light, alpha, and Fe-peak element abundances in the galactic bulge

    International Nuclear Information System (INIS)

    Johnson, Christian I.; Rich, R. Michael; Kobayashi, Chiaki; Kunder, Andrea; Koch, Andreas

    2014-01-01

    We present radial velocities and chemical abundances of O, Na, Mg, Al, Si, Ca, Cr, Fe, Co, Ni, and Cu for a sample of 156 red giant branch stars in two Galactic bulge fields centered near (l, b) = (+5.25,–3.02) and (0,–12). The (+5.25,–3.02) field also includes observations of the bulge globular cluster NGC 6553. The results are based on high-resolution (R ∼ 20,000), high signal-to-noise ration (S/N ≳ 70) FLAMES-GIRAFFE spectra obtained through the European Southern Observatory archive. However, we only selected a subset of the original observations that included spectra with both high S/N and that did not show strong TiO absorption bands. This work extends previous analyses of this data set beyond Fe and the α-elements Mg, Si, Ca, and Ti. While we find reasonable agreement with past work, the data presented here indicate that the bulge may exhibit a different chemical composition than the local thick disk, especially at [Fe/H] ≳ –0.5. In particular, the bulge [α/Fe] ratios may remain enhanced to a slightly higher [Fe/H] than the thick disk, and the Fe-peak elements Co, Ni, and Cu appear enhanced compared to the disk. There is also some evidence that the [Na/Fe] (but not [Al/Fe]) trends between the bulge and local disk may be different at low and high metallicity. We also find that the velocity dispersion decreases as a function of increasing [Fe/H] for both fields, and do not detect any significant cold, high-velocity populations. A comparison with chemical enrichment models indicates that a significant fraction of hypernovae may be required to explain the bulge abundance trends, and that initial mass functions that are steep, top-heavy (and do not include strong outflow), or truncated to avoid including contributions from stars >40 M ☉ are ruled out, in particular because of disagreement with the Fe-peak abundance data. For most elements, the NGC 6553 stars exhibit abundance trends nearly identical to comparable metallicity bulge field stars

  18. Light, alpha, and Fe-peak element abundances in the galactic bulge

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Christian I. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, MS-15, Cambridge, MA 02138 (United States); Rich, R. Michael [Department of Physics and Astronomy, UCLA, 430 Portola Plaza, Box 951547, Los Angeles, CA 90095-1547 (United States); Kobayashi, Chiaki [Centre for Astrophysics Research, University of Hertfordshire, Hatfield AL10 9AB (United Kingdom); Kunder, Andrea [Leibniz-Institute für Astrophysik Potsdam (AIP), Ander Sternwarte 16, D-14482, Potsdam (Germany); Koch, Andreas, E-mail: cjohnson@cfa.harvard.edu, E-mail: rmr@astro.ucla.edu, E-mail: c.kobayashi@herts.ac.uk, E-mail: akunder@aip.de, E-mail: akoch@lsw.uni-heidelberg.de [Zentrum für Astronomie der Universität Heidelberg, Landessternwarte, Königstuhl 12, Heidelberg (Germany)

    2014-10-01

    We present radial velocities and chemical abundances of O, Na, Mg, Al, Si, Ca, Cr, Fe, Co, Ni, and Cu for a sample of 156 red giant branch stars in two Galactic bulge fields centered near (l, b) = (+5.25,–3.02) and (0,–12). The (+5.25,–3.02) field also includes observations of the bulge globular cluster NGC 6553. The results are based on high-resolution (R ∼ 20,000), high signal-to-noise ration (S/N ≳ 70) FLAMES-GIRAFFE spectra obtained through the European Southern Observatory archive. However, we only selected a subset of the original observations that included spectra with both high S/N and that did not show strong TiO absorption bands. This work extends previous analyses of this data set beyond Fe and the α-elements Mg, Si, Ca, and Ti. While we find reasonable agreement with past work, the data presented here indicate that the bulge may exhibit a different chemical composition than the local thick disk, especially at [Fe/H] ≳ –0.5. In particular, the bulge [α/Fe] ratios may remain enhanced to a slightly higher [Fe/H] than the thick disk, and the Fe-peak elements Co, Ni, and Cu appear enhanced compared to the disk. There is also some evidence that the [Na/Fe] (but not [Al/Fe]) trends between the bulge and local disk may be different at low and high metallicity. We also find that the velocity dispersion decreases as a function of increasing [Fe/H] for both fields, and do not detect any significant cold, high-velocity populations. A comparison with chemical enrichment models indicates that a significant fraction of hypernovae may be required to explain the bulge abundance trends, and that initial mass functions that are steep, top-heavy (and do not include strong outflow), or truncated to avoid including contributions from stars >40 M {sub ☉} are ruled out, in particular because of disagreement with the Fe-peak abundance data. For most elements, the NGC 6553 stars exhibit abundance trends nearly identical to comparable metallicity bulge field

  19. An application of the tensor virial theorem to hole + vortex + bulge systems

    Science.gov (United States)

    Caimmi, R.

    2009-04-01

    The tensor virial theorem for subsystems is formulated for three-component systems and further effort is devoted to a special case where the inner subsystems and the central region of the outer one are homogeneous, the last surrounded by an isothermal homeoid. The virial equations are explicitly written under the additional restrictions: (i) similar and similarly placed inner subsystems, and (ii) spherical outer subsystem. An application is made to hole + vortex + bulge systems, in the limit of flattened inner subsystems, which implies three virial equations in three unknowns. Using the Faber-Jackson relation, R∝σ02, the standard M- σ0 form (M∝σ04) is deduced from qualitative considerations. The projected bulge velocity dispersion to projected vortex velocity ratio, η=(σ)33/{[(v)qq]2+[(σ)qq]2}, as a function of the fractional radius, y=R/R, and the fractional masses, m=M/M and m=M/M, is studied in the range of interest, 0⩽m=M/M⩽5 [Escala, A., 2006. ApJ, 648, L13] and 229⩽m⩽795 [Marconi, A., Hunt, L.H., 2003. ApJ 589, L21], consistent with observations. The related curves appear to be similar to Maxwell velocity distributions, which implies a fixed value of η below the maximum corresponds to two different configurations: a compact bulge on the left of the maximum, and an extended bulge on the right. All curves lie very close one to the other on the left of the maximum, and parallel one to the other on the right. On the other hand, fixed m or m, and y, are found to imply more massive bulges passing from bottom to top along a vertical line on the (Oyη) plane, and vice versa. The model is applied to NGC 4374 and NGC 4486, taking the fractional mass, m, and the fractional radius, y, as unknowns, and the bulge mass is inferred from the knowledge of the hole mass, and compared with results from different methods. In presence of a massive vortex (m=5), the hole mass has to be reduced by a factor 2-3 with respect to the case of a massless vortex, to get

  20. First detection of the white dwarf cooling sequence of the galactic bulge

    Energy Technology Data Exchange (ETDEWEB)

    Calamida, A.; Sahu, K. C.; Anderson, J.; Casertano, S.; Brown, T.; Sokol, J.; Bond, H. E.; Ferguson, H.; Livio, M.; Valenti, J. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Cassisi, S.; Buonanno, R.; Pietrinferni, A. [Osservatorio Astronomico di Teramo—INAF, Via M. Maggini, I-64100 Teramo (Italy); Salaris, M. [Astrophysics Research Institute, Liverpool John Moores University, 146 Brownlow Hill, Liverpool L3 5RF (United Kingdom); Ferraro, I. [Osservatorio Astronomico di Roma—INAF, Via Frascati 33, I-00040 Monte Porzio Catone (Italy); Clarkson, W., E-mail: calamida@stsci.edu [University of Michigan-Dearborn, 4901 Evergreen Road, Dearborn, MI 48128 (United States)

    2014-08-01

    We present Hubble Space Telescope data of the low-reddening Sagittarius window in the Galactic bulge. The Sagittarius Window Eclipsing Extrasolar Planet Search field (∼3'× 3'), together with three more Advanced Camera for Surveys and eight Wide-Field Camera 3 fields, were observed in the F606W and F814W filters, approximately every two weeks for 2 yr, with the principal aim of detecting a hidden population of isolated black holes and neutron stars through astrometric microlensing. Proper motions were measured with an accuracy of ≈0.1 mas yr{sup –1} (≈4 km s{sup –1}) at F606W ≈ 25.5 mag, and better than ≈0.5 mas yr{sup –1} (≈20 km s{sup –1}) at F606W ≈ 28 mag, in both axes. Proper-motion measurements allowed us to separate disk and bulge stars and obtain a clean bulge color-magnitude diagram. We then identified for the first time a white dwarf (WD) cooling sequence in the Galactic bulge, together with a dozen candidate extreme horizontal branch stars. The comparison between theory and observations shows that a substantial fraction of the WDs (≈30%) are systematically redder than the cooling tracks for CO-core H-rich and He-rich envelope WDs. This evidence would suggest the presence of a significant number of low-mass WDs and WD-main-sequence binaries in the bulge. This hypothesis is further supported by the finding of two dwarf novae in outburst, two short-period (P ≲ 1 day) ellipsoidal variables, and a few candidate cataclysmic variables in the same field.

  1. Construction and functional characterization of double and triple mutants of parallel beta-bulge of ubiquitin.

    Science.gov (United States)

    Sharma, Mrinal; Prabha, C Ratna

    2011-12-01

    Ubiquitin, a small eukaryotic protein serving as a post-translational modification on many important proteins, plays central role in cellular homeostasis and cell cycle regulation. Ubiquitin features two beta-bulges, the second beta-bulge, located at the C-terminal region of the protein along with type II turn, holds 3 residues Glu64(1), Ser65(2) and Gln2(X). Percent frequency of occurrence of such a sequence in parallel beta-bulge is very low. However, the sequence and structure have been conserved in ubiquitin through out the evolution. Present study involves replacement of residues in unusual beta-bulge of ubiquitin by introducing mutations in combination through site directed mutagenesis, generating double and triple mutants and their functional characterization. Mutant ubiquitins cloned in yeast expression vector YEp96 tested for growth profile, viability assay and heat stress complementation study have revealed significant decrease in growth rate, loss of viability and non-complementation of heat sensitive phenotype with UbE64G-S65D and UbQ2N-E64G-S65D mutations. However, UbQ2N-S65D did not show any negative effects in the above assays. Present results show that, replacement of residues in beta-bulge of ubiquitin exerts severe effects on growth and viability in Saccharomyces cerevisiae due to functional failure of the mutant ubiquitins UbE64G-S65D and UbQ2N-E64G-S65D.

  2. First detection of the white dwarf cooling sequence of the galactic bulge

    International Nuclear Information System (INIS)

    Calamida, A.; Sahu, K. C.; Anderson, J.; Casertano, S.; Brown, T.; Sokol, J.; Bond, H. E.; Ferguson, H.; Livio, M.; Valenti, J.; Cassisi, S.; Buonanno, R.; Pietrinferni, A.; Salaris, M.; Ferraro, I.; Clarkson, W.

    2014-01-01

    We present Hubble Space Telescope data of the low-reddening Sagittarius window in the Galactic bulge. The Sagittarius Window Eclipsing Extrasolar Planet Search field (∼3'× 3'), together with three more Advanced Camera for Surveys and eight Wide-Field Camera 3 fields, were observed in the F606W and F814W filters, approximately every two weeks for 2 yr, with the principal aim of detecting a hidden population of isolated black holes and neutron stars through astrometric microlensing. Proper motions were measured with an accuracy of ≈0.1 mas yr –1 (≈4 km s –1 ) at F606W ≈ 25.5 mag, and better than ≈0.5 mas yr –1 (≈20 km s –1 ) at F606W ≈ 28 mag, in both axes. Proper-motion measurements allowed us to separate disk and bulge stars and obtain a clean bulge color-magnitude diagram. We then identified for the first time a white dwarf (WD) cooling sequence in the Galactic bulge, together with a dozen candidate extreme horizontal branch stars. The comparison between theory and observations shows that a substantial fraction of the WDs (≈30%) are systematically redder than the cooling tracks for CO-core H-rich and He-rich envelope WDs. This evidence would suggest the presence of a significant number of low-mass WDs and WD-main-sequence binaries in the bulge. This hypothesis is further supported by the finding of two dwarf novae in outburst, two short-period (P ≲ 1 day) ellipsoidal variables, and a few candidate cataclysmic variables in the same field.

  3. Roles of the nucleolus in the CAG RNA-mediated toxicity.

    Science.gov (United States)

    Tsoi, Ho; Chan, Ho Yin Edwin

    2014-06-01

    The nucleolus is a subnuclear compartment within the cell nucleus that serves as the site for ribosomal RNA (rRNA) transcription and the assembly of ribosome subunits. Apart from its classical role in ribosomal biogenesis, a number of cellular regulatory roles have recently been assigned to the nucleolus, including governing the induction of apoptosis. "Nucleolar stress" is a term that is used to describe a signaling pathway through which the nucleolus communicates with other subcellular compartments, including the mitochondria, to induce apoptosis. It is an effective mechanism for eliminating cells that are incapable of performing protein synthesis efficiently due to ribosome biogenesis defects. The down-regulation of rRNA transcription is a common cause of nucleolar function disruption that subsequently triggers nucleolar stress, and has been associated with the pathogenesis of neurological disorders such as spinocerebellar ataxias (SCAs) and Huntington's diseases (HD). This article discusses recent advances in mechanistic studies of how expanded CAG trinucleotide repeat RNA transcripts trigger nucleolar stress in SCAs, HD and other trinucleotide repeat disorders. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Milky Way demographics with the VVV survey. I. The 84-million star colour-magnitude diagram of the Galactic bulge

    Science.gov (United States)

    Saito, R. K.; Minniti, D.; Dias, B.; Hempel, M.; Rejkuba, M.; Alonso-García, J.; Barbuy, B.; Catelan, M.; Emerson, J. P.; Gonzalez, O. A.; Lucas, P. W.; Zoccali, M.

    2012-08-01

    Context. The Milky Way (MW) bulge is a fundamental Galactic component for understanding the formation and evolution of galaxies, in particular our own. The ESO Public Survey VISTA Variables in the Vía Láctea is a deep near-IR survey mapping the Galactic bulge and southern plane. Particularly for the bulge area, VVV is covering ~315 deg2. Data taken during 2010 and 2011 covered the entire bulge area in the JHKs bands. Aims: We used VVV data for the whole bulge area as a single and homogeneous data set to build for the first time a single colour - magnitude diagram (CMD) for the entire Galactic bulge. Methods: Photometric data in the JHKs bands were combined to produce a single and huge data set containing 173 150 467 sources in the three bands, for the ~315 deg2 covered by VVV in the bulge. Selecting only the data points flagged as stellar, the total number of sources is 84 095 284. Results: We built the largest colour-magnitude diagrams published up to date, containing 173.1+ million sources for all data points, and more than 84.0 million sources accounting for the stellar sources only. The CMD has a complex shape, mostly owing to the complexity of the stellar population and the effects of extinction and reddening towards the Galactic centre. The red clump (RC) giants are seen double in magnitude at b ~ -8° -10°, while in the inner part (b ~ -3°) they appear to be spreading in colour, or even splitting into a secondary peak. Stellar population models show the predominance of main-sequence and giant stars. The analysis of the outermost bulge area reveals a well-defined sequence of late K and M dwarfs, seen at (J - Ks) ~ 0.7-0.9 mag and Ks ≳ 14 mag. Conclusions: The interpretation of the CMD yields important information about the MW bulge, showing the fingerprint of its structure and content. We report a well-defined red dwarf sequence in the outermost bulge, which is important for the planetary transit searches of VVV. The double RC in magnitude seen in the

  5. X-ray bursters and the X-ray sources of the galactic bulge

    Science.gov (United States)

    Lewin, W. H. G.; Joss, P. C.

    An attempt is made to distill from observational and theoretical information on the galactic bulge X-ray sources in general, and on the X-ray burst sources in particular, those aspects which seem to have the greatest relevance to the understanding of these sources. Galactic bulge sources appear to be collapsed objects of roughly solar mass, in most cases neutron stars, which are accreting matter from low-mass stellar companions. Type I bursts seem to result from thermonuclear flashes in the surface layers of some of these neutron stars, while the type II bursts from the Rapid Burster are almost certainly due to an instability in the accretion flow onto a neutron star. It is concluded that the studies cited offer a new and powerful observational handle on the fundamental properties of neutron stars and of the interacting binary systems in which they are often contained.

  6. The BRAVE Program. I. Improved Bulge Stellar Velocity Dispersion Estimates for a Sample of Active Galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Batiste, Merida; Bentz, Misty C.; Manne-Nicholas, Emily R. [Department of Physics and Astronomy, Georgia State University, 25 Park Place, Atlanta, GA 30303 (United States); Onken, Christopher A. [Research School of Astronomy and Astrophysics, The Australian National University, Canberra, ACT 2611 (Australia); Bershady, Matthew A., E-mail: batiste@astro.gsu.edu [Department of Astronomy, University of Wisconsin, 475 N. Charter Street, Madison, WI 53706 (United States)

    2017-02-01

    We present new bulge stellar velocity dispersion measurements for 10 active galaxies with secure M {sub BH} determinations from reverberation mapping. These new velocity dispersion measurements are based on spatially resolved kinematics from integral-field (IFU) spectroscopy. In all but one case, the field of view of the IFU extends beyond the effective radius of the galaxy, and in the case of Mrk 79 it extends to almost one half the effective radius. This combination of spatial resolution and field of view allows for secure determinations of stellar velocity dispersion within the effective radius for all 10 target galaxies. Spatially resolved maps of the first ( V ) and second ( σ {sub ⋆}) moments of the line of sight velocity distribution indicate the presence of kinematic substructure in most cases. In future projects we plan to explore methods of correcting for the effects of kinematic substructure in the derived bulge stellar velocity dispersion measurements.

  7. The SWELLS survey - VI. Hierarchical inference of the initial mass functions of bulges and discs

    DEFF Research Database (Denmark)

    Brewer, Brendon J.; Marshal, Philip J.; Auger, Matthew W.

    2014-01-01

    ) and stellar masses (constrained by optical and near-infrared colours in the context of a stellar population synthesis model, up to an IMF normalization parameter). Using minimal assumptions apart from the physical constraint that the total stellar mass m* within any aperture must be less than the total mass...... mtot with in the aperture, we find that the bulges of the galaxies cannot have IMFs heavier (i.e. implying high mass per unit luminosity) than Salpeter, while the disc IMFs are not well constrained by this data set.We also discuss the necessity for hierarchical modelling when combining incomplete...... information about multiple astronomical objects. This modelling approach allows us to place upper limits on the size of any departures from universality. More data, including spatially resolved kinematics (as in Paper V) and stellar population diagnostics over a range of bulge and disc masses, are needed...

  8. Forming limit diagram of aluminum AA6063 tubes at high temperatures by bulge tests

    International Nuclear Information System (INIS)

    Hashemi, Seyed Jalal; Naeini, Hassan Moslemi; Liaghat, Gholamhossein; Tafti, Rooholla Azizi; Rahmani, Farzad

    2014-01-01

    A free bulge test and ductile fracture criteria were used to obtain the forming limit diagrams (FLD) of aluminum alloy AA6063 tubes at high temperatures. Ductile fracture criteria were calibrated using the results of uniaxial tension tests at various elevated temperatures and different strain rates through adjusting the Zener-Holloman parameter. High temperature free bulge test of tubes was simulated in finite element software Abaqus, and tube bursting was predicted using ductile fracture criteria under different loading paths. FLDs which were obtained from finite element simulation were compared to experimental results to select the most accurate criterion for prediction of forming limit diagram. According to the results, all studied ductile fracture criteria predict similarly when forming condition is close to the uniaxial tension, while Ayada criterion predicts the FLD at 473 K and 573 K very well.

  9. Forming limit diagram of aluminum AA6063 tubes at high temperatures by bulge tests

    Energy Technology Data Exchange (ETDEWEB)

    Hashemi, Seyed Jalal; Naeini, Hassan Moslemi; Liaghat, Gholamhossein [Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Tafti, Rooholla Azizi [Yazd University, Yazd (Iran, Islamic Republic of); Rahmani, Farzad [Kar Higher Education Institute, Qazvin (Iran, Islamic Republic of)

    2014-11-15

    A free bulge test and ductile fracture criteria were used to obtain the forming limit diagrams (FLD) of aluminum alloy AA6063 tubes at high temperatures. Ductile fracture criteria were calibrated using the results of uniaxial tension tests at various elevated temperatures and different strain rates through adjusting the Zener-Holloman parameter. High temperature free bulge test of tubes was simulated in finite element software Abaqus, and tube bursting was predicted using ductile fracture criteria under different loading paths. FLDs which were obtained from finite element simulation were compared to experimental results to select the most accurate criterion for prediction of forming limit diagram. According to the results, all studied ductile fracture criteria predict similarly when forming condition is close to the uniaxial tension, while Ayada criterion predicts the FLD at 473 K and 573 K very well.

  10. Chemical evolution of the Galactic bulge as traced by microlensed dwarf and subgiant stars

    OpenAIRE

    Bensby, T.; Johnson, J. A.; Cohen, J.; Feltzing, S.; Udalski, A.; Gould, A.; Huang, W.; Thompson, I.; Simmerer, J.; Adén, D.

    2009-01-01

    Aims. Our aims are twofold. First we aim to evaluate the robustness and accuracy of stellar parameters and detailed elemental abundances that can be derived from high-resolution spectroscopic observations of microlensed dwarf and subgiant stars. We then aim to use microlensed dwarf and subgiant stars to investigate the abundance structure and chemical evolution of the Milky Way Bulge. Contrary to the cool giant stars, with their extremely crowded spectra, the dwarf stars are hotter, their spe...

  11. An Optimal Strategy for Accurate Bulge-to-disk Decomposition of Disk Galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Gao Hua [Department of Astronomy, School of Physics, Peking University, Beijing 100871 (China); Ho, Luis C. [Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing 100871 (China)

    2017-08-20

    The development of two-dimensional (2D) bulge-to-disk decomposition techniques has shown their advantages over traditional one-dimensional (1D) techniques, especially for galaxies with non-axisymmetric features. However, the full potential of 2D techniques has yet to be fully exploited. Secondary morphological features in nearby disk galaxies, such as bars, lenses, rings, disk breaks, and spiral arms, are seldom accounted for in 2D image decompositions, even though some image-fitting codes, such as GALFIT, are capable of handling them. We present detailed, 2D multi-model and multi-component decomposition of high-quality R -band images of a representative sample of nearby disk galaxies selected from the Carnegie-Irvine Galaxy Survey, using the latest version of GALFIT. The sample consists of five barred and five unbarred galaxies, spanning Hubble types from S0 to Sc. Traditional 1D decomposition is also presented for comparison. In detailed case studies of the 10 galaxies, we successfully model the secondary morphological features. Through a comparison of best-fit parameters obtained from different input surface brightness models, we identify morphological features that significantly impact bulge measurements. We show that nuclear and inner lenses/rings and disk breaks must be properly taken into account to obtain accurate bulge parameters, whereas outer lenses/rings and spiral arms have a negligible effect. We provide an optimal strategy to measure bulge parameters of typical disk galaxies, as well as prescriptions to estimate realistic uncertainties of them, which will benefit subsequent decomposition of a larger galaxy sample.

  12. An Optimal Strategy for Accurate Bulge-to-disk Decomposition of Disk Galaxies

    Science.gov (United States)

    Gao, Hua; Ho, Luis C.

    2017-08-01

    The development of two-dimensional (2D) bulge-to-disk decomposition techniques has shown their advantages over traditional one-dimensional (1D) techniques, especially for galaxies with non-axisymmetric features. However, the full potential of 2D techniques has yet to be fully exploited. Secondary morphological features in nearby disk galaxies, such as bars, lenses, rings, disk breaks, and spiral arms, are seldom accounted for in 2D image decompositions, even though some image-fitting codes, such as GALFIT, are capable of handling them. We present detailed, 2D multi-model and multi-component decomposition of high-quality R-band images of a representative sample of nearby disk galaxies selected from the Carnegie-Irvine Galaxy Survey, using the latest version of GALFIT. The sample consists of five barred and five unbarred galaxies, spanning Hubble types from S0 to Sc. Traditional 1D decomposition is also presented for comparison. In detailed case studies of the 10 galaxies, we successfully model the secondary morphological features. Through a comparison of best-fit parameters obtained from different input surface brightness models, we identify morphological features that significantly impact bulge measurements. We show that nuclear and inner lenses/rings and disk breaks must be properly taken into account to obtain accurate bulge parameters, whereas outer lenses/rings and spiral arms have a negligible effect. We provide an optimal strategy to measure bulge parameters of typical disk galaxies, as well as prescriptions to estimate realistic uncertainties of them, which will benefit subsequent decomposition of a larger galaxy sample.

  13. An Optimal Strategy for Accurate Bulge-to-disk Decomposition of Disk Galaxies

    International Nuclear Information System (INIS)

    Gao Hua; Ho, Luis C.

    2017-01-01

    The development of two-dimensional (2D) bulge-to-disk decomposition techniques has shown their advantages over traditional one-dimensional (1D) techniques, especially for galaxies with non-axisymmetric features. However, the full potential of 2D techniques has yet to be fully exploited. Secondary morphological features in nearby disk galaxies, such as bars, lenses, rings, disk breaks, and spiral arms, are seldom accounted for in 2D image decompositions, even though some image-fitting codes, such as GALFIT, are capable of handling them. We present detailed, 2D multi-model and multi-component decomposition of high-quality R -band images of a representative sample of nearby disk galaxies selected from the Carnegie-Irvine Galaxy Survey, using the latest version of GALFIT. The sample consists of five barred and five unbarred galaxies, spanning Hubble types from S0 to Sc. Traditional 1D decomposition is also presented for comparison. In detailed case studies of the 10 galaxies, we successfully model the secondary morphological features. Through a comparison of best-fit parameters obtained from different input surface brightness models, we identify morphological features that significantly impact bulge measurements. We show that nuclear and inner lenses/rings and disk breaks must be properly taken into account to obtain accurate bulge parameters, whereas outer lenses/rings and spiral arms have a negligible effect. We provide an optimal strategy to measure bulge parameters of typical disk galaxies, as well as prescriptions to estimate realistic uncertainties of them, which will benefit subsequent decomposition of a larger galaxy sample.

  14. Chemically Dissected Rotation Curves of the Galactic Bulge from Main-sequence Proper Motions

    Science.gov (United States)

    Clarkson, William I.; Calamida, Annalisa; Sahu, Kailash C.; Brown, Thomas M.; Gennaro, Mario; Avila, Roberto J.; Valenti, Jeff; Debattista, Victor P.; Rich, R. Michael; Minniti, Dante; Zoccali, Manuela; Aufdemberge, Emily R.

    2018-05-01

    We report results from an exploratory study implementing a new probe of Galactic evolution using archival Hubble Space Telescope imaging observations. Precise proper motions are combined with photometric relative metallicity and temperature indices, to produce the proper-motion rotation curves of the Galactic bulge separately for metal-poor and metal-rich main-sequence samples. This provides a “pencil-beam” complement to large-scale wide-field surveys, which to date have focused on the more traditional bright giant branch tracers. We find strong evidence that the Galactic bulge rotation curves drawn from “metal-rich” and “metal-poor” samples are indeed discrepant. The “metal-rich” sample shows greater rotation amplitude and a steeper gradient against line-of-sight distance, as well as possibly a stronger central concentration along the line of sight. This may represent a new detection of differing orbital anisotropy between metal-rich and metal-poor bulge objects. We also investigate selection effects that would be implied for the longitudinal proper-motion cut often used to isolate a “pure-bulge” sample. Extensive investigation of synthetic stellar populations suggests that instrumental and observational artifacts are unlikely to account for the observed rotation curve differences. Thus, proper-motion-based rotation curves can be used to probe chemodynamical correlations for main-sequence tracer stars, which are orders of magnitude more numerous in the Galactic bulge than the bright giant branch tracers. We discuss briefly the prospect of using this new tool to constrain detailed models of Galactic formation and evolution. Based on observations made with the NASA/ESA Hubble Space Telescope and obtained from the data archive at the Space Telescope Science Institute. STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555.

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

    Energy Technology Data Exchange (ETDEWEB)

    Minniti, Dante; Gómez, Matías [Departamento de Física, Facultad de Ciencias Exactas, Universidad Andrés Bello, Av. Fernandez Concha 700, Las Condes, Santiago (Chile); Geisler, Douglas; Fernández-Trincado, Jose G. [Departamento de Astronomía, Casilla 160-C, Universidad de Concepción, Casilla 160-C, Concepción (Chile); Alonso-García, Javier; Beamín, Juan Carlos; Borissova, Jura; Catelan, Marcio; Ramos, Rodrigo Contreras; Kurtev, Radostin; Pullen, Joyce [Instituto Milenio de Astrofísica, Santiago (Chile); Palma, Tali; Clariá, Juan J. [Observatorio Astronómico, Universidad Nacional de Córdoba, Laprida 854, Córdoba (Argentina); Cohen, Roger E. [Space Telescope Science Institute, 2700 San Martin Drive, Baltimore (United States); Dias, Bruno [European Southern Observatory, Alonso de Cordova 3107, Vitacura, Santiago (Chile); Hempel, Maren [Pontificia Universidad Católica de Chile, Instituto de Astrofísica, Av. Vicuña Mackenna 4860, Santiago (Chile); Ivanov, Valentin D. [European Southern Observatory, Karl-Schwarszchild-Str. 2, D-85748 Garching bei Muenchen (Germany); Lucas, Phillip W. [Dept. of Astronomy, University of Hertfordshire, Hertfordshire (United Kingdom); Moni-Bidin, Christian; Alegría, Sebastian Ramírez [Instituto de Astronomía, Universidad Católica del Norte, Antofagasta (Chile); and others

    2017-11-10

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

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

    International Nuclear Information System (INIS)

    Chun, Sang-Hyun; Kang, Minhee; Jung, DooSeok; Sohn, Young-Jong

    2015-01-01

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

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

    Science.gov (United States)

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

    2001-12-01

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

  18. TWO RED CLUMPS AND THE X-SHAPED MILKY WAY BULGE

    International Nuclear Information System (INIS)

    McWilliam, Andrew; Zoccali, Manuela

    2010-01-01

    From Two Micron All Sky Survey infrared photometry, we find two red clump (RC) populations coexisting in fields toward the Galactic bulge at latitudes |b|>5. 0 5, ranging over ∼13 0 in longitude and 20 0 in latitude. These RC peaks indicate two stellar populations separated by ∼2.3 kpc; at (l, b) = (+1, - 8) the two RCs are located at 6.5 and 8.8 ± 0.2 kpc. The double-peaked RC is inconsistent with a tilted bar morphology. Most of our fields show the two RCs at roughly constant distance with longitude, also inconsistent with a tilted bar; however, an underlying bar may be present. Stellar densities in the two RCs change dramatically with longitude: on the positive longitude side the foreground RC is dominant, while the background RC dominates negative longitudes. A line connecting the maxima of the foreground and background populations is tilted to the line of sight by ∼20 0 ±4 0 , similar to claims for the tilt of a Galactic bar. The distance between the two RCs decreases toward the Galactic plane; seen edge-on the bulge is X-shaped, resembling some extragalactic bulges and the results of N-body simulations. The center of this X is consistent with the distance to the Galactic center, although better agreement would occur if the bulge is 2-3 Gyr younger than 47 Tuc. Our observations may be understood if the two RC populations emanate, nearly tangentially, from the Galactic bar ends, in a funnel shape. Alternatively, the X, or double funnel, may continue to the Galactic center. From the Sun, this would appear peanut/box shaped, but X-shaped when viewed tangentially.

  19. Two Red Clumps and the X-shaped Milky Way Bulge

    Science.gov (United States)

    McWilliam, Andrew; Zoccali, Manuela

    2010-12-01

    From Two Micron All Sky Survey infrared photometry, we find two red clump (RC) populations coexisting in fields toward the Galactic bulge at latitudes |b|>5fdg5, ranging over ~13° in longitude and 20° in latitude. These RC peaks indicate two stellar populations separated by ~2.3 kpc at (l, b) = (+1, - 8) the two RCs are located at 6.5 and 8.8 ± 0.2 kpc. The double-peaked RC is inconsistent with a tilted bar morphology. Most of our fields show the two RCs at roughly constant distance with longitude, also inconsistent with a tilted bar; however, an underlying bar may be present. Stellar densities in the two RCs change dramatically with longitude: on the positive longitude side the foreground RC is dominant, while the background RC dominates negative longitudes. A line connecting the maxima of the foreground and background populations is tilted to the line of sight by ~20°±4°, similar to claims for the tilt of a Galactic bar. The distance between the two RCs decreases toward the Galactic plane; seen edge-on the bulge is X-shaped, resembling some extragalactic bulges and the results of N-body simulations. The center of this X is consistent with the distance to the Galactic center, although better agreement would occur if the bulge is 2-3 Gyr younger than 47 Tuc. Our observations may be understood if the two RC populations emanate, nearly tangentially, from the Galactic bar ends, in a funnel shape. Alternatively, the X, or double funnel, may continue to the Galactic center. From the Sun, this would appear peanut/box shaped, but X-shaped when viewed tangentially.

  20. Research on Al-alloy sheet forming formability during warm/hot sheet hydroforming based on elliptical warm bulging test

    Science.gov (United States)

    Cai, Gaoshen; Wu, Chuanyu; Gao, Zepu; Lang, Lihui; Alexandrov, Sergei

    2018-05-01

    An elliptical warm/hot sheet bulging test under different temperatures and pressure rates was carried out to predict Al-alloy sheet forming limit during warm/hot sheet hydroforming. Using relevant formulas of ultimate strain to calculate and dispose experimental data, forming limit curves (FLCS) in tension-tension state of strain (TTSS) area are obtained. Combining with the basic experimental data obtained by uniaxial tensile test under the equivalent condition with bulging test, complete forming limit diagrams (FLDS) of Al-alloy are established. Using a quadratic polynomial curve fitting method, material constants of fitting function are calculated and a prediction model equation for sheet metal forming limit is established, by which the corresponding forming limit curves in TTSS area can be obtained. The bulging test and fitting results indicated that the sheet metal FLCS obtained were very accurate. Also, the model equation can be used to instruct warm/hot sheet bulging test.

  1. Deep JHK Photometry and the Infrared Luminosity Function of the Galactic Bulge

    Science.gov (United States)

    Tiede, Glenn P.; Frogel, Jay A.; Terndrup, D. M.

    1995-03-01

    We derive the deepest, most complete near-IR luminosity function for Galactic bulge stars yet obtained based on new JHK photometry for stars in two fields of Baade's Window. When combined with previously published data, we are able to construct a luminosity function over the range 5.5 Blanco, V.M., & Whitford, A.E. 1990, ApJ, 353, 494). Between b = -3 and -12 we find a gradient in [Fe/H] of -0.06 +/- 0.03 dex/degree, consistent with other, independent derivations. We derive a helium abundance for Baade's Window with the R and R(') methods and find that Y = 0.27 +/- 0.03. Finally, we find that the bolometric corrections for bulge K giants (V - K >= 2) are in excellent agreement with empirical derivations based on observations of globular cluster and local field stars. However, for the redder M giants we find, as did Frogel and Whitford 1987, that the bolometric corrections differ by several tenths of a magnitude from those derived for field giants and adopted in the Revised Yale Isochrones. This difference most likely arises from the excess molecular blanketing in the V and I bands of the bulge giants relative to that seen in field stars.

  2. The population of single and binary white dwarfs of the Galactic bulge

    Science.gov (United States)

    Torres, S.; García-Berro, E.; Cojocaru, R.; Calamida, A.

    2018-05-01

    Recent Hubble Space Telescope observations have unveiled the white dwarf cooling sequence of the Galactic bulge. Although the degenerate sequence can be well fitted employing the most up-to-date theoretical cooling sequences, observations show a systematic excess of red objects that cannot be explained by the theoretical models of single carbon-oxygen white dwarfs of the appropriate masses. Here, we present a population synthesis study of the white dwarf cooling sequence of the Galactic bulge that takes into account the populations of both single white dwarfs and binary systems containing at least one white dwarf. These calculations incorporate state-of-the-art cooling sequences for white dwarfs with hydrogen-rich and hydrogen-deficient atmospheres, for both white dwarfs with carbon-oxygen and helium cores, and also take into account detailed prescriptions of the evolutionary history of binary systems. Our Monte Carlo simulator also incorporates all the known observational biases. This allows us to model with a high degree of realism the white dwarf population of the Galactic bulge. We find that the observed excess of red stars can be partially attributed to white dwarf plus main sequence binaries, and to cataclysmic variables or dwarf novae. Our best fit is obtained with a higher binary fraction and an initial mass function slope steeper than standard values, as well as with the inclusion of differential reddening and blending. Our results also show that the possible contribution of double degenerate systems or young and thick-discbulge stars is negligible.

  3. Nonlinear Local Bending Response and Bulging Factors for Longitudinal and Circumferential Cracks in Pressurized Cylindrical Shells

    Science.gov (United States)

    Young, Richard D.; Rose, Cheryl A.; Starnes, James H., Jr.

    2000-01-01

    Results of a geometrically nonlinear finite element parametric study to determine curvature correction factors or bulging factors that account for increased stresses due to curvature for longitudinal and circumferential cracks in unstiffened pressurized cylindrical shells are presented. Geometric parameters varied in the study include the shell radius, the shell wall thickness, and the crack length. The major results are presented in the form of contour plots of the bulging factor as a function of two nondimensional parameters: the shell curvature parameter, lambda, which is a function of the shell geometry, Poisson's ratio, and the crack length; and a loading parameter, eta, which is a function of the shell geometry, material properties, and the applied internal pressure. These plots identify the ranges of the shell curvature and loading parameters for which the effects of geometric nonlinearity are significant. Simple empirical expressions for the bulging factor are then derived from the numerical results and shown to predict accurately the nonlinear response of shells with longitudinal and circumferential cracks. The numerical results are also compared with analytical solutions based on linear shallow shell theory for thin shells, and with some other semi-empirical solutions from the literature, and limitations on the use of these other expressions are suggested.

  4. POWERFUL RADIO EMISSION FROM LOW-MASS SUPERMASSIVE BLACK HOLES FAVORS DISK-LIKE BULGES

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.; Xu, Y.; Xu, D. W.; Wei, J. Y., E-mail: wj@bao.ac.cn [CAS Key Laboratory of Space Astronomy and Technology, National Astronomical Observatories, Chinese Academy of Sciences, Beijing (China)

    2016-12-10

    The origin of spin of low-mass supermassive black holes (SMBHs) is still a puzzle at present. We report here a study on the host galaxies of a sample of radio-selected nearby ( z < 0.05) Seyfert 2 galaxies with a BH mass of 10{sup 6–7} M{sub ⊙}. By modeling the SDSS r -band images of these galaxies through a two-dimensional bulge+disk decomposition, we identify a new dependence of SMBH's radio power on host bulge surface brightness profiles, in which more powerful radio emission comes from an SMBH associated with a more disk-like bulge. This result means low-mass and high-mass SMBHs are spun up by two entirely different modes that correspond to two different evolutionary paths. A low-mass SMBH is spun up by a gas accretion with significant disk-like rotational dynamics of the host galaxy in the secular evolution, while a high-mass one by a BH–BH merger in the merger evolution.

  5. Star formation history of the Galactic bulge from deep HST imaging of low reddening windows

    Science.gov (United States)

    Bernard, Edouard J.; Schultheis, Mathias; Di Matteo, Paola; Hill, Vanessa; Haywood, Misha; Calamida, Annalisa

    2018-04-01

    Despite the huge amount of photometric and spectroscopic efforts targetting the Galactic bulge over the past few years, its age distribution remains controversial owing to both the complexity of determining the age of individual stars and the difficult observing conditions. Taking advantage of the recent release of very deep, proper-motion-cleaned colour-magnitude diagrams (CMDs) of four low reddening windows obtained with the Hubble Space Telescope (HST), we used the CMD-fitting technique to calculate the star formation history (SFH) of the bulge at -2° > b > -4° along the minor axis. We find that over 80 percent of the stars formed before 8 Gyr ago, but that a significant fraction of the super-solar metallicity stars are younger than this age. Considering only the stars that are within reach of the current generation of spectrographs (i.e. V≲ 21), we find that 10 percent of the bulge stars are younger than 5 Gyr, while this fraction rises to 20-25 percent in the metal-rich peak. The age-metallicity relation is well parametrized by a linear fit implying an enrichment rate of dZ/dt ˜ 0.005 Gyr-1. Our metallicity distribution function accurately reproduces that observed by several spectroscopic surveys of Baade's window, with the bulk of stars having metal-content in the range [Fe/H]˜-0.7 to ˜0.6, along with a sparse tail to much lower metallicities.

  6. DISCOVERY OF A PAIR OF CLASSICAL CEPHEIDS IN AN INVISIBLE CLUSTER BEYOND THE GALACTIC BULGE

    Energy Technology Data Exchange (ETDEWEB)

    Dékány, I.; Palma, T. [Millennium Institute of Astrophysics, Santiago (Chile); Minniti, D. [Departamento de Ciencias Físicas, Universidad Andres Bello, República 220, Santiago (Chile); Hajdu, G.; Alonso-García, J.; Hempel, M.; Catelan, M. [Instituto de Astrofísica, Facultad de Física, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Santiago (Chile); Gieren, W. [Departamento de Astronomía, Universidad de Concepción, Casilla 160 C, Concepción (Chile); Majaess, D. [Department of Astronomy and Physics, Saint Mary’s University, Halifax, NS B3H 3C3 (Canada)

    2015-01-20

    We report the discovery of a pair of extremely reddened classical Cepheid variable stars located in the Galactic plane behind the bulge, using near-infrared (NIR) time-series photometry from the VISTA Variables in the Vía Láctea Survey. This is the first time that such objects have ever been found in the opposite side of the Galactic plane. The Cepheids have almost identical periods, apparent brightnesses, and colors. From the NIR Leavitt law, we determine their distances with ∼1.5% precision and ∼8% accuracy. We find that they have a same total extinction of A(V)≃32 mag, and are located at the same heliocentric distance of 〈d〉=11.4±0.9 kpc, and less than 1 pc from the true Galactic plane. Their similar periods indicate that the Cepheids are also coeval, with an age of ∼48±3 Myr, according to theoretical models. They are separated by an angular distance of only 18.″3, corresponding to a projected separation of ∼1 pc. Their position coincides with the expected location of the Far 3 kpc Arm behind the bulge. Such a tight pair of similar classical Cepheids indicates the presence of an underlying young open cluster that is both hidden behind heavy extinction and disguised by the dense stellar field of the bulge. All our attempts to directly detect this “invisible cluster” have failed, and deeper observations are needed. (letters)

  7. DISCOVERY OF RR LYRAE STARS IN THE NUCLEAR BULGE OF THE MILKY WAY

    Energy Technology Data Exchange (ETDEWEB)

    Minniti, Dante; Ramos, Rodrigo Contreras; Zoccali, Manuela; Gran, Felipe [Instituto Milenio de Astrofisica, Santiago (Chile); Rejkuba, Marina; Valenti, Elena [European Southern Observatory, Karl-Schwarszchild-Str. 2, D-85748 Garching bei Muenchen (Germany); Gonzalez, Oscar A., E-mail: dante@astrofisica.cl, E-mail: rcontrer@astro.puc.cl [UK Astronomy Technology Centre, Royal Observatory, Blackford Hill, Edinburgh, EH9 3HJ (United Kingdom)

    2016-10-10

    Galactic nuclei, such as that of the Milky Way, are extreme regions with high stellar densities, and in most cases, the hosts of a supermassive black hole. One of the scenarios proposed for the formation of the Galactic nucleus is merging of primordial globular clusters. An implication of this model is that this region should host stars that are characteristically found in old Milky Way globular clusters. RR Lyrae stars are primary distance indicators, well known representatives of old and metal-poor stellar populations, and therefore are regularly found in globular clusters. Here we report the discovery of a dozen RR Lyrae type ab stars in the vicinity of the Galactic center, i.e., in the so-called nuclear stellar bulge of the Milky Way. This discovery provides the first direct observational evidence that the Galactic nuclear stellar bulge contains ancient stars (>10 Gyr old). Based on this we conclude that merging globular clusters likely contributed to the build-up of the high stellar density in the nuclear stellar bulge of the Milky Way.

  8. Chemical Characterization of the Inner Galactic bulge: North-South Symmetry

    Science.gov (United States)

    Nandakumar, G.; Ryde, N.; Schultheis, M.; Thorsbro, B.; Jönsson, H.; Barklem, P. S.; Rich, R. M.; Fragkoudi, F.

    2018-05-01

    While the number of stars in the Galactic bulge with detailed chemical abundance measurements is increasing rapidly, the inner Galactic bulge (|b| detect a bimodal MDF with a metal-rich peak at ˜ +0.3 dex and a metal-poor peak at ˜ -0.5 dex, and no stars with [Fe/H] > +0.6 dex. The Galactic Center field reveals in contrast a mainly metal-rich population with a mean metallicity of +0.3 dex. We derived [Mg/Fe] and [Si/Fe] abundances which are consistent with trends from the outer bulge. We confirm for the supersolar metallicity stars the decreasing trend in [Mg/Fe] and [Si/Fe] as expected from chemical evolution models. With the caveat of a relatively small sample, we do not find significant differences in the chemical abundances between the Northern and the Southern fields, hence the evidence is consistent with symmetry in chemistry between North and South.

  9. Plasmasphere dynamics in the duskside bulge region: A new look at old topic

    Science.gov (United States)

    Carpenter, D. L.; Giles, B. L.; Chappell, C. R.; Decreau, P. M. E.; Anderson, R. R.; Persoon, A. M.; Smith, A. J.; Corcuff, Y.; Canu, P.

    1993-01-01

    Data acquired during several multiday periods in 1982 at ground stations Siple, Halley, and Kerguelen and on satellites Dynamics Explorer 1, International Sun Earth Explorer 1, and GEOS 2 have been used to investigate thermal plasma structure and dynamics in the duskside plasmasphere bulge region of the Earth. The distribution of thermal plasma in the dusk bulge sector is difficult to describe realistically, in part because of the time integral manner in which the thermal plasma distribution depends upon on the effects of bulk cross-B flow and interchange plasma flows along B. While relatively simple MHD models can be useful for qualitatively predicting certain effects of enhanced convection on a quiet plasmasphere, such as an initial sunward entrainment of the outer regions, they are of limited value in predicting the duskside thermal plasma structures that are observed. Furthermore, use of such models can be misleading if one fails to realize that they do not address the question of the formation of the steep plasmapause profile or provide for a possible role of instabilities or other irreversible processes in plasmapause formation. Our specific findings, which are based both upon the present case studies and upon earlier work, include the following: (1) during active periods the plasmasphere appears to become divided into two entities, a main plasmasphere and a duskside bulge region. (2) in the aftermath of an increase in convection activity, the main plasmasphere tends (from a statistical point of view) to become roughly circular in equatorial cross section, with only a slight bulge at dusk; (3) the abrupt westward edge of the duskside bulge observed from whistlers represents a state in the evolution of sunward extending streamers; (4) in the aftermath of a weak magnetic storm, 10 to 30% of the plasma 'removed' from the outer plasmasphere appears to remain in the afternoon-dusk sector beyond the main plasmasphere. (5) outlying dense plasma structures may

  10. Transcription arrest by a G quadruplex forming-trinucleotide repeat sequence from the human c-myb gene.

    Science.gov (United States)

    Broxson, Christopher; Beckett, Joshua; Tornaletti, Silvia

    2011-05-17

    Non canonical DNA structures correspond to genomic regions particularly susceptible to genetic instability. The transcription process facilitates formation of these structures and plays a major role in generating the instability associated with these genomic sites. However, little is known about how non canonical structures are processed when encountered by an elongating RNA polymerase. Here we have studied the behavior of T7 RNA polymerase (T7RNAP) when encountering a G quadruplex forming-(GGA)(4) repeat located in the human c-myb proto-oncogene. To make direct correlations between formation of the structure and effects on transcription, we have taken advantage of the ability of the T7 polymerase to transcribe single-stranded substrates and of G4 DNA to form in single-stranded G-rich sequences in the presence of potassium ions. Under physiological KCl concentrations, we found that T7 RNAP transcription was arrested at two sites that mapped to the c-myb (GGA)(4) repeat sequence. The extent of arrest did not change with time, indicating that the c-myb repeat represented an absolute block and not a transient pause to T7 RNAP. Consistent with G4 DNA formation, arrest was not observed in the absence of KCl or in the presence of LiCl. Furthermore, mutations in the c-myb (GGA)(4) repeat, expected to prevent transition to G4, also eliminated the transcription block. We show T7 RNAP arrest at the c-myb repeat in double-stranded DNA under conditions mimicking the cellular concentration of biomolecules and potassium ions, suggesting that the G4 structure formed in the c-myb repeat may represent a transcription roadblock in vivo. Our results support a mechanism of transcription-coupled DNA repair initiated by arrest of transcription at G4 structures.

  11. Improved nucleic acid descriptors for siRNA efficacy prediction.

    Science.gov (United States)

    Sciabola, Simone; Cao, Qing; Orozco, Modesto; Faustino, Ignacio; Stanton, Robert V

    2013-02-01

    Although considerable progress has been made recently in understanding how gene silencing is mediated by the RNAi pathway, the rational design of effective sequences is still a challenging task. In this article, we demonstrate that including three-dimensional descriptors improved the discrimination between active and inactive small interfering RNAs (siRNAs) in a statistical model. Five descriptor types were used: (i) nucleotide position along the siRNA sequence, (ii) nucleotide composition in terms of presence/absence of specific combinations of di- and trinucleotides, (iii) nucleotide interactions by means of a modified auto- and cross-covariance function, (iv) nucleotide thermodynamic stability derived by the nearest neighbor model representation and (v) nucleic acid structure flexibility. The duplex flexibility descriptors are derived from extended molecular dynamics simulations, which are able to describe the sequence-dependent elastic properties of RNA duplexes, even for non-standard oligonucleotides. The matrix of descriptors was analysed using three statistical packages in R (partial least squares, random forest, and support vector machine), and the most predictive model was implemented in a modeling tool we have made publicly available through SourceForge. Our implementation of new RNA descriptors coupled with appropriate statistical algorithms resulted in improved model performance for the selection of siRNA candidates when compared with publicly available siRNA prediction tools and previously published test sets. Additional validation studies based on in-house RNA interference projects confirmed the robustness of the scoring procedure in prospective studies.

  12. Rate-determining Step of Flap Endonuclease 1 (FEN1) Reflects a Kinetic Bias against Long Flaps and Trinucleotide Repeat Sequences.

    Science.gov (United States)

    Tarantino, Mary E; Bilotti, Katharina; Huang, Ji; Delaney, Sarah

    2015-08-21

    Flap endonuclease 1 (FEN1) is a structure-specific nuclease responsible for removing 5'-flaps formed during Okazaki fragment maturation and long patch base excision repair. In this work, we use rapid quench flow techniques to examine the rates of 5'-flap removal on DNA substrates of varying length and sequence. Of particular interest are flaps containing trinucleotide repeats (TNR), which have been proposed to affect FEN1 activity and cause genetic instability. We report that FEN1 processes substrates containing flaps of 30 nucleotides or fewer at comparable single-turnover rates. However, for flaps longer than 30 nucleotides, FEN1 kinetically discriminates substrates based on flap length and flap sequence. In particular, FEN1 removes flaps containing TNR sequences at a rate slower than mixed sequence flaps of the same length. Furthermore, multiple-turnover kinetic analysis reveals that the rate-determining step of FEN1 switches as a function of flap length from product release to chemistry (or a step prior to chemistry). These results provide a kinetic perspective on the role of FEN1 in DNA replication and repair and contribute to our understanding of FEN1 in mediating genetic instability of TNR sequences. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. CO J = 2-1 EMISSION FROM EVOLVED STARS IN THE GALACTIC BULGE

    Energy Technology Data Exchange (ETDEWEB)

    Sargent, Benjamin A.; Meixner, M. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Patel, N. A. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Otsuka, M.; Srinivasan, S. [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 10617, Taiwan (China); Riebel, D., E-mail: baspci@rit.edu [Department of Physics and Astronomy, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States)

    2013-03-01

    We observe a sample of eight evolved stars in the Galactic bulge in the CO J = 2-1 line using the Submillimeter Array with angular resolution of 1''-4''. These stars have been detected previously at infrared wavelengths, and several of them have OH maser emission. We detect CO J = 2-1 emission from three of the sources in the sample: OH 359.943 +0.260, [SLO2003] A12, and [SLO2003] A51. We do not detect the remaining five stars in the sample because of heavy contamination from the galactic CO emission. Combining CO data with observations at infrared wavelengths constraining dust mass loss from these stars, we determine the gas-to-dust ratios of the Galactic bulge stars for which CO emission is detected. For OH 359.943 +0.260, we determine a gas mass-loss rate of 7.9 ({+-}2.2) Multiplication-Sign 10{sup -5} M {sub Sun} yr{sup -1} and a gas-to-dust ratio of 310 ({+-}89). For [SLO2003] A12, we find a gas mass-loss rate of 5.4 ({+-}2.8) Multiplication-Sign 10{sup -5} M {sub Sun} yr{sup -1} and a gas-to-dust ratio of 220 ({+-}110). For [SLO2003] A51, we find a gas mass-loss rate of 3.4 ({+-}3.0) Multiplication-Sign 10{sup -5} M {sub Sun} yr{sup -1} and a gas-to-dust ratio of 160 ({+-}140), reflecting the low quality of our tentative detection of the CO J = 2-1 emission from A51. We find that the CO J = 2-1 detections of OH/IR stars in the Galactic bulge require lower average CO J = 2-1 backgrounds.

  14. DRAFTS: A DEEP, RAPID ARCHIVAL FLARE TRANSIENT SEARCH IN THE GALACTIC BULGE

    International Nuclear Information System (INIS)

    Osten, Rachel A.; Sahu, Kailash; Kowalski, Adam; Hawley, Suzanne L.

    2012-01-01

    We utilize the Sagittarius Window Eclipsing Extrasolar Planet Search Hubble Space Telescope/Advanced Camera for Surveys data set for a Deep Rapid Archival Flare Transient Search to constrain the flare rate toward the older stellar population in the Galactic bulge. During seven days of monitoring 229,293 stars brighter than V = 29.5, we find evidence for flaring activity in 105 stars between V = 20 and V = 28. We divided the sample into non-variable stars and variable stars whose light curves contain large-scale variability. The flare rate on variable stars is ∼700 times that of non-variable stars, with a significant correlation between the amount of underlying stellar variability and peak flare amplitude. The flare energy loss rates are generally higher than those of nearby well-studied single dMe flare stars. The distribution of proper motions is consistent with the flaring stars being at the distance and age of the Galactic bulge. If they are single dwarfs, then they span a range of ≈1.0-0.25 M ☉ . A majority of the flaring stars exhibit periodic photometric modulations with P < 3 days. If these are tidally locked magnetically active binary systems, then their fraction in the bulge is enhanced by a factor of ∼20 compared to the local value. These stars may be useful for placing constraints on the angular momentum evolution of cool close binary stars. Our results expand the type of stars studied for flares in the optical band, and suggest that future sensitive optical time-domain studies will have to contend with a larger sample of flaring stars than the M dwarf flare stars usually considered.

  15. Eyes - bulging

    Science.gov (United States)

    ... different ages. In: Lambert SR, Lyons CJ, eds. Taylor and Hoyt's Pediatric Ophthalmology and Strabismus . 5th ed. Philadelphia, PA: Elsevier; 2017:chap 96. Orge FH, Grigorian F. Examination and common problems of the neonatal eye. ...

  16. Characterization of Friction Stir Welded Tubes by Means of Tube Bulge Test

    International Nuclear Information System (INIS)

    D'Urso, G.; Longo, M.; Giardini, C.

    2011-01-01

    Mechanical properties of friction stir welded joints are generally evaluated by means of conventional tensile test. This testing method might provide insufficient information because maximum strain obtained in tensile test before necking is small; moreover, the application of tensile test is limited when the joint path is not linear or even when the welds are executed on curved surfaces. Therefore, in some cases, it would be preferable to obtain the joints properties from other testing methods. Tube bulge test can be a valid solution for testing circumferential or longitudinal welds executed on tubular workpieces. The present work investigates the mechanical properties and the formability of friction stir welded tubes by means of tube bulge tests. The experimental campaign was performed on tubular specimens having a thickness of 3 mm and an external diameter of 40 mm, obtained starting from two semi-tubes longitudinally friction stir welded. The first step, regarding the fabrication of tubes, was performed combining a conventional forming process and friction stir welding. Sheets in Al-Mg-Si-Cu alloy AA6060 T6 were adopted for this purpose. Plates having a dimension of 225x60 mm were bent (with a bending axis parallel to the main dimension) in order to obtain semi-tubes. A particular care was devoted to the fabrication of forming devices (punch and die) in order to minimize the springback effects. Semi-tubes were then friction stir welded by means of a CNC machine tool. Some preliminary tests were carried out by varying the welding parameters, namely feed rate and rotational speed. A very simple tool having flat shoulder and cylindrical pin was used. The second step of the research was based on testing the welded tubes by means of tube bulge test. A specific equipment having axial actuators with a conical shape was adopted for this study. Some analyses were carried out on the tubes bulged up to a certain pressure level. In particular, the burst pressure and the

  17. RNA Crystallization

    Science.gov (United States)

    Golden, Barbara L.; Kundrot, Craig E.

    2003-01-01

    RNA molecules may be crystallized using variations of the methods developed for protein crystallography. As the technology has become available to syntheisize and purify RNA molecules in the quantities and with the quality that is required for crystallography, the field of RNA structure has exploded. The first consideration when crystallizing an RNA is the sequence, which may be varied in a rational way to enhance crystallizability or prevent formation of alternate structures. Once a sequence has been designed, the RNA may be synthesized chemically by solid-state synthesis, or it may be produced enzymatically using RNA polymerase and an appropriate DNA template. Purification of milligram quantities of RNA can be accomplished by HPLC or gel electrophoresis. As with proteins, crystallization of RNA is usually accomplished by vapor diffusion techniques. There are several considerations that are either unique to RNA crystallization or more important for RNA crystallization. Techniques for design, synthesis, purification, and crystallization of RNAs will be reviewed here.

  18. Fracture toughness of silicon nitride thin films of different thicknesses as measured by bulge tests

    International Nuclear Information System (INIS)

    Merle, B.; Goeken, M.

    2011-01-01

    A bulge test setup was used to determine the fracture toughness of amorphous low-pressure chemical vapor deposited (LPCVD) silicon nitride films with various thicknesses in the range 40-108 nm. A crack-like slit was milled in the center of each free-standing film with a focused ion beam, and the membrane was deformed in the bulge test until failure occurred. The fracture toughness K IC was calculated from the pre-crack length and the stress at failure. It is shown that the membrane is in a transition state between pure plane-stress and plane-strain which, however, had a negligible influence on the measurement of the fracture toughness, because of the high brittleness of silicon nitride and its low Young's modulus over yield strength ratio. The fracture toughness K IC was found to be constant at 6.3 ± 0.4 MPa m 1/2 over the whole thickness range studied, which compares well with bulk values. This means that the fracture toughness, like the Young's modulus, is a size-independent quantity for LPCVD silicon nitride. This presumably holds true for all amorphous brittle ceramic materials.

  19. On the kinematic separation of field and cluster stars across the bulge globular NGC 6528

    Energy Technology Data Exchange (ETDEWEB)

    Lagioia, E. P.; Bono, G.; Buonanno, R. [Dipartimento di Fisica, Università degli Studi di Roma-Tor Vergata, via della Ricerca Scientifica 1, I-00133 Roma (Italy); Milone, A. P. [Research School of Astronomy and Astrophysics, The Australian National University, Cotter Road, Weston, ACT 2611 (Australia); Stetson, P. B. [Dominion Astrophysical Observatory, Herzberg Institute of Astrophysics, National Research Council, 5071 West Saanich Road, Victoria, BC V9E 2E7 (Canada); Prada Moroni, P. G. [Dipartimento di Fisica, Università di Pisa, I-56127 Pisa (Italy); Dall' Ora, M. [INAF-Osservatorio Astronomico di Capodimonte, Salita Moiariello 16, I-80131 Napoli (Italy); Aparicio, A.; Monelli, M. [Instituto de Astrofìsica de Canarias, E-38200 La Laguna, Tenerife, Canary Islands (Spain); Calamida, A.; Ferraro, I.; Iannicola, G. [INAF-Osservatorio Astronomico di Roma, Via Frascati 33, I-00044 Monte Porzio Catone (Italy); Gilmozzi, R. [European Southern Observatory, Karl-Schwarzschild-Straße 2, D-85748 Garching (Germany); Matsunaga, N. [Kiso Observatory, Institute of Astronomy, School of Science, The University of Tokyo, 10762-30, Mitake, Kiso-machi, Kiso-gun, 3 Nagano 97-0101 (Japan); Walker, A., E-mail: eplagioia@roma2.infn.it [Cerro Tololo Inter-American Observatory, National Optical Astronomy Observatory, Casilla 603, La Serena (Chile)

    2014-02-10

    We present deep and precise multi-band photometry of the Galactic bulge globular cluster NGC 6528. The current data set includes optical and near-infrared images collected with ACS/WFC, WFC3/UVIS, and WFC3/IR on board the Hubble Space Telescope. The images cover a time interval of almost 10 yr, and we have been able to carry out a proper-motion separation between cluster and field stars. We performed a detailed comparison in the m {sub F814W}, m {sub F606W} – m {sub F814W} color-magnitude diagram with two empirical calibrators observed in the same bands. We found that NGC 6528 is coeval with and more metal-rich than 47 Tuc. Moreover, it appears older and more metal-poor than the super-metal-rich open cluster NGC 6791. The current evidence is supported by several diagnostics (red horizontal branch, red giant branch bump, shape of the sub-giant branch, slope of the main sequence) that are minimally affected by uncertainties in reddening and distance. We fit the optical observations with theoretical isochrones based on a scaled-solar chemical mixture and found an age of 11 ± 1 Gyr and an iron abundance slightly above solar ([Fe/H] = +0.20). The iron abundance and the old cluster age further support the recent spectroscopic findings suggesting a rapid chemical enrichment of the Galactic bulge.

  20. On the physical nature of globular cluster candidates in the Milky Way bulge

    Science.gov (United States)

    Piatti, Andrés E.

    2018-06-01

    We present results from 2MASS JKs photometry on the physical reality of recently reported globular cluster (GC) candidates in the Milky Way (MW) bulge. We relied our analysis on photometric membership probabilities that allowed us to distinguish real stellar aggregates from the composite field star population. When building colour-magnitude diagrams and stellar density maps for stars at different membership probability levels, the genuine GC candidate populations are clearly highlighted. We then used the tip of the red giant branch (RGB) as distance estimator, resulting in heliocentric distances that place many of the objects in regions near the MW bulge, where no GC had been previously recognized. Some few GC candidates resulted to be MW halo/disc objects. Metallicities estimated from the standard RGB method are in agreement with the values expected according to the position of the GC candidates in the Galaxy. Finally, we derived, for the first time, their structural parameters. We found that the studied objects have core, half-light, and tidal radii in the ranges spanned by the population of known MW GCs. Their internal dynamical evolutionary stages will be described properly when their masses are estimated.

  1. RNA Origami

    DEFF Research Database (Denmark)

    Sparvath, Steffen Lynge

    introducerede vores gruppe den enkeltstrengede RNA-origami metode, der giver mulighed for cotranscriptional foldning af veldefinerede nanostrukturer, og er en central del af arbejdet præsenteret heri. Denne ph.d.-afhandling udforsker potentielle anvendelser af RNA-origami nanostrukturer, som nanomedicin eller...... biosensorer. Afhandlingen består af en introduktion til RNA-nanoteknologi feltet, en introduktion af enkeltstrenget RNA-origami design, og fire studier, der beskriver design, produktion og karakterisering af både strukturelle og funktionelle RNA-origamier. Flere RNA-origami designs er blevet undersøgt, og...... projekterne, der indgår i denne afhandling, inkluderer de nyeste fremskridt indenfor strukturel RNA-nanoteknologi og udvikling af funktionelle RNA-baserede enheder. Det første studie beskriver konstruktion og karakterisering af en enkeltstrenget 6-helix RNA-origami stuktur, som er den første demonstration af...

  2. Decrease in the CGG{sub n} trinucleotide repeat mutation of the fragile X syndrome to normal size range during paternal transmission

    Energy Technology Data Exchange (ETDEWEB)

    Vaeisaenen, M.L.; Haataja, R.; Leisti, J. [Oulu Univ. Hospital (Finland)

    1996-09-01

    The fragile X syndrome, the most common inherited form of mental retardation, is caused by the expansion of a CGG{sub n} trinucleotide repeat in the FMR-1 gene. Although the repeat number usually increases during transmission, few cases with reduction of an expanded CGG{sub n} repeat back to the normal size range have been reported. We describe for the first time a family in which such reduction has occurred in the paternal transmission. The paternal premutation ({Delta} = 300 hp) was not detected in one of the five daughters or in the son of this daughter, although he had the grandpaternal RFLP haplotype. Instead, fragments indicating the normal CGG{sub n} repeat size were seen on a Southern blot probed with StB12.3. PCR analysis of the CGG{sub n} repeat confirmed this; in addition to a maternal allele of 30 repeats, an allele of 34 repeats was detected in the daughter and, further, in her son. Sequencing of this new allele revealed a pure CGG{sub n} repeat configuration without AGG interruptions. No evidence for a somatic mosaicism of a premutation allele in the daughter or a normal allele in her father was detected when investigating DNA derived from blood lymphocytes and skin fibroblasts. Another unusual finding in this family was lack of the PCR product of the microsatellite marker RS46 (DXS548) in one of the grandmaternal X chromosomes, detected as incompatible inheritance of RS46 alleles. The results suggest an intergenerational reduction in the CGG{sub n} repeat from premutation size to the normal size range and stable transmission of the contracted repeat to the next generation. However, paternal germ-line mosaicism could not be excluded as an alternative explanation for the reverse mutation. 37 refs., 4 figs.

  3. Looking for imprints of the first stellar generations in metal-poor bulge field stars

    Science.gov (United States)

    Siqueira-Mello, C.; Chiappini, C.; Barbuy, B.; Freeman, K.; Ness, M.; Depagne, E.; Cantelli, E.; Pignatari, M.; Hirschi, R.; Frischknecht, U.; Meynet, G.; Maeder, A.

    2016-09-01

    Context. Efforts to look for signatures of the first stars have concentrated on metal-poor halo objects. However, the low end of the bulge metallicity distribution has been shown to host some of the oldest objects in the Milky Way and hence this Galactic component potentially offers interesting targets to look at imprints of the first stellar generations. As a pilot project, we selected bulge field stars already identified in the ARGOS survey as having [Fe/H] ≈-1 and oversolar [α/Fe] ratios, and we used FLAMES-UVES to obtain detailed abundances of key elements that are believed to reveal imprints of the first stellar generations. Aims: The main purpose of this study is to analyse selected ARGOS stars using new high-resolution (R ~ 45 000) and high-signal-to-noise (S/N> 100) spectra. We aim to derive their stellar parameters and elemental ratios, in particular the abundances of C, N, the α-elements O, Mg, Si, Ca, and Ti, the odd-Z elements Na and Al, the neutron-capture s-process dominated elements Y, Zr, La, and Ba, and the r-element Eu. Methods: High-resolution spectra of five field giant stars were obtained at the 8 m VLT UT2-Kueyen telescope with the UVES spectrograph in FLAMES-UVES configuration. Spectroscopic parameters were derived based on the excitation and ionization equilibrium of Fe I and Fe II. The abundance analysis was performed with a MARCS LTE spherical model atmosphere grid and the Turbospectrum spectrum synthesis code. Results: We confirm that the analysed stars are moderately metal-poor (-1.04 ≤ [Fe/H] ≤-0.43), non-carbon-enhanced (non-CEMP) with [C/Fe] ≤ + 0.2, and α-enhanced. We find that our three most metal-poor stars are nitrogen enhanced. The α-enhancement suggests that these stars were formed from a gas enriched by core-collapse supernovae, and that the values are in agreement with results in the literature for bulge stars in the same metallicity range. No abundance anomalies (Na - O, Al - O, Al - Mg anti-correlations) were

  4. Detailed analysis of RNA-protein interactions within the bacterial ribosomal protein L5/5S rRNA complex.

    OpenAIRE

    Perederina, Anna; Nevskaya, Natalia; Nikonov, Oleg; Nikulin, Alexei; Dumas, Philippe; Yao, Min; Tanaka, Isao; Garber, Maria; Gongadze, George; Nikonov, Stanislav

    2002-01-01

    The crystal structure of ribosomal protein L5 from Thermus thermophilus complexed with a 34-nt fragment comprising helix III and loop C of Escherichia coli 5S rRNA has been determined at 2.5 A resolution. The protein specifically interacts with the bulged nucleotides at the top of loop C of 5S rRNA. The rRNA and protein contact surfaces are strongly stabilized by intramolecular interactions. Charged and polar atoms forming the network of conserved intermolecular hydrogen bonds are located in ...

  5. Computational strategies for the automated design of RNA nanoscale structures from building blocks using NanoTiler.

    Science.gov (United States)

    Bindewald, Eckart; Grunewald, Calvin; Boyle, Brett; O'Connor, Mary; Shapiro, Bruce A

    2008-10-01

    One approach to designing RNA nanoscale structures is to use known RNA structural motifs such as junctions, kissing loops or bulges and to construct a molecular model by connecting these building blocks with helical struts. We previously developed an algorithm for detecting internal loops, junctions and kissing loops in RNA structures. Here we present algorithms for automating or assisting many of the steps that are involved in creating RNA structures from building blocks: (1) assembling building blocks into nanostructures using either a combinatorial search or constraint satisfaction; (2) optimizing RNA 3D ring structures to improve ring closure; (3) sequence optimisation; (4) creating a unique non-degenerate RNA topology descriptor. This effectively creates a computational pipeline for generating molecular models of RNA nanostructures and more specifically RNA ring structures with optimized sequences from RNA building blocks. We show several examples of how the algorithms can be utilized to generate RNA tecto-shapes.

  6. Computational strategies for the automated design of RNA nanoscale structures from building blocks using NanoTiler☆

    Science.gov (United States)

    Bindewald, Eckart; Grunewald, Calvin; Boyle, Brett; O’Connor, Mary; Shapiro, Bruce A.

    2013-01-01

    One approach to designing RNA nanoscale structures is to use known RNA structural motifs such as junctions, kissing loops or bulges and to construct a molecular model by connecting these building blocks with helical struts. We previously developed an algorithm for detecting internal loops, junctions and kissing loops in RNA structures. Here we present algorithms for automating or assisting many of the steps that are involved in creating RNA structures from building blocks: (1) assembling building blocks into nanostructures using either a combinatorial search or constraint satisfaction; (2) optimizing RNA 3D ring structures to improve ring closure; (3) sequence optimisation; (4) creating a unique non-degenerate RNA topology descriptor. This effectively creates a computational pipeline for generating molecular models of RNA nanostructures and more specifically RNA ring structures with optimized sequences from RNA building blocks. We show several examples of how the algorithms can be utilized to generate RNA tecto-shapes. PMID:18838281

  7. The Black Hole Mass-Bulge Luminosity Relationship for Active Galactic Nuclei From Reverberation Mapping and Hubble Space Telescope Imaging

    DEFF Research Database (Denmark)

    Bentz, Misty C.; Peterson, Bradley M.; Pogge, Richard W.

    2009-01-01

    We investigate the relationship between black hole mass and bulge luminosity for active galactic nuclei (AGNs) with reverberation-based black hole mass measurements and bulge luminosities from two-dimensional decompositions of Hubble Space Telescope host galaxy images. We find that the slope...... of the relationship for AGNs is 0.76-0.85 with an uncertainty of ~0.1, somewhat shallower than the M BH vprop L 1.0±0.1 relationship that has been fit to nearby quiescent galaxies with dynamical black hole mass measurements. This difference is somewhat perplexing, as the AGN black hole masses include an overall...

  8. Conformation and dynamics of nucleotides in bulges and symmetric internal loops in duplex DNA studied by EPR and fluorescence spectroscopies

    International Nuclear Information System (INIS)

    Cekan, Pavol; Sigurdsson, Snorri Th.

    2012-01-01

    Highlights: ► Bulges and loops were studied by both EPR and fluorescence spectroscopies using the probe Ç/Ç f . ► One-base bulge was in a temperature-dependent equilibrium between looped-out and stacked states. ► Bases in two- and three-base bulges were stacked at all temperatures, resulting in DNA bending. ► Bases were stacked in symmetrical two- to five-base internal loops, according to EPR data. ► Unexpectedly high fluorescence for the smaller loops indicated local structural perturbations. -- Abstract: The dynamics and conformation of base bulges and internal loops in duplex DNA were studied using the bifunctional spectroscopic probe Ç, which becomes fluorescent (Ç f ) upon reduction of the nitroxide functional group, along with EPR and fluorescence spectroscopies. A one-base bulge was in a conformational equilibrium between looped-out and stacked states, the former favored at higher temperature and the latter at lower temperature. Stacking of bulge bases was favored in two- and three-base bulges, independent of temperature, resulting in DNA bending as evidenced by increased fluorescence of Ç f . EPR spectra of Ç-labeled three-, four- and five-base symmetrical interior DNA bulges at 20 °C showed low mobility, indicating that the spin-label was stacked within the loop. The spin-label mobility at 37 °C increased as the loops became larger. A considerable variation in fluorescence between different loops was observed, as well as a temperature-dependence within constructs. Fluorescence unexpectedly increased as the size of the loop decreased at 2 °C. Fluorescence of the smallest loops, where a single T·T mismatch was located between the stem region and the probe, was even larger than for the single strand, indicating a considerable local structural deformation of these loops from regular B-DNA. These results show the value of combining EPR and fluorescence spectroscopy to study non-helical regions of nucleic acids.

  9. RNA secondary structure prediction using soft computing.

    Science.gov (United States)

    Ray, Shubhra Sankar; Pal, Sankar K

    2013-01-01

    Prediction of RNA structure is invaluable in creating new drugs and understanding genetic diseases. Several deterministic algorithms and soft computing-based techniques have been developed for more than a decade to determine the structure from a known RNA sequence. Soft computing gained importance with the need to get approximate solutions for RNA sequences by considering the issues related with kinetic effects, cotranscriptional folding, and estimation of certain energy parameters. A brief description of some of the soft computing-based techniques, developed for RNA secondary structure prediction, is presented along with their relevance. The basic concepts of RNA and its different structural elements like helix, bulge, hairpin loop, internal loop, and multiloop are described. These are followed by different methodologies, employing genetic algorithms, artificial neural networks, and fuzzy logic. The role of various metaheuristics, like simulated annealing, particle swarm optimization, ant colony optimization, and tabu search is also discussed. A relative comparison among different techniques, in predicting 12 known RNA secondary structures, is presented, as an example. Future challenging issues are then mentioned.

  10. Chemical evolution of the Galactic bulge as traced by microlensed dwarf and subgiant stars: II. Ages, metallicities, detailed elemental abundances, and connections to the Galactic thick disc

    NARCIS (Netherlands)

    Bensby, T.; Feltzing, S.; Johnson, J.A.; Gould, A.; Adén, D.; Asplund, M.; Meléndez, J.; Gal-Yam, A.; Lucatello, S.; Sana, H.; Sumi, T.; Miyake, N.; Suzuki, D.; Han, C.; Bond, I.; Udalski, A.

    2010-01-01

    Context. The Bulge is the least understood major stellar population of the Milky Way. Most of what we know about the formation and evolution of the Bulge comes from bright giant stars. The underlying assumption that giants represent all the stars, and accurately trace the chemical evolution of a

  11. THE PANCHROMATIC HUBBLE ANDROMEDA TREASURY. I. BRIGHT UV STARS IN THE BULGE OF M31

    International Nuclear Information System (INIS)

    Rosenfield, Philip; Johnson, L. Clifton; Dalcanton, Julianne J.; Williams, Benjamin F.; Gilbert, Karoline M.; Girardi, Léo; Bressan, Alessandro; Lang, Dustin; Guhathakurta, Puragra; Dorman, Claire E.; Howley, Kirsten M.; Lauer, Tod R.; Olsen, Knut A. G.; Bell, Eric F.; Bianchi, Luciana; Caldwell, Nelson; Dolphin, Andrew; Kalirai, Jason; Larsen, Søren S.; Rix, Hans-Walter

    2012-01-01

    As part of the Panchromatic Hubble Andromeda Treasury multi-cycle program, we observed a 12' × 6.'5 area of the bulge of M31 with the WFC3/UVIS filters F275W and F336W. From these data we have assembled a sample of ∼4000 UV-bright, old stars, vastly larger than previously available. We use updated Padova stellar evolutionary tracks to classify these hot stars into three classes: Post-AGB stars (P-AGB), Post-Early AGB (PE-AGB) stars, and AGB-manqué stars. P-AGB stars are the end result of the asymptotic giant branch (AGB) phase and are expected in a wide range of stellar populations, whereas PE-AGB and AGB-manqué (together referred to as the hot post-horizontal branch; HP-HB) stars are the result of insufficient envelope masses to allow a full AGB phase, and are expected to be particularly prominent at high helium or α abundances when the mass loss on the red giant branch is high. Our data support previous claims that most UV-bright sources in the bulge are likely hot (extreme) horizontal branch (EHB) stars and their progeny. We construct the first radial profiles of these stellar populations and show that they are highly centrally concentrated, even more so than the integrated UV or optical light. However, we find that this UV-bright population does not dominate the total UV luminosity at any radius, as we are detecting only the progeny of the EHB stars that are the likely source of the UV excess. We calculate that only a few percent of main-sequence stars in the central bulge can have gone through the HP-HB phase and that this percentage decreases strongly with distance from the center. We also find that the surface density of hot UV-bright stars has the same radial variation as that of low-mass X-ray binaries. We discuss age, metallicity, and abundance variations as possible explanations for the observed radial variation in the UV-bright population.

  12. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9

    Science.gov (United States)

    Sternberg, Samuel H.; Redding, Sy; Jinek, Martin; Greene, Eric C.; Doudna, Jennifer A.

    2014-03-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA heteroduplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA.

  13. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9.

    Science.gov (United States)

    Sternberg, Samuel H; Redding, Sy; Jinek, Martin; Greene, Eric C; Doudna, Jennifer A

    2014-03-06

    The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA heteroduplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA.

  14. RR Lyrae star distance scale and kinematics from inner bulge to 50 kpc

    Directory of Open Access Journals (Sweden)

    Dambis Andrei

    2017-01-01

    Full Text Available We use the currently most complete sample of ∼ 3500 type ab RR Lyraes in our Galaxy with available radial-velocity and [Fe/H] measurements to perform a statisticalparallax analysis for a subsample of ∼ 600 type ab RR Lyraes located within 5 kpc from the Sun to refine the parameters of optical and WISE W1-band period-metallicityluminosity relations and adjust our preliminary distances. The new zero point implies the rescaled estimates for the solar Galactocentric distance (RG = 7.99 ± 0.37 kpc and the LMC distance modulus (DMLMC = 18.39 ±0.09. We use the kinematic data for the entire sample to explore the dependence of the halo and thick-disk RR Lyrae velocity ellipsoids on Galactocentric distance from the inner bulge out to R ∼ 50 kpc.

  15. REDSHIFT EVOLUTION IN BLACK HOLE-BULGE RELATIONS: TESTING C IV-BASED BLACK HOLE MASSES

    International Nuclear Information System (INIS)

    Greene, Jenny E.; Peng, Chien Y.; Ludwig, Randi R.

    2010-01-01

    We re-examine claims for redshift evolution in black hole-bulge scaling relations based on lensed quasars. In particular, we refine the black hole (BH) mass estimates using measurements of Balmer lines from near-infrared spectroscopy obtained with Triplespec at Apache Point Observatory. In support of previous work, we find a large scatter between Balmer and UV line widths, both Mg IIλλ2796, 2803 and C IVλλ1548, 1550. There is tentative evidence that C III]λ1909, despite being a blend of multiple transitions, may correlate well with Mg II, although a larger sample is needed for a real calibration. Most importantly, we find no systematic changes in the estimated BH masses for the lensed sample based on Balmer lines, providing additional support to the interpretation that black holes were overly massive compared to their host galaxies at high redshift.

  16. Selective Alkylation of C-Rich Bulge Motifs in Nucleic Acids by Quinone Methide Derivatives.

    Science.gov (United States)

    Lönnberg, Tuomas; Hutchinson, Mark; Rokita, Steven

    2015-09-07

    A quinone methide precursor featuring a bis-cyclen anchoring moiety has been synthesized and its capacity to alkylate oligonucleotide targets quantified in the presence and absence of divalent metal ions (Zn(2+) , Ni(2+) and Cd(2+) ). The oligonucleotides were designed for testing the sequence and secondary structure specificity of the reaction. Gel electrophoretic analysis revealed predominant alkylation of C-rich bulges, regardless of the presence of divalent metal ions or even the bis-cyclen anchor. This C-selectivity appears to be an intrinsic property of the quinone methide electrophile as reflected by its reaction with an equimolar mixture of the 2'-deoxynucleosides. Only dA-N1 and dC-N3 alkylation products were detected initially and only the dC adduct persisted for detection under conditions of the gel electrophoretic analysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Limb darkening of a K giant in the galactic bulge : Planet photometry of MACHO 97-BLG-28

    NARCIS (Netherlands)

    Albrow, MD; Beaulieu, JP; Caldwell, JAR; Dominik, M; Greenhill, J; Hill, K; Kane, S; Martin, R; Menzies, J; Pel, JW; Pollard, K; Sackett, PD; Sahu, KC; Vermaak, P; Watson, R; Williams, A; Sahu, MS

    1999-01-01

    We present the PLANET photometric data set(10) for the binary-lens microlensing event MACHO 97-BLG-28, consisting of 696 I- and V-band measurements, and analyze it to determine the radial surface brightness profile of the Galactic bulge source star. The microlensed source, demonstrated to be a K

  18. Study of mechanical-magnetic and electromagnetic properties of PZT/Ni film systems by a novel bulge technique

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Q.; Zhou, W.; Ding, J.; Xiao, M. [School of Materials Science and Engineering, Xiangtan University, Hunan 411105 (China); Key Laboratory of Film Materials and Devices of Science and Technology Department of Hunan Province, Xiangtan University, Hunan 411105 (China); Yu, Z.J.; Xu, H. [State Key Lab for Turbulence and Complex Systems, Peking University, Beijing 100871 (China); Mao, W.G., E-mail: ssamao@126.com [School of Materials Science and Engineering, Xiangtan University, Hunan 411105 (China); Key Laboratory of Film Materials and Devices of Science and Technology Department of Hunan Province, Xiangtan University, Hunan 411105 (China); Pei, Y.M.; Li, F.X. [State Key Lab for Turbulence and Complex Systems, Peking University, Beijing 100871 (China); Feng, X. [AML, Department of Engineering Mechanics, Tsinghua University, Beijing 100084 (China); Fang, D.N., E-mail: fangdn@pku.edu.cn [State Key Lab for Turbulence and Complex Systems, Peking University, Beijing 100871 (China); Institute of Advanced Structure Technology, Beijing Institute of Technology, Beijing 100081 (China)

    2017-02-01

    A novel multiple functional bulge apparatus was designed to study the mechanical-electronic-magnetic characteristics of electromagnetic materials. The elastic modulus difference effect of Ni thin film was observed and it was about 22.16% in the demagnetized and magnetization saturated states. The mechanical-magnetic behaviors of Ni and lead-titanate zirconate (PZT)/Ni films were in-situ measured by using the new bulge systems, respectively. The evolutions of three key material properties in hysteresis loop including saturation magnetization, remanent magnetization and coercive field were discussed in detail, respectively. The mechanisms of mechanical-magnetic coupled behaviors of Ni and PZT/Ni films were analyzed with the aid of the competitive relationship of stress and magnetization. Similarly, the electronic-magnetic characteristics of PZT/Ni films were in-situ measured by using this experimental system. The evolution of saturated magnetization, remanent magnetization and coercive field Kerr signals were discussed with the magneto-elastic anisotropy energy point. In this paper, a suitable mechanical-electronic-magnetic bulge measurement system was established, which would provide a good choice for further understanding the multi field coupling characteristics of electromagnetic film materials. - Highlights: • A novel bulge apparatus was designed to study electromagnetic materials. • The mechanical-magnetic features of Ni film were studied by this new apparatus. • The ΔE effect of Ni film was observed and analyzed. • The mechanical electronic-magnetic characteristics of PZT/Ni film were discussed.

  19. Galactic Angular Momentum in Cosmological Zoom-in Simulations. I. Disk and Bulge Components and the Galaxy-Halo Connection

    Science.gov (United States)

    Sokołowska, Aleksandra; Capelo, Pedro R.; Fall, S. Michael; Mayer, Lucio; Shen, Sijing; Bonoli, Silvia

    2017-02-01

    We investigate the angular momentum evolution of four disk galaxies residing in Milky-Way-sized halos formed in cosmological zoom-in simulations with various sub-grid physics and merging histories. We decompose these galaxies, kinematically and photometrically, into their disk and bulge components. The simulated galaxies and their components lie on the observed sequences in the j *-M * diagram, relating the specific angular momentum and mass of the stellar component. We find that galaxies in low-density environments follow the relation {j}* \\propto {M}* α past major mergers, with α ˜ 0.6 in the case of strong feedback, when bulge-to-disk ratios are relatively constant, and α ˜ 1.4 in the other cases, when secular processes operate on shorter timescales. We compute the retention factors (I.e., the ratio of the specific angular momenta of stars and dark matter) for both disks and bulges and show that they vary relatively slowly after averaging over numerous but brief fluctuations. For disks, the retention factors are usually close to unity, while for bulges, they are a few times smaller. Our simulations therefore indicate that galaxies and their halos grow in a quasi-homologous way.

  20. Galactic Bulge Giants: Probing Stellar and Galactic Evolution. 1. Catalogue of Spitzer IRAC and MIPS Sources (PREPRINT)

    Science.gov (United States)

    Uttenthaler, Stefan; Stute, Matthias; Sahai, Raghvendra; Blommaert, Joris A.; Schultheis, Mathias; Kraemer, Kathleen E.; Groenewegen, Martin A.; Price, Stephan D.

    2010-01-01

    Aims. We aim at measuring mass-loss rates and the luminosities of a statistically large sample of Galactic bulge stars at several galactocentric radii. The sensitivity of previous infrared surveys of the bulge has been rather limited, thus fundamental questions for late stellar evolution, such as the stage at which substantial mass-loss begins on the red giant branch and its dependence on fundamental stellar properties, remain unanswered. We aim at providing evidence and answers to these questions. Methods. To this end, we observed seven 15 15 arcmin2 fields in the nuclear bulge and its vicinity with unprecedented sensitivity using the IRAC and MIPS imaging instruments on-board the Spitzer Space Telescope. In each of the fields, tens of thousands of point sources were detected. Results. In the first paper based on this data set, we present the observations, data reduction, the final catalogue of sources, and a detailed comparison to previous mid-IR surveys of the Galactic bulge, as well as to theoretical isochrones. We find in general good agreement with other surveys and the isochrones, supporting the high quality of our catalogue.

  1. LONG-TERM EVOLUTION OF DOME-SHAPED MACULA: Increased Macular Bulge is Associated With Extended Macular Atrophy.

    Science.gov (United States)

    Soudier, Guillaume; Gaudric, Alain; Gualino, Vincent; Massin, Pascale; Nardin, Mathieu; Tadayoni, Ramin; Speeg-Schatz, Claude; Gaucher, David

    2016-05-01

    Dome-shaped macula (DSM) may cause impaired vision. This study analyzed the long-term evolution of DSM, most particularly macular changes: serous retinal detachment, retinal pigment epithelium atrophy, and DSM bulge increase. Twenty-nine eyes presenting with DSM were retrospectively studied. Clinical data, color photographs, fluorescein angiographs, and optical coherence tomography examinations were reviewed. Patients were followed up from 6 months to 111 months (mean, 37.89 months). The height of the macular bulge, the size of retinal pigment epithelium macular atrophy, and serous retinal detachment progression were studied. Other macular changes were noted. Mean vision remained stable. Dome-shaped macula height increased significantly from 338.9 μm to 364.3 μm (P = 0.007). Serous retinal detachment was present initially in 15 of 29 eyes; it increased in 4 cases and resolved spontaneously in 7. Macular retinal pigment epithelium atrophy correlated with the bulge height (P = 0.015), and it enlarged during follow-up (1.12 vs. 1.34, P = 0.04). Other macular anomalies were present initially or appeared during follow-up: macular pucker, choroidal neovascularization (CNV), subretinal pigmentary clumps, and flat irregular pigmented epithelium detachment. A few treatments were proven in serous retinal detachment cases but were ineffective in restoring vision. In DSM, vision may be stable for years while macular changes progress: the macular bulge increases as does retinal pigment epithelium atrophy.

  2. Self-consistent Bulge/Disk/Halo Galaxy Dynamical Modeling Using Integral Field Kinematics

    Science.gov (United States)

    Taranu, D. S.; Obreschkow, D.; Dubinski, J. J.; Fogarty, L. M. R.; van de Sande, J.; Catinella, B.; Cortese, L.; Moffett, A.; Robotham, A. S. G.; Allen, J. T.; Bland-Hawthorn, J.; Bryant, J. J.; Colless, M.; Croom, S. M.; D'Eugenio, F.; Davies, R. L.; Drinkwater, M. J.; Driver, S. P.; Goodwin, M.; Konstantopoulos, I. S.; Lawrence, J. S.; López-Sánchez, Á. R.; Lorente, N. P. F.; Medling, A. M.; Mould, J. R.; Owers, M. S.; Power, C.; Richards, S. N.; Tonini, C.

    2017-11-01

    We introduce a method for modeling disk galaxies designed to take full advantage of data from integral field spectroscopy (IFS). The method fits equilibrium models to simultaneously reproduce the surface brightness, rotation, and velocity dispersion profiles of a galaxy. The models are fully self-consistent 6D distribution functions for a galaxy with a Sérsic profile stellar bulge, exponential disk, and parametric dark-matter halo, generated by an updated version of GalactICS. By creating realistic flux-weighted maps of the kinematic moments (flux, mean velocity, and dispersion), we simultaneously fit photometric and spectroscopic data using both maximum-likelihood and Bayesian (MCMC) techniques. We apply the method to a GAMA spiral galaxy (G79635) with kinematics from the SAMI Galaxy Survey and deep g- and r-band photometry from the VST-KiDS survey, comparing parameter constraints with those from traditional 2D bulge-disk decomposition. Our method returns broadly consistent results for shared parameters while constraining the mass-to-light ratios of stellar components and reproducing the H I-inferred circular velocity well beyond the limits of the SAMI data. Although the method is tailored for fitting integral field kinematic data, it can use other dynamical constraints like central fiber dispersions and H I circular velocities, and is well-suited for modeling galaxies with a combination of deep imaging and H I and/or optical spectra (resolved or otherwise). Our implementation (MagRite) is computationally efficient and can generate well-resolved models and kinematic maps in under a minute on modern processors.

  3. PRECISE BLACK HOLE MASSES FROM MEGAMASER DISKS: BLACK HOLE-BULGE RELATIONS AT LOW MASS

    International Nuclear Information System (INIS)

    Greene, Jenny E.; Peng, Chien Y.; Kim, Minjin; Kuo, Cheng-Yu; Braatz, James A.; Impellizzeri, C. M. Violette; Condon, James J.; Lo, K. Y.; Henkel, Christian; Reid, Mark J.

    2010-01-01

    The black hole (BH)-bulge correlations have greatly influenced the last decade of efforts to understand galaxy evolution. Current knowledge of these correlations is limited predominantly to high BH masses (M BH ∼>10 8 M sun ) that can be measured using direct stellar, gas, and maser kinematics. These objects, however, do not represent the demographics of more typical L 2 O megamasers in circumnuclear disks. The masers trace the Keplerian rotation of circumnuclear molecular disks starting at radii of a few tenths of a pc from the central BH. Modeling of the rotation curves, presented by Kuo et al., yields BH masses with exquisite precision. We present stellar velocity dispersion measurements for a sample of nine megamaser disk galaxies based on long-slit observations using the B and C spectrograph on the Dupont telescope and the Dual Imaging Spectrograph on the 3.5 m telescope at Apache Point. We also perform bulge-to-disk decomposition of a subset of five of these galaxies with Sloan Digital Sky Survey imaging. The maser galaxies as a group fall below the M BH -σ * relation defined by elliptical galaxies. We show, now with very precise BH mass measurements, that the low-scatter power-law relation between M BH and σ * seen in elliptical galaxies is not universal. The elliptical galaxy M BH -σ * relation cannot be used to derive the BH mass function at low mass or the zero point for active BH masses. The processes (perhaps BH self-regulation or minor merging) that operate at higher mass have not effectively established an M BH -σ * relation in this low-mass regime.

  4. Ultraviolet spectrophotometry of 2A 1822--371: A bulge on the accretion disk

    International Nuclear Information System (INIS)

    Mason, K.O.; Cordova, F.A.

    1982-01-01

    The X-ray source 2A 1822--371 has been observed with the IUE satellite over an 8 hour period. Long and short wavelength exposures of duration 45 or 60 minutes were alternated in order to resolve the 5.57 hr photometric modulation of the star. The data provide evidence that the shape of the 5.57 hr modulation evolves smoothly with energy between extremes defined by the optical and X-ray curves. The far-UV light curve is more deeply modulated than the X-ray light curve. The combined ultraviolet and the UBV band optical data can be fitted with a single blackbody of temperature 2.7 x 10 4 K, or an optically thick disk model with parameters T/sub asterisk/ = 1.2 x 10 5 K and R/sub out//R/sub in/approx.30. A single power-law model does not adequately represent the continuum. There is evidence of absorption due to the 2200 A interstellar feature whose depth requires a color excess, E(B--V)approx.0.1, with 3 sigma upper and lower bounds of 0.29 and 0.01. Emission lines of C IV 1550 A and N V 1240 A are detected in the UV spectrum. The work of Mason et al. and White et al. suggests that the optical and ultraviolet emission arises in an accretion disk, whereas the X-radiation is emitted from a scattering cloud that envelopes a central compact object. In the present paper, the 5.57 hr optical, X-ray and ultraviolet modulation of 2A 1822--371 is intrepreted as the result of partial occultation of the emitting region by a comparison star and a bulge on the outer accretion disk. X-ray heating of the bulge will probably also contribute to the modulation at optical and ultraviolet wavelengths

  5. CHEMICAL ABUNDANCE ANALYSIS OF A NEUTRON-CAPTURE ENHANCED RED GIANT IN THE BULGE PLAUT FIELD

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Christian I.; Rich, R. Michael [Department of Physics and Astronomy, UCLA, 430 Portola Plaza, Box 951547, Los Angeles, CA 90095-1547 (United States); McWilliam, Andrew, E-mail: cijohnson@astro.ucla.edu, E-mail: rmr@astro.ucla.edu, E-mail: cjohnson@cfa.harvard.edu, E-mail: andy@obs.carnegiescience.edu [Observatories of the Carnegie Institution of Washington, Pasadena, CA 91101 (United States)

    2013-09-20

    We present chemical abundances for 27 elements ranging from oxygen to erbium in the metal-poor ([Fe/H] = –1.67) bulge red giant branch star 2MASS 18174532-3353235. The results are based on equivalent width and spectrum synthesis analyses of a high-resolution (R ∼ 30, 000) spectrum obtained with the Magellan-MIKE spectrograph. While the light (Z ∼< 30) element abundance patterns match those of similar metallicity bulge and halo stars, the strongly enhanced heavy element abundances are more similar to 'r-II' halo stars (e.g., CS 22892-052) typically found at [Fe/H] ∼< – 2.5. We find that the heaviest elements (Z ≥ 56) closely follow the scaled-solar r-process abundance pattern. We do not find evidence supporting significant s-process contributions; however, the intermediate mass elements (e.g., Y and Zr) appear to have been produced through a different process than the heaviest elements. The light and heavy element abundance patterns of 2MASS 18174532-3353235 are in good agreement with the more metal-poor r-process enhanced stars CS 22892-052 and BD +17{sup o}3248. 2MASS 18174532-3353235 also shares many chemical characteristics with the similar metallicity but comparatively α-poor Ursa Minor dwarf galaxy giant COS 82. Interestingly, the Mo and Ru abundances of 2MASS 18174532-3353235 are also strongly enhanced and follow a similar trend recently found to be common in moderately metal-poor main-sequence turn-off halo stars.

  6. Structure and Dynamics of RNA Repeat Expansions That Cause Huntington's Disease and Myotonic Dystrophy Type 1.

    Science.gov (United States)

    Chen, Jonathan L; VanEtten, Damian M; Fountain, Matthew A; Yildirim, Ilyas; Disney, Matthew D

    2017-07-11

    RNA repeat expansions cause a host of incurable, genetically defined diseases. The most common class of RNA repeats consists of trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one-hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs, while those of r(3×CUG) prefer one- or two-hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form and that the loop regions are dynamic. The results will be useful for understanding the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.

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

    Science.gov (United States)

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

    2013-01-01

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

  8. Was the Milky Way Bulge Formed from the Buckling Disk Instability, Hierarchical Collapse, Accretion of Clumps, or All of the Above?

    Science.gov (United States)

    Nataf, David M.

    2017-09-01

    The assembly of the Milky Way bulge is an old topic in astronomy, one now in a period of renewed and rapid development. That is due to tremendous advances in observations of bulge stars, motivating observations of both local and high-redshift galaxies, and increasingly sophisticated simulations. The dominant scenario for bulge formation is that of the Milky Way as a nearly pure disk galaxy, with the inner disk having formed a bar and buckled. This can potentially explain virtually all bulge stars with [Fe/H] ≳ -1.0, which comprise 95% of the stellar population. The evidence is the incredible success in N-body models of this type in making non-trivial, non-generic predictions, such as the rotation curve and velocity dispersion measured from radial velocities, and the spatial morphologies of the peanut/X-shape and the long bar. The classical bulge scenario, whereby the bulge formed from early dissipative collapse and mergers, remains viable for stars with [Fe/H] ≲ -1.0 and potentially a minority of the other stars. A classical bulge is expected from Λ-CDM cosmological simulations, can accentuate the properties of an existing bar in a hybrid system, and is most consistent with the bulge abundance trends such as [Mg/Fe], which are elevated relative to both the thin and thick disks. Finally, the clumpy-galaxy scenario is considered, as it is the correct description of most Milky Way precursors given observations of high-redshift galaxies. Simulations predict that these star-forming clumps will sometimes migrate to the centres of galaxies where they may form a bulge, and galaxies often include a bulge clump as well. They will possibly form a bar with properties consistent with those of the Milky Way, such as the exponential profile and metallicity gradient. Given the relative successes of these scenarios, the Milky Way bulge is plausibly of composite origin, with a classical bulge and/or inner halo numerically dominant for stars with [Fe/H] ≲ -1.0, a buckling

  9. CHARACTERIZATION OF A SAMPLE OF INTERMEDIATE-TYPE ACTIVE GALACTIC NUCLEI. II. HOST BULGE PROPERTIES AND BLACK HOLE MASS ESTIMATES

    Energy Technology Data Exchange (ETDEWEB)

    Benitez, Erika; Cruz-Gonzalez, Irene; Martinez, Benoni; Jimenez-Bailon, Elena [Instituto de Astronomia, Universidad Nacional Autonoma de Mexico, Apdo. Postal 70-264, Mexico D.F. 04510 (Mexico); Mendez-Abreu, Jairo; Lopez-Martin, Luis [Instituto de Astrofisica de Canarias, E-38200 La Laguna, Tenerife (Spain); Fuentes-Carrera, Isaura [Escuela Superior de Fisica y Matematicas, Instituto Politecnico Nacional (ESFM-IPN), U.P. Adolfo Lopez Mateos, Mexico D.F. 07730 (Mexico); Chavushyan, Vahram [Instituto Nacional de Astrofisica, Optica y Electronica, Apdo. Postal 51-216, 72000 Puebla (Mexico); Leon-Tavares, Jonathan, E-mail: erika@astro.unam.mx [Aalto University Metsaehovi Radio Observatory, Metsaehovintie 114, 02540 Kylmaelae (Finland)

    2013-02-15

    We present a study of the host bulge properties and their relations with the black hole mass for a sample of 10 intermediate-type active galactic nuclei (AGNs). Our sample consists mainly of early-type spirals, four of them hosting a bar. For 70{sup +10} {sub -17}% of the galaxies, we have been able to determine the type of the bulge, and find that these objects probably harbor a pseudobulge or a combination of classical bulge/pseudobulge, suggesting that pseudobulges might be frequent in intermediate-type AGNs. In our sample, 50% {+-} 14% of the objects show double-peaked emission lines. Therefore, narrow double-peaked emission lines seem to be frequent in galaxies harboring a pseudobulge or a combination of classical bulge/pseudobulge. Depending on the bulge type, we estimated the black hole mass using the corresponding M {sub BH}-{sigma}* relation and found them within a range of 5.69 {+-} 0.21 < log M {sup {sigma}}*{sub BH} < 8.09 {+-} 0.24. Comparing these M {sup {sigma}}*{sub BH} values with masses derived from the FWHM of H{beta} and the continuum luminosity at 5100 A from their SDSS-DR7 spectra (M {sub BH}), we find that 8 out of 10 (80{sup +7} {sub -17}%) galaxies have black hole masses that are compatible within a factor of 3. This result would support that M {sub BH} and M {sup {sigma}}*{sub BH} are the same for intermediate-type AGNs, as has been found for type 1 AGNs. However, when the type of the bulge is taken into account, only three out of the seven (43{sup +18} {sub -15}%) objects of the sample have their M {sup {sigma}}*{sub BH} and M {sub BH} compatible within 3{sigma} errors. We also find that estimations based on the M {sub BH}-{sigma}* relation for pseudobulges are not compatible in 50% {+-} 20% of the objects.

  10. Magnesium isotopes in giants in the Milky Way inner disk and bulge: First results with 3D stellar atmospheres.

    Science.gov (United States)

    Thygesen, Anders; Sbordone, Luca; Christlieb, Norbert; Asplund, Martin

    2015-01-01

    The Milky Way bulge is one of the most poorly understood components of our galaxy and its formation history is still a matter of debate (early collapse vs. disk instability). All knowledge of its chemical evolution history has been so far derived by measuring elemental abundances: no isotopic mixtures have been measured so far in the Bulge. While quite challenging, isotopic measurements can be accomplished with present instruments in bulge stars for a few elements, Magnesium being one of them.Of the three stable Mg isotopes, the most common one, 24Mg, is mainly produced by α capture in SN II, while the other two, 25Mg and 26Mg, can be produced efficiently in massive AGB stars, through the 22Ne(α, n)25Mg(n, γ)26Mg reactions as well as the Mg-Al chain. Moreover, SN II production of 25Mg and 26Mg increases with increasing progenitor metallicity, so in older stellar populations, where only the signature of metal-poor SNe is to be expected, one should not see a significant 25Mg or 26Mg fraction. However, if larger 25Mg/24Mg and 26Mg/24Mg ratios are observed, relative to what is produced in SNe, this is a clear sign of an AGB contribution. As such, Mg isotopic ratios are a very useful probe of AGB pollution onset and chemical enrichment timescale in a stellar population.Here, we present the first ever measurements of Mg isotopes in 7 red giant stars in the Milky Way bulge and inner disk, including two stars in the bulge globular cluster NGC6522. The isotopic abundances have been derived from high resolution, high signal-to-noise VLT-UVES spectra using both standard 1D atmospheric models as well as state-of-the-art 3D hydrodynamical models and spectrosynthesis. The use of 3D atmospheric models impacts the derived ratios and this work represents the first derivation of Mg isotopes using full 3D spectrosynthesis. These results yield new constraints on the proposed formation scenarios of the Milky Way bulge.

  11. SUB-SATURN PLANET MOA-2008-BLG-310Lb: LIKELY TO BE IN THE GALACTIC BULGE

    International Nuclear Information System (INIS)

    Janczak, Julia; Dong, Subo; Kozlowski, Szymon

    2010-01-01

    We report the detection of sub-Saturn-mass planet MOA-2008-BLG-310Lb and argue that it is the strongest candidate yet for a bulge planet. Deviations from the single-lens fit are smoothed out by finite-source effects and therefore are not immediately apparent from the light curve. Nevertheless, we find that a model in which the primary has a planetary companion is favored over the single-lens model by Δχ 2 ∼ 880 for an additional 3 degrees of freedom. Detailed analysis yields a planet/star mass ratio q = (3.3 ± 0.3) x 10 -4 and an angular separation between the planet and star within 10% of the angular Einstein radius. The small angular Einstein radius, θ E = 0.155 ± 0.011 mas, constrains the distance to the lens to be D L >6.0 kpc if it is a star (M L >0.08 M sun ). This is the only microlensing exoplanet host discovered so far that must be in the bulge if it is a star. By analyzing VLT NACO adaptive optics images taken near the baseline of the event, we detect additional blended light that is aligned to within 130 mas of the lensed source. This light is plausibly from the lens, but could also be due to a companion to the lens or source, or possibly an unassociated star. If the blended light is indeed due to the lens, we can estimate the mass of the lens, M L = 0.67 ± 0.14 M sun , planet mass m = 74 ± 17 M + , and projected separation between the planet and host, 1.25 ± 0.10 AU, putting it right on the 'snow line'. If not, then the planet has lower mass, is closer to its host and is colder. To distinguish among these possibilities on reasonable timescales would require obtaining Hubble Space Telescope images almost immediately, before the source-lens relative motion of μ= 5 mas yr -1 causes them to separate substantially.

  12. Numerical calculation and analysis of single-curvature polyhedron hydro-bulging process for manufacturing spherical vessels

    International Nuclear Information System (INIS)

    Dong Jianling; Zhang Fengke; Yin Dejian

    2005-01-01

    Single-curvature polyhedron hydro-bulging technology is a new technology for manufacturing spherical vessels and it has a good application foreground. This technology has been used in practice. But the designing and manufacturing of polyhedron is based on experiences, and the final quality of spherical vessels cannot be forecast quantitatively. In the paper, the FEM code, MARC, is used to simulate the hydrobulging process of a single-curvature polyhedron, including loading and offloading. And the distributions of stress and strain are acquired as well as other important data. Comparing with the experimental results, it shows that single-curvature polyhedron hydro-bulging process can be simulated well by the FEM code. (authors)

  13. Rubber bulge forming of single-stage bellows of TiNi shape memory alloy using the displacement control method

    International Nuclear Information System (INIS)

    Senba, Hiromasa; Yamaji, Toru; Okita, Keisuke; Okabe, Nagatoshi; Yamauchi, Kiyoshi; Matsumoto, Kenya

    2005-01-01

    This paper deals with the bulge process for forming the single-stage bellows of TiNi shape memory alloys, which is proposed as a new type of seismic applications, and especially considering the material's special behavior. Thin walled tubes with 20% cold work, whose composition is Ti-51.0 at% Ni, were prepared. First they are appropriately heat-treated and then the rubber bulge process is introduced for the tubes under the condition of austenite phase at room temperature. Displacement control method is adapted to the process. Theoretical prediction of change in outer diameter of the tube on compression is derived, and modified taking into account the progress of the stress-induced martensite transformation on tube's surface by observing the detachment of the oxide layer of the surface. Finally theoretical relationship between compressive displacement and the outer diameter of the tube, which is the most important for the design of the bellows shape, is cleared. (author)

  14. Understanding how surface chemistry and topography enhance fog harvesting based on the superwetting surface with patterned hemispherical bulges.

    Science.gov (United States)

    Zhong, Lieshuang; Zhu, Hai; Wu, Yang; Guo, Zhiguang

    2018-09-01

    The Namib Desert beetle-Stenocara can adapt to the arid environment by its fog harvesting ability. A series of samples with different topography and wettability that mimicked the elytra of the beetle were fabricated to study the effect of these factors on fog harvesting. The superhydrophobic bulgy sample harvested 1.5 times the amount of water than the sample with combinational pattern of hydrophilic bulgy/superhydrophobic surrounding and 2.83 times than the superhydrophobic surface without bulge. These bulges focused the droplets around them which endowed droplets with higher velocity and induced the highest dynamic pressure atop them. Superhydrophobicity was beneficial for the departure of harvested water on the surface of sample. The bulgy topography, together with surface wettability, dominated the process of water supply and water removal. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. RNA-dependent RNA polymerase of hepatitis C virus binds to its coding region RNA stem-loop structure, 5BSL3.2, and its negative strand.

    Science.gov (United States)

    Kanamori, Hiroshi; Yuhashi, Kazuhito; Ohnishi, Shin; Koike, Kazuhiko; Kodama, Tatsuhiko

    2010-05-01

    The hepatitis C virus NS5B RNA-dependent RNA polymerase (RdRp) is a key enzyme involved in viral replication. Interaction between NS5B RdRp and the viral RNA sequence is likely to be an important step in viral RNA replication. The C-terminal half of the NS5B-coding sequence, which contains the important cis-acting replication element, has been identified as an NS5B-binding sequence. In the present study, we confirm the specific binding of NS5B to one of the RNA stem-loop structures in the region, 5BSL3.2. In addition, we show that NS5B binds to the complementary strand of 5BSL3.2 (5BSL3.2N). The bulge structure of 5BSL3.2N was shown to be indispensable for tight binding to NS5B. In vitro RdRp activity was inhibited by 5BSL3.2N, indicating the importance of the RNA element in the polymerization by RdRp. These results suggest the involvement of the RNA stem-loop structure of the negative strand in the replication process.

  16. Structure of noncoding RNA is a determinant of function of RNA binding proteins in transcriptional regulation

    Directory of Open Access Journals (Sweden)

    Oyoshi Takanori

    2012-01-01

    Full Text Available Abstract The majority of the noncoding regions of mammalian genomes have been found to be transcribed to generate noncoding RNAs (ncRNAs, resulting in intense interest in their biological roles. During the past decade, numerous ncRNAs and aptamers have been identified as regulators of transcription. 6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase. B2 RNA, which has stem-loops and unstructured single-stranded regions, represses transcription of mRNA in response to various stresses, including heat shock in mouse cells. The interaction of TLS (translocated in liposarcoma with CBP/p300 was induced by ncRNAs that bind to TLS, and this in turn results in inhibition of CBP/p300 histone acetyltransferase (HAT activity in human cells. Transcription regulator EWS (Ewing's sarcoma, which is highly related to TLS, and TLS specifically bind to G-quadruplex structures in vitro. The carboxy terminus containing the Arg-Gly-Gly (RGG repeat domains in these proteins are necessary for cis-repression of transcription activation and HAT activity by the N-terminal glutamine-rich domain. Especially, the RGG domain in the carboxy terminus of EWS is important for the G-quadruplex specific binding. Together, these data suggest that functions of EWS and TLS are modulated by specific structures of ncRNAs.

  17. Effect of laser energy on the deformation behavior in microscale laser bulge forming

    International Nuclear Information System (INIS)

    Zheng Chao; Sun Sheng; Ji Zhong; Wang Wei

    2010-01-01

    Microscale laser bulge forming is a high strain rate microforming method using high-amplitude shock wave pressure induced by pulsed laser irradiation. The process can serve as a rapidly established and high precision technique to impress microfeatures on thin sheet metals and holds promise of manufacturing complex miniaturized devices. The present paper investigated the forming process using both numerical and experimental methods. The effect of laser energy on microformability of pure copper was discussed in detail. A 3D measuring laser microscope was adopted to measure deformed regions under different laser energy levels. The deformation measurements showed that the experimental and numerical results were in good agreement. With the verified simulation model, the residual stress distribution at different laser energy was predicted and analyzed. The springback was found as a key factor to determine the distribution and magnitude of the compressive residual stress. In addition, the absorbent coating and the surface morphology of the formed samples were observed through the scanning electron microscope. The observation confirmed that the shock forming process was non-thermal attributed to the protection of the absorbent coating.

  18. Characterization of zinc alloy by sheet bulging test with analytical models and digital image correlation

    Science.gov (United States)

    Vitu, L.; Laforge, N.; Malécot, P.; Boudeau, N.; Manov, S.; Milesi, M.

    2018-05-01

    Zinc alloys are used in a wide range of application such as electronics, automotive and building construction. Their various shapes are generally obtained by metal forming operation such as stamping. Therefore, it is important to characterize the material with adequate characterization tests. Sheet Bulging Test (SBT) is well recognized in the metal forming community. Different theoretical models of the literature for the evaluation of thickness and radius of the deformed sheet in SBT have been studied in order to get the hardening curve of different materials. These theoretical models present the advantage that the experimental procedure is very simple. But Koç et al. showed their limitation, since the combination of thickness and radius evaluations depend on the material. As Zinc alloys are strongly anisotropic with a special crystalline structure, a procedure is adopted for characterizing the hardening curve of a Zinc alloy. The anisotropy is first studied with tensile test, and SBT with elliptical dies is also investigated. Parallel to this, Digital Image Correlation (DIC) measures are carried out. The results obtained from theoretical models and DIC measures are compared. Measures done on post-mortem specimens complete the comparisons. Finally, DIC measures give better results and the resulting hardening curve of the studied zinc alloy is provided.

  19. Black Holes and Galactic Density Cusps III From Black Hole to Bulge

    CERN Document Server

    Henriksen, Richard N; Macmillan, Joseph D

    2011-01-01

    Aims. In this paper we continue our study of density cusps that may contain central black holes. Methods. We recall our attempts to use distribution functions with a memory of self-similar relaxation, but mostly they apply only in restricted regions of the global system. We are forced to consider related distribution functions that are steady but not self-similar. Results. One remarkably simple distribution function that has a filled loss cone describes a bulge that transits from a near black hole domain to an outer 'zero flux' regime where$\\rho\\propto r^{-7/4}$. The transition passes from an initial inverse square profile through a region having a 1/r density profile. The structure is likely to be developed at an early stage in the growth of a galaxy. A central black hole is shown to grow exponentially in this background with an e-folding time of a few million years. Conclusions. We derive our results from first principles, using only the angular momentum integral in spherical symmetry. The initial relaxatio...

  20. THE EVOLUTION OF THE KINEMATICS OF NEBULAR SHELLS IN PLANETARY NEBULAE IN THE MILKY WAY BULGE

    International Nuclear Information System (INIS)

    Richer, Michael G.; Lopez, Jose Alberto; Garcia-Diaz, Maria Teresa; Clark, David M.; Pereyra, Margarita; Diaz-Mendez, Enrique

    2010-01-01

    We study the line widths in the [O III]λ5007 and Hα lines for two groups of planetary nebulae in the Milky Way bulge based upon spectroscopy obtained at the Observatorio Astronomico Nacional in the Sierra San Pedro Martir (OAN-SPM) using the Manchester Echelle Spectrograph. The first sample includes objects early in their evolution, having high Hβ luminosities, but [O III]λ5007/Hβ 0.5. These planetary nebulae represent evolutionary phases preceding and following those of the objects studied by Richer et al. in 2008. Our sample of planetary nebulae with weak [O III]λ5007 has a line width distribution similar to that of the expansion velocities of the envelopes of asymptotic giant branch stars and shifted to systematically lower values as compared to the less evolved objects studied by Richer et al. The sample with strong He II λ4686 has a line width distribution indistinguishable from that of the more evolved objects from Richer et al., but a distribution in angular size that is systematically larger and so they are clearly more evolved. These data and those of Richer et al. form a homogeneous sample from a single Galactic population of planetary nebulae, from the earliest evolutionary stages until the cessation of nuclear burning in the central star. They confirm the long-standing predictions of hydrodynamical models of planetary nebulae, where the kinematics of the nebular shell are driven by the evolution of the central star.

  1. ULTRA-DEEP GEMINI NEAR-INFRARED OBSERVATIONS OF THE BULGE GLOBULAR CLUSTER NGC 6624

    Energy Technology Data Exchange (ETDEWEB)

    Saracino, S.; Dalessandro, E.; Ferraro, F. R.; Lanzoni, B.; Miocchi, P. [Dipartimento di Fisica e Astronomia, Università di Bologna, Viale Berti Pichat 6/2, I-40127 Bologna (Italy); Geisler, D.; Mauro, F.; Cohen, R. E.; Villanova, S. [Departamento de Astronomía, Universidad de Concepción, Casilla 160-C, Concepción (Chile); Origlia, L. [INAF—Osservatorio Astronomico di Bologna, via Ranzani 1, I-40127 Bologna (Italy); Bidin, C. Moni, E-mail: sara.saracino@unibo.it [Instituto de Astronomía, Universidad Católica del Norte, Av. Angamos 0610, Antofagasta (Chile)

    2016-11-20

    We used ultra-deep J and K {sub s} images secured with the near-infrared (NIR) GSAOI camera assisted by the multi-conjugate adaptive optics system GeMS at the GEMINI South Telescope in Chile, to obtain a ( K {sub s} , J - K {sub s} ) color–magnitude diagram (CMD) for the bulge globular cluster NGC 6624. We obtained the deepest and most accurate NIR CMD from the ground for this cluster, by reaching K {sub s} ∼ 21.5, approximately 8 mag below the horizontal branch level. The entire extension of the Main Sequence (MS) is nicely sampled and at K {sub s} ∼ 20 we detected the so-called MS “knee” in a purely NIR CMD. By taking advantage of the exquisite quality of the data, we estimated the absolute age of NGC 6624 ( t {sub age} = 12.0 ± 0.5 Gyr), which turns out to be in good agreement with previous studies in the literature. We also analyzed the luminosity and mass functions of MS stars down to M ∼ 0.45 M{sub ⊙}, finding evidence of a significant increase of low-mass stars at increasing distances from the cluster center. This is a clear signature of mass segregation, confirming that NGC 6624 is in an advanced stage of dynamical evolution.

  2. OGLE-III MICROLENSING EVENTS AND THE STRUCTURE OF THE GALACTIC BULGE

    Energy Technology Data Exchange (ETDEWEB)

    Wyrzykowski, Łukasz; Rynkiewicz, Alicja E.; Skowron, Jan; Kozłowski, Szymon; Udalski, Andrzej; Szymański, Michał K.; Kubiak, Marcin; Soszyński, Igor; Pietrzyński, Grzegorz; Poleski, Radosław; Pietrukowicz, Paweł; Pawlak, Michał, E-mail: lw@astrouw.edu.pl [Warsaw University Astronomical Observatory, Al. Ujazdowskie 4, 00-478 Warszawa (Poland)

    2015-01-01

    We present and study the largest and most comprehensive catalog of microlensing events ever constructed. The sample of standard microlensing events comprises 3718 unique events from 2001-2009 with 1409 events that had not been detected before in real-time by the Early Warning System of the Optical Gravitational Lensing Experiment. The search pipeline uses machine learning algorithms to help find rare phenomena among 150 million objects and to derive the detection efficiency. Applications of the catalog can be numerous, from analyzing individual events to large statistical studies of the Galactic mass, kinematics distributions, and planetary abundances. We derive maps of the mean Einstein ring crossing time of events spanning 31 deg{sup 2} toward the Galactic center and compare the observed distributions with the most recent models. We find good agreement within the observed region and we see the signature of the tilt of the bar in the microlensing data. However, the asymmetry of the mean timescales seems to rise more steeply than predicted, indicating either a somewhat different orientation of the bar or a larger bar width. The map of events with sources in the Galactic bulge shows a dependence of the mean timescale on the Galactic latitude, signaling an increasing contribution from disk lenses closer to the plane relative to the height of the disk. Our data present a perfect set for comparing and enhancing new models of the central parts of the Milky Way and creating a three-dimensional picture of the Galaxy.

  3. Extinction maps toward the Milky Way bulge: Two-dimensional and three-dimensional tests with apogee

    Energy Technology Data Exchange (ETDEWEB)

    Schultheis, M. [Université de Nice Sophia-Antipolis, CNRS, Observatoire de Côte d' Azur, Laboratoire Lagrange, 06304 Nice Cedex 4 (France); Zasowski, G. [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); Allende Prieto, C. [Instituto de Astrofísica de Canarias, Calle Vía Láctea s/n, E-38205 La Laguna, Tenerife (Spain); Anders, F.; Chiappini, C. [Leibniz-Institut für Astrophysik Potsdam (AIP), D-14482 Potsdam (Germany); Beaton, R. L.; García Pérez, A. E.; Majewski, S. R. [Department of Astronomy, University of Virginia, Charlottesville, VA 22904 (United States); Beers, T. C. [National Optical Astronomy Observatory, Tucson, AZ 85719 (United States); Bizyaev, D. [Apache Point Observatory, Sunspot, NM 88349 (United States); Frinchaboy, P. M. [Department of Physics and Astronomy, Texas Christian University, TCU Box 298840, Fort Worth, TX 76129 (United States); Ge, J. [Astronomy Department, University of Florida, Gainesville, FL 32611 (United States); Hearty, F.; Schneider, D. P. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Holtzman, J. [New Mexico State University, Las Cruces, NM 88003 (United States); Muna, D. [Department of Astronomy, The Ohio State University, Columbus, OH 43210 (United States); Nidever, D. [Department of Astronomy, University of Michigan, Ann Arbor, MI 48109 (United States); Shetrone, M., E-mail: mathias.schultheis@oca.eu, E-mail: gail.zasowski@gmail.com [McDonald Observatory, The University of Texas at Austin, Austin, TX 78712 (United States)

    2014-07-01

    Galactic interstellar extinction maps are powerful and necessary tools for Milky Way structure and stellar population analyses, particularly toward the heavily reddened bulge and in the midplane. However, due to the difficulty of obtaining reliable extinction measures and distances for a large number of stars that are independent of these maps, tests of their accuracy and systematics have been limited. Our goal is to assess a variety of photometric stellar extinction estimates, including both two-dimensional and three-dimensional extinction maps, using independent extinction measures based on a large spectroscopic sample of stars toward the Milky Way bulge. We employ stellar atmospheric parameters derived from high-resolution H-band Apache Point Observatory Galactic Evolution Experiment (APOGEE) spectra, combined with theoretical stellar isochrones, to calculate line-of-sight extinction and distances for a sample of more than 2400 giants toward the Milky Way bulge. We compare these extinction values to those predicted by individual near-IR and near+mid-IR stellar colors, two-dimensional bulge extinction maps, and three-dimensional extinction maps. The long baseline, near+mid-IR stellar colors are, on average, the most accurate predictors of the APOGEE extinction estimates, and the two-dimensional and three-dimensional extinction maps derived from different stellar populations along different sightlines show varying degrees of reliability. We present the results of all of the comparisons and discuss reasons for the observed discrepancies. We also demonstrate how the particular stellar atmospheric models adopted can have a strong impact on this type of analysis, and discuss related caveats.

  4. Extinction maps toward the Milky Way bulge: Two-dimensional and three-dimensional tests with apogee

    International Nuclear Information System (INIS)

    Schultheis, M.; Zasowski, G.; Allende Prieto, C.; Anders, F.; Chiappini, C.; Beaton, R. L.; García Pérez, A. E.; Majewski, S. R.; Beers, T. C.; Bizyaev, D.; Frinchaboy, P. M.; Ge, J.; Hearty, F.; Schneider, D. P.; Holtzman, J.; Muna, D.; Nidever, D.; Shetrone, M.

    2014-01-01

    Galactic interstellar extinction maps are powerful and necessary tools for Milky Way structure and stellar population analyses, particularly toward the heavily reddened bulge and in the midplane. However, due to the difficulty of obtaining reliable extinction measures and distances for a large number of stars that are independent of these maps, tests of their accuracy and systematics have been limited. Our goal is to assess a variety of photometric stellar extinction estimates, including both two-dimensional and three-dimensional extinction maps, using independent extinction measures based on a large spectroscopic sample of stars toward the Milky Way bulge. We employ stellar atmospheric parameters derived from high-resolution H-band Apache Point Observatory Galactic Evolution Experiment (APOGEE) spectra, combined with theoretical stellar isochrones, to calculate line-of-sight extinction and distances for a sample of more than 2400 giants toward the Milky Way bulge. We compare these extinction values to those predicted by individual near-IR and near+mid-IR stellar colors, two-dimensional bulge extinction maps, and three-dimensional extinction maps. The long baseline, near+mid-IR stellar colors are, on average, the most accurate predictors of the APOGEE extinction estimates, and the two-dimensional and three-dimensional extinction maps derived from different stellar populations along different sightlines show varying degrees of reliability. We present the results of all of the comparisons and discuss reasons for the observed discrepancies. We also demonstrate how the particular stellar atmospheric models adopted can have a strong impact on this type of analysis, and discuss related caveats.

  5. Dissecting the assembly and star formation history of disks and bulges in nearby spirals using the VENGA IFU survey

    Science.gov (United States)

    Carrillo, Andreia Jessica; Jogee, Shardha; Kaplan, Kyle; Weinzirl, Tim; Blanc, Guillermo A.

    2017-06-01

    Integral field spectroscopy of nearby galaxies provides a powerful and unparalleled tool for studying how galaxies assemble the different components -- the bulge, bar, and disk-- that define the Hubble sequence. We explore the assembly and star formation history of these components using galaxies in the VIRUS-P Exploration of Nearby Galaxies (VENGA) survey of 30 nearby spiral galaxies. Compared to other integral field spectroscopy studies of spirals, our study benefits from high spatial sampling and resolution (typically a few 100 pc), large coverage from the bulge to the outer disk, broad wavelength range (3600-6800 A), and medium spectral resolution (120 km/s at 5000 A). In this poster, we present the methodology and data illustrating the exquisite, high-quality, spatially-resolved spectra out to large radii, and the distribution, kinematics, and metallicity of stars and ionized gas. We discuss the next steps in deriving the star formation history (SFH) of bulge, bar, and disk components, and elucidating their assembly pathway by comparing their SFH and structural properties to theoretical models of galaxy evolution. This project is supported by the NSF grants AST-1614798 and AST-1413652.

  6. THE BLACK HOLE MASS-BULGE LUMINOSITY RELATIONSHIP FOR ACTIVE GALACTIC NUCLEI FROM REVERBERATION MAPPING AND HUBBLE SPACE TELESCOPE IMAGING

    International Nuclear Information System (INIS)

    Bentz, Misty C.; Peterson, Bradley M.; Pogge, Richard W.; Vestergaard, Marianne

    2009-01-01

    We investigate the relationship between black hole mass and bulge luminosity for active galactic nuclei (AGNs) with reverberation-based black hole mass measurements and bulge luminosities from two-dimensional decompositions of Hubble Space Telescope host galaxy images. We find that the slope of the relationship for AGNs is 0.76-0.85 with an uncertainty of ∼0.1, somewhat shallower than the M BH ∝ L 1.0±0.1 relationship that has been fit to nearby quiescent galaxies with dynamical black hole mass measurements. This difference is somewhat perplexing, as the AGN black hole masses include an overall scaling factor that brings the AGN M BH -σ * relationship into agreement with that of quiescent galaxies. We discuss biases that may be inherent to the AGN and quiescent galaxy samples and could cause the apparent inconsistency in the forms of their M BH -L bulge relationships. Recent work by Graham, however, presents a similar slope of ∼0.8 for the quiescent galaxies and may bring the relationship for AGNs and quiescent galaxies into agreement.

  7. Invasive placenta previa: Placental bulge with distorted uterine outline and uterine serosal hypervascularity at 1.5T MRI - useful features for differentiating placenta percreta from placenta accreta.

    Science.gov (United States)

    Chen, Xin; Shan, Ruiqin; Zhao, Lianxin; Song, Qingxu; Zuo, Changting; Zhang, Xinjuan; Wang, Shanshan; Shi, Honglu; Gao, Fei; Qian, Tianyi; Wang, Guangbin; Limperopoulos, Catherine

    2018-02-01

    To characterise MRI features of invasive placenta previa and to identify specific features for differentiating placenta percreta (PP) from placenta accreta (PA). Forty-five women with PP and 93 women with PA who underwent 1.5T placental MRI were included. Two radiologists independently evaluated the MRI features of invasive placenta previa, including our novel type of placental bulge (i.e. placental bulge type-II, characterized by placental bulge with distorted uterine outline). Pearson's chi-squared or Fisher's two-sided exact test was performed to compare the MRI features between PP and PA. Logistic stepwise regression analysis and the area under the receiver operating characteristic curve (AUC) were performed to select the optimal features for differentiating PP from PA. Significant differences were found in nine MRI features between women with PP and those with PA (P Placental bulge type-II and uterine serosal hypervascularity were independently associated with PP (odds ratio = 48.618, P Placental bulge type-II and uterine serosal hypervascularity are useful MRI features for differentiating PP from PA. • Placental bulge type-II demonstrated the strongest independent association with PP. • Uterine serosal hypervascularity is a useful feature for differentiating PP from PA. • MRI features associated with abnormal vessels increase the risk of massive haemorrhage.

  8. Detailed analysis of RNA-protein interactions within the bacterial ribosomal protein L5/5S rRNA complex.

    Science.gov (United States)

    Perederina, Anna; Nevskaya, Natalia; Nikonov, Oleg; Nikulin, Alexei; Dumas, Philippe; Yao, Min; Tanaka, Isao; Garber, Maria; Gongadze, George; Nikonov, Stanislav

    2002-12-01

    The crystal structure of ribosomal protein L5 from Thermus thermophilus complexed with a 34-nt fragment comprising helix III and loop C of Escherichia coli 5S rRNA has been determined at 2.5 A resolution. The protein specifically interacts with the bulged nucleotides at the top of loop C of 5S rRNA. The rRNA and protein contact surfaces are strongly stabilized by intramolecular interactions. Charged and polar atoms forming the network of conserved intermolecular hydrogen bonds are located in two narrow planar parallel layers belonging to the protein and rRNA, respectively. The regions, including these atoms conserved in Bacteria and Archaea, can be considered an RNA-protein recognition module. Comparison of the T. thermophilus L5 structure in the RNA-bound form with the isolated Bacillus stearothermophilus L5 structure shows that the RNA-recognition module on the protein surface does not undergo significant changes upon RNA binding. In the crystal of the complex, the protein interacts with another RNA molecule in the asymmetric unit through the beta-sheet concave surface. This protein/RNA interface simulates the interaction of L5 with 23S rRNA observed in the Haloarcula marismortui 50S ribosomal subunit.

  9. A G-quadruplex-containing RNA activates fluorescence in a GFP-like fluorophore

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hao; Suslov, Nikolai B.; Li, Nan-Sheng; Shelke, Sandip A.; Evans, Molly E.; Koldobskaya, Yelena; Rice, Phoebe A.; Piccirilli, Joseph A. [UC

    2014-08-21

    Spinach is an in vitro–selected RNA aptamer that binds a GFP-like ligand and activates its green fluorescence. Spinach is thus an RNA analog of GFP and has potentially widespread applications for in vivo labeling and imaging. We used antibody-assisted crystallography to determine the structures of Spinach both with and without bound fluorophore at 2.2-Å and 2.4-Å resolution, respectively. Spinach RNA has an elongated structure containing two helical domains separated by an internal bulge that folds into a G-quadruplex motif of unusual topology. The G-quadruplex motif and adjacent nucleotides comprise a partially preformed binding site for the fluorophore. The fluorophore binds in a planar conformation and makes extensive aromatic stacking and hydrogen bond interactions with the RNA. Our findings provide a foundation for structure-based engineering of new fluorophore-binding RNA aptamers.

  10. Ultra-deep GEMINI Near-infrared Observations of the Bulge Globular Cluster NGC 6624.

    Science.gov (United States)

    Saracino, S.; Dalessandro, E.; Ferraro, F. R.; Geisler, D.; Mauro, F.; Lanzoni, B.; Origlia, L.; Miocchi, P.; Cohen, R. E.; Villanova, S.; Moni Bidin, C.

    2016-11-01

    We used ultra-deep J and K s images secured with the near-infrared (NIR) GSAOI camera assisted by the multi-conjugate adaptive optics system GeMS at the GEMINI South Telescope in Chile, to obtain a (K s , J - K s ) color-magnitude diagram (CMD) for the bulge globular cluster NGC 6624. We obtained the deepest and most accurate NIR CMD from the ground for this cluster, by reaching K s ˜ 21.5, approximately 8 mag below the horizontal branch level. The entire extension of the Main Sequence (MS) is nicely sampled and at K s ˜ 20 we detected the so-called MS “knee” in a purely NIR CMD. By taking advantage of the exquisite quality of the data, we estimated the absolute age of NGC 6624 (t age = 12.0 ± 0.5 Gyr), which turns out to be in good agreement with previous studies in the literature. We also analyzed the luminosity and mass functions of MS stars down to M ˜ 0.45 M⊙, finding evidence of a significant increase of low-mass stars at increasing distances from the cluster center. This is a clear signature of mass segregation, confirming that NGC 6624 is in an advanced stage of dynamical evolution. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência, Tecnologia e Inovação (Brazil) and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina). Based on observations gathered with ESO-VISTA telescope (program ID 179.B-2002).

  11. The septal bulge--an early echocardiographic sign in hypertensive heart disease.

    Science.gov (United States)

    Gaudron, Philipp Daniel; Liu, Dan; Scholz, Friederike; Hu, Kai; Florescu, Christiane; Herrmann, Sebastian; Bijnens, Bart; Ertl, Georg; Störk, Stefan; Weidemann, Frank

    2016-01-01

    Patients in the early stage of hypertensive heart disease tend to have normal echocardiographic findings. The aim of this study was to investigate whether pathology-specific echocardiographic morphologic and functional parameters can help to detect subclinical hypertensive heart disease. One hundred ten consecutive patients without a history and medication for arterial hypertension (AH) or other cardiac diseases were enrolled. Standard echocardiography and two-dimensional speckle-tracking-imaging analysis were performed. Resting blood pressure (BP) measurement, cycle ergometer test (CET), and 24-hour ambulatory BP monitoring (ABPM) were conducted. Patients were referred to "septal bulge (SB)" group (basal-septal wall thickness ≥ 2 mm thicker than mid-septal wall thickness) or "no-SB" group. Echocardiographic SB was found in 48 (43.6%) of 110 patients. In this SB group, 38 (79.2%) patients showed AH either by CET or ABPM. In contrast, in the no-SB group (n = 62), 59 (95.2%) patients had no positive test for AH by CET or ABPM. When AH was solely defined by resting BP, SB was a reasonable predictive sign for AH (sensitivity 73%, specificity 76%). However, when AH was confirmed by CET or ABPM the echocardiographic SB strongly predicted clinical AH (sensitivity 93%, specificity 86%). In addition, regional myocardial deformation of the basal-septum in SB group was significantly lower than in no-SB group (14 ± 4% vs. 17 ± 4%; P heart disease. Sophisticated BP evaluation including resting BP, ABPM, and CET should be performed in all patients with an accidental finding of a SB in echocardiography. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Rates for parallax-shifted microlensing events from ground-based observations of the galactic bulge

    International Nuclear Information System (INIS)

    Buchalter, A.; Kamionkowski, M.

    1997-01-01

    The parallax effect in ground-based microlensing (ML) observations consists of a distortion to the standard ML light curve arising from the Earth's orbital motion. This can be used to partially remove the degeneracy among the system parameters in the event timescale, t 0 . In most cases, the resolution in current ML surveys is not accurate enough to observe this effect, but parallax could conceivably be detected with frequent follow-up observations of ML events in progress, providing the photometric errors are small enough. We calculate the expected fraction of ML events where the shape distortions will be observable by such follow-up observations, adopting Galactic models for the lens and source distributions that are consistent with observed microlensing timescale distributions. We study the dependence of the rates for parallax-shifted events on the frequency of follow-up observations and on the precision of the photometry. For example, we find that for hourly observations with typical photometric errors of 0.01 mag, 6% of events where the lens is in the bulge, and 31% of events where the lens is in the disk (or ∼10% of events overall), will give rise to a measurable parallax shift at the 95% confidence level. These fractions may be increased by improved photometric accuracy and increased sampling frequency. While long-duration events are favored, the surveys would be effective in picking out such distortions in events with timescales as low as t 0 ∼20 days. We study the dependence of these fractions on the assumed disk mass function and find that a higher parallax incidence is favored by mass functions with higher mean masses. Parallax measurements yield the reduced transverse speed, v, which gives both the relative transverse speed and lens mass as a function of distance. We give examples of the accuracies with which v may be measured in typical parallax events. (Abstract Truncated)

  13. Towards understanding the dynamics of the bar/bulge region in our Galaxy

    Directory of Open Access Journals (Sweden)

    Athanassoula E.

    2012-02-01

    Full Text Available I review some of the work on bars which is closely linked to the bar/bulge system in our Galaxy. Several independent studies, using totally independent methods, come to the same results about the 3D structure of a bar, i.e., that a bar is composed of a vertically thick inner part and a vertically thin outer part. I give examples of this from simulations and substantiate the discussion with input from orbital structure analysis and from observations. The thick part has a considerably shorter radial extent than the thin part. I then see how this applies to our Galaxy, where two bars have been reported, the COBE/DIRBE bar and the Long bar. Comparing their extents and making the reasonable and necessary assumption that our Galaxy has properties similar to those of other galaxies of similar type, leads to the conclusion that these two bars can not form a standard double bar system. I then discuss arguments in favour of the two bars being simply different parts of the same bar, the COBE/DIRBE bar being the thick inner part and the Long bar being the thin outer part of this bar. I also very briefly discuss some related new results. I first consider bar formation and evolution in disc galaxies with a gaseous component – including star formation, feedback and evolution – and a triaxial halo. Then I consider bar formation in a fully cosmological context using hydrodynamical LCDM simulations, where the host galaxies grow, accrete matter and significantly evolve during the formation and evolution of the bar.

  14. Microsecond-Scale MD Simulations of HIV-1 DIS Kissing-Loop Complexes Predict Bulged-In Conformation of the Bulged Bases and Reveal Interesting Differences between Available Variants of the AMBER RNA Force Fields

    Czech Academy of Sciences Publication Activity Database

    Havrila, Marek; Zgarbová, M.; Jurečka, P.; Banáš, P.; Krepl, Miroslav; Otyepka, M.; Šponer, Jiří

    2015-01-01

    Roč. 119, č. 49 (2015), s. 15176-15190 ISSN 1520-6106 R&D Projects: GA ČR(CZ) GBP305/12/G034 Institutional support: RVO:68081707 Keywords : MOLECULAR-DYNAMICS SIMULATIONS * DIMERIZATION INITIATION SITE * QUANTUM-CHEMICAL COMPUTATIONS Subject RIV: BO - Biophysics Impact factor: 3.187, year: 2015

  15. RNA oxidation

    DEFF Research Database (Denmark)

    Kjaer, L. K.; Cejvanovic, V.; Henriken, T.

    2015-01-01

    .9 significant hazard ratio for death compared with the quartile with the lowest 8oxoGuo excretion when adjusted for age, sex, BMI, smoker status, s-HbA1c, urine protein excretion and s-cholesterol. We conclude that it is now established that RNA oxidation is an independent risk factor for death in type 2...

  16. Astrid-2 and ground-based observations of the auroral bulge in the middle of the nightside convection throat

    Directory of Open Access Journals (Sweden)

    G. T. Marklund

    2001-06-01

    Full Text Available Results concerning the electrodynamics of the nightside auroral bulge are presented based on simultaneous satellite and ground-based observations. The satellite data include Astrid-2 measurements of electric fields, currents and particles from a midnight auroral oval crossing and Polar UVI images of the large-scale auroral distribution. The ground-based observations include STARE and SuperDARN electric fields and magnetic records from the Greenland and MIRACLE magnetometer network, the latter including stations from northern Scandinavia north to Svalbard. At the time of the Astrid-2 crossing the ground-based data reveal intense electrojet activity, both to the east and west of the Astrid-2 trajectory, related to the Polar observations of the auroral bulge but not necessarily to a typical substorm. The energetic electron fluxes measured by Astrid-2 across the auroral oval were generally weak being consistent with a gap observed in the auroral luminosity distribution. The electric field across the oval was directed westward, intensifying close to the poleward boundary followed by a decrease in the polar cap. The combined observations suggests that Astrid-2 was moving close to the separatrix between the dusk and dawn convection cells in a region of low conductivity. The constant westward direction of the electric field across the oval indicates that current continuity was maintained, not by polarisation electric fields (as in a Cowling channel, but solely by localized up- and downward field-aligned currents in good agreement with the Astrid-2 magnetometer data. The absence of a polarisation electric field and thus of an intense westward closure current between the dawn and dusk convection cells is consistent with the relatively weak precipitation and low conductivity in the convection throat. Thus, the Cowling current model is not adequate for describing the electrodynamics of the nightside auroral bulge treated here.Key words. Ionosphere (auroral

  17. THE VVV SURVEY REVEALS CLASSICAL CEPHEIDS TRACING A YOUNG AND THIN STELLAR DISK ACROSS THE GALAXY’S BULGE

    Energy Technology Data Exchange (ETDEWEB)

    Dékány, I. [Instituto Milenio de Astrofísica, Santiago (Chile); Minniti, D. [Departamento de Física, Facultad de Ciencias Exactas, Universidad Andres Bello, República 220, Santiago (Chile); Majaess, D. [Saint Mary’s University, Halifax, Nova Scotia (Canada); Zoccali, M.; Hajdu, G.; Catelan, M. [Instituto de Astrofísica, Facultad de Física, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Santiago (Chile); Alonso-García, J. [Unidad de Astronomía, Fac. Cs. Básicas, Universidad de Antofagasta, Avda. U. de Antofagasta 02800, Antofagasta (Chile); Gieren, W. [Departamento de Astronomía, Universidad de Concepción, Casilla 160-C, Concepción (Chile); Borissova, J., E-mail: idekany@astro.puc.cl [Instituto de Física y Astronomía, Universidad de Valparaíso, Av. Gran Bretaña 1111, Valparaso (Chile)

    2015-10-20

    Solid insight into the physics of the inner Milky Way is key to understanding our Galaxy’s evolution, but extreme dust obscuration has historically hindered efforts to map the area along the Galactic mid-plane. New comprehensive near-infrared time-series photometry from the VVV Survey has revealed 35 classical Cepheids, tracing a previously unobserved component of the inner Galaxy, namely a ubiquitous inner thin disk of young stars along the Galactic mid-plane, traversing across the bulge. The discovered period (age) spread of these classical Cepheids implies a continuous supply of newly formed stars in the central region of the Galaxy over the last 100 million years.

  18. Disc extrusions and bulges in nonspecific low back pain and sciatica: Exploratory randomised controlled trial comparing yoga therapy and normal medical treatment.

    Science.gov (United States)

    Monro, Robin; Bhardwaj, Abhishek Kumar; Gupta, Ram Kumar; Telles, Shirley; Allen, Beth; Little, Paul

    2015-01-01

    Previous trials of yoga therapy for nonspecific low back pain (nsLBP) (without sciatica) showed beneficial effects. To test effects of yoga therapy on pain and disability associated with lumbar disc extrusions and bulges. Parallel-group, randomised, controlled trial. Sixty-one adults from rural population, aged 20-45, with nsLBP or sciatica, and disc extrusions or bulges. Randomised to yoga (n=30) and control (n=31). Yoga: 3-month yoga course of group classes and home practice, designed to ensure safety for disc extrusions. normal medical care. OUTCOME MEASURES (3-4 months) Primary: Roland Morris Disability Questionnaire (RMDQ); worst pain in past two weeks. Secondary: Aberdeen Low Back Pain Scale; straight leg raise test; structural changes. Disc projections per case ranged from one bulge or one extrusion to three bulges plus two extrusions. Sixty-two percent had sciatica. Intention-to-treat analysis of the RMDQ data, adjusted for age, sex and baseline RMDQ scores, gave a Yoga Group score 3.29 points lower than Control Group (0.98, 5.61; p=0.006) at 3 months. No other significant differences in the endpoints occurred. No adverse effects of yoga were reported. Yoga therapy can be safe and beneficial for patients with nsLBP or sciatica, accompanied by disc extrusions and bulges.

  19. Invasive placenta previa. Placental bulge with distorted uterine outline and uterine serosal hypervascularity at 1.5T MRI - useful features for differentiating placenta percreta from placenta accreta

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xin; Zhang, Xinjuan; Wang, Shanshan; Shi, Honglu; Gao, Fei; Wang, Guangbin [Shandong University, Department of MR, Shandong Medical Imaging Research Institute, Jinan, Shandong (China); Shan, Ruiqin [Jinan Maternity and Child Care Hospital, Department of Obstetrics, Jinan (China); Zhao, Lianxin [Qilu Hospital of Shandong University, Department of Radiology, Jinan, Shandong (China); Song, Qingxu [Qilu Hospital of Shandong University, Department of Radiation Oncology, Jinan, Shandong (China); Zuo, Changting [Shandong Provincial Hospital Affiliated to Shandong University, Department of Obstetrics and Gynaecology, Jinan, Shandong (China); Qian, Tianyi [MR Collaborations NE Asia, Siemens Healthcare, Beijing (China); Limperopoulos, Catherine [Children' s National Health System, Division of Diagnostic Imaging and Radiology, Washington, DC (United States); George Washington University School of Medicine, Department of Radiology, Washington, DC (United States)

    2018-02-15

    To characterise MRI features of invasive placenta previa and to identify specific features for differentiating placenta percreta (PP) from placenta accreta (PA). Forty-five women with PP and 93 women with PA who underwent 1.5T placental MRI were included. Two radiologists independently evaluated the MRI features of invasive placenta previa, including our novel type of placental bulge (i.e. placental bulge type-II, characterized by placental bulge with distorted uterine outline). Pearson's chi-squared or Fisher's two-sided exact test was performed to compare the MRI features between PP and PA. Logistic stepwise regression analysis and the area under the receiver operating characteristic curve (AUC) were performed to select the optimal features for differentiating PP from PA. Significant differences were found in nine MRI features between women with PP and those with PA (P <0.05). Placental bulge type-II and uterine serosal hypervascularity were independently associated with PP (odds ratio = 48.618, P < 0.001; odds ratio = 4.165, P = 0.018 respectively), and the combination of the two MRI features to distinguish PP from PA yielded an AUC of 0.92 for its predictive performance. Placental bulge type-II and uterine serosal hypervascularity are useful MRI features for differentiating PP from PA. (orig.)

  20. Invasive placenta previa. Placental bulge with distorted uterine outline and uterine serosal hypervascularity at 1.5T MRI - useful features for differentiating placenta percreta from placenta accreta

    International Nuclear Information System (INIS)

    Chen, Xin; Zhang, Xinjuan; Wang, Shanshan; Shi, Honglu; Gao, Fei; Wang, Guangbin; Shan, Ruiqin; Zhao, Lianxin; Song, Qingxu; Zuo, Changting; Qian, Tianyi; Limperopoulos, Catherine

    2018-01-01

    To characterise MRI features of invasive placenta previa and to identify specific features for differentiating placenta percreta (PP) from placenta accreta (PA). Forty-five women with PP and 93 women with PA who underwent 1.5T placental MRI were included. Two radiologists independently evaluated the MRI features of invasive placenta previa, including our novel type of placental bulge (i.e. placental bulge type-II, characterized by placental bulge with distorted uterine outline). Pearson's chi-squared or Fisher's two-sided exact test was performed to compare the MRI features between PP and PA. Logistic stepwise regression analysis and the area under the receiver operating characteristic curve (AUC) were performed to select the optimal features for differentiating PP from PA. Significant differences were found in nine MRI features between women with PP and those with PA (P <0.05). Placental bulge type-II and uterine serosal hypervascularity were independently associated with PP (odds ratio = 48.618, P < 0.001; odds ratio = 4.165, P = 0.018 respectively), and the combination of the two MRI features to distinguish PP from PA yielded an AUC of 0.92 for its predictive performance. Placental bulge type-II and uterine serosal hypervascularity are useful MRI features for differentiating PP from PA. (orig.)

  1. Using artificial microRNA sponges to achieve microRNA loss-of-function in cancer cells.

    Science.gov (United States)

    Tay, Felix Chang; Lim, Jia Kai; Zhu, Haibao; Hin, Lau Cia; Wang, Shu

    2015-01-01

    Widely observed dysregulation of microRNAs (miRNAs) in human cancer has led to substantial speculation regarding possible functions of these short, non-coding RNAs in cancer development and manipulation of miRNA expression to treat cancer. To achieve miRNA loss-of-function, miRNA sponge technology has been developed to use plasmid or viral vectors for intracellular expression of tandemly arrayed, bulged miRNA binding sites complementary to a miRNA target to saturate its ability to regulate natural mRNAs. A strong viral promoter can be used in miRNA sponge vectors to generate high-level expression of the competitive inhibitor transcripts for either transient or long-term inhibition of miRNA function. Taking the advantage of sharing a common seed sequence by members of a miRNA family, this technology is especially useful in knocking down the expression of a family of miRNAs, providing a powerful means for simultaneous inhibition of multiple miRNAs of interest with a single inhibitor. Knockdown of overexpressed oncogenic miRNAs with the technology can be a rational therapeutic strategy for cancer, whereas inhibition of tumor-suppressive miRNAs by the sponges will be useful in deciphering functions of miRNAs in oncogenesis. Herein, we discuss the design of miRNA sponge expression vectors and the use of the vectors to gain better understanding of miRNA's roles in cancer biology and as an alternative tool for anticancer gene therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. The MACHO Project Sample of Galactic Bulge High-Amplitude Scuti Stars: Pulsation Behavior and Stellar Properties

    International Nuclear Information System (INIS)

    Bennett, D.P.; Cook, K.H.; Freeman, K.C.; Geha, M.; Griest, K.; Lehner, M.J.; Marshall, S.L.; McNamara, B.J.; Minniti, D.; Nelson, C.; Peterson, B.A.; Popowski, P.; Pratt, M.R.; Quinn, P.J.; Rodgers, A.W.; Sutherland, W.; Templeton, M.R.; Vandehei, T.; Welch, D.L.

    1999-01-01

    We have detected 90 objects with periods and lightcurve structure similar to those of field(delta) Scuti stars, using the Massive Compact Halo Object (MACHO) Project database of Galactic bulge photometry. If we assume similar extinction values for all candidates and absolute magnitudes similar to those of other field high-amplitude(delta) Scuti stars (HADS), the majority of these objects lie in or near the Galactic bulge. At least two of these objects are likely foreground(delta) Scuti stars, one of which may be an evolved nonradial pulsator, similar to other evolved, disk-population(delta) Scuti stars. We have analyzed the light curves of these objects and find that they are similar to the light curves of field(delta) Scuti stars and the(delta) Scuti stars found by the Optical Gravitational Lens Experiment (OGLE). However, the amplitude distribution of these sources lies between those of low- and high-amplitude(delta) Scuti stars, which suggests that they may be an intermediate population. We have found nine double-mode HADS with frequency ratios ranging from 0.75 to 0.79, four probable double- and multiple-mode objects, and another four objects with marginal detections of secondary modes. The low frequencies (5-14 cycles d(sup -1)) and the observed period ratios of(approx)0.77 suggest that the majority of these objects are evolved stars pulsating in fundamental or first overtone radial modes

  3. The MACHO Project Sample of Galactic Bulge High-Amplitude {delta} Scuti Stars: Pulsation Behavior and Stellar Properties

    Energy Technology Data Exchange (ETDEWEB)

    Alcock, C.; Allsman, R. A.; Alves, D. R.; Axelrod, T. S.; Becker, A. C.; Bennett, D. P.; Cook, K. H.; Freeman, K. C.; Geha, M.; Griest, K. (and others)

    2000-06-20

    We have detected 90 objects with periods and light-curve structures similar to those of field {delta} Scuti stars using the Massive Compact Halo Object (MACHO) Project database of Galactic bulge photometry. If we assume similar extinction values for all candidates and absolute magnitudes similar to those of other field high-amplitude {delta} Scuti stars (HADS), the majority of these objects lie in or near the Galactic bulge. At least two of these objects are likely foreground {delta} Scuti stars, one of which may be an evolved nonradial pulsator, similar to other evolved, disk-population {delta} Scuti stars. We have analyzed the light curves of these objects and find that they are similar to the light curves of field {delta} Scuti stars and the {delta} Scuti stars found by the Optical Gravitational Lens Experiment (OGLE). However, the amplitude distribution of these sources lies between those of low- and high-amplitude {delta} Scuti stars, which suggests that they may be an intermediate population. We have found nine double-mode HADS with frequency ratios ranging from 0.75 to 0.79, four probable double- and multiple-mode objects, and another four objects with marginal detections of secondary modes. The low frequencies (5-14 cycles day-1) and the observed period ratios of {approx}0.77 suggest that the majority of these objects are evolved stars pulsating in fundamental or first overtone radial modes. (c) 2000 The American Astronomical Society.

  4. COEVOLUTION BETWEEN SUPERMASSIVE BLACK HOLES AND BULGES IS NOT VIA INTERNAL FEEDBACK REGULATION BUT BY RATIONED GAS SUPPLY DUE TO ANGULAR MOMENTUM DISTRIBUTION

    Energy Technology Data Exchange (ETDEWEB)

    Cen, Renyue, E-mail: cen@astro.princeton.edu [Princeton University Observatory, Princeton, NJ 08544 (United States)

    2015-05-20

    We reason that without physical fine-tuning, neither the supermassive black holes (SMBHs) nor the stellar bulges can self-regulate or inter-regulate by driving away already fallen cold gas to produce the observed correlation between them. We suggest an alternative scenario where the observed mass ratios of the SMBHs to bulges reflect the angular momentum distribution of infallen gas such that the mass reaching the stable accretion disk is a small fraction of that reaching the bulge region, averaged over the cosmological timescales. We test this scenario using high-resolution, large-scale cosmological hydrodynamic simulations, without active galactic nucleus (AGN) feedback, assuming the angular momentum distribution of gas landing in the bulge region yields a Mestel disk that is supported by independent simulations resolving the Bondi radii of SMBHs. A mass ratio of 0.1%–0.3% between the very low angular momentum gas that free falls to the subparsec region to accrete to the SMBH and the overall star formation rate is found. This ratio is found to increase with increasing redshift to within a factor of ∼2, suggesting that the SMBH-to-bulge ratio is nearly redshift independent, with a modest increase with redshift, which is a testable prediction. Furthermore, the duty cycle of AGNs with high Eddington ratios is expected to increase significantly with redshift. Finally, while SMBHs and bulges are found to coevolve on ∼30–150 Myr timescales or longer, there is indication that on still smaller timescales, the SMBH accretion and star formation may be less correlated.

  5. In vitro synthesis of minus-strand RNA by an isolated cereal yellow dwarf virus RNA-dependent RNA polymerase requires VPg and a stem-loop structure at the 3' end of the virus RNA.

    Science.gov (United States)

    Osman, Toba A M; Coutts, Robert H A; Buck, Kenneth W

    2006-11-01

    Cereal yellow dwarf virus (CYDV) RNA has a 5'-terminal genome-linked protein (VPg). We have expressed the VPg region of the CYDV genome in bacteria and used the purified protein (bVPg) to raise an antiserum which was able to detect free VPg in extracts of CYDV-infected oat plants. A template-dependent RNA-dependent RNA polymerase (RdRp) has been produced from a CYDV membrane-bound RNA polymerase by treatment with BAL 31 nuclease. The RdRp was template specific, being able to utilize templates from CYDV plus- and minus-strand RNAs but not those of three unrelated viruses, Red clover necrotic mosaic virus, Cucumber mosaic virus, and Tobacco mosaic virus. RNA synthesis catalyzed by the RdRp required a 3'-terminal GU sequence and the presence of bVPg. Additionally, synthesis of minus-strand RNA on a plus-strand RNA template required the presence of a putative stem-loop structure near the 3' terminus of CYDV RNA. The base-paired stem, a single-nucleotide (A) bulge in the stem, and the sequence of a tetraloop were all required for the template activity. Evidence was produced showing that minus-strand synthesis in vitro was initiated by priming by bVPg at the 3' end of the template. The data are consistent with a model in which the RdRp binds to the stem-loop structure which positions the active site to recognize the 3'-terminal GU sequence for initiation of RNA synthesis by the addition of an A residue to VPg.

  6. A Kinematic Link Between Boxy Bulges, Stellar Bars, and Nuclear Activity in NGC 3079 and NGC 4388

    Science.gov (United States)

    Veilleux, S.; Bland-Hawthrorn, J.; Cecil, Gerald

    1999-01-01

    We present direct kinematic evidence for bar streaming in two active galaxies with boxy stellar bulges. The Hawaii Imaging Fabry-Perot Interferometer was used on the Canada-France-Hawaii 3.6-m telescope and the University of Hawaii 2.2-m telescope to derive the two-dimensional velocity field of the line-emitting gas in the disks of the Sc galaxy NGC 3079 and the Sb galaxy NGC 4388. In contrast to previous work based on long-slit data, the detection of the bar potential from the Fabry-Perot data does not rely on the existence of inner Lindblad resonances or strong bar-induced shocks. Simple kinematic models which approximate the intrinsic gas orbits as nonintersecting, inclined elliptical annuli that conserve angular momentum characterize the observed velocity fields. In NGC 3079, bar streaming motions with moderately eccentric orbits (e = b/a approx. 0.7) aligned along PA = 130 deg. intrinsic to the disk (PA = 97 deg. on the sky) are detected out to R(sub b) = 3.6 kpc. The orbits become increasingly circular beyond that radius (e = 1 at R(sub d) approx. = 6 kpc). The best model for NGC 4388 includes highly eccentric orbits (e approx. 0.3) for R(sub) less than or equal to 1.5 kpc which are aligned along PA = 135 deg. intrinsic to the disk (PA = 100 deg. on the sky). The observed "spiral arms" are produced by having the orbits become increasingly circular from the ends of the bar to the edge of the disk (R(sub d) approx. = 5 kpc), and the intrinsic bar PA shifting from 135 deg. to 90 deg.. Box-shaped bulges in both NGC 3079 and NGC 4388 are confirmed using new near-infrared images to reduce dust obscuration. Morphological analysis of starlight in these galaxies is combined with the gas kinematics derived from the Fabry-Perot spectra to test evolutionary models of stellar bars that involve transitory boxy bulges, and to quantify the importance of such bars in fueling active nuclei. Our data support the evolutionary bar models, but fail to prove convincingly that the

  7. Identification of cis-acting elements on positive-strand subgenomic mRNA required for the synthesis of negative-strand counterpart in bovine coronavirus.

    Science.gov (United States)

    Yeh, Po-Yuan; Wu, Hung-Yi

    2014-07-30

    It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(-)-strand] complement. However, the cis-acting elements on the positive-strand [(+)-strand] sgmRNA required for (-)-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV) sgmRNA 7 required for the synthesis of its (-)-strand counterpart by deletion mutagenesis. The major findings are as follows. (1) Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (-)-strand sgmRNA complement. (2) Deletions of the 3' untranslated region (UTR) bulged stem-loop showed no effect on (-)-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (-)-strand sgmRNA. (3) Nucleotides positioned from -15 to -34 of the sgmRNA 7 3'-terminal region are required for efficient (-)-strand sgmRNA synthesis. (4) Nucleotide species at the 3'-most position (-1) of sgmRNA 7 is correlated to the efficiency of (-)-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (-)-strand sgmRNA synthesis in BCoV.

  8. Galaxy evolution. Evidence for mature bulges and an inside-out quenching phase 3 billion years after the Big Bang.

    Science.gov (United States)

    Tacchella, S; Carollo, C M; Renzini, A; Förster Schreiber, N M; Lang, P; Wuyts, S; Cresci, G; Dekel, A; Genzel, R; Lilly, S J; Mancini, C; Newman, S; Onodera, M; Shapley, A; Tacconi, L; Woo, J; Zamorani, G

    2015-04-17

    Most present-day galaxies with stellar masses ≥10(11) solar masses show no ongoing star formation and are dense spheroids. Ten billion years ago, similarly massive galaxies were typically forming stars at rates of hundreds solar masses per year. It is debated how star formation ceased, on which time scales, and how this "quenching" relates to the emergence of dense spheroids. We measured stellar mass and star-formation rate surface density distributions in star-forming galaxies at redshift 2.2 with ~1-kiloparsec resolution. We find that, in the most massive galaxies, star formation is quenched from the inside out, on time scales less than 1 billion years in the inner regions, up to a few billion years in the outer disks. These galaxies sustain high star-formation activity at large radii, while hosting fully grown and already quenched bulges in their cores. Copyright © 2015, American Association for the Advancement of Science.

  9. Understanding the extremely low fracture toughness of freestanding gold thin films by in-situ bulge testing in an AFM

    Energy Technology Data Exchange (ETDEWEB)

    Preiß, Eva I., E-mail: eva.preiss@fau.de; Merle, Benoit; Göken, Mathias

    2017-04-13

    The fracture toughness of freestanding gold films with thicknesses between 60 nm and 320 nm was determined by bulge testing to be around 2 MPa m{sup 1/2}. This surprisingly low value confirms the trend also observed for other metals that thin films exhibit only a fraction of the bulk fracture toughness. In order to understand this behavior, the fracture process of freestanding gold films with a crack introduced by focused ion beam (FIB) milling was observed in-situ in an atomic force microscope (AFM). AFM scans of the crack tip region show stable crack growth mainly along grain boundaries. Plastic deformation is localized in a narrow corridor in front of the crack tip. A large plastic zone, as one would typically expect under plane stress, is not observed. Instead, strong local necking is evidenced. We conclude that the spatial confinement of the plastic deformation is the primary reason for the low fracture toughness of metallic thin films.

  10. Velocity dispersions in the bulges of spiral and SO galaxies. II. Further observations and a simple three-component model for spiral galaxies

    International Nuclear Information System (INIS)

    Whitmore, B.C.; Kirshner, R.P.

    1981-01-01

    We have obtained velocity dispersions for 24 galaxies in the Virgo cluster to supplement our earlier results. A 2000 channel intensified Reticon scanner has again been used on the 1.3 m telescope of McGraw-Hill Observatory, and a Fourier quotient technique has been employed to yield dispersions. We have confirmed our earlier result that spiral bulges exhibit a relation between total luminosity and velocity dispersion with the form L proportional sigma 4 , but with velocity dispersions that are 17 +- 8% smaller than elliptical galaxies at the same absolute magnitude. However, possible systematic errors may still affect the reality of this gap. The scatter in the L proportional sigma 4 relationship is substantially larger for the spiral bulges than for the elliptical galaxies. This larger scatter probably indicates that spiral bulges comprise a more heterogeneous sample than do elliptical galaxies. we also find that the bulge components of SO galaxies follow a L proportional sigma 4 relation with no gap with the ellipticals. The similarity in this relation for the spheroidal components of spiral, SO, and elliptical galaxies indicates that the systems are dynamically similar

  11. INTEGRAL Galactic bulge monitoring observations of GRO J1750-27 (AX J1749.1-2639), H1743-322 and SLX 1746-331

    DEFF Research Database (Denmark)

    Kuulkers, E.; Beckmann, V.; Shaw, S.

    2008-01-01

    A new season of the INTEGRAL Galactic Bulge monitoring program (see ATels #438, #874, #1005; Kuulkers et al. 2007, A&A 466, 595) started, with observations on UT 11 Feb 2008, 16:33-18:07. We here report on results from three currently active transient sources. The IBIS/ISGRI and JEM-X1 images sho...

  12. Extracellular RNA Communication (ExRNA)

    Data.gov (United States)

    Federal Laboratory Consortium — Until recently, scientists believed RNA worked mostly inside the cell that produced it. Some types of RNA help translate genes into proteins that are necessary for...

  13. Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops.

    Science.gov (United States)

    Phan, Andy; Mailey, Katherine; Saeki, Jessica; Gu, Xiaobo; Schroeder, Susan J

    2017-05-01

    Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased toward small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with >6 nucleotides (nt) that occur frequently in viral RNA. This article presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Uracil and protonated cytosine base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with >6 nt are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2 × 2 have been measured. These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites. © 2017 Phan et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  14. Molecular archaeology of Flaviviridae untranslated regions: duplicated RNA structures in the replication enhancer of flaviviruses and pestiviruses emerged via convergent evolution.

    Directory of Open Access Journals (Sweden)

    Dmitri J Gritsun

    Full Text Available RNA secondary structures in the 3'untranslated regions (3'UTR of the viruses of the family Flaviviridae, previously identified as essential (promoters or beneficial (enhancers for replication, have been analysed. Duplicated enhancer elements are revealed as a global feature in the evolution of the 3'UTR of distantly related viruses within the genera Flavivirus and Pestivirus. For the flaviviruses, duplicated structures occur in the 3'UTR of all four distantly related ecological virus subgroups (tick-borne, mosquito-borne, no known vector and insect-specific flaviviruses (ISFV. RNA structural differences distinguish tick-borne flaviviruses with discrete pathogenetic characteristics. For Aedes- and Culex-associated ISFV, secondary RNA structures with different conformations display numerous short ssRNA direct repeats, exposed as loops and bulges. Long quadruplicate regions comprise almost the entire 3'UTR of Culex-associated ISFV. Extended duplicated sequence and associated RNA structures were also discovered in the 3'UTR of pestiviruses. In both the Flavivirus and Pestivirus genera, duplicated RNA structures were localized to the enhancer regions of the 3'UTR suggesting an adaptive role predominantly in wild-type viruses. We propose sequence reiteration might act as a scaffold for dimerization of proteins involved in assembly of viral replicase complexes. Numerous nucleotide repeats exposed as loops/bulges might also interfere with host immune responses acting as a molecular sponge to sequester key host proteins or microRNAs.

  15. Molecular Archaeology of Flaviviridae Untranslated Regions: Duplicated RNA Structures in the Replication Enhancer of Flaviviruses and Pestiviruses Emerged via Convergent Evolution

    Science.gov (United States)

    Gritsun, Dmitri J.; Jones, Ian M.; Gould, Ernest A.; Gritsun, Tamara S.

    2014-01-01

    RNA secondary structures in the 3′untranslated regions (3′UTR) of the viruses of the family Flaviviridae, previously identified as essential (promoters) or beneficial (enhancers) for replication, have been analysed. Duplicated enhancer elements are revealed as a global feature in the evolution of the 3′UTR of distantly related viruses within the genera Flavivirus and Pestivirus. For the flaviviruses, duplicated structures occur in the 3′UTR of all four distantly related ecological virus subgroups (tick-borne, mosquito-borne, no known vector and insect-specific flaviviruses (ISFV). RNA structural differences distinguish tick-borne flaviviruses with discrete pathogenetic characteristics. For Aedes- and Culex-associated ISFV, secondary RNA structures with different conformations display numerous short ssRNA direct repeats, exposed as loops and bulges. Long quadruplicate regions comprise almost the entire 3′UTR of Culex-associated ISFV. Extended duplicated sequence and associated RNA structures were also discovered in the 3′UTR of pestiviruses. In both the Flavivirus and Pestivirus genera, duplicated RNA structures were localized to the enhancer regions of the 3′UTR suggesting an adaptive role predominantly in wild-type viruses. We propose sequence reiteration might act as a scaffold for dimerization of proteins involved in assembly of viral replicase complexes. Numerous nucleotide repeats exposed as loops/bulges might also interfere with host immune responses acting as a molecular sponge to sequester key host proteins or microRNAs. PMID:24647143

  16. CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference.

    Science.gov (United States)

    Hochstrasser, Megan L; Taylor, David W; Bhat, Prashant; Guegler, Chantal K; Sternberg, Samuel H; Nogales, Eva; Doudna, Jennifer A

    2014-05-06

    In bacteria, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) DNA-targeting complex Cascade (CRISPR-associated complex for antiviral defense) uses CRISPR RNA (crRNA) guides to bind complementary DNA targets at sites adjacent to a trinucleotide signature sequence called the protospacer adjacent motif (PAM). The Cascade complex then recruits Cas3, a nuclease-helicase that catalyzes unwinding and cleavage of foreign double-stranded DNA (dsDNA) bearing a sequence matching that of the crRNA. Cascade comprises the CasA-E proteins and one crRNA, forming a structure that binds and unwinds dsDNA to form an R loop in which the target strand of the DNA base pairs with the 32-nt RNA guide sequence. Single-particle electron microscopy reconstructions of dsDNA-bound Cascade with and without Cas3 reveal that Cascade positions the PAM-proximal end of the DNA duplex at the CasA subunit and near the site of Cas3 association. The finding that the DNA target and Cas3 colocalize with CasA implicates this subunit in a key target-validation step during DNA interference. We show biochemically that base pairing of the PAM region is unnecessary for target binding but critical for Cas3-mediated degradation. In addition, the L1 loop of CasA, previously implicated in PAM recognition, is essential for Cas3 activation following target binding by Cascade. Together, these data show that the CasA subunit of Cascade functions as an essential partner of Cas3 by recognizing DNA target sites and positioning Cas3 adjacent to the PAM to ensure cleavage.

  17. Variations in ion and neutral composition at Venus - Evidence of solar control of the formation of the predawn bulges in H/+/ and He1

    Science.gov (United States)

    Taylor, H. A., Jr.; Mayr, H.; Brinton, H.; Niemann, H.; Hartle, R.; Daniell, R. E., Jr.

    1982-01-01

    A comparison of ion and neutral composition measurements at Venus for periods of greatly different solar activity provides qualitative evidence of solar control of the day-to-night transport of light ion and neutral species. Concentrations of H(+) and He in the predawn bulge near solar maximum in November, 1979, exhibit a depletion signature correlated with a pronounced modulation in the solar F10.7 and EUV fluxes. This perturbation, not observed in the predawn region during an earlier period of relative quiet solar conditions, is interpreted as resulting from pronounced changes in solar heating and photoionization on the dayside, which in turn modulate the transport of ions and neutrals into the bulge region.

  18. Study on dynamic buckling behavior of a cylindrical liquid storage tanks under seismic excitation. 1st report, effects of liquid pressure on elephant foot bulge

    International Nuclear Information System (INIS)

    Ito, Tomohiro; Morita, Hideyuki; Sugiyama, Akihisa; Kawamoto, Yoji; Sirai, Eiji; Ogo, Hideyasu

    2004-01-01

    When a thin walled cylindrical liquid storage tank is exposed to a very large seismic base excitation, buckling phenomena may be caused such as bending buckling where diamond buckling pattern or elephant foot bulge pattern will be found at the bottom portion, and shear buckling at the middle portion of the tank. In this study, dynamic buckling tests were performed using scale models of thin cylindrical liquid storage tanks for the nuclear power plants. The input seismic acceleration was increased until the elephant foot bulge occurred and the vibrational behavior before and after buckling was investigated. And the effects of static and dynamic liquid pressure on the bending buckling patterns and the buckling critical force was investigated by fundamental tests using small tank models. (author)

  19. Study with the sigma data base of the galactic bulge hard x-ray and gamma-ray sources

    International Nuclear Information System (INIS)

    Vargas, Marielle

    1997-01-01

    The Sigma coded-mask telescope on board the Granat spacecraft produces sky images in the hard X-ray and soft gamma-ray energy domain (30-1300 keV) with an angular resolution of 15 arc minutes. The observations of the 18 Angstroms x 17 Angstroms region around the Galactic Center, performed with Sigma regularly during seven years, allowed the detection of a cluster of 17 sources showing activity beyond 40 ke V. This cluster is identified with the Galactic Bulge and its core coincides with the Galactic Center. Each of these sources reveals matter accretion by a collapse star in binary system. Its nature is determined by the luminosity and the spectral behavior recorded beyond 40 keV. Three accreting black holes show peculiar transient activities and comparable flare luminosities providing a criterion to evaluate distance of other specimens located elsewhere in the Galaxy. No sign of activity has been detected from the very center of the Galaxy where a supermassive black hole would be placed and would accrete the surrounding matter. (author) [fr

  20. Chemical evolution of the Galactic bulge as traced by microlensed dwarf and subgiant stars. Detailed abundance analysis of OGLE-2008-BLG-209S

    OpenAIRE

    Bensby, T.; Johnson, J. A.; Cohen, J.; Feltzing, S.; Udalski, A.; Gould, A.; Huang, W.; Thompson, I.; Simmerer, J.; Adén, D.

    2009-01-01

    AIMS. Our aims are twofold. First we aim to evaluate the robustness and accuracy of stellar parameters and detailed elemental abundances that can be derived from high-resolution spectroscopic observations of microlensed dwarf and subgiant stars. We then aim to use microlensed dwarf and subgiant stars to investigate the abundance structure and chemical evolution of the Milky Way Bulge. [ABRIDGED] METHODS. We present a detailed elemental abundance analysis of OGLE-2008-BLG-209S, the source star...

  1. The panchromatic Hubble Andromeda treasury. VII. The steep mid-ultraviolet to near-infrared extinction curve in the central 200 pc of the M31 Bulge

    International Nuclear Information System (INIS)

    Dong, Hui; Lauer, Tod R.; Olsen, Knut; Saha, Abhijit; Li, Zhiyuan; Wang, Q. D.; Dalcanton, Julianne; Fouesneau, Morgan; Gordon, Karl; Bell, Eric; Bianchi, Luciana

    2014-01-01

    We measure the extinction curve in the central 200 pc of M31 at mid-ultraviolet to near-infrared wavelengths (from 1928 Å to 1.5 μm), using Swift/UVOT and Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3)/Advanced Camera for Surveys (ACS) observations in 13 bands. Taking advantage of the high angular resolution of the HST/WFC3 and ACS detectors, we develop a method to simultaneously determine the relative extinction and the fraction of obscured starlight for five dusty complexes located in the circumnuclear region. The extinction curves of these clumps (R V = 2.4-2.5) are steeper than the average Galactic one (R V = 3.1), but are similar to optical and near-infrared curves recently measured toward the Galactic bulge (R V ∼ 2.5). This similarity suggests that steep extinction curves may be common in the inner bulge of galaxies. In the ultraviolet, the extinction curves of these clumps are also unusual. We find that one dusty clump (size < 2 pc) exhibits a strong UV bump (extinction at 2175 Å), more than three standard deviation higher than that predicted by common models. Although the high stellar metallicity of the M31 bulge indicates that there are sufficient carbon and silicon to produce large dust grains, the grains may have been destroyed by supernova explosions or past activity of the central supermassive black hole, resulting in the observed steepened extinction curve.

  2. The panchromatic Hubble Andromeda treasury. VII. The steep mid-ultraviolet to near-infrared extinction curve in the central 200 pc of the M31 Bulge

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Hui; Lauer, Tod R.; Olsen, Knut; Saha, Abhijit [National Optical Astronomy Observatory, Tucson, AZ 85719 (United States); Li, Zhiyuan [School of Astronomy and Space Science, Nanjing University, Nanjing 210093 (China); Wang, Q. D. [Department of Astronomy, University of Massachusetts, Amherst, MA 01003 (United States); Dalcanton, Julianne; Fouesneau, Morgan [Astronomy Department, University of Washington, Seattle, WA 98195 (United States); Gordon, Karl [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Bell, Eric [Department of Astronomy, University of Michigan, Ann Arbor, MI 48109 (United States); Bianchi, Luciana, E-mail: hdong@noao.edu [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States)

    2014-04-20

    We measure the extinction curve in the central 200 pc of M31 at mid-ultraviolet to near-infrared wavelengths (from 1928 Å to 1.5 μm), using Swift/UVOT and Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3)/Advanced Camera for Surveys (ACS) observations in 13 bands. Taking advantage of the high angular resolution of the HST/WFC3 and ACS detectors, we develop a method to simultaneously determine the relative extinction and the fraction of obscured starlight for five dusty complexes located in the circumnuclear region. The extinction curves of these clumps (R{sub V} = 2.4-2.5) are steeper than the average Galactic one (R{sub V} = 3.1), but are similar to optical and near-infrared curves recently measured toward the Galactic bulge (R{sub V} ∼ 2.5). This similarity suggests that steep extinction curves may be common in the inner bulge of galaxies. In the ultraviolet, the extinction curves of these clumps are also unusual. We find that one dusty clump (size < 2 pc) exhibits a strong UV bump (extinction at 2175 Å), more than three standard deviation higher than that predicted by common models. Although the high stellar metallicity of the M31 bulge indicates that there are sufficient carbon and silicon to produce large dust grains, the grains may have been destroyed by supernova explosions or past activity of the central supermassive black hole, resulting in the observed steepened extinction curve.

  3. Normal black holes in bulge-less galaxies: the largely quiescent, merger-free growth of black holes over cosmic time

    Science.gov (United States)

    Martin, G.; Kaviraj, S.; Volonteri, M.; Simmons, B. D.; Devriendt, J. E. G.; Lintott, C. J.; Smethurst, R. J.; Dubois, Y.; Pichon, C.

    2018-05-01

    Understanding the processes that drive the formation of black holes (BHs) is a key topic in observational cosmology. While the observed MBH-MBulge correlation in bulge-dominated galaxies is thought to be produced by major mergers, the existence of an MBH-M⋆ relation, across all galaxy morphological types, suggests that BHs may be largely built by secular processes. Recent evidence that bulge-less galaxies, which are unlikely to have had significant mergers, are offset from the MBH-MBulge relation, but lie on the MBH-M⋆ relation, has strengthened this hypothesis. Nevertheless, the small size and heterogeneity of current data sets, coupled with the difficulty in measuring precise BH masses, make it challenging to address this issue using empirical studies alone. Here, we use Horizon-AGN, a cosmological hydrodynamical simulation to probe the role of mergers in BH growth over cosmic time. We show that (1) as suggested by observations, simulated bulge-less galaxies lie offset from the main MBH-MBulge relation, but on the MBH-M⋆ relation, (2) the positions of galaxies on the MBH-M⋆ relation are not affected by their merger histories, and (3) only ˜35 per cent of the BH mass in today's massive galaxies is directly attributable to merging - the majority (˜65 per cent) of BH growth, therefore, takes place gradually, via secular processes, over cosmic time.

  4. Combinatorics of RNA-RNA interaction

    DEFF Research Database (Denmark)

    Li, Thomas J X; Reidys, Christian

    2012-01-01

    RNA-RNA binding is an important phenomenon observed for many classes of non-coding RNAs and plays a crucial role in a number of regulatory processes. Recently several MFE folding algorithms for predicting the joint structure of two interacting RNA molecules have been proposed. Here joint structure...... means that in a diagram representation the intramolecular bonds of each partner are pseudoknot-free, that the intermolecular binding pairs are noncrossing, and that there is no so-called "zigzag" configuration. This paper presents the combinatorics of RNA interaction structures including...

  5. Methylation-mediated deamination of 5-methylcytosine appears to give rise to mutations causing human inherited disease in CpNpG trinucleotides, as well as in CpG dinucleotides

    Directory of Open Access Journals (Sweden)

    Cooper David N

    2010-08-01

    Full Text Available Abstract The cytosine-guanine (CpG dinucleotide has long been known to be a hotspot for pathological mutation in the human genome. This hypermutability is related to its role as the major site of cytosine methylation with the attendant risk of spontaneous deamination of 5-methylcytosine (5mC to yield thymine. Cytosine methylation, however, also occurs in the context of CpNpG sites in the human genome, an unsurprising finding since the intrinsic symmetry of CpNpG renders it capable of supporting a semi-conservative model of replication of the methylation pattern. Recently, it has become clear that significant DNA methylation occurs in a CpHpG context (where H = A, C or T in a variety of human somatic tissues. If we assume that CpHpG methylation also occurs in the germline, and that 5mC deamination can occur within a CpHpG context, then we might surmise that methylated CpHpG sites could also constitute mutation hotspots causing human genetic disease. To test this postulate, 54,625 missense and nonsense mutations from 2,113 genes causing inherited disease were retrieved from the Human Gene Mutation Database http://www.hgmd.org. Some 18.2 per cent of these pathological lesions were found to be C → T and G → A transitions located in CpG dinucleotides (compatible with a model of methylation-mediated deamination of 5mC, an approximately ten-fold higher proportion than would have been expected by chance alone. The corresponding proportion for the CpHpG trinucleotide was 9.9 per cent, an approximately two-fold higher proportion than would have been expected by chance. We therefore estimate that ~5 per cent of missense/nonsense mutations causing human inherited disease may be attributable to methylation-mediated deamination of 5mC within a CpHpG context.

  6. Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy.

    Science.gov (United States)

    Hu, Jiaxin; Rong, Ziye; Gong, Xin; Zhou, Zhengyang; Sharma, Vivek K; Xing, Chao; Watts, Jonathan K; Corey, David R; Mootha, V Vinod

    2018-03-15

    Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has ∼2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.

  7. Extrapolative microRNA precursor based SSR mining from tea EST database in respect to agronomic traits.

    Science.gov (United States)

    Hazra, Anjan; Dasgupta, Nirjhar; Sengupta, Chandan; Das, Sauren

    2017-07-06

    Tea (Camellia sinensis, (L.) Kuntze) is considered as most popular drink across the world and it is widely consumed beverage for its several health-benefit characteristics. These positive traits primarily rely on its regulatory networks of different metabolic pathways. Development of microsatellite markers from the conserved genomic regions are being worthwhile for reviewing the genetic diversity of closely related species or self-pollinated species. Although several SSR markers have been reported, in tea, the trait-specific Simple Sequence Repeat (SSR) markers, leading to be useful in marker assisted breeding technique, are yet to be identified. Micro RNAs are short, non-coding RNA molecules, involved in post transcriptional mode of gene regulation and thus effects on related phenotype. Present study deals with identification of the microsatellite motifs within the reported and predicted miRNA precursors that are effectively followed by designing of primers from SSR flanking regions in order to PCR validation. In addition to the earlier reports, two new miRNAs are predicting here from tea expressed tag sequence database. Furthermore, 18 SSR motifs are found to be in 13 of all 33 predicted miRNAs. Trinucleotide motifs are most abundant among all followed by dinucleotides. Since, miRNA based SSR markers are evidenced to have significant role on genetic fingerprinting study, these outcomes would pave the way in developing novel markers for tagging tea specific agronomic traits as well as substantiating non-conventional breeding program.

  8. REDDENING AND EXTINCTION TOWARD THE GALACTIC BULGE FROM OGLE-III: THE INNER MILKY WAY'S R{sub V} {approx} 2.5 EXTINCTION CURVE

    Energy Technology Data Exchange (ETDEWEB)

    Nataf, David M.; Gould, Andrew; Johnson, Jennifer A.; Skowron, Jan [Department of Astronomy, Ohio State University, 140 W. 18th Ave., Columbus, OH 43210 (United States); Fouque, Pascal [Universite de Toulouse, UPS-OMP, IRAP, Toulouse (France); Gonzalez, Oscar A. [European Southern Observatory, Karl-Schwarzschild-Strasse 2, D-85748 Garching (Germany); Udalski, Andrzej; Szymanski, Michal K.; Kubiak, Marcin; Pietrzynski, Grzegorz; Soszynski, Igor; Ulaczyk, Krzysztof; Wyrzykowski, Lukasz; Poleski, Radoslaw, E-mail: nataf@astronomy.ohio-state.edu [Warsaw University Observatory, Al. Ujazdowskie 4, 00-478 Warszawa (Poland)

    2013-06-01

    We combine VI photometry from OGLE-III with VISTA Variables in The Via Lactea survey and Two Micron All Sky Survey measurements of E(J - K{sub s} ) to resolve the longstanding problem of the non-standard optical extinction toward the Galactic bulge. We show that the extinction is well fit by the relation A{sub I} = 0.7465 Multiplication-Sign E(V - I) + 1.3700 Multiplication-Sign E(J - K{sub s} ), or, equivalently, A{sub I} = 1.217 Multiplication-Sign E(V - I)(1 + 1.126 Multiplication-Sign (E(J - K{sub s} )/E(V - I) - 0.3433)). The optical and near-IR reddening law toward the inner Galaxy approximately follows an R{sub V} Almost-Equal-To 2.5 extinction curve with a dispersion {sigma}{sub R{sub V}}{approx}0.2, consistent with extragalactic investigations of the hosts of Type Ia SNe. Differential reddening is shown to be significant on scales as small as our mean field size of 6'. The intrinsic luminosity parameters of the Galactic bulge red clump (RC) are derived to be (M{sub I,RC},{sigma}{sub I,RC,0}, (V-I){sub RC,0},{sigma}{sub (V-I){sub R{sub C}}}, (J-K{sub s}){sub RC,0}) = (-0.12, 0.09, 1.06, 0.121, 0.66). Our measurements of the RC brightness, brightness dispersion, and number counts allow us to estimate several Galactic bulge structural parameters. We estimate a distance to the Galactic center of 8.20 kpc. We measure an upper bound on the tilt {alpha} Almost-Equal-To 40 Degree-Sign between the bulge's major axis and the Sun-Galactic center line of sight, though our brightness peaks are consistent with predictions of an N-body model oriented at {alpha} Almost-Equal-To 25 Degree-Sign . The number of RC stars suggests a total stellar mass for the Galactic bulge of {approx}2.3 Multiplication-Sign 10{sup 10} M{sub Sun} if one assumes a canonical Salpeter initial mass function (IMF), or {approx}1.6 Multiplication-Sign 10{sup 10} M{sub Sun} if one assumes a bottom-light Zoccali IMF.

  9. Genome-Wide Development of MicroRNA-Based SSR Markers in Medicago truncatula with Their Transferability Analysis and Utilization in Related Legume Species.

    Science.gov (United States)

    Min, Xueyang; Zhang, Zhengshe; Liu, Yisong; Wei, Xingyi; Liu, Zhipeng; Wang, Yanrong; Liu, Wenxian

    2017-11-18

    Microsatellite (simple sequence repeats, SSRs) marker is one of the most widely used markers in marker-assisted breeding. As one type of functional markers, MicroRNA-based SSR (miRNA-SSR) markers have been exploited mainly in animals, but the development and characterization of miRNA-SSR markers in plants are still limited. In the present study, miRNA-SSR markers for Medicago truncatula ( M. truncatula ) were developed and their cross-species transferability in six leguminous species was evaluated. A total of 169 primer pairs were successfully designed from 130 M. truncatula miRNA genes, the majority of which were mononucleotide repeats (70.41%), followed by dinucleotide repeats (14.20%), compound repeats (11.24%) and trinucleotide repeats (4.14%). Functional classification of SSR-containing miRNA genes showed that all targets could be grouped into three Gene Ontology (GO) categories: 17 in biological process, 11 in molecular function, and 14 in cellular component. The miRNA-SSR markers showed high transferability in other six leguminous species, ranged from 74.56% to 90.53%. Furthermore, 25 Mt - miRNA-SSR markers were used to evaluate polymorphisms in 20 alfalfa accessions, and the polymorphism information content (PIC) values ranged from 0.39 to 0.89 with an average of 0.71, the allele number per marker varied from 3 to 18 with an average of 7.88, indicating a high level of informativeness. The present study is the first time developed and characterized of M. truncatula miRNA-SSRs and demonstrated their utility in transferability, these novel markers will be valuable for genetic diversity analysis, marker-assisted selection and genotyping in leguminous species.

  10. Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures

    Science.gov (United States)

    Sloma, Michael F.; Mathews, David H.

    2016-01-01

    RNA secondary structure prediction is widely used to analyze RNA sequences. In an RNA partition function calculation, free energy nearest neighbor parameters are used in a dynamic programming algorithm to estimate statistical properties of the secondary structure ensemble. Previously, partition functions have largely been used to estimate the probability that a given pair of nucleotides form a base pair, the conditional stacking probability, the accessibility to binding of a continuous stretch of nucleotides, or a representative sample of RNA structures. Here it is demonstrated that an RNA partition function can also be used to calculate the exact probability of formation of hairpin loops, internal loops, bulge loops, or multibranch loops at a given position. This calculation can also be used to estimate the probability of formation of specific helices. Benchmarking on a set of RNA sequences with known secondary structures indicated that loops that were calculated to be more probable were more likely to be present in the known structure than less probable loops. Furthermore, highly probable loops are more likely to be in the known structure than the set of loops predicted in the lowest free energy structures. PMID:27852924

  11. New insights into the promoterless transcription of DNA coligo templates by RNA polymerase III.

    Science.gov (United States)

    Lama, Lodoe; Seidl, Christine I; Ryan, Kevin

    2014-01-01

    Chemically synthesized DNA can carry small RNA sequence information but converting that information into small RNA is generally thought to require large double-stranded promoters in the context of plasmids, viruses and genes. We previously found evidence that circularized oligodeoxynucleotides (coligos) containing certain sequences and secondary structures can template the synthesis of small RNA by RNA polymerase III in vitro and in human cells. By using immunoprecipitated RNA polymerase III we now report corroborating evidence that this enzyme is the sole polymerase responsible for coligo transcription. The immobilized polymerase enabled experiments showing that coligo transcripts can be formed through transcription termination without subsequent 3' end trimming. To better define the determinants of productive transcription, a structure-activity relationship study was performed using over 20 new coligos. The results show that unpaired nucleotides in the coligo stem facilitate circumtranscription, but also that internal loops and bulges should be kept small to avoid secondary transcription initiation sites. A polymerase termination sequence embedded in the double-stranded region of a hairpin-encoding coligo stem can antagonize transcription. Using lessons learned from new and old coligos, we demonstrate how to convert poorly transcribed coligos into productive templates. Our findings support the possibility that coligos may prove useful as chemically synthesized vectors for the ectopic expression of small RNA in human cells.

  12. Nuclear planetology: understanding habitable planets as Galactic bulge stellar remnants (black dwarfs) in a Hertzsprung-Russell (HR) diagram

    Science.gov (United States)

    Roller, Goetz

    2016-04-01

    model constraining the evolution of a rocky planet like Earth or Mercury from a stellar precursor of the oldest population to a Fe-C BLD, shifting through different spectral classes in a HR diagram after massive decompression and tremendous energy losses. In the light of WD/BLD cosmochronology [1], solar system bodies like Earth, Mercury and Moon are regarded as captured interlopers from the Galactic bulge, Earth and Moon possibly representing remnants of an old binary system. Such a preliminary scenario is supported by similar ages obtained from WD's for the Galactic halo [1] and, independently, by means of 187Re-232Th-238U nuclear geochronometry [2, 4, 5], together with recent observations extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way [6]. This might be further elucidated in the near future by Th/U cosmochronometry based upon a nuclear production ratio Th/U = 0.96 [5] and additionally by means of a newly developed nucleogeochronometric age dating method for stellar spectroscopy, which will be presented in a forthcoming paper. The model shall stimulate geochemical data interpretation from a different perspective to constrain the (thermal) evolution of a habitable planet as to its geo-, bio-, hydro- and atmosphere. [1] Fontaine et al. (2001), Public. Astron. Soc. of the Pacific 113, 409-435. [2] Roller (2015), Abstract T34B-0407, AGU Spring Meeting 2015. [3] Arevalo et al. (2010), Chem. Geol. 271, 70-85. [4] Roller (2015), Geophys. Res. Abstr. 17, EGU2015-2399. [5] Roller (2015), 78th Annu. Meeting Met. Soc., Abstract #5041. [6] Howes et al. (2015), Nature 527, 484-487.

  13. Factors associated with delivery at or after 28 weeks gestation in women with bulging fetal membranes before 26 weeks gestation.

    Science.gov (United States)

    Ito, Akiko; Maseki, Yoshiaki; Ikeda, Sayako; Tezuka, Atsuko; Kuribayashi, Momoko; Furuhashi, Madoka

    2017-09-01

    To elucidate the factors that contribute to prolonged pregnancy and promote neonate survival in women with bulging fetal membranes. A database was reviewed to identify women with singleton pregnancies who underwent amniocentesis on admission to determine amniotic fluid neutrophil elastase levels before 26 + 0 weeks gestation between July 2001 and January 2015. Following delivery, the placentas of these patients were examined for histologic chorioamnionitis. Ninety-seven women delivered before 28 weeks gestation, and 117 women delivered at or after 28 weeks gestation. Rescue cerclage performed via the McDonald procedure (adjusted odds ratio [aOR]: 3.78; 95% confidence interval [CI]: 1.35-11.80) was associated with a higher likelihood of reaching at least 28 weeks gestation before delivery, whereas protruding membranes (aOR: 0.38; 95% CI: 0.18-0.78), elevated amniotic neutrophil elastase levels (≥0.15 μg/ml) (aOR, 0.41; 95% CI: 0.20-0.82) and elevated peripheral C-reactive protein levels (≥0.4 mg/dl) (aOR: 0.34; 95% CI: 0.180.65) were associated with a significantly reduced likelihood of reaching this gestational age before delivery. Among women who underwent rescue cerclage, amniorrhexis was associated with a negative prognosis (aOR: 0.18; 95% CI: 0.05-0.51). Intra-amniotic inflammation, protrusion of fetal membranes and amniorrhexis are factors that may prevent pregnancy prolongation. Rescue cerclage improves pregnancy outcomes.

  14. Turn stability in beta-hairpin peptides: Investigation of peptides containing 3:5 type I G1 bulge turns.

    Science.gov (United States)

    Blandl, Tamas; Cochran, Andrea G; Skelton, Nicholas J

    2003-02-01

    The turn-forming ability of a series of three-residue sequences was investigated by substituting them into a well-characterized beta-hairpin peptide. The starting scaffold, bhpW, is a disulfide-cyclized 10-residue peptide that folds into a stable beta-hairpin with two antiparallel strands connected by a two-residue reverse turn. Substitution of the central two residues with the three-residue test sequences leads to less stable hairpins, as judged by thiol-disulfide equilibrium measurements. However, analysis of NMR parameters indicated that each molecule retains a significant folded population, and that the type of turn adopted by the three-residue sequence is the same in all cases. The solution structure of a selected peptide with a PDG turn contained an antiparallel beta-hairpin with a 3:5 type I + G1 bulge turn. Analysis of the energetic contributions of individual turn residues in the series of peptides indicates that substitution effects have significant context dependence, limiting the predictive power of individual amino acid propensities for turn formation. The most stable and least stable sequences were also substituted into a more stable disulfide-cyclized scaffold and a linear beta-hairpin scaffold. The relative stabilities remained the same, suggesting that experimental measurements in the bhpW context are a useful way to evaluate turn stability for use in protein design projects. Moreover, these scaffolds are capable of displaying a diverse set of turns, which can be exploited for the mimicry of protein loops or for generating libraries of reverse turns.

  15. Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants.

    Directory of Open Access Journals (Sweden)

    Timo Schomann

    Full Text Available Stem-cell-based repair of auditory neurons may represent an attractive therapeutic option to restore sensorineural hearing loss. Hair-follicle-bulge-derived stem cells (HFBSCs are promising candidates for this type of therapy, because they (1 have migratory properties, enabling migration after transplantation, (2 can differentiate into sensory neurons and glial cells, and (3 can easily be harvested in relatively high numbers. However, HFBSCs have never been used for this purpose. We hypothesized that HFBSCs can be used for cell-based repair of the auditory nerve and we have examined their migration and incorporation into cochlear modiolus explants and their subsequent differentiation. Modiolus explants obtained from adult wild-type mice were cultured in the presence of EF1α-copGFP-transduced HFBSCs, constitutively expressing copepod green fluorescent protein (copGFP. Also, modiolus explants without hair cells were co-cultured with DCX-copGFP-transduced HFBSCs, which demonstrate copGFP upon doublecortin expression during neuronal differentiation. Velocity of HFBSC migration towards modiolus explants was calculated, and after two weeks, co-cultures were fixed and processed for immunohistochemical staining. EF1α-copGFP HFBSC migration velocity was fast: 80.5 ± 6.1 μm/h. After arrival in the explant, the cells formed a fascicular pattern and changed their phenotype into an ATOH1-positive neuronal cell type. DCX-copGFP HFBSCs became green-fluorescent after integration into the explants, confirming neuronal differentiation of the cells. These results show that HFBSC-derived neuronal progenitors are migratory and can integrate into cochlear modiolus explants, while adapting their phenotype depending on this micro-environment. Thus, HFBSCs show potential to be employed in cell-based therapies for auditory nerve repair.

  16. RNA modifications by oxidation

    DEFF Research Database (Denmark)

    Poulsen, Henrik E; Specht, Elisabeth; Broedbaek, Kasper

    2012-01-01

    to encompass various classes of novel regulatory RNAs, including, e.g., microRNAs. It is well known that DNA is constantly oxidized and repaired by complex genome maintenance mechanisms. Analogously, RNA also undergoes significant oxidation, and there are now convincing data suggesting that oxidation......The past decade has provided exciting insights into a novel class of central (small) RNA molecules intimately involved in gene regulation. Only a small percentage of our DNA is translated into proteins by mRNA, yet 80% or more of the DNA is transcribed into RNA, and this RNA has been found......, and the consequent loss of integrity of RNA, is a mechanism for disease development. Oxidized RNA is found in a large variety of diseases, and interest has been especially devoted to degenerative brain diseases such as Alzheimer disease, in which up to 50-70% of specific mRNA molecules are reported oxidized, whereas...

  17. Working with RNA

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    Working with RNA is not a special discipline in molecular biology. However, RNA is chemically and structurally different from DNA and a few simple work rules have to be implemented to maintain the integrity of the RNA. Alkaline pH, high temperatures, and heavy metal ions should be avoided when po...

  18. Molecular recognition of pyr mRNA by the Bacillus subtilis attenuation regulatory protein PyrR

    Science.gov (United States)

    Bonner, Eric R.; D’Elia, John N.; Billips, Benjamin K.; Switzer, Robert L.

    2001-01-01

    The pyrimidine nucleotide biosynthesis (pyr) operon in Bacillus subtilis is regulated by transcriptional attenuation. The PyrR protein binds in a uridine nucleotide-dependent manner to three attenuation sites at the 5′-end of pyr mRNA. PyrR binds an RNA-binding loop, allowing a terminator hairpin to form and repressing the downstream genes. The binding of PyrR to defined RNA molecules was characterized by a gel mobility shift assay. Titration indicated that PyrR binds RNA in an equimolar ratio. PyrR bound more tightly to the binding loops from the second (BL2 RNA) and third (BL3 RNA) attenuation sites than to the binding loop from the first (BL1 RNA) attenuation site. PyrR bound BL2 RNA 4–5-fold tighter in the presence of saturating UMP or UDP and 150- fold tighter with saturating UTP, suggesting that UTP is the more important co-regulator. The minimal RNA that bound tightly to PyrR was 28 nt long. Thirty-one structural variants of BL2 RNA were tested for PyrR binding affinity. Two highly conserved regions of the RNA, the terminal loop and top of the upper stem and a purine-rich internal bulge and the base pairs below it, were crucial for tight binding. Conserved elements of RNA secondary structure were also required for tight binding. PyrR protected conserved areas of the binding loop in hydroxyl radical footprinting experiments. PyrR likely recognizes conserved RNA sequences, but only if they are properly positioned in the correct secondary structure. PMID:11726695

  19. Large scale comparative codon-pair context analysis unveils general rules that fine-tune evolution of mRNA primary structure.

    Directory of Open Access Journals (Sweden)

    Gabriela Moura

    Full Text Available BACKGROUND: Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. METHODOLOGIES/PRINCIPAL FINDINGS: We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. CONCLUSIONS: The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage.

  20. Methods for RNA Analysis

    DEFF Research Database (Denmark)

    Olivarius, Signe

    of the transcriptome, 5’ end capture of RNA is combined with next-generation sequencing for high-throughput quantitative assessment of transcription start sites by two different methods. The methods presented here allow for functional investigation of coding as well as noncoding RNA and contribute to future...... RNAs rely on interactions with proteins, the establishment of protein-binding profiles is essential for the characterization of RNAs. Aiming to facilitate RNA analysis, this thesis introduces proteomics- as well as transcriptomics-based methods for the functional characterization of RNA. First, RNA...

  1. Cytoplasmic Z-RNA

    International Nuclear Information System (INIS)

    Zarling, D.A.; Calhoun, C.J.; Hardin, C.C.; Zarling, A.H.

    1987-01-01

    Specific immunochemical probes for Z-RNA were generated and characterized to search for possible Z-RNA-like double helices in cells. Z-RNA was detected in the cytoplasm of fixed protozoan cells by immunofluorescence microscopy using these anti-Z-RNA IgCs. In contrast, autoimmune or experimentally elicited anti-DNA antibodies, specifically reactive with B-DNA or Z-DNA, stained the nuclei. Pre-or nonimmune IgGs did not bind to the cells. RNase A or T1 digestion eliminated anti-Z-RNA IgG binding to cytoplasmic determinants; however, DNase I or mung bean nuclease had no effect. Doxorubicin and ethidium bromide prevented anti-Z-RNA antibody binding; however, actinomycin D, which does not bind double-stranded RNA, did not. Anti-Z-RNA immunofluorescence was specifically blocked in competition assays by synthetic Z-RNA but not Z-DNA, A-RNA, or single-stranded RNAs. Thus, some cytoplasmic sequences in fixed cells exist in the left-handed Z-RNA conformation

  2. Analyses of a whole-genome inter-clade recombination map of hepatitis delta virus suggest a host polymerase-driven and viral RNA structure-promoted template-switching mechanism for viral RNA recombination

    Science.gov (United States)

    Chao, Mei; Wang, Tzu-Chi; Lin, Chia-Chi; Yung-Liang Wang, Robert; Lin, Wen-Bin; Lee, Shang-En; Cheng, Ying-Yu; Yeh, Chau-Ting; Iang, Shan-Bei

    2017-01-01

    The genome of hepatitis delta virus (HDV) is a 1.7-kb single-stranded circular RNA that folds into an unbranched rod-like structure and has ribozyme activity. HDV redirects host RNA polymerase(s) (RNAP) to perform viral RNA-directed RNA transcription. RNA recombination is known to contribute to the genetic heterogeneity of HDV, but its molecular mechanism is poorly understood. Here, we established a whole-genome HDV-1/HDV-4 recombination map using two cloned sequences coexisting in cultured cells. Our functional analyses of the resulting chimeric delta antigens (the only viral-encoded protein) and recombinant genomes provide insights into how recombination promotes the genotypic and phenotypic diversity of HDV. Our examination of crossover distribution and subsequent mutagenesis analyses demonstrated that ribozyme activity on HDV genome, which is required for viral replication, also contributes to the generation of an inter-clade junction. These data provide circumstantial evidence supporting our contention that HDV RNA recombination occurs via a replication-dependent mechanism. Furthermore, we identify an intrinsic asymmetric bulge on the HDV genome, which appears to promote recombination events in the vicinity. We therefore propose a mammalian RNAP-driven and viral-RNA-structure-promoted template-switching mechanism for HDV genetic recombination. The present findings improve our understanding of the capacities of the host RNAP beyond typical DNA-directed transcription. PMID:28977829

  3. Evolution of the RNase P RNA structural domain in Leptospira spp.

    Science.gov (United States)

    Ravishankar, Vigneshwaran; Ahmed, Ahmed; Sivagnanam, Ulaganathan; Muthuraman, Krishnaraja; Karthikaichamy, Anbarasu; Wilson, Herald A; Devendran, Ajay; Hartskeerl, Rudy A; Raj, Stephen M L

    2014-12-01

    We have employed the RNase P RNA (RPR) gene, which is present as single copy in chromosome I of Leptospira spp. to investigate the phylogeny of structural domains present in the RNA subunit of the tRNA processing enzyme, RNase P. RPR gene sequences of 150 strains derived from NCBI database along with sequences determined from 8 reference strains were examined to fathom strain specific structural differences present in leptospiral RPR. Sequence variations in the RPR gene impacted on the configuration of loops, stems and bulges found in the RPR highlighting species and strain specific structural motifs. In vitro transcribed leptospiral RPR ribozymes are demonstrated to process pre-tRNA into mature tRNA in consonance with the positioning of Leptospira in the taxonomic domain of bacteria. RPR sequence datasets used to construct a phylogenetic tree exemplified the segregation of strains into their respective lineages with a (re)speciation of strain SH 9 to Leptospira borgpetersenii, strains Fiocruz LV 3954 and Fiocruz LV 4135 to Leptospira santarosai, strain CBC 613 to Leptospira kirschneri and strain HAI 1536 to Leptospira noguchii. Furthermore, it allowed characterization of an isolate P2653, presumptively characterized as either serovar Hebdomadis, Kremastos or Longnan to Leptospira weilii, serovar Longnan. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  4. Effect of disulfide and sulfhydryl reagents on abortive and productive elongation catalyzed by ''Escheridia coli'' RNA polymerase

    International Nuclear Information System (INIS)

    Radlowski, M.; Job, D.

    1994-01-01

    The effect of disulfide and sulfhydryl reagents on the rate of abortive and productive elongation has been studied using ''Escherichia coli'' RNA polymerase holoenzyme and poly[d(A-T)] as template. In the presence of UTP as a single substrate and UpA as a primer, the enzyme catalyzed efficiently the synthesis of the trinucleotide product UpApU. Incubation of RNA polymerase with 1 mM 2-mercaptoethanol resulted in a 5-fold increase of the rate of UpApU synthesis. In contrast, incubation of the enzyme with 1 mM 5,5'-dithio-bis(2-nitrobenzoic) acid resulted in a 6-fold decrease of the rate of abortive elongation. Determination of the steady state kinetic constants associated with UpApU synthesis disclosed that the disulfide and sulfhydryl reagents mainly affected the rate of UpApU release from the ternary transcription complexes and therefore influenced the stability of such complexes. (author). 15 refs, 1 fig., 1 tab

  5. Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus

    Directory of Open Access Journals (Sweden)

    Po-Yuan Yeh

    2014-07-01

    Full Text Available It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−-strand] complement. However, the cis-acting elements on the positive-strand [(+-strand] sgmRNA required for (−-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV sgmRNA 7 required for the synthesis of its (−-strand counterpart by deletion mutagenesis. The major findings are as follows. (1 Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−-strand sgmRNA complement. (2 Deletions of the 3' untranslated region (UTR bulged stem-loop showed no effect on (−-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−-strand sgmRNA. (3 Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−-strand sgmRNA synthesis. (4 Nucleotide species at the 3'-most position (−1 of sgmRNA 7 is correlated to the efficiency of (−-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−-strand sgmRNA synthesis in BCoV.

  6. RNA decay by messenger RNA interferases

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, Mikkel; Overgaard, Martin; Winther, Kristoffer Skovbo

    2008-01-01

    Two abundant toxin-antitoxin (TA) gene families, relBE and mazEF, encode mRNA cleaving enzymes whose ectopic overexpression abruptly inhibits translation and thereby induces a bacteriostatic condition. Here we describe and discuss protocols for the overproduction, purification, and analysis of mR...... cleaving enzymes such as RelE of Escherichia coli and the corresponding antitoxin RelB. In particular, we describe a set of plasmid vectors useful for the detailed analysis of cleavage sites in model mRNAs.......Two abundant toxin-antitoxin (TA) gene families, relBE and mazEF, encode mRNA cleaving enzymes whose ectopic overexpression abruptly inhibits translation and thereby induces a bacteriostatic condition. Here we describe and discuss protocols for the overproduction, purification, and analysis of mRNA...

  7. Topology of RNA-RNA interaction structures

    DEFF Research Database (Denmark)

    Andersen, Jørgen Ellegaard; Huang, Fenix Wenda; Penner, Robert

    2012-01-01

    Abstract The topological filtration of interacting RNA complexes is studied, and the role is analyzed of certain diagrams called irreducible shadows, which form suitable building blocks for more general structures. We prove that, for two interacting RNAs, called interaction structures, there exist...

  8. RNA Localization in Astrocytes

    DEFF Research Database (Denmark)

    Thomsen, Rune

    2012-01-01

    , regulation of the blood brain barrier and glial scar tissue formation. Despite the involvement in various CNS functions only a limited number of studies have addressed mRNA localization in astrocytes. This PhD project was initially focused on developing and implementing methods that could be used to asses mRNA......Messenger RNA (mRNA) localization is a mechanism by which polarized cells can regulate protein synthesis to specific subcellular compartments in a spatial and temporal manner, and plays a pivotal role in multiple physiological processes from embryonic development to cell differentiation...... localization in astrocyte protrusions, and following look into the subcellular localization pattern of specific mRNA species of both primary astrocytes isolated from cortical hemispheres of newborn mice, and the mouse astrocyte cell line, C8S. The Boyden chamber cell fractionation assay was optimized, in a way...

  9. Design and kinetic analysis of hammerhead ribozyme and DNAzyme that specifically cleave TEL-AML1 chimeric mRNA

    International Nuclear Information System (INIS)

    Choi, Woo-Hyung; Choi, Bo-Ra; Kim, Jae Hyun; Yeo, Woon-Seok; Oh, Sangtaek; Kim, Dong-Eun

    2008-01-01

    In order to develop the oligonucleotides to abolish an expression of TEL-AML1 chimeric RNA, which is a genetic aberration that causes the acute lymphoblastic leukemia (ALL), hammerhead ribozymes and deoxyoligoribozymes that can specifically cleave TEL-AML1 fusion RNA were designed. Constructs of the deoxyribozyme with an asymmetric substrate binding arm (Dz26) and the hammerhead ribozyme with a 4 nt-bulged substrate binding arm in the stem III (buRz28) were able to cleave TEL-AML1 chimeric RNA specifically at sites close to the junction in vitro, without cleaving the normal TEL and AML1 RNA. Single-turnover kinetic analysis under enzyme-excess condition revealed that the buRz28 is superior to the Dz26 in terms of substrate binding and RNA-cleavage. In conjunction with current progress in a gene-delivery technology, the designed oligonucleotides that specifically cleave the TEL-AML1 chimeric mRNA are hoped to be applicable for the treatment of ALL in vivo

  10. Database proton NMR chemical shifts for RNA signal assignment and validation

    Energy Technology Data Exchange (ETDEWEB)

    Barton, Shawn; Heng Xiao [University of Maryland, Baltimore County, Howard Hughes Medical Institute (United States); Johnson, Bruce A., E-mail: bruce@onemoonscientific.com [University of Maryland, Baltimore County, Department of Chemistry and Biochemistry (United States); Summers, Michael F., E-mail: summers@hhmi.umbc.edu [University of Maryland, Baltimore County, Howard Hughes Medical Institute (United States)

    2013-01-15

    The Biological Magnetic Resonance Data Bank contains NMR chemical shift depositions for 132 RNAs and RNA-containing complexes. We have analyzed the {sup 1}H NMR chemical shifts reported for non-exchangeable protons of residues that reside within A-form helical regions of these RNAs. The analysis focused on the central base pair within a stretch of three adjacent base pairs (BP triplets), and included both Watson-Crick (WC; G:C, A:U) and G:U wobble pairs. Chemical shift values were included for all 4{sup 3} possible WC-BP triplets, as well as 137 additional triplets that contain one or more G:U wobbles. Sequence-dependent chemical shift correlations were identified, including correlations involving terminating base pairs within the triplets and canonical and non-canonical structures adjacent to the BP triplets (i.e. bulges, loops, WC and non-WC BPs), despite the fact that the NMR data were obtained under different conditions of pH, buffer, ionic strength, and temperature. A computer program (RNAShifts) was developed that enables convenient comparison of RNA {sup 1}H NMR assignments with database predictions, which should facilitate future signal assignment/validation efforts and enable rapid identification of non-canonical RNA structures and RNA-ligand/protein interaction sites.

  11. Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge.

    Science.gov (United States)

    Jung, Jaeyun; Yeom, Chanjoo; Choi, Yeon-Sook; Kim, Sinae; Lee, EunJi; Park, Min Ji; Kang, Sang Wook; Kim, Sung Bae; Chang, Suhwan

    2015-08-21

    The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a multi-potent miRNA sponge inhibiting multiple miRNAs simultaneously. As a model system, we targeted miR-21, miR-155 and miR-221/222, known as oncogenic miRNAs in multiple tumors including breast and pancreatic cancers. To achieve efficient knockdown, we generated perfect and bulged-matched miRNA binding sites (MBS) and introduced multiple copies of MBS, ranging from one to five, in the multi-potent miRNA sponge. Luciferase reporter assay showed the multi-potent miRNA sponge efficiently inhibited 4 miRNAs in breast and pancreatic cancer cells. Furthermore, a stable and inducible version of the multi-potent miRNA sponge cell line showed the miRNA sponge efficiently reduces the level of 4 target miRNAs and increase target protein level of these oncogenic miRNAs. Finally, we showed the miRNA sponge sensitize cells to cancer drug and attenuate cell migratory activity. Altogether, our study demonstrates the multi-potent miRNA sponge is a useful tool to examine the functional impact of simultaneous inhibition of multiple miRNAs and proposes a therapeutic potential.

  12. Assembling RNA Nanoparticles.

    Science.gov (United States)

    Xiao, Shou-Jun

    2017-01-01

    RNA nanoparticles are designed and self-assembled according to noncanonical interactions of naturally conserved RNA motifs and/or canonical Watson-Crick base-pairing interactions, which have potential applications in gene therapy and nanomedicine. These artificially engineered nanoparticles are mainly synthesized from in vitro transcribed RNAs, purified by denaturing and native polyacrylamide gel electrophoresis (PAGE), and characterized with native PAGE, AFM, and TEM technologies. The protocols of in vitro transcription, denaturing and native PAGE, and RNA nanoparticle self-assembly are described in detail.

  13. Plant RNA binding proteins for control of RNA virus infection

    Directory of Open Access Journals (Sweden)

    Sung Un eHuh

    2013-12-01

    Full Text Available Plant RNA viruses have effective strategies to infect host plants through either direct or indirect interactions with various host proteins, thus suppressing the host immune system. When plant RNA viruses enter host cells exposed RNAs of viruses are recognized by the host immune system through processes such as siRNA-dependent silencing. Interestingly, some host RNA binding proteins have been involved in the inhibition of RNA virus replication, movement, and translation through RNA-specific binding. Host plants intensively use RNA binding proteins for defense against viral infections in nature. In this mini review, we will summarize the function of some host RNA binding proteins which act in a sequence-specific binding manner to the infecting virus RNA. It is important to understand how plants effectively suppresses RNA virus infections via RNA binding proteins, and this defense system can be potentially developed as a synthetic virus defense strategy for use in crop engineering.

  14. Shapes of interacting RNA complexes

    DEFF Research Database (Denmark)

    Fu, Benjamin Mingming; Reidys, Christian

    2014-01-01

    Shapes of interacting RNA complexes are studied using a filtration via their topological genus. A shape of an RNA complex is obtained by (iteratively) collapsing stacks and eliminating hairpin loops.This shape-projection preserves the topological core of the RNA complex and for fixed topological...... genus there are only finitely many such shapes. Our main result is a new bijection that relates the shapes of RNA complexes with shapes of RNA structures. This allows to compute the shape polynomial of RNA complexes via the shape polynomial of RNA structures. We furthermore present a linear time uniform...... sampling algorithm for shapes of RNA complexes of fixed topological genus....

  15. Remote Network Access (RNA)

    National Research Council Canada - National Science Library

    2002-01-01

    .... Remote Network Access (RNA) includes or is associated with all communication devices/software, firewalls, intrusion detection systems and virus protection applications to ensure security of the OIG, DoD, Network from remote...

  16. RNA/PNA Approach

    Indian Academy of Sciences (India)

    In this approach we want to develop structural analogue of the leader that might have higher affinity towards the Phosphoprotein, but would impair the dimerization process and viral leader RNA binding.

  17. INTEGRAL Galactic Bulge monitoring: transient activity from KS 1741-293, MXB 1730-335, and IGR J17498-2921

    Science.gov (United States)

    Chenevez, J.; Brandt, S.; Kuulkers, E.; Alfonso-Garzón, J.; Beckmann, V.; Bird, T.; Courvoisier, Th.; Del Santo, M.; Domingo, A.; Ebisawa, K.; Jonker, P.; Kretschmar, P.; Markwardt, C.; Oosterbroek, T.; Paizis, A.; Pottschmidt, K.; Sánchez-Fernández, C.; Wijnands, R.

    2011-09-01

    As part of its regular monitoring of the Galactic Bulge (see ATel #438) INTEGRAL observed this region of the sky on September 13, 2011, between UTC 9:14:50 and 12:56:26. Both the JEM-X and the IBIS/ISGRI instruments detect the transient neutron star low-mass X-ray binary KS 1741-293 at the following flux levels: JEM-X: 6 ±3 mCrab (3-10 keV) and 14 ±6 mCrab (10-25 keV) ISGRI: 11 ±2 mCrab (18-40 keV) and 13 ±2 mCrab (40-100 keV) We note that the activity of this source already started two weeks ago as has been reported by Linares et al.

  18. Non normal and non quadratic anisotropic plasticity coupled with ductile damage in sheet metal forming: Application to the hydro bulging test

    International Nuclear Information System (INIS)

    Badreddine, Houssem; Saanouni, Khemaies; Dogui, Abdelwaheb

    2007-01-01

    In this work an improved material model is proposed that shows good agreement with experimental data for both hardening curves and plastic strain ratios in uniaxial and equibiaxial proportional loading paths for steel metal until the final fracture. This model is based on non associative and non normal flow rule using two different orthotropic equivalent stresses in both yield criterion and plastic potential functions. For the plastic potential the classical Hill 1948 quadratic equivalent stress is considered while for the yield criterion the Karafillis and Boyce 1993 non quadratic equivalent stress is used taking into account the non linear mixed (kinematic and isotropic) hardening. Applications are made to hydro bulging tests using both circular and elliptical dies. The results obtained with different particular cases of the model such as the normal quadratic and the non normal non quadratic cases are compared and discussed with respect to the experimental results

  19. Ages of the Bulge Globular Clusters NGC 6522 and NGC 6626 (M28) from HST Proper-motion-cleaned Color–Magnitude Diagrams

    Science.gov (United States)

    Kerber, L. O.; Nardiello, D.; Ortolani, S.; Barbuy, B.; Bica, E.; Cassisi, S.; Libralato, M.; Vieira, R. G.

    2018-01-01

    Bulge globular clusters (GCs) with metallicities [Fe/H] ≲ ‑1.0 and blue horizontal branches are candidates to harbor the oldest populations in the Galaxy. Based on the analysis of HST proper-motion-cleaned color–magnitude diagrams in filters F435W and F625W, we determine physical parameters for the old bulge GCs NGC 6522 and NGC 6626 (M28), both with well-defined blue horizontal branches. We compare these results with similar data for the inner halo cluster NGC 6362. These clusters have similar metallicities (‑1.3 ≤ [Fe/H] ≤ ‑1.0) obtained from high-resolution spectroscopy. We derive ages, distance moduli, and reddening values by means of statistical comparisons between observed and synthetic fiducial lines employing likelihood statistics and the Markov chain Monte Carlo method. The synthetic fiducial lines were generated using α-enhanced BaSTI and Dartmouth stellar evolutionary models, adopting both canonical (Y ∼ 0.25) and enhanced (Y ∼ 0.30–0.33) helium abundances. RR Lyrae stars were employed to determine the HB magnitude level, providing an independent indicator to constrain the apparent distance modulus and the helium enhancement. The shape of the observed fiducial line could be compatible with some helium enhancement for NGC 6522 and NGC 6626, but the average magnitudes of RR Lyrae stars tend to rule out this hypothesis. Assuming canonical helium abundances, BaSTI and Dartmouth models indicate that all three clusters are coeval, with ages between ∼12.5 and 13.0 Gyr. The present study also reveals that NGC 6522 has at least two stellar populations, since its CMD shows a significantly wide subgiant branch compatible with 14% ± 2% and 86% ± 5% for first and second generations, respectively. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute.

  20. Comment on "Characterizing the population of pulsars in the Galactic bulge with the Fermi large area telescope" [arXiv:1705.00009v1

    Science.gov (United States)

    Bartels, Richard; Hooper, Dan; Linden, Tim; Mishra-Sharma, Siddharth; Rodd, Nicholas L.; Safdi, Benjamin R.; Slatyer, Tracy R.

    2018-06-01

    The Fermi-LAT Collaboration recently presented a new catalog of gamma-ray sources located within the 40 ° × 40 ° region around the Galactic Center Ajello et al. (2017) - the Second Fermi Inner Galaxy (2FIG) catalog. Utilizing this catalog, they analyzed models for the spatial distribution and luminosity function of sources with a pulsar-like gamma-ray spectrum. Ajello et al. (2017) v1 also claimed to detect, in addition to a disk-like population of pulsar-like sources, an approximately 7 σ preference for an additional centrally concentrated population of pulsar-like sources, which they referred to as a "Galactic Bulge" population. Such a population would be of great interest, as it would support a pulsar interpretation of the gamma-ray excess that has long been observed in this region. In an effort to further explore the implications of this new source catalog, we attempted to reproduce the results presented by the Fermi-LAT Collaboration, but failed to do so. Mimicking as closely as possible the analysis techniques undertaken in Ajello et al. (2017), we instead find that our likelihood analysis favors a very different spatial distribution and luminosity function for these sources. Most notably, our results do not exhibit a strong preference for a "Galactic Bulge" population of pulsars. Furthermore, we find that masking the regions immediately surrounding each of the 2FIG pulsar candidates does not significantly impact the spectrum or intensity of the Galactic Center gamma-ray excess. Although these results refute the claim of strong evidence for a centrally concentrated pulsar population presented in Ajello et al. (2017), they neither rule out nor provide support for the possibility that the Galactic Center excess is generated by a population of low-luminosity and currently largely unobserved pulsars. In a spirit of maximal openness and transparency, we have made our analysis code available at https://github.com/bsafdi/GCE-2FIG.

  1. Crystal structure of the bacteriophage Qβ coat protein in complex with the RNA operator of the replicase gene.

    Science.gov (United States)

    Rumnieks, Janis; Tars, Kaspars

    2014-03-06

    The coat proteins of single-stranded RNA bacteriophages specifically recognize and bind to a hairpin structure in their genome at the beginning of the replicase gene. The interaction serves to repress the synthesis of the replicase enzyme late in infection and contributes to the specific encapsidation of phage RNA. While this mechanism is conserved throughout the Leviviridae family, the coat protein and operator sequences from different phages show remarkable variation, serving as prime examples for the co-evolution of protein and RNA structure. To better understand the protein-RNA interactions in this virus family, we have determined the three-dimensional structure of the coat protein from bacteriophage Qβ bound to its cognate translational operator. The RNA binding mode of Qβ coat protein shares several features with that of the widely studied phage MS2, but only one nucleotide base in the hairpin loop makes sequence-specific contacts with the protein. Unlike in other RNA phages, the Qβ coat protein does not utilize an adenine-recognition pocket for binding a bulged adenine base in the hairpin stem but instead uses a stacking interaction with a tyrosine side chain to accommodate the base. The extended loop between β strands E and F of Qβ coat protein makes contacts with the lower part of the RNA stem, explaining the greater length dependence of the RNA helix for optimal binding to the protein. Consequently, the complex structure allows the proposal of a mechanism by which the Qβ coat protein recognizes and discriminates in favor of its cognate RNA. © 2013.

  2. Switching off small RNA regulation with trap-mRNA

    DEFF Research Database (Denmark)

    Overgaard, Martin; Johansen, Jesper; Møller-Jensen, Jakob

    2009-01-01

    to operate at the level of transcription initiation. By employing a highly sensitive genetic screen we uncovered a novel RNA-based regulatory principle in which induction of a trap-mRNA leads to selective degradation of a small regulatory RNA molecule, thereby abolishing the sRNA-based silencing of its...

  3. A ribosome without RNA

    Directory of Open Access Journals (Sweden)

    Harold S Bernhardt

    2015-11-01

    Full Text Available It was Francis Crick who first asked why the ribosome contains so much RNA, and discussed the implications of this for the direct flow of genetic information from DNA to protein. Remarkable advances in our understanding of the ribosome and protein synthesis, including the recent publication of two mammalian mitochondrial ribosome structures, have shed new light on this intriguing aspect of evolution in molecular biology. We examine here whether RNA is indispensable for coded protein synthesis, or whether an all-protein ‘ribosome’ (or ‘synthosome’ might be possible, with a protein enzyme catalyzing peptide synthesis, and release factor-like protein adaptors able to read a message composed of deoxyribonucleotides. We also compare the RNA world hypothesis with the alternative ‘proteins first’ hypothesis in terms of their different understandings of the evolution of the ribosome, and whether this might have been preceded by an ancestral form of nonribosomal peptide synthesis catalyzed by protein enzymes.

  4. Structure and conformational dynamics of the domain 5 RNA hairpin of a bacterial group II intron revealed by solution nuclear magnetic resonance and molecular dynamics simulations.

    Science.gov (United States)

    Pechlaner, Maria; Sigel, Roland K O; van Gunsteren, Wilfred F; Dolenc, Jožica

    2013-10-08

    Nuclear magnetic resonance (NMR) nuclear Overhauser enhancement (NOE) data obtained for a 35-nucleotide RNA segment of a bacterial group II intron indicate a helical hairpin structure in which three parts, a terminal pentaloop, a bulge, and a G-A mismatch, display no Watson-Crick base pairing. The 668 NOE upper distance bounds for atom pairs are insufficient to uniquely determine the conformation of these segments. Therefore, molecular dynamics simulations including time-averaged distance restraints have been used to obtain a conformational ensemble compatible with the observed NMR data. The ensemble shows alternating hydrogen bonding patterns for the mentioned segments. In particular, in the pentaloop and in the bulge, the hydrogen bonding networks correspond to distinct conformational clusters that could not be captured by using conventional single-structure refinement techniques. This implies that, to obtain a realistic picture of the conformational ensemble of such flexible biomolecules, it is necessary to properly account for the conformational variability in the structure refinement of RNA fragments.

  5. RNA Regulation of Estrogen

    Science.gov (United States)

    2010-08-01

    Berglund, Rodger Voelker, Paul Barber and Julien Diegel 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING...estrogen  receptors  [reviewed  in  (3,  4)],  also   functions   by  interacting  directly  with  RNA  to  alter  RNA...Mog myelin oligodendrocyte glycoprotein 6.06 207115_x_at mbtd1 mbt domain containing 1 6.06 208004_at Prol1 proline rich, lacrimal 1 6.06 205247_at

  6. RNA Regulation by Estrogen

    Science.gov (United States)

    2011-08-01

    Julien Diegel, Amy Mahady, and Micah Bodner 5e. TASK NUMBER E-Mail: aberglund@molbio.uoregon.edu 5f. WORK UNIT NUMBER 7. PERFORMING...4)],  also   functions   by  interacting  directly  with  RNA  to  alter  RNA  processing  events  such  as  splicing...1 6.06 208004_at Prol1 proline rich, lacrimal 1 6.06 205247_at NOTCH4 Notch homolog 4 (Drosophila) 6.06 211203_s_at Cntn1 contactin 1 6.06 220689_at

  7. Sensing of RNA viruses

    DEFF Research Database (Denmark)

    Jensen, Søren; Thomsen, Allan Randrup

    2012-01-01

    pathogen-associated molecular patterns have emerged in great detail. This review presents an overview of our current knowledge regarding the receptors used to detect RNA virus invasion, the molecular structures these receptors sense, and the involved downstream signaling pathways.......Our knowledge regarding the contribution of the innate immune system in recognizing and subsequently initiating a host response to an invasion of RNA virus has been rapidly growing over the last decade. Descriptions of the receptors involved and the molecular mechanisms they employ to sense viral...

  8. RNA STRAND: The RNA Secondary Structure and Statistical Analysis Database

    Directory of Open Access Journals (Sweden)

    Andronescu Mirela

    2008-08-01

    Full Text Available Abstract Background The ability to access, search and analyse secondary structures of a large set of known RNA molecules is very important for deriving improved RNA energy models, for evaluating computational predictions of RNA secondary structures and for a better understanding of RNA folding. Currently there is no database that can easily provide these capabilities for almost all RNA molecules with known secondary structures. Results In this paper we describe RNA STRAND – the RNA secondary STRucture and statistical ANalysis Database, a curated database containing known secondary structures of any type and organism. Our new database provides a wide collection of known RNA secondary structures drawn from public databases, searchable and downloadable in a common format. Comprehensive statistical information on the secondary structures in our database is provided using the RNA Secondary Structure Analyser, a new tool we have developed to analyse RNA secondary structures. The information thus obtained is valuable for understanding to which extent and with which probability certain structural motifs can appear. We outline several ways in which the data provided in RNA STRAND can facilitate research on RNA structure, including the improvement of RNA energy models and evaluation of secondary structure prediction programs. In order to keep up-to-date with new RNA secondary structure experiments, we offer the necessary tools to add solved RNA secondary structures to our database and invite researchers to contribute to RNA STRAND. Conclusion RNA STRAND is a carefully assembled database of trusted RNA secondary structures, with easy on-line tools for searching, analyzing and downloading user selected entries, and is publicly available at http://www.rnasoft.ca/strand.

  9. Studying RNA-protein interactions in vivo by RNA immunoprecipitation

    DEFF Research Database (Denmark)

    Selth, Luke A; Close, Pierre; Svejstrup, Jesper Q

    2011-01-01

    and have significant effects on gene expression. RNA immunoprecipitation (RIP) is a powerful technique used to detect direct and indirect interactions between individual proteins and specific RNA molecules in vivo. Here, we describe RIP methods for both yeast and mammalian cells.......The crucial roles played by RNA-binding proteins in all aspects of RNA metabolism, particularly in the regulation of transcription, have become increasingly evident. Moreover, other factors that do not directly interact with RNA molecules can nevertheless function proximally to RNA polymerases...

  10. Branched RNA: A New Architecture for RNA Interference

    Directory of Open Access Journals (Sweden)

    Anna Aviñó

    2011-01-01

    Full Text Available Branched RNAs with two and four strands were synthesized. These structures were used to obtain branched siRNA. The branched siRNA duplexes had similar inhibitory capacity as those of unmodified siRNA duplexes, as deduced from gene silencing experiments of the TNF-α protein. Branched RNAs are considered novel structures for siRNA technology, and they provide an innovative tool for specific gene inhibition. As the method described here is compatible with most RNA modifications described to date, these compounds may be further functionalized to obtain more potent siRNA derivatives and can be attached to suitable delivery systems.

  11. The RNA gene information: retroelement-microRNA entangling as the RNA quantum code.

    Science.gov (United States)

    Fujii, Yoichi Robertus

    2013-01-01

    MicroRNA (miRNA) and retroelements may be a master of regulator in our life, which are evolutionally involved in the origin of species. To support the Darwinism from the aspect of molecular evolution process, it has tremendously been interested in the molecular information of naive RNA. The RNA wave model 2000 consists of four concepts that have altered from original idea of the miRNA genes for crosstalk among embryonic stem cells, their niche cells, and retroelements as a carrier vesicle of the RNA genes. (1) the miRNA gene as a mobile genetic element induces transcriptional and posttranscriptional silencing via networking-processes (no hierarchical architecture); (2) the RNA information supplied by the miRNA genes expands to intracellular, intercellular, intraorgan, interorgan, intraspecies, and interspecies under the cycle of life into the global environment; (3) the mobile miRNAs can self-proliferate; and (4) cells contain two types information as resident and genomic miRNAs. Based on RNA wave, we have developed an interest in investigation of the transformation from RNA information to quantum bits as physicochemical characters of RNA with the measurement of RNA electron spin. When it would have been given that the fundamental bases for the acquired characters in genetics can be controlled by RNA gene information, it may be available to apply for challenging against RNA gene diseases, such as stress-induced diseases.

  12. Plant RNA Regulatory Network and RNA Granules in Virus Infection

    Directory of Open Access Journals (Sweden)

    Kristiina Mäkinen

    2017-12-01

    Full Text Available Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and

  13. Plant RNA Regulatory Network and RNA Granules in Virus Infection.

    Science.gov (United States)

    Mäkinen, Kristiina; Lõhmus, Andres; Pollari, Maija

    2017-01-01

    Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and their individual

  14. RNA-Catalyzed Polymerization and Replication of RNA

    Science.gov (United States)

    Horning, D. P.; Samantha, B.; Tjhung, K. F.; Joyce, G. F.

    2017-07-01

    In an effort to reconstruct RNA-based life, in vitro evolution was used to obtain an RNA polymerase ribozyme that can synthesize a variety of complex functional RNAs and can catalyze the exponential amplification of short RNAs.

  15. Natural RNA circles function as efficient microRNA sponges

    DEFF Research Database (Denmark)

    Hansen, Thomas Birkballe; Jensen, Trine I; Clausen, Bettina Hjelm

    2013-01-01

    MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called comp......MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so......-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more...... sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA....

  16. Strategies underlying RNA silencing suppression by negative strand RNA viruses

    NARCIS (Netherlands)

    Hemmes, J.C.

    2007-01-01

    The research described in this thesis focused on the strategies of negative strand RNA viruses to counteract antiviral RNA silencing. In plants and insects, RNA silencing has been shown to act as a sequence specific antiviral defence mechanism that is characterised by the processing of double

  17. RNA Interference - Towards RNA becoming a Medicine -42 ...

    Indian Academy of Sciences (India)

    research. A brief history of the development ofRNAi is shown in. Box 2. Mechanism of ... new RNA strand using target RNA as the template and thereby converting it ... thought to excise precursor stRNA from their -70 nt stem loop precursor to ...

  18. Hepatitis B virus nuclear export elements: RNA stem-loop α and β, key parts of the HBV post-transcriptional regulatory element.

    Science.gov (United States)

    Lim, Chun Shen; Brown, Chris M

    2016-09-01

    Many viruses contain RNA elements that modulate splicing and/or promote nuclear export of their RNAs. The RNAs of the major human pathogen, hepatitis B virus (HBV) contain a large (~600 bases) composite cis-acting 'post-transcriptional regulatory element' (PRE). This element promotes expression from these naturally intronless transcripts. Indeed, the related woodchuck hepadnavirus PRE (WPRE) is used to enhance expression in gene therapy and other expression vectors. These PRE are likely to act through a combination of mechanisms, including promotion of RNA nuclear export. Functional components of both the HBV PRE and WPRE are 2 conserved RNA cis-acting stem-loop (SL) structures, SLα and SLβ. They are within the coding regions of polymerase (P) gene, and both P and X genes, respectively. Based on previous studies using mutagenesis and/or nuclear magnetic resonance (NMR), here we propose 2 covariance models for SLα and SLβ. The model for the 30-nucleotide SLα contains a G-bulge and a CNGG(U) apical loop of which the first and the fourth loop residues form a CG pair and the fifth loop residue is bulged out, as observed in the NMR structure. The model for the 23-nucleotide SLβ contains a 7-base-pair stem and a 9-nucleotide loop. Comparison of the models with other RNA structural elements, as well as similarity searches of human transcriptome and viral genomes demonstrate that SLα and SLβ are specific to HBV transcripts. However, they are well conserved among the hepadnaviruses of non-human primates, the woodchuck and ground squirrel.

  19. Semiautomated improvement of RNA alignments

    DEFF Research Database (Denmark)

    Andersen, Ebbe Sloth; Lind-Thomsen, Allan; Knudsen, Bjarne

    2007-01-01

    connects to external tools to provide a flexible semiautomatic editing environment. A new method, Pcluster, is introduced for dividing the sequences of an RNA alignment into subgroups with secondary structure differences. Pcluster was used to evaluate 574 seed alignments obtained from the Rfam database...... and we identified 71 alignments with significant prediction of inconsistent base pairs and 102 alignments with significant prediction of novel base pairs. Four RNA families were used to illustrate how SARSE can be used to manually or automatically correct the inconsistent base pairs detected by Pcluster......: the mir-399 RNA, vertebrate telomase RNA (vert-TR), bacterial transfer-messenger RNA (tmRNA), and the signal recognition particle (SRP) RNA. The general use of the method is illustrated by the ability to accommodate pseudoknots and handle even large and divergent RNA families. The open architecture...

  20. Comparative RNA genomics

    DEFF Research Database (Denmark)

    Backofen, Rolf; Gorodkin, Jan; Hofacker, Ivo L.

    2018-01-01

    Over the last two decades it has become clear that RNA is much more than just a boring intermediate in protein expression. Ancient RNAs still appear in the core information metabolism and comprise a surprisingly large component in bacterial gene regulation. A common theme with these types of mostly...... small RNAs is their reliance of conserved secondary structures. Large scale sequencing projects, on the other hand, have profoundly changed our understanding of eukaryotic genomes. Pervasively transcribed, they give rise to a plethora of large and evolutionarily extremely flexible noncoding RNAs...... that exert a vastly diverse array of molecule functions. In this chapter we provide a—necessarily incomplete—overview of the current state of comparative analysis of noncoding RNAs, emphasizing computational approaches as a means to gain a global picture of the modern RNA world....

  1. MicroRNA from tuberculosis RNA: A bioinformatics study

    OpenAIRE

    Wiwanitkit, Somsri; Wiwanitkit, Viroj

    2012-01-01

    The role of microRNA in the pathogenesis of pulmonary tuberculosis is the interesting topic in chest medicine at present. Recently, it was proposed that the microRNA can be a useful biomarker for monitoring of pulmonary tuberculosis and might be the important part in pathogenesis of disease. Here, the authors perform a bioinformatics study to assess the microRNA within known tuberculosis RNA. The microRNA part can be detected and this can be important key information in further study of the p...

  2. RNA binding and replication by the poliovirus RNA polymerase

    International Nuclear Information System (INIS)

    Oberste, M.S.

    1988-01-01

    RNA binding and RNA synthesis by the poliovirus RNA-dependent RNA polymerase were studied in vitro using purified polymerase. Templates for binding and RNA synthesis studies were natural RNAs, homopolymeric RNAs, or subgenomic poliovirus-specific RNAs synthesized in vitro from cDNA clones using SP6 or T7 RNA polymerases. The binding of the purified polymerase to poliovirion and other RNAs was studied using a protein-RNA nitrocellulose filter binding assay. A cellular poly(A)-binding protein was found in the viral polymerase preparations, but was easily separated from the polymerase by chromatography on poly(A) Sepharose. The binding of purified polymerase to 32 P-labeled ribohomopolymeric RNAs was examined, and the order of binding observed was poly(G) >>> poly(U) > poly(C) > poly(A). The K a for polymerase binding to poliovirion RNA and to a full-length negative strand transcript was about 1 x 10 9 M -1 . The polymerase binds to a subgenomic RNAs which contain the 3' end of the genome with a K a similar to that for virion RNA, but binds less well to 18S rRNA, globin mRNA, and subgenomic RNAs which lack portions of the 3' noncoding region

  3. Genetic relatedness of orbiviruses by RNA-RNA blot hybridization

    International Nuclear Information System (INIS)

    Bodkin, D.K.

    1985-01-01

    RNA-RNA blot hybridization was developed in order to identify type-specific genes among double-stranded (ds) RNA viruses, to assess the genetic relatedness of dsRNA viruses and to classify new strains. Viral dsRNA segments were electrophoresed through 10% polyacrylamide gels, transferred to membranes, and hybridized to [5' 32 P]-pCp labeled genomic RNA from a related strain. Hybridization was performed at 52 0 C, 50% formamide, 5X SSC. Under these conditions heterologous RNA species must share ≥ 74% sequence homology in order to form stable dsRNA hybrids. Cognate genes of nine members of the Palyam serogroup of orbiviruses were identified and their sequence relatedness to the prototype. Palyam virus, was determined. Reciprocal blot hybridizations were performed using radiolabeled genomic RNA of all members of the Palyam serogroup. Unique and variant genes were identified by lack of cross-homology or by weak homology between segments. Since genes 2 and 6 exhibited the highest degree of sequence variability, response to the vertebrate immune system may be a major cause of sequence divergence among members of a single serogroup. Changuinola serogroup isolates were compared by dot-blot hybridization, while Colorado tick fever (CTF) serogroup isolates were compared by the RNA-RNA blot hybridization procedure described for reovirus and Palyam serogroup isolates. Preliminary blot hybridization data were also obtained on the relatedness of members of different Orbivirus serogroups

  4. RNA-SSPT: RNA Secondary Structure Prediction Tools.

    Science.gov (United States)

    Ahmad, Freed; Mahboob, Shahid; Gulzar, Tahsin; Din, Salah U; Hanif, Tanzeela; Ahmad, Hifza; Afzal, Muhammad

    2013-01-01

    The prediction of RNA structure is useful for understanding evolution for both in silico and in vitro studies. Physical methods like NMR studies to predict RNA secondary structure are expensive and difficult. Computational RNA secondary structure prediction is easier. Comparative sequence analysis provides the best solution. But secondary structure prediction of a single RNA sequence is challenging. RNA-SSPT is a tool that computationally predicts secondary structure of a single RNA sequence. Most of the RNA secondary structure prediction tools do not allow pseudoknots in the structure or are unable to locate them. Nussinov dynamic programming algorithm has been implemented in RNA-SSPT. The current studies shows only energetically most favorable secondary structure is required and the algorithm modification is also available that produces base pairs to lower the total free energy of the secondary structure. For visualization of RNA secondary structure, NAVIEW in C language is used and modified in C# for tool requirement. RNA-SSPT is built in C# using Dot Net 2.0 in Microsoft Visual Studio 2005 Professional edition. The accuracy of RNA-SSPT is tested in terms of Sensitivity and Positive Predicted Value. It is a tool which serves both secondary structure prediction and secondary structure visualization purposes.

  5. Cooperative RNP assembly: Complementary rescue of structural defects by protein and RNA subunits of archaeal RNase P

    Science.gov (United States)

    Chen, Wen-Yi; Xu, Yiren; Cho, I-Ming; Oruganti, Sri Vidya; Foster, Mark P.; Gopalan, Venkat

    2011-01-01

    RNase P is a ribonucleoprotein (RNP) complex that utilizes a Mg2+-dependent RNA catalyst to cleave the 5′-leader of precursor tRNAs (pre-tRNAs) and generate mature tRNAs. The bacterial RNase P protein (RPP) aids RNase P RNA (RPR) catalysis by promoting substrate binding, Mg2+ coordination, and product release. Archaeal RNase P comprises an RPR and at least four RPPs, which have eukaryal homologs and function as two binary complexes (POP5•RPP30 and RPP21•RPP29). In this study, we employed a previously characterized substrate-enzyme conjugate [pre-tRNATyr-Methanocaldococcus jannaschii (Mja) RPR] to investigate the functional role of a universally conserved uridine in a bulge-helix structure in archaeal RPRs. Deletion of this bulged uridine resulted in an 80-fold decrease in the self-cleavage rate of pre-tRNATyr-MjaΔU RPR compared to the wildtype, and this defect was partially ameliorated upon addition of either RPP pair. The catalytic defect in the archaeal mutant RPR mirrors that reported in a bacterial RPR and highlights a parallel in their active sites. Furthermore, an N-terminal deletion mutant of Pyrococcus furiosus (Pfu) RPP29 that is defective in assembling with its binary partner RPP21, as assessed by isothermal titration calorimetry and NMR spectroscopy, is functional when reconstituted with the cognate Pfu RPR. Collectively, these results indicate that archaeal RPPs are able to compensate for structural defects in their cognate RPR and vice-versa, and provide striking examples of the cooperative subunit interactions critical for driving archaeal RNase P towards its functional conformation. (236 words) PMID:21683084

  6. High-affinity interaction of hnRNP A1 with conserved RNA structural elements is required for translation and replication of enterovirus 71.

    Science.gov (United States)

    Levengood, Jeffrey D; Tolbert, Michele; Li, Mei-Ling; Tolbert, Blanton S

    2013-07-01

    Human Enterovirus 71 (EV71) is an emerging pathogen of infectious disease and a serious threat to public health. Currently, there are no antivirals or vaccines to slow down or prevent EV71 infections, thus underscoring the urgency to better understand mechanisms of host-enterovirus interactions. EV71 uses a type I internal ribosome entry site (IRES) to recruit the 40S ribosomal subunit via a pathway that requires the cytoplasmic localization of hnRNP A1, which acts as an IRES trans-activating factor. The mechanism of how hnRNP A1 trans activates EV71 RNA translation is unknown, however. Here, we report that the UP1 domain of hnRNP A1 interacts specifically with stem loop II (SLII) of the IRES, via a thermodynamically well-defined biphasic transition that involves conserved bulge 5'-AYAGY-3' and hairpin 5'-RY(U/A)CCA-3' loops. Calorimetric titrations of wild-type and mutant SLII constructs reveal these structural elements are essential to form a high-affinity UP1-SLII complex. Mutations that alter the bulge and hairpin primary or secondary structures abrogate the biphasic transition and destabilize the complex. Notably, mutations within the bulge that destabilize the complex correlate with a large reduction in IRES-dependent translational activity and impair EV71 replication. Taken together, this study shows that a conserved SLII structure is necessary to form a functional hnRNP A1-IRES complex, suggesting that small molecules that target this stem loop may have novel antiviral properties.

  7. RNA meets disease in paradise.

    Science.gov (United States)

    Winter, Julia; Roth, Anna; Diederichs, Sven

    2011-01-01

    Getting off the train in Jena-Paradies, 60 participants joined for the 12 (th) Young Scientist Meeting of the German Society for Cell Biology (DGZ) entitled "RNA & Disease". Excellent speakers from around the world, graduate students, postdocs and young group leaders enjoyed a meeting in a familiar atmosphere to exchange inspiring new data and vibrant scientific discussions about the fascinating history and exciting future of non-coding RNA research including microRNA, piRNA and long non-coding RNA as well as their function in cancer, diabetes and neurodegenerative diseases.

  8. From "Cellular" RNA to "Smart" RNA: Multiple Roles of RNA in Genome Stability and Beyond.

    Science.gov (United States)

    Michelini, Flavia; Jalihal, Ameya P; Francia, Sofia; Meers, Chance; Neeb, Zachary T; Rossiello, Francesca; Gioia, Ubaldo; Aguado, Julio; Jones-Weinert, Corey; Luke, Brian; Biamonti, Giuseppe; Nowacki, Mariusz; Storici, Francesca; Carninci, Piero; Walter, Nils G; Fagagna, Fabrizio d'Adda di

    2018-03-30

    Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.

  9. Functional specialization of the plant miR396 regulatory network through distinct microRNA-target interactions.

    Directory of Open Access Journals (Sweden)

    Juan M Debernardi

    2012-01-01

    Full Text Available MicroRNAs (miRNAs are ∼21 nt small RNAs that regulate gene expression in animals and plants. They can be grouped into families comprising different genes encoding similar or identical mature miRNAs. Several miRNA families are deeply conserved in plant lineages and regulate key aspects of plant development, hormone signaling, and stress response. The ancient miRNA miR396 regulates conserved targets belonging to the GROWTH-REGULATING FACTOR (GRF family of transcription factors, which are known to control cell proliferation in Arabidopsis leaves. In this work, we characterized the regulation of an additional target for miR396, the transcription factor bHLH74, that is necessary for Arabidopsis normal development. bHLH74 homologs with a miR396 target site could only be detected in the sister families Brassicaceae and Cleomaceae. Still, bHLH74 repression by miR396 is required for margin and vein pattern formation of Arabidopsis leaves. MiR396 contributes to the spatio-temporal regulation of GRF and bHLH74 expression during leaf development. Furthermore, a survey of miR396 sequences in different species showed variations in the 5' portion of the miRNA, a region known to be important for miRNA activity. Analysis of different miR396 variants in Arabidopsis thaliana revealed that they have an enhanced activity toward GRF transcription factors. The interaction between the GRF target site and miR396 has a bulge between positions 7 and 8 of the miRNA. Our data indicate that such bulge modulates the strength of the miR396-mediated repression and that this modulation is essential to shape the precise spatio-temporal pattern of GRF2 expression. The results show that ancient miRNAs can regulate conserved targets with varied efficiency in different species, and we further propose that they could acquire new targets whose control might also be biologically relevant.

  10. Transfer RNA and human disease

    Directory of Open Access Journals (Sweden)

    Jamie A Abbott

    2014-06-01

    Full Text Available Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA genes are hotspots for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase, mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing. Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

  11. Transfer RNA and human disease.

    Science.gov (United States)

    Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M

    2014-01-01

    Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

  12. RNA Thermodynamic Structural Entropy.

    Science.gov (United States)

    Garcia-Martin, Juan Antonio; Clote, Peter

    2015-01-01

    Conformational entropy for atomic-level, three dimensional biomolecules is known experimentally to play an important role in protein-ligand discrimination, yet reliable computation of entropy remains a difficult problem. Here we describe the first two accurate and efficient algorithms to compute the conformational entropy for RNA secondary structures, with respect to the Turner energy model, where free energy parameters are determined from UV absorption experiments. An algorithm to compute the derivational entropy for RNA secondary structures had previously been introduced, using stochastic context free grammars (SCFGs). However, the numerical value of derivational entropy depends heavily on the chosen context free grammar and on the training set used to estimate rule probabilities. Using data from the Rfam database, we determine that both of our thermodynamic methods, which agree in numerical value, are substantially faster than the SCFG method. Thermodynamic structural entropy is much smaller than derivational entropy, and the correlation between length-normalized thermodynamic entropy and derivational entropy is moderately weak to poor. In applications, we plot the structural entropy as a function of temperature for known thermoswitches, such as the repression of heat shock gene expression (ROSE) element, we determine that the correlation between hammerhead ribozyme cleavage activity and total free energy is improved by including an additional free energy term arising from conformational entropy, and we plot the structural entropy of windows of the HIV-1 genome. Our software RNAentropy can compute structural entropy for any user-specified temperature, and supports both the Turner'99 and Turner'04 energy parameters. It follows that RNAentropy is state-of-the-art software to compute RNA secondary structure conformational entropy. Source code is available at https://github.com/clotelab/RNAentropy/; a full web server is available at http

  13. RNA Thermodynamic Structural Entropy.

    Directory of Open Access Journals (Sweden)

    Juan Antonio Garcia-Martin

    Full Text Available Conformational entropy for atomic-level, three dimensional biomolecules is known experimentally to play an important role in protein-ligand discrimination, yet reliable computation of entropy remains a difficult problem. Here we describe the first two accurate and efficient algorithms to compute the conformational entropy for RNA secondary structures, with respect to the Turner energy model, where free energy parameters are determined from UV absorption experiments. An algorithm to compute the derivational entropy for RNA secondary structures had previously been introduced, using stochastic context free grammars (SCFGs. However, the numerical value of derivational entropy depends heavily on the chosen context free grammar and on the training set used to estimate rule probabilities. Using data from the Rfam database, we determine that both of our thermodynamic methods, which agree in numerical value, are substantially faster than the SCFG method. Thermodynamic structural entropy is much smaller than derivational entropy, and the correlation between length-normalized thermodynamic entropy and derivational entropy is moderately weak to poor. In applications, we plot the structural entropy as a function of temperature for known thermoswitches, such as the repression of heat shock gene expression (ROSE element, we determine that the correlation between hammerhead ribozyme cleavage activity and total free energy is improved by including an additional free energy term arising from conformational entropy, and we plot the structural entropy of windows of the HIV-1 genome. Our software RNAentropy can compute structural entropy for any user-specified temperature, and supports both the Turner'99 and Turner'04 energy parameters. It follows that RNAentropy is state-of-the-art software to compute RNA secondary structure conformational entropy. Source code is available at https://github.com/clotelab/RNAentropy/; a full web server is available at http

  14. Identifying microRNA/mRNA dysregulations in ovarian cancer.

    Science.gov (United States)

    Miles, Gregory D; Seiler, Michael; Rodriguez, Lorna; Rajagopal, Gunaretnam; Bhanot, Gyan

    2012-03-27

    MicroRNAs are a class of noncoding RNA molecules that co-regulate the expression of multiple genes via mRNA transcript degradation or translation inhibition. Since they often target entire pathways, they may be better drug targets than genes or proteins. MicroRNAs are known to be dysregulated in many tumours and associated with aggressive or poor prognosis phenotypes. Since they regulate mRNA in a tissue specific manner, their functional mRNA targets are poorly understood. In previous work, we developed a method to identify direct mRNA targets of microRNA using patient matched microRNA/mRNA expression data using an anti-correlation signature. This method, applied to clear cell Renal Cell Carcinoma (ccRCC), revealed many new regulatory pathways compromised in ccRCC. In the present paper, we apply this method to identify dysregulated microRNA/mRNA mechanisms in ovarian cancer using data from The Cancer Genome Atlas (TCGA). TCGA Microarray data was normalized and samples whose class labels (tumour or normal) were ambiguous with respect to consensus ensemble K-Means clustering were removed. Significantly anti-correlated and correlated genes/microRNA differentially expressed between tumour and normal samples were identified. TargetScan was used to identify gene targets of microRNA. We identified novel microRNA/mRNA mechanisms in ovarian cancer. For example, the expression level of RAD51AP1 was found to be strongly anti-correlated with the expression of hsa-miR-140-3p, which was significantly down-regulated in the tumour samples. The anti-correlation signature was present separately in the tumour and normal samples, suggesting a direct causal dysregulation of RAD51AP1 by hsa-miR-140-3p in the ovary. Other pairs of potentially biological relevance include: hsa-miR-145/E2F3, hsa-miR-139-5p/TOP2A, and hsa-miR-133a/GCLC. We also identified sets of positively correlated microRNA/mRNA pairs that are most likely result from indirect regulatory mechanisms. Our findings identify

  15. RNA-PAIRS: RNA probabilistic assignment of imino resonance shifts

    International Nuclear Information System (INIS)

    Bahrami, Arash; Clos, Lawrence J.; Markley, John L.; Butcher, Samuel E.; Eghbalnia, Hamid R.

    2012-01-01

    The significant biological role of RNA has further highlighted the need for improving the accuracy, efficiency and the reach of methods for investigating RNA structure and function. Nuclear magnetic resonance (NMR) spectroscopy is vital to furthering the goals of RNA structural biology because of its distinctive capabilities. However, the dispersion pattern in the NMR spectra of RNA makes automated resonance assignment, a key step in NMR investigation of biomolecules, remarkably challenging. Herein we present RNA Probabilistic Assignment of Imino Resonance Shifts (RNA-PAIRS), a method for the automated assignment of RNA imino resonances with synchronized verification and correction of predicted secondary structure. RNA-PAIRS represents an advance in modeling the assignment paradigm because it seeds the probabilistic network for assignment with experimental NMR data, and predicted RNA secondary structure, simultaneously and from the start. Subsequently, RNA-PAIRS sets in motion a dynamic network that reverberates between predictions and experimental evidence in order to reconcile and rectify resonance assignments and secondary structure information. The procedure is halted when assignments and base-parings are deemed to be most consistent with observed crosspeaks. The current implementation of RNA-PAIRS uses an initial peak list derived from proton-nitrogen heteronuclear multiple quantum correlation ( 1 H– 15 N 2D HMQC) and proton–proton nuclear Overhauser enhancement spectroscopy ( 1 H– 1 H 2D NOESY) experiments. We have evaluated the performance of RNA-PAIRS by using it to analyze NMR datasets from 26 previously studied RNAs, including a 111-nucleotide complex. For moderately sized RNA molecules, and over a range of comparatively complex structural motifs, the average assignment accuracy exceeds 90%, while the average base pair prediction accuracy exceeded 93%. RNA-PAIRS yielded accurate assignments and base pairings consistent with imino resonances for a

  16. RNA-PAIRS: RNA probabilistic assignment of imino resonance shifts

    Energy Technology Data Exchange (ETDEWEB)

    Bahrami, Arash; Clos, Lawrence J.; Markley, John L.; Butcher, Samuel E. [National Magnetic Resonance Facility at Madison (United States); Eghbalnia, Hamid R., E-mail: eghbalhd@uc.edu [University of Cincinnati, Department of Molecular and Cellular Physiology (United States)

    2012-04-15

    The significant biological role of RNA has further highlighted the need for improving the accuracy, efficiency and the reach of methods for investigating RNA structure and function. Nuclear magnetic resonance (NMR) spectroscopy is vital to furthering the goals of RNA structural biology because of its distinctive capabilities. However, the dispersion pattern in the NMR spectra of RNA makes automated resonance assignment, a key step in NMR investigation of biomolecules, remarkably challenging. Herein we present RNA Probabilistic Assignment of Imino Resonance Shifts (RNA-PAIRS), a method for the automated assignment of RNA imino resonances with synchronized verification and correction of predicted secondary structure. RNA-PAIRS represents an advance in modeling the assignment paradigm because it seeds the probabilistic network for assignment with experimental NMR data, and predicted RNA secondary structure, simultaneously and from the start. Subsequently, RNA-PAIRS sets in motion a dynamic network that reverberates between predictions and experimental evidence in order to reconcile and rectify resonance assignments and secondary structure information. The procedure is halted when assignments and base-parings are deemed to be most consistent with observed crosspeaks. The current implementation of RNA-PAIRS uses an initial peak list derived from proton-nitrogen heteronuclear multiple quantum correlation ({sup 1}H-{sup 15}N 2D HMQC) and proton-proton nuclear Overhauser enhancement spectroscopy ({sup 1}H-{sup 1}H 2D NOESY) experiments. We have evaluated the performance of RNA-PAIRS by using it to analyze NMR datasets from 26 previously studied RNAs, including a 111-nucleotide complex. For moderately sized RNA molecules, and over a range of comparatively complex structural motifs, the average assignment accuracy exceeds 90%, while the average base pair prediction accuracy exceeded 93%. RNA-PAIRS yielded accurate assignments and base pairings consistent with imino

  17. RNA SURVEILLANCE– AN EMERGING ROLE FOR RNA REGULATORY NETWORKS IN AGING

    OpenAIRE

    Montano, Monty; Long, Kimberly

    2010-01-01

    In this review, we describe recent advances in the field of RNA regulatory biology and relate these advances to aging science. We introduce a new term, RNA surveillance, an RNA regulatory process that is conserved in metazoans, and describe how RNA surveillance represents molecular cross-talk between two emerging RNA regulatory systems – RNA interference and RNA editing. We discuss how RNA surveillance mechanisms influence mRNA and microRNA expression and activity during lifespan. Additionall...

  18. On RNA-RNA interaction structures of fixed topological genus.

    Science.gov (United States)

    Fu, Benjamin M M; Han, Hillary S W; Reidys, Christian M

    2015-04-01

    Interacting RNA complexes are studied via bicellular maps using a filtration via their topological genus. Our main result is a new bijection for RNA-RNA interaction structures and a linear time uniform sampling algorithm for RNA complexes of fixed topological genus. The bijection allows to either reduce the topological genus of a bicellular map directly, or to lose connectivity by decomposing the complex into a pair of single stranded RNA structures. Our main result is proved bijectively. It provides an explicit algorithm of how to rewire the corresponding complexes and an unambiguous decomposition grammar. Using the concept of genus induction, we construct bicellular maps of fixed topological genus g uniformly in linear time. We present various statistics on these topological RNA complexes and compare our findings with biological complexes. Furthermore we show how to construct loop-energy based complexes using our decomposition grammar. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. antaRNA: ant colony-based RNA sequence design.

    Science.gov (United States)

    Kleinkauf, Robert; Mann, Martin; Backofen, Rolf

    2015-10-01

    RNA sequence design is studied at least as long as the classical folding problem. Although for the latter the functional fold of an RNA molecule is to be found ,: inverse folding tries to identify RNA sequences that fold into a function-specific target structure. In combination with RNA-based biotechnology and synthetic biology ,: reliable RNA sequence design becomes a crucial step to generate novel biochemical components. In this article ,: the computational tool antaRNA is presented. It is capable of compiling RNA sequences for a given structure that comply in addition with an adjustable full range objective GC-content distribution ,: specific sequence constraints and additional fuzzy structure constraints. antaRNA applies ant colony optimization meta-heuristics and its superior performance is shown on a biological datasets. http://www.bioinf.uni-freiburg.de/Software/antaRNA CONTACT: backofen@informatik.uni-freiburg.de Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  20. RNA İNTERFERANS (RNAİ)

    OpenAIRE

    GÜNDOĞDU, Ramazan; ÇELİK, Venhar

    2009-01-01

    RNA interferans, uygun çift zincirli RNA’nın hücreye girdiği zaman, endojenik komplementer mRNA dizisinin parçalanmasına yol açan, transkripsiyon sonrası gen susturma mekanizmasıdır. RNA interferans, Dicer adı verilen bir RNase III enzimi tarafından çift zincirli RNA’nın küçük engelleyici RNA’lara (siRNA) kesilmesi ile başlamaktadır. Bu siRNA’lar daha sonra, bir multiprotein-RNA nükleaz kompleksi olan, RNA- indükleyici baskılama kompleksine (RISC) bağlanır. RISC, siRNA’ları komplementer mRNA’...

  1. Radiation sensitivity of messenger RNA

    International Nuclear Information System (INIS)

    Ponta, H.; Pfennig-Yeh, M.L.; Herrlich, P.; Karlsruhe Univ.; Wagner, E.F.; Schweiger, M.

    1979-01-01

    Messenger RNA function is inactivated by irradiation with ultraviolet light. A unit length mRNA (in bases) is 2-3 times more sensitive than a unit length of DNA (in base pairs) with respect to the inactivation of template function. These data stem from four experimental systems all of which do not repair DNA: the translation of E. coli mRNA in rifampicin-treated cells, of T7 mRNA in infected E.coli, of f2 phage RNA in vivo, and of stable mRNA in chromosomeless minicells. The comparison of relative sensitivities to UV is relevant to the technique of UV mapping of transcription units which enjoys increasing popularity in pro- and eukaryotic genetic research. (orig.) [de

  2. Radiation sensitivity of messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Ponta, H; Pfennig-Yeh, M L; Herrlich, P [Kernforschungszentrum Karlsruhe G.m.b.H. (Germany, F.R.). Inst. fuer Genetik und Toxikologie von Spaltstoffen; Karlsruhe Univ. (TH) (Germany, F.R.). Inst. fuer Genetik); Wagner, E F; Schweiger, M [Innsbruck Univ. (Austria). Inst. fuer Biochemie

    1979-08-01

    Messenger RNA function is inactivated by irradiation with ultraviolet light. A unit length mRNA (in bases) is 2-3 times more sensitive than a unit length of DNA (in base pairs) with respect to the inactivation of template function. These data stem from four experimental systems all of which do not repair DNA: the translation of E. coli mRNA in rifampicin-treated cells, of T7 mRNA in infected E.coli, of f2 phage RNA in vivo, and of stable mRNA in chromosomeless minicells. The comparison of relative sensitivities to UV is relevant to the technique of UV mapping of transcription units which enjoys increasing popularity in pro- and eukaryotic genetic research.

  3. RNase-assisted RNA chromatography

    Science.gov (United States)

    Michlewski, Gracjan; Cáceres, Javier F.

    2010-01-01

    RNA chromatography combined with mass spectrometry represents a widely used experimental approach to identify RNA-binding proteins that recognize specific RNA targets. An important drawback of most of these protocols is the high background due to direct or indirect nonspecific binding of cellular proteins to the beads. In many cases this can hamper the detection of individual proteins due to their low levels and/or comigration with contaminating proteins. Increasing the salt concentration during washing steps can reduce background, but at the cost of using less physiological salt concentrations and the likely loss of important RNA-binding proteins that are less stringently bound to a given RNA, as well as the disassembly of protein or ribonucleoprotein complexes. Here, we describe an improved RNA chromatography method that relies on the use of a cocktail of RNases in the elution step. This results in the release of proteins specifically associated with the RNA ligand and almost complete elimination of background noise, allowing a more sensitive and thorough detection of RNA-binding proteins recognizing a specific RNA transcript. PMID:20571124

  4. RNA interference in Lepidoptera

    DEFF Research Database (Denmark)

    Terenius, Ole; Papanicolaou, Alexie; Garbutt, Jennie S.

    2011-01-01

    in RNAi experiments in Lepidoptera are discussed. The review also points to a need to further investigate the mechanism of RNAi in lepidopteran insects and its possible connection to the innate immune response. Our general understanding of RNAi in Lepidoptera will be further aided in the future as our...... experiments have not been collected in such a way that they are possible to analyze. In this review, we have collected detailed data from more than 150 experiments including all to date published and many unpublished experiments. Despite a large variation in the data, trends that are found are that RNAi...... is particularly successful in the family Saturniidae and in genes involved in immunity. On the contrary, gene expression in epidermal tissues seems to be most difficult to silence. In addition, gene silencing by feeding dsRNA requires high concentrations for success. Possible causes for the variability of success...

  5. Concepts and introduction to RNA bioinformatics

    DEFF Research Database (Denmark)

    Gorodkin, Jan; Hofacker, Ivo L.; Ruzzo, Walter L.

    2014-01-01

    RNA bioinformatics and computational RNA biology have emerged from implementing methods for predicting the secondary structure of single sequences. The field has evolved to exploit multiple sequences to take evolutionary information into account, such as compensating (and structure preserving) base...... for interactions between RNA and proteins.Here, we introduce the basic concepts of predicting RNA secondary structure relevant to the further analyses of RNA sequences. We also provide pointers to methods addressing various aspects of RNA bioinformatics and computational RNA biology....

  6. Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

    OpenAIRE

    Zhang, Yunpeng; Liu, Wei; Xu, Yanjun; Li, Chunquan; Wang, Yingying; Yang, Haixiu; Zhang, Chunlong; Su, Fei; Li, Yixue; Li, Xia

    2015-01-01

    Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it i...

  7. Bifurcations in the interplay of messenger RNA, protein and nonprotein coding RNA

    International Nuclear Information System (INIS)

    Zhdanov, Vladimir P

    2008-01-01

    The interplay of messenger RNA (mRNA), protein, produced via translation of this RNA, and nonprotein coding RNA (ncRNA) may include regulation of the ncRNA production by protein and (i) ncRNA-protein association resulting in suppression of the protein regulatory activity or (ii) ncRNA-mRNA association resulting in degradation of the miRNA-mRNA complex. The kinetic models describing these two scenarios are found to predict bistability provided that protein suppresses the ncRNA formation

  8. 34A, miRNA-944, miRNA-101 and miRNA-218 in cervical cancer

    African Journals Online (AJOL)

    RNAs (21 - 24 nucleotides in length) that are critical for many important processes such as development, ... RNA extraction and reverse transcription. Total RNA was extracted from each of the experimental groups using ... used as an endogenous control to normalize the expression of miRNA-143, miRNA-34A, miRNA-.

  9. Nuclear Export of Messenger RNA

    Directory of Open Access Journals (Sweden)

    Jun Katahira

    2015-03-01

    Full Text Available Transport of messenger RNA (mRNA from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex.

  10. RNA viruses in the sea.

    Science.gov (United States)

    Lang, Andrew S; Rise, Matthew L; Culley, Alexander I; Steward, Grieg F

    2009-03-01

    Viruses are ubiquitous in the sea and appear to outnumber all other forms of marine life by at least an order of magnitude. Through selective infection, viruses influence nutrient cycling, community structure, and evolution in the ocean. Over the past 20 years we have learned a great deal about the diversity and ecology of the viruses that constitute the marine virioplankton, but until recently the emphasis has been on DNA viruses. Along with expanding knowledge about RNA viruses that infect important marine animals, recent isolations of RNA viruses that infect single-celled eukaryotes and molecular analyses of the RNA virioplankton have revealed that marine RNA viruses are novel, widespread, and genetically diverse. Discoveries in marine RNA virology are broadening our understanding of the biology, ecology, and evolution of viruses, and the epidemiology of viral diseases, but there is still much that we need to learn about the ecology and diversity of RNA viruses before we can fully appreciate their contributions to the dynamics of marine ecosystems. As a step toward making sense of how RNA viruses contribute to the extraordinary viral diversity in the sea, we summarize in this review what is currently known about RNA viruses that infect marine organisms.

  11. Nuclear Export of Messenger RNA

    Science.gov (United States)

    Katahira, Jun

    2015-01-01

    Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP) particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex. PMID:25836925

  12. MOA-2011-BLG-262Lb: A sub-Earth-mass moon orbiting a gas giant primary or a high velocity planetary system in the galactic Bulge

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, D. P. [Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556 (United States); Batista, V. [Department of Astronomy, Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Bond, I. A.; Ling, C. H. [Institute of Natural and Mathematical Sciences, Massey University, Auckland 0745 (New Zealand); Bennett, C. S. [Department of Physics, Massachussets Institute of Technology, Cambridge, MA 02139 (United States); Suzuki, D.; Koshimoto, N. [Department of Earth and Space Science, Osaka University, Osaka 560-0043 (Japan); Beaulieu, J.-P. [UPMC-CNRS, UMR 7095, Institut d' Astrophysique de Paris, 98bis Boulevard Arago, F-75014 Paris (France); Udalski, A. [Warsaw University Observatory, Al. Ujazdowskie 4, 00-478 Warszawa (Poland); Donatowicz, J. [Technische Universität Wien, Wieder Hauptst. 8-10, A-1040 Vienna (Austria); Bozza, V. [Dipartimento di Fisica, Università di Salerno, Via Ponte Don Melillo 132, I-84084 Fisciano (Italy); Abe, F.; Fukunaga, D.; Itow, Y.; Masuda, K.; Matsubara, Y.; Muraki, Y. [Solar-Terrestrial Environment Laboratory, Nagoya University, Nagoya 464-8601 (Japan); Botzler, C. S.; Freeman, M. [Department of Physics, University of Auckland, Private Bag 92-019, Auckland 1001 (New Zealand); Fukui, A., E-mail: bennett@nd.edu [Okayama Astrophysical Observatory, National Astronomical Observatory of Japan, Okayama 719-0232 (Japan); Collaboration: MOA Collaboration; PLANET Collaboration; μFUN Collaboration; OGLE Collaboration; RoboNet Collaboration; and others

    2014-04-20

    We present the first microlensing candidate for a free-floating exoplanet-exomoon system, MOA-2011-BLG-262, with a primary lens mass of M {sub host} ∼ 4 Jupiter masses hosting a sub-Earth mass moon. The argument for an exomoon hinges on the system being relatively close to the Sun. The data constrain the product M{sub L} π{sub rel} where M{sub L} is the lens system mass and π{sub rel} is the lens-source relative parallax. If the lens system is nearby (large π{sub rel}), then M{sub L} is small (a few Jupiter masses) and the companion is a sub-Earth-mass exomoon. The best-fit solution has a large lens-source relative proper motion, μ{sub rel} = 19.6 ± 1.6 mas yr{sup –1}, which would rule out a distant lens system unless the source star has an unusually high proper motion. However, data from the OGLE collaboration nearly rule out a high source proper motion, so the exoplanet+exomoon model is the favored interpretation for the best fit model. However, there is an alternate solution that has a lower proper motion and fits the data almost as well. This solution is compatible with a distant (so stellar) host. A Bayesian analysis does not favor the exoplanet+exomoon interpretation, so Occam's razor favors a lens system in the bulge with host and companion masses of M{sub host}=0.12{sub −0.06}{sup +0.19} M{sub ⊙} and m{sub comp}=18{sub −10}{sup +28} M{sub ⊕}, at a projected separation of a{sub ⊥}=0.84{sub −0.14}{sup +0.25} AU. The existence of this degeneracy is an unlucky accident, so current microlensing experiments are in principle sensitive to exomoons. In some circumstances, it will be possible to definitively establish the mass of such lens systems through the microlensing parallax effect. Future experiments will be sensitive to less extreme exomoons.

  13. Transfecting Human Monocytes with RNA.

    Science.gov (United States)

    Dannull, Jens; Nair, Smita K

    2016-01-01

    Targeting monocytes as a delivery system for drugs or nucleic acids, and thereby harnessing their natural tissue-infiltrating capacity, has become an area of intense investigation in both basic and clinical research. Herein we describe an efficient method to deliver mRNA (messenger RNA) or siRNA (small interfering RNA) into human monocytes by electroporation. This method can be applied in the laboratory to monocytes isolated via magnetic bead-based techniques, or in a clinical setting using monocytes that were collected via counterflow centrifugation elutriation using the Elutra(®) Cell Separation System. We further demonstrate that electroporation of monocytes with RNA represents a robust and highly relevant approach to modify monocytes for cell-based therapies. Last, the procedure described can readily be adapted to monocytes from different species, hence facilitating research in animal models.

  14. Fast prediction of RNA-RNA interaction using heuristic algorithm.

    Science.gov (United States)

    Montaseri, Soheila

    2015-01-01

    Interaction between two RNA molecules plays a crucial role in many medical and biological processes such as gene expression regulation. In this process, an RNA molecule prohibits the translation of another RNA molecule by establishing stable interactions with it. Some algorithms have been formed to predict the structure of the RNA-RNA interaction. High computational time is a common challenge in most of the presented algorithms. In this context, a heuristic method is introduced to accurately predict the interaction between two RNAs based on minimum free energy (MFE). This algorithm uses a few dot matrices for finding the secondary structure of each RNA and binding sites between two RNAs. Furthermore, a parallel version of this method is presented. We describe the algorithm's concurrency and parallelism for a multicore chip. The proposed algorithm has been performed on some datasets including CopA-CopT, R1inv-R2inv, Tar-Tar*, DIS-DIS, and IncRNA54-RepZ in Escherichia coli bacteria. The method has high validity and efficiency, and it is run in low computational time in comparison to other approaches.

  15. The RNA synthesis machinery of negative-stranded RNA viruses

    Energy Technology Data Exchange (ETDEWEB)

    Ortín, Juan, E-mail: jortin@cnb.csic.es [Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CSIC) and CIBER de Enfermedades Respiratorias (ISCIII), Madrid (Spain); Martín-Benito, Jaime, E-mail: jmartinb@cnb.csic.es [Department of Macromolecular Structures, Centro Nacional de Biotecnología (CSIC), Madrid (Spain)

    2015-05-15

    The group of Negative-Stranded RNA Viruses (NSVs) includes many human pathogens, like the influenza, measles, mumps, respiratory syncytial or Ebola viruses, which produce frequent epidemics of disease and occasional, high mortality outbreaks by transmission from animal reservoirs. The genome of NSVs consists of one to several single-stranded, negative-polarity RNA molecules that are always assembled into mega Dalton-sized complexes by association to many nucleoprotein monomers. These RNA-protein complexes or ribonucleoproteins function as templates for transcription and replication by action of the viral RNA polymerase and accessory proteins. Here we review our knowledge on these large RNA-synthesis machines, including the structure of their components, the interactions among them and their enzymatic activities, and we discuss models showing how they perform the virus transcription and replication programmes. - Highlights: • Overall organisation of NSV RNA synthesis machines. • Structure and function of the ribonucleoprotein components: Atomic structure of the RNA polymerase complex. • Commonalities and differences between segmented- and non-segmented NSVs. • Transcription versus replication programmes.

  16. The RNA synthesis machinery of negative-stranded RNA viruses

    International Nuclear Information System (INIS)

    Ortín, Juan; Martín-Benito, Jaime

    2015-01-01

    The group of Negative-Stranded RNA Viruses (NSVs) includes many human pathogens, like the influenza, measles, mumps, respiratory syncytial or Ebola viruses, which produce frequent epidemics of disease and occasional, high mortality outbreaks by transmission from animal reservoirs. The genome of NSVs consists of one to several single-stranded, negative-polarity RNA molecules that are always assembled into mega Dalton-sized complexes by association to many nucleoprotein monomers. These RNA-protein complexes or ribonucleoproteins function as templates for transcription and replication by action of the viral RNA polymerase and accessory proteins. Here we review our knowledge on these large RNA-synthesis machines, including the structure of their components, the interactions among them and their enzymatic activities, and we discuss models showing how they perform the virus transcription and replication programmes. - Highlights: • Overall organisation of NSV RNA synthesis machines. • Structure and function of the ribonucleoprotein components: Atomic structure of the RNA polymerase complex. • Commonalities and differences between segmented- and non-segmented NSVs. • Transcription versus replication programmes

  17. Generation of miRNA sponge constructs

    NARCIS (Netherlands)

    Kluiver, Joost; Slezak-Prochazka, Izabella; Smigielska-Czepiel, Katarzyna; Halsema, Nancy; Kroesen, Bart-Jan; van den Berg, Anke

    2012-01-01

    MicroRNA (miRNA) sponges are RNA molecules with repeated miRNA antisense sequences that can sequester miRNAs from their endogenous targets and thus serve as a decoy. Stably expressed miRNA sponges are especially valuable for long-term loss-of-function studies and can be used in vitro and in vivo. We

  18. microRNA-independent recruitment of Argonaute 1 to nanos mRNA through the Smaug RNA-binding protein

    OpenAIRE

    Pinder, Benjamin D; Smibert, Craig A

    2012-01-01

    Argonaute 1 directly interacts with the RNA binding protein Smaug in Drosophila, is thereby recruited to the Smaug target nanos mRNA and is required for Smaug-mediated translational repression of the nanos mRNA.

  19. IntaRNA 2.0: enhanced and customizable prediction of RNA-RNA interactions.

    Science.gov (United States)

    Mann, Martin; Wright, Patrick R; Backofen, Rolf

    2017-07-03

    The IntaRNA algorithm enables fast and accurate prediction of RNA-RNA hybrids by incorporating seed constraints and interaction site accessibility. Here, we introduce IntaRNAv2, which enables enhanced parameterization as well as fully customizable control over the prediction modes and output formats. Based on up to date benchmark data, the enhanced predictive quality is shown and further improvements due to more restrictive seed constraints are highlighted. The extended web interface provides visualizations of the new minimal energy profiles for RNA-RNA interactions. These allow a detailed investigation of interaction alternatives and can reveal potential interaction site multiplicity. IntaRNAv2 is freely available (source and binary), and distributed via the conda package manager. Furthermore, it has been included into the Galaxy workflow framework and its already established web interface enables ad hoc usage. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Direct, rapid RNA sequence analysis

    International Nuclear Information System (INIS)

    Peattie, D.A.

    1987-01-01

    The original methods of RNA sequence analysis were based on enzymatic production and chromatographic separation of overlapping oligonucleotide fragments from within an RNA molecule followed by identification of the mononucleotides comprising the oligomer. Over the past decade the field of nucleic acid sequencing has changed dramatically, however, and RNA molecules now can be sequenced in a variety of more streamlined fashions. Most of the more recent advances in RNA sequencing have involved one-dimensional electrophoretic separation of 32 P-end-labeled oligoribonucleotides on polyacrylamide gels. In this chapter the author discusses two of these methods for determining the nucleotide sequences of RNA molecules rapidly: the chemical method and the enzymatic method. Both methods are direct and degradative, i.e., they rely on fragmatic and chemical approaches should be utilized. The single-strand-specific ribonucleases (A, T 1 , T 2 , and S 1 ) provide an efficient means to locate double-helical regions rapidly, and the chemical reactions provide a means to determine the RNA sequence within these regions. In addition, the chemical reactions allow one to assign interactions to specific atoms and to distinguish secondary interactions from tertiary ones. If the RNA molecule is small enough to be sequenced directly by the enzymatic or chemical method, the probing reactions can be done easily at the same time as sequencing reactions

  1. Cofactors in the RNA World

    Science.gov (United States)

    Ditzler, Mark A.

    2014-01-01

    RNA world theories figure prominently in many scenarios for the origin and early evolution of life. These theories posit that RNA molecules played a much larger role in ancient biology than they do now, acting both as the dominant biocatalysts and as the repository of genetic information. Many features of modern RNA biology are potential examples of molecular fossils from an RNA world, such as the pervasive involvement of nucleotides in coenzymes, the existence of natural aptamers that bind these coenzymes, the existence of natural ribozymes, a biosynthetic pathway in which deoxynucleotides are produced from ribonucleotides, and the central role of ribosomal RNA in protein synthesis in the peptidyl transferase center of the ribosome. Here, we uses both a top-down approach that evaluates RNA function in modern biology and a bottom-up approach that examines the capacities of RNA independent of modern biology. These complementary approaches exploit multiple in vitro evolution techniques coupled with high-throughput sequencing and bioinformatics analysis. Together these complementary approaches advance our understanding of the most primitive organisms, their early evolution, and their eventual transition to modern biochemistry.

  2. Efficient RNA structure comparison algorithms.

    Science.gov (United States)

    Arslan, Abdullah N; Anandan, Jithendar; Fry, Eric; Monschke, Keith; Ganneboina, Nitin; Bowerman, Jason

    2017-12-01

    Recently proposed relative addressing-based ([Formula: see text]) RNA secondary structure representation has important features by which an RNA structure database can be stored into a suffix array. A fast substructure search algorithm has been proposed based on binary search on this suffix array. Using this substructure search algorithm, we present a fast algorithm that finds the largest common substructure of given multiple RNA structures in [Formula: see text] format. The multiple RNA structure comparison problem is NP-hard in its general formulation. We introduced a new problem for comparing multiple RNA structures. This problem has more strict similarity definition and objective, and we propose an algorithm that solves this problem efficiently. We also develop another comparison algorithm that iteratively calls this algorithm to locate nonoverlapping large common substructures in compared RNAs. With the new resulting tools, we improved the RNASSAC website (linked from http://faculty.tamuc.edu/aarslan ). This website now also includes two drawing tools: one specialized for preparing RNA substructures that can be used as input by the search tool, and another one for automatically drawing the entire RNA structure from a given structure sequence.

  3. A review on architecture of the gag-pol ribosomal frameshifting RNA in human immunodeficiency virus: a variability survey of virus genotypes.

    Science.gov (United States)

    Qiao, Qi; Yan, Yanhua; Guo, Jinmei; Du, Shuqiang; Zhang, Jiangtao; Jia, Ruyue; Ren, Haimin; Qiao, Yuanbiao; Li, Qingshan

    2017-06-01

    Programmed '-1' ribosomal frameshifting is necessary for expressing the pol gene overlapped from a gag of human immunodeficiency virus. A viral RNA structure that requires base pairing across the overlapping sequence region suggests a mechanism of regulating ribosome and helicase traffic during expression. To get precise roles of an element around the frameshift site, a review on architecture of the frameshifting RNA is performed in combination of reported information with augments of a representative set of 19 viral samples. In spite of a different length for the viral RNAs, a canonical comparison on the element sequence allocation is performed for viewing variability associations between virus genotypes. Additionally, recent and historical insights recognized in frameshifting regulation are looked back as for indel and single nucleotide polymorphism of RNA. As specially noted, structural changes at a frameshift site, the spacer sequence, and a three-helix junction element, as well as two Watson-Crick base pairs near a bulge and a C-G pair close a loop, are the most vital strategies for the virus frameshifting regulations. All of structural changes, which are dependent upon specific sequence variations, facilitate an elucidation about the RNA element conformation-dependent mechanism for frameshifting. These facts on disrupting base pair interactions also allow solving the problem of competition between ribosome and helicase on a same RNA template, common to single-stranded RNA viruses. In a broad perspective, each new insight of frameshifting regulation in the competition systems introduced by the RNA element construct changes will offer a compelling target for antiviral therapy.

  4. Alternative RNA splicing and cancer

    Science.gov (United States)

    Liu, Sali; Cheng, Chonghui

    2015-01-01

    Alternative splicing of pre-messenger RNA (mRNA) is a fundamental mechanism by which a gene can give rise to multiple distinct mRNA transcripts, yielding protein isoforms with different, even opposing, functions. With the recognition that alternative splicing occurs in nearly all human genes, its relationship with cancer-associated pathways has emerged as a rapidly growing field. In this review, we summarize recent findings that have implicated the critical role of alternative splicing in cancer and discuss current understandings of the mechanisms underlying dysregulated alternative splicing in cancer cells. PMID:23765697

  5. The ViennaRNA web services.

    Science.gov (United States)

    Gruber, Andreas R; Bernhart, Stephan H; Lorenz, Ronny

    2015-01-01

    The ViennaRNA package is a widely used collection of programs for thermodynamic RNA secondary structure prediction. Over the years, many additional tools have been developed building on the core programs of the package to also address issues related to noncoding RNA detection, RNA folding kinetics, or efficient sequence design considering RNA-RNA hybridizations. The ViennaRNA web services provide easy and user-friendly web access to these tools. This chapter describes how to use this online platform to perform tasks such as prediction of minimum free energy structures, prediction of RNA-RNA hybrids, or noncoding RNA detection. The ViennaRNA web services can be used free of charge and can be accessed via http://rna.tbi.univie.ac.at.

  6. Rapid Generation of MicroRNA Sponges for MicroRNA Inhibition

    NARCIS (Netherlands)

    Kluiver, Joost; Gibcus, Johan H.; Hettinga, Chris; Adema, Annelies; Richter, Mareike K. S.; Halsema, Nancy; Slezak-Prochazka, Izabella; Ding, Ye; Kroesen, Bart-Jan; van den Berg, Anke

    2012-01-01

    MicroRNA (miRNA) sponges are transcripts with repeated miRNA antisense sequences that can sequester miRNAs from endogenous targets. MiRNA sponges are valuable tools for miRNA loss-of-function studies both in vitro and in vivo. We developed a fast and flexible method to generate miRNA sponges and

  7. Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

    Directory of Open Access Journals (Sweden)

    Yunpeng Zhang

    2015-01-01

    Full Text Available Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it is important to identify subtype specific miRNA-mRNA modules. In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data. We applied our method on a heterogeneous disease, multiple myeloma (MM, to identify MM subtype specific MFRMs. The constructed miRNA-mRNA regulatory networks provide modular outlook at subtype specific miRNA-mRNA interactions. Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes. These subtype specific MFRMs may aid in the further elucidation of the pathogenesis of each subtype and may serve to guide MM subtype diagnosis and treatment.

  8. Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop

    Science.gov (United States)

    Upert, Gregory; Di Giorgio, Audrey; Upadhyay, Alok; Manvar, Dinesh; Pandey, Nootan; Pandey, Virendra N.; Patino, Nadia

    2012-01-01

    Human immunodeficiency virus-1 (HIV-1) replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR), to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP) cation-based vectors that efficiently deliver nucleotide analogs (PNAs) into the cytoplasm of cells. In particular, we showed that the TPP conjugate of a linear 16-mer PNA targeting the apical stem-loop region of TAR impedes Tat-mediated transactivation of the HIV-1 LTR in vitro and also in cell culture systems. In this communication, we conjugated TPP to cyclic and hairpin PNAs targeting the loop region of HIV-1 TAR and evaluated their antiviral efficacy in a cell culture system. We found that TPP-cyclic PNAs containing only 8 residues, showed higher antiviral potency compared to hairpin PNAs of 12 or 16 residues. We further noted that the TPP-conjugates of the 8-mer cyclic PNA as well as the 16-mer linear PNA displayed similar antiviral efficacy. However, cyclic PNAs were shown to be highly specific to their target sequences. This communication emphasizes on the importance of small constrained cyclic PNAs over both linear and hairpin structures for targeting biologically relevant RNA hairpins. PMID:23029603

  9. Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop

    Directory of Open Access Journals (Sweden)

    Gregory Upert

    2012-01-01

    Full Text Available Human immunodeficiency virus-1 (HIV-1 replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR, to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP cation-based vectors that efficiently deliver nucleotide analogs (PNAs into the cytoplasm of cells. In particular, we showed that the TPP conjugate of a linear 16-mer PNA targeting the apical stem-loop region of TAR impedes Tat-mediated transactivation of the HIV-1 LTR in vitro and also in cell culture systems. In this communication, we conjugated TPP to cyclic and hairpin PNAs targeting the loop region of HIV-1 TAR and evaluated their antiviral efficacy in a cell culture system. We found that TPP-cyclic PNAs containing only 8 residues, showed higher antiviral potency compared to hairpin PNAs of 12 or 16 residues. We further noted that the TPP-conjugates of the 8-mer cyclic PNA as well as the 16-mer linear PNA displayed similar antiviral efficacy. However, cyclic PNAs were shown to be highly specific to their target sequences. This communication emphasizes on the importance of small constrained cyclic PNAs over both linear and hairpin structures for targeting biologically relevant RNA hairpins.

  10. Predicting and Modeling RNA Architecture

    Science.gov (United States)

    Westhof, Eric; Masquida, Benoît; Jossinet, Fabrice

    2011-01-01

    SUMMARY A general approach for modeling the architecture of large and structured RNA molecules is described. The method exploits the modularity and the hierarchical folding of RNA architecture that is viewed as the assembly of preformed double-stranded helices defined by Watson-Crick base pairs and RNA modules maintained by non-Watson-Crick base pairs. Despite the extensive molecular neutrality observed in RNA structures, specificity in RNA folding is achieved through global constraints like lengths of helices, coaxiality of helical stacks, and structures adopted at the junctions of helices. The Assemble integrated suite of computer tools allows for sequence and structure analysis as well as interactive modeling by homology or ab initio assembly with possibilities for fitting within electronic density maps. The local key role of non-Watson-Crick pairs guides RNA architecture formation and offers metrics for assessing the accuracy of three-dimensional models in a more useful way than usual root mean square deviation (RMSD) values. PMID:20504963

  11. Shielding the messenger (RNA): microRNA-based anticancer therapies

    Science.gov (United States)

    Sotillo, Elena; Thomas-Tikhonenko, Andrei

    2011-01-01

    It has been a decade since scientists realized that microRNAs (miRNAs) are not an oddity invented by worms to regulate gene expression at post-transcriptional levels. Rather, many of these 21–22-nucleotide-short RNAs exist in invertebrates and vertebrates alike and some of them are in fact highly conserved. miRNAs are now recognized as an important class of non-coding small RNAs that inhibit gene expression by targeting mRNA stability and translation. In the last ten years, our knowledge of the miRNAs world was expanding at vertiginous speed, propelled by the development of computational engines for miRNA identification and target prediction, biochemical tools and techniques to modulate miRNA activity, and last but not least, the emergence of miRNA-centric animal models. One important conclusion that has emerged from this effort is that many microRNAs and their cognate targets are strongly implicated in cancer, either as oncogenes or tumor and metastasis suppressors. In this review we will discuss the diverse role that miRNAs play in cancer initiation and progression and also the tools with which miRNA expression could be corrected in vivo. While the idea of targeting microRNAs towards therapeutic ends is getting considerable traction, basic, translational, and clinical research done in the next few years will tell whether this promise is well-founded. PMID:21514318

  12. Chaperoning 5S RNA assembly.

    Science.gov (United States)

    Madru, Clément; Lebaron, Simon; Blaud, Magali; Delbos, Lila; Pipoli, Juliana; Pasmant, Eric; Réty, Stéphane; Leulliot, Nicolas

    2015-07-01

    In eukaryotes, three of the four ribosomal RNAs (rRNAs)—the 5.8S, 18S, and 25S/28S rRNAs—are processed from a single pre-rRNA transcript and assembled into ribosomes. The fourth rRNA, the 5S rRNA, is transcribed by RNA polymerase III and is assembled into the 5S ribonucleoprotein particle (RNP), containing ribosomal proteins Rpl5/uL18 and Rpl11/uL5, prior to its incorporation into preribosomes. In mammals, the 5S RNP is also a central regulator of the homeostasis of the tumor suppressor p53. The nucleolar localization of the 5S RNP and its assembly into preribosomes are performed by a specialized complex composed of Rpf2 and Rrs1 in yeast or Bxdc1 and hRrs1 in humans. Here we report the structural and functional characterization of the Rpf2-Rrs1 complex alone, in complex with the 5S RNA, and within pre-60S ribosomes. We show that the Rpf2-Rrs1 complex contains a specialized 5S RNA E-loop-binding module, contacts the Rpl5 protein, and also contacts the ribosome assembly factor Rsa4 and the 25S RNA. We propose that the Rpf2-Rrs1 complex establishes a network of interactions that guide the incorporation of the 5S RNP in preribosomes in the initial conformation prior to its rotation to form the central protuberance found in the mature large ribosomal subunit. © 2015 Madru et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Differential Regulation of rRNA and tRNA Transcription from the rRNA-tRNA Composite Operon in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Hiraku Takada

    Full Text Available Escherichia coli contains seven rRNA operons, each consisting of the genes for three rRNAs (16S, 23S and 5S rRNA in this order and one or two tRNA genes in the spacer between 16S and 23S rRNA genes and one or two tRNA genes in the 3' proximal region. All of these rRNA and tRNA genes are transcribed from two promoters, P1 and P2, into single large precursors that are afterward processed to individual rRNAs and tRNAs by a set of RNases. In the course of Genomic SELEX screening of promoters recognized by RNA polymerase (RNAP holoenzyme containing RpoD sigma, a strong binding site was identified within 16S rRNA gene in each of all seven rRNA operons. The binding in vitro of RNAP RpoD holoenzyme to an internal promoter, referred to the promoter of riRNA (an internal RNA of the rRNA operon, within each 16S rRNA gene was confirmed by gel shift assay and AFM observation. Using this riRNA promoter within the rrnD operon as a representative, transcription in vitro was detected with use of the purified RpoD holoenzyme, confirming the presence of a constitutive promoter in this region. LacZ reporter assay indicated that this riRNA promoter is functional in vivo. The location of riRNA promoter in vivo as identified using a set of reporter plasmids agrees well with that identified in vitro. Based on transcription profile in vitro and Northern blot analysis in vivo, the majority of transcript initiated from this riRNA promoter was estimated to terminate near the beginning of 23S rRNA gene, indicating that riRNA leads to produce the spacer-coded tRNA. Under starved conditions, transcription of the rRNA operon is markedly repressed to reduce the intracellular level of ribosomes, but the levels of both riRNA and its processed tRNAGlu stayed unaffected, implying that riRNA plays a role in the continued steady-state synthesis of tRNAs from the spacers of rRNA operons. We then propose that the tRNA genes organized within the spacers of rRNA-tRNA composite operons

  14. RegRNA: an integrated web server for identifying regulatory RNA motifs and elements

    OpenAIRE

    Huang, Hsi-Yuan; Chien, Chia-Hung; Jen, Kuan-Hua; Huang, Hsien-Da

    2006-01-01

    Numerous regulatory structural motifs have been identified as playing essential roles in transcriptional and post-transcriptional regulation of gene expression. RegRNA is an integrated web server for identifying the homologs of regulatory RNA motifs and elements against an input mRNA sequence. Both sequence homologs and structural homologs of regulatory RNA motifs can be recognized. The regulatory RNA motifs supported in RegRNA are categorized into several classes: (i) motifs in mRNA 5′-untra...

  15. Analysis of intermolecular RNA-RNA recombination by rubella virus

    International Nuclear Information System (INIS)

    Adams, Sandra D.; Tzeng, W.-P.; Chen, M.-H.; Frey, Teryl K.

    2003-01-01

    To investigate whether rubella virus (RUB) undergoes intermolecular RNA-RNA recombination, cells were cotransfected with pairs of in vitro transcripts from genomic cDNA plasmid vectors engineered to contain nonoverlapping deletions: the replicative transcript maintained the 5'-proximal nonstructural (NS) ORF (which contained the replicase, making it RNA replication competent), had a deletion in the 3'-proximal structural protein (SP) ORF, and maintained the 3' end of the genome, including the putative 3' cis-acting elements (CSE), while the nonreplicative transcript consisted of the 3' half of the genome including the SP-ORF and 3' CSE. Cotransfection yielded plaque-forming virus that synthesized the standard genomic and subgenomic RNAs and thus was generated by RNA-RNA recombination. Using transcripts tagged with a 3'-terminal deletion, it was found that recombinants contained the 3' end derived from the replicative strand, indicating a cis-preference for initiation of negative-strand synthesis. In cotransfections in which the replicative transcript lacked the 3' CSE, recombination occurred, albeit at lower efficiency, indicating that initiation in trans from the NS-ORF can occur. The 3' CSE was sufficient as a nonreplicative transcript, showing that it can serve as a promoter for negative-strand RNA synthesis. While deletion mutagenesis showed that the presence of the junction untranslated region (J-UTR) between the ORFs appeared to be necessary on both transcripts for recombination in this region of the genome, analysis with transcripts tagged with restriction sites showed that the J-UTR was not a hot spot for recombination compared to neighboring regions in both ORFs. Sequence analysis of recombinants revealed that both precise (homologous) and imprecise recombination (aberrant, homologous resulting in duplications) occurred; however, imprecise recombination only involved the J-UTR or the 3' end of the NS-ORF and the J-UTR (maintaining the NS-ORF), indicating

  16. MicroRNA mimicry blocks pulmonary fibrosis

    NARCIS (Netherlands)

    Montgomery, Rusty L; Yu, Guoying; Latimer, Paul A; Stack, Christianna; Robinson, Kathryn; Dalby, Christina M; Kaminski, Naftali; van Rooij, Eva

    2014-01-01

    Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular

  17. Biochemistry and Function of the RNA Exosomes

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon; Chlebowski, Aleksander; Dziembowski, Andrzej

    2012-01-01

    Discovery of the evolutionary conserved RNA exosome was a milestone in RNA biology. First identified as an activity essential for the processing of ribosomal RNA, the exosome has since proved to be central for RNA processing and degradation in both the nucleus and the cytoplasm of eukaryotic cell...

  18. The crystal structure of tRNA

    Indian Academy of Sciences (India)

    Madhu

    of yeast alanine tRNA by Robert Holley's group at Cornell. University ... decode nonsense codons) with John Smith and Brenner. However, my ... tRNA from 10 g of unfractionated tRNA. ... tRNA crystals were, in fact, protein (Hendrikson et al.

  19. A discontinuous RNA platform mediates RNA virus replication: building an integrated model for RNA-based regulation of viral processes.

    Directory of Open Access Journals (Sweden)

    Baodong Wu

    2009-03-01

    Full Text Available Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA-RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA-RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA-based interaction spanning approximately 3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes.

  20. Glia to axon RNA transfer.

    Science.gov (United States)

    Sotelo, José Roberto; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José Roberto; Calliari, Aldo; Cal, Karina; Bresque, Mariana; Dipaolo, Andrés; Farias, Joaquina; Mercer, John A

    2014-03-01

    The existence of RNA in axons has been a matter of dispute for decades. Evidence for RNA and ribosomes has now accumulated to a point at which it is difficult to question, much of the disputes turned to the origin of these axonal RNAs. In this review, we focus on studies addressing the origin of axonal RNAs and ribosomes. The neuronal soma as the source of most axonal RNAs has been demonstrated and is indisputable. However, the surrounding glial cells may be a supplemental source of axonal RNAs, a matter scarcely investigated in the literature. Here, we review the few papers that have demonstrated that glial-to-axon RNA transfer is not only feasible, but likely. We describe this process in both invertebrate axons and vertebrate axons. Schwann cell to axon ribosomes transfer was conclusively demonstrated (Court et al. [2008]: J. Neurosci 28:11024-11029; Court et al. [2011]: Glia 59:1529-1539). However, mRNA transfer still remains to be demonstrated in a conclusive way. The intercellular transport of mRNA has interesting implications, particularly with respect to the integration of glial and axonal function. This evolving field is likely to impact our understanding of the cell biology of the axon in both normal and pathological conditions. Most importantly, if the synthesis of proteins in the axon can be controlled by interacting glia, the possibilities for clinical interventions in injury and neurodegeneration are greatly increased. Copyright © 2013 Wiley Periodicals, Inc.

  1. On topological RNA interaction structures.

    Science.gov (United States)

    Qin, Jing; Reidys, Christian M

    2013-07-01

    Recently a folding algorithm of topological RNA pseudoknot structures was presented in Reidys et al. (2011). This algorithm folds single-stranded γ-structures, that is, RNA structures composed by distinct motifs of bounded topological genus. In this article, we set the theoretical foundations for the folding of the two backbone analogues of γ structures: the RNA γ-interaction structures. These are RNA-RNA interaction structures that are constructed by a finite number of building blocks over two backbones having genus at most γ. Combinatorial properties of γ-interaction structures are of practical interest since they have direct implications for the folding of topological interaction structures. We compute the generating function of γ-interaction structures and show that it is algebraic, which implies that the numbers of interaction structures can be computed recursively. We obtain simple asymptotic formulas for 0- and 1-interaction structures. The simplest class of interaction structures are the 0-interaction structures, which represent the two backbone analogues of secondary structures.

  2. Tapping the RNA world for therapeutics.

    Science.gov (United States)

    Lieberman, Judy

    2018-04-16

    A recent revolution in RNA biology has led to the identification of new RNA classes with unanticipated functions, new types of RNA modifications, an unexpected multiplicity of alternative transcripts and widespread transcription of extragenic regions. This development in basic RNA biology has spawned a corresponding revolution in RNA-based strategies to generate new types of therapeutics. Here, I review RNA-based drug design and discuss barriers to broader applications and possible ways to overcome them. Because they target nucleic acids rather than proteins, RNA-based drugs promise to greatly extend the domain of 'druggable' targets beyond what can be achieved with small molecules and biologics.

  3. RNA-Based Vaccines in Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Megan A. McNamara

    2015-01-01

    Full Text Available RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

  4. A Regulatory RNA Inducing Transgenerationally Inherited Phenotypes

    DEFF Research Database (Denmark)

    Jensen, Lea Møller

    . The variation in Arabidopsis enables different regulatory networks and mechanisms to shape the phenotypic characteristics. The thesis describes the identification of regulatory RNA encoded by an enzyme encoding gene. The RNA regulates by inducing transgenerationally inherited phenotypes. The function of the RNA...... is dependent on the genetic background illustrating that polymorphisms are found in either interactors or target genes of the RNA. Furthermore, the RNA provides a mechanistic link between accumulation of glucosinolate and onset of flowering....

  5. Screening of Modified RNA duplexes

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Bramsen, Jesper Bertram; Kjems, Jørgen

    protection against a fish pathogenic virus. This protection corresponded with an interferon response in the fish. Here we use this fish model to screen siRNAs containing various chemical modifications of the RNA backbone for their antiviral activity, the overall aim being identification of an siRNA form......Because of sequence specific gene targeting activity siRNAs are regarded as promising active compounds in gene medicine. But one serious problem with delivering siRNAs as treatment is the now well-established non-specific activities of some RNA duplexes. Cellular reactions towards double stranded...... RNAs include the 2´-5´ oligoadenylate synthetase system, the protein kinase R, RIG-I and Toll-like receptor activated pathways all resulting in antiviral defence mechanism. We have previously shown that antiviral innate immune reactions against double stranded RNAs could be detected in vivo as partial...

  6. TargetRNA: a tool for predicting targets of small RNA action in bacteria

    OpenAIRE

    Tjaden, Brian

    2008-01-01

    Many small RNA (sRNA) genes in bacteria act as posttranscriptional regulators of target messenger RNAs. Here, we present TargetRNA, a web tool for predicting mRNA targets of sRNA action in bacteria. TargetRNA takes as input a genomic sequence that may correspond to an sRNA gene. TargetRNA then uses a dynamic programming algorithm to search each annotated message in a specified genome for mRNAs that evince basepair-binding potential to the input sRNA sequence. Based on the calculated basepair-...

  7. RNA-dependent RNA polymerases from cowpea mosaic virus-infected cowpea leaves

    NARCIS (Netherlands)

    Dorssers, L.

    1983-01-01

    The aim of the research described in this thesis was the purification and identification of the RNA-dependent RNA polymerase engaged in replicating viral RNA in cowpea mosaic virus (CPMV)- infected cowpea leaves.

    Previously, an RNA-dependent RNA polymerase produced upon infection of

  8. RNA Study Using DNA Nanotechnology.

    Science.gov (United States)

    Tadakuma, Hisashi; Masubuchi, Takeya; Ueda, Takuya

    2016-01-01

    Transcription is one of the fundamental steps of gene expression, where RNA polymerases (RNAPs) bind to their template genes and make RNAs. In addition to RNAP and the template gene, many molecules such as transcription factors are involved. The interaction and the effect of these factors depend on the geometry. Molecular layout of these factors, RNAP and gene is thus important. DNA nanotechnology is a promising technology that allows controlling of the molecular layout in the range of nanometer to micrometer scale with nanometer resolution; thus, it is expected to expand the RNA study beyond the current limit. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Isolation of Microarray-Grade Total RNA, MicroRNA, and DNA from a Single PAXgene Blood RNA Tube

    DEFF Research Database (Denmark)

    Kruhøffer, Mogens; Andersen, Lars Dyrskjøt; Voss, Thorsten

    2007-01-01

    We have developed a procedure for isolation of microRNA and genomic DNA in addition to total RNA from whole blood stabilized in PAXgene Blood RNA tubes. The procedure is based on automatic extraction on a BioRobot MDx and includes isolation of DNA from a fraction of the stabilized blood...... and recovery of small RNA species that are otherwise lost. The procedure presented here is suitable for large-scale experiments and is amenable to further automation. Procured total RNA and DNA was tested using Affymetrix Expression and single-nucleotide polymorphism GeneChips, respectively, and isolated micro......RNA was tested using spotted locked nucleic acid-based microarrays. We conclude that the yield and quality of total RNA, microRNA, and DNA from a single PAXgene blood RNA tube is sufficient for downstream microarray analysis....

  10. microRNA-independent recruitment of Argonaute 1 to nanos mRNA through the Smaug RNA-binding protein.

    Science.gov (United States)

    Pinder, Benjamin D; Smibert, Craig A

    2013-01-01

    Argonaute (Ago) proteins are typically recruited to target messenger RNAs via an associated small RNA such as a microRNA (miRNA). Here, we describe a new mechanism of Ago recruitment through the Drosophila Smaug RNA-binding protein. We show that Smaug interacts with the Ago1 protein, and that Ago1 interacts with and is required for the translational repression of the Smaug target, nanos mRNA. The Ago1/nanos mRNA interaction does not require a miRNA, but it does require Smaug. Taken together, our data suggest a model whereby Smaug directly recruits Ago1 to nanos mRNA in a miRNA-independent manner, thereby repressing translation.

  11. Cyclophilin B stimulates RNA synthesis by the HCV RNA dependent RNA polymerase.

    Science.gov (United States)

    Heck, Julie A; Meng, Xiao; Frick, David N

    2009-04-01

    Cyclophilins are cellular peptidyl isomerases that have been implicated in regulating hepatitis C virus (HCV) replication. Cyclophilin B (CypB) is a target of cyclosporin A (CsA), an immunosuppressive drug recently shown to suppress HCV replication in cell culture. Watashi et al. recently demonstrated that CypB is important for efficient HCV replication, and proposed that it mediates the anti-HCV effects of CsA through an interaction with NS5B [Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell 2005;19:111-22]. We examined the effects of purified CypB proteins on the enzymatic activity of NS5B. Recombinant CypB purified from insect cells directly stimulated NS5B-catalyzed RNA synthesis. CypB increased RNA synthesis by NS5B derived from genotype 1a, 1b, and 2a HCV strains. Stimulation appears to arise from an increase in productive RNA binding. NS5B residue Pro540, a previously proposed target of CypB peptidyl-prolyl isomerase activity, is not required for stimulation of RNA synthesis.

  12. Role of CBCA in RNA biogenesis

    DEFF Research Database (Denmark)

    Iasillo, Claudia

    RNA transcription and RNA processing are key steps in eukaryotic gene expression, which includes, therefore, RNA synthesis by RNA polymerase enzymes and a range of modifications of the pre-mRNA before the transcript can leave the nucleus and reach the cytoplasm for translation. Interestingly......, a large body of evidence suggests that these RNA processing events occur often already during transcription. One of these modifications, the co-transcriptional 5’ end capping of a nascent RNA, is occurring specifically during RNA polymerase II (RNAPII) transcription. The 5’ cap exerts its role via...... the nuclear Cap Binding Complex (CBC). This thesis focuses on the protein ARS2, which binds the CBC to form the CBCA complex. CBCA can further associate with different proteins playing different roles in RNA metabolism. For example, CBCA binds the Nuclear Exosome Targeting Complex (NEXT), which...

  13. Hydration dependent dynamics in RNA

    International Nuclear Information System (INIS)

    Olsen, Greg L.; Bardaro, Michael F.; Echodu, Dorothy C.; Drobny, Gary P.; Varani, Gabriele

    2009-01-01

    The essential role played by local and collective motions in RNA function has led to a growing interest in the characterization of RNA dynamics. Recent investigations have revealed that even relatively simple RNAs experience complex motions over multiple time scales covering the entire ms-ps motional range. In this work, we use deuterium solid-state NMR to systematically investigate motions in HIV-1 TAR RNA as a function of hydration. We probe dynamics at three uridine residues in different structural environments ranging from helical to completely unrestrained. We observe distinct and substantial changes in 2 H solid-state relaxation times and lineshapes at each site as hydration levels increase. By comparing solid-state and solution state 13 C relaxation measurements, we establish that ns-μs motions that may be indicative of collective dynamics suddenly arise in the RNA as hydration reaches a critical point coincident with the onset of bulk hydration. Beyond that point, we observe smaller changes in relaxation rates and lineshapes in these highly hydrated solid samples, compared to the dramatic activation of motion occurring at moderate hydration

  14. RNA Editing in Plant Mitochondria

    Science.gov (United States)

    Hiesel, Rudolf; Wissinger, Bernd; Schuster, Wolfgang; Brennicke, Axel

    1989-12-01

    Comparative sequence analysis of genomic and complementary DNA clones from several mitochondrial genes in the higher plant Oenothera revealed nucleotide sequence divergences between the genomic and the messenger RNA-derived sequences. These sequence alterations could be most easily explained by specific post-transcriptional nucleotide modifications. Most of the nucleotide exchanges in coding regions lead to altered codons in the mRNA that specify amino acids better conserved in evolution than those encoded by the genomic DNA. Several instances show that the genomic arginine codon CGG is edited in the mRNA to the tryptophan codon TGG in amino acid positions that are highly conserved as tryptophan in the homologous proteins of other species. This editing suggests that the standard genetic code is used in plant mitochondria and resolves the frequent coincidence of CGG codons and tryptophan in different plant species. The apparently frequent and non-species-specific equivalency of CGG and TGG codons in particular suggests that RNA editing is a common feature of all higher plant mitochondria.

  15. Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal

    OpenAIRE

    Narayanan, Krishna; Chen, Chun-Jen; Maeda, Junko; Makino, Shinji

    2003-01-01

    For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) protein is the first step described in the process of viral RNA packaging. In the murine coronavirus a selective interaction between the viral transmembrane envelope protein M and the viral ribonucleoprotein complex, composed of N protein and viral RNA containing a short cis-acting RNA element, the packaging signal, determines the selective RNA packaging into vi...

  16. Modular arrangement of regulatory RNA elements.

    Science.gov (United States)

    Roßmanith, Johanna; Narberhaus, Franz

    2017-03-04

    Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities. Here, we compare natural examples of tandem riboswitches with recently designed artificial RNA regulators suggesting substantial modularity of regulatory RNA elements. Challenges associated with modular RNA design are discussed.

  17. MicroRNA Delivery for Regenerative Medicine

    OpenAIRE

    Peng, Bo; Chen, Yongming; Leong, Kam W.

    2015-01-01

    MicroRNA (miRNA) directs post-transcriptional regulation of a network of genes by targeting mRNA. Although relatively recent in development, many miRNAs direct differentiation of various stem cells including induced pluripotent stem cells (iPSCs), a major player in regenerative medicine. An effective and safe delivery of miRNA holds the key to translating miRNA technologies. Both viral and nonviral delivery systems have seen success in miRNA delivery, and each approach possesses advantages an...

  18. Viral RNA polymerase scanning and the gymnastics of Sendai virus RNA synthesis

    International Nuclear Information System (INIS)

    Kolakofsky, Daniel; Le Mercier, Philippe; Iseni, Frederic; Garcin, Dominique

    2004-01-01

    mRNA synthesis from nonsegmented negative-strand RNA virus (NNV) genomes is unique in that the genome RNA is embedded in an N protein assembly (the nucleocapsid) and the viral RNA polymerase does not dissociate from the template after release of each mRNA, but rather scans the genome RNA for the next gene-start site. A revised model for NNV RNA synthesis is presented, in which RNA polymerase scanning plays a prominent role. Polymerase scanning of the template is known to occur as the viral transcriptase negotiates gene junctions without falling off the template

  19. iDoRNA: An Interacting Domain-based Tool for Designing RNA-RNA Interaction Systems

    Directory of Open Access Journals (Sweden)

    Jittrawan Thaiprasit

    2016-03-01

    Full Text Available RNA-RNA interactions play a crucial role in gene regulation in living organisms. They have gained increasing interest in the field of synthetic biology because of their potential applications in medicine and biotechnology. However, few novel regulators based on RNA-RNA interactions with desired structures and functions have been developed due to the challenges of developing design tools. Recently, we proposed a novel tool, called iDoDe, for designing RNA-RNA interacting sequences by first decomposing RNA structures into interacting domains and then designing each domain using a stochastic algorithm. However, iDoDe did not provide an optimal solution because it still lacks a mechanism to optimize the design. In this work, we have further developed the tool by incorporating a genetic algorithm (GA to find an RNA solution with maximized structural similarity and minimized hybridized RNA energy, and renamed the tool iDoRNA. A set of suitable parameters for the genetic algorithm were determined and found to be a weighting factor of 0.7, a crossover rate of 0.9, a mutation rate of 0.1, and the number of individuals per population set to 8. We demonstrated the performance of iDoRNA in comparison with iDoDe by using six RNA-RNA interaction models. It was found that iDoRNA could efficiently generate all models of interacting RNAs with far more accuracy and required far less computational time than iDoDe. Moreover, we compared the design performance of our tool against existing design tools using forty-four RNA-RNA interaction models. The results showed that the performance of iDoRNA is better than RiboMaker when considering the ensemble defect, the fitness score and computation time usage. However, it appears that iDoRNA is outperformed by NUPACK and RNAiFold 2.0 when considering the ensemble defect. Nevertheless, iDoRNA can still be an useful alternative tool for designing novel RNA-RNA interactions in synthetic biology research. The source code of iDoRNA

  20. Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers

    Science.gov (United States)

    Feng, Li; Li, Feng; Sun, Zeguo; Wu, Tan; Shi, Xinrui; Li, Jing; Li, Xia

    2016-01-01

    Recent studies indicate that long noncoding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) to indirectly regulate mRNAs through shared microRNAs, which represents a novel layer of RNA crosstalk and plays critical roles in the development of tumor. However, the global regulation landscape and characterization of these lncRNA related ceRNA crosstalk in cancers is still largely unknown. Here, we systematically characterized the lncRNA related ceRNA interactions across 12 major cancers and the normal physiological states by integrating multidimensional molecule profiles of more than 5000 samples. Our study suggest the large difference of ceRNA regulation between normal and tumor states and the higher similarity across similar tissue origin of tumors. The ceRNA related molecules have more conserved features in tumor networks and they play critical roles in both the normal and tumorigenesis processes. Besides, lncRNAs in the pan-cancer ceRNA network may be potential biomarkers of tumor. By exploring hub lncRNAs, we found that these conserved key lncRNAs dominate variable tumor hallmark processes across pan-cancers. Network dynamic analysis highlights the critical roles of ceRNA regulation in tumorigenesis. By analyzing conserved ceRNA interactions, we found that miRNA mediate ceRNA regulation showed different patterns across pan-cancer; while analyzing the cancer specific ceRNA interactions reveal that lncRNAs synergistically regulated tumor driver genes of cancer hallmarks. Finally, we found that ceRNA modules have the potential to predict patient survival. Overall, our study systematically dissected the lncRNA related ceRNA networks in pan-cancer that shed new light on understanding the molecular mechanism of tumorigenesis. PMID:27580177

  1. Application of Live-Cell RNA Imaging Techniques to the Study of Retroviral RNA Trafficking

    Directory of Open Access Journals (Sweden)

    Darrin V. Bann

    2012-06-01

    Full Text Available Retroviruses produce full-length RNA that serves both as a genomic RNA (gRNA, which is encapsidated into virus particles, and as an mRNA, which directs the synthesis of viral structural proteins. However, we are only beginning to understand the cellular and viral factors that influence trafficking of retroviral RNA and the selection of the RNA for encapsidation or translation. Live cell imaging studies of retroviral RNA trafficking have provided important insight into many aspects of the retrovirus life cycle including transcription dynamics, nuclear export of viral RNA, translational regulation, membrane targeting, and condensation of the gRNA during virion assembly. Here, we review cutting-edge techniques to visualize single RNA molecules in live cells and discuss the application of these systems to studying retroviral RNA trafficking.

  2. How the RNA isolation method can affect microRNA microarray results

    DEFF Research Database (Denmark)

    Podolska, Agnieszka; Kaczkowski, Bogumil; Litman, Thomas

    2011-01-01

    RNA microarray analysis on porcine brain tissue. One method is a phenol-guanidine isothiocyanate-based procedure that permits isolation of total RNA. The second method, miRVana™ microRNA isolation, is column based and recovers the small RNA fraction alone. We found that microarray analyses give different results...... that depend on the RNA fraction used, in particular because some microRNAs appear very sensitive to the RNA isolation method. We conclude that precautions need to be taken when comparing microarray studies based on RNA isolated with different methods.......The quality of RNA is crucial in gene expression experiments. RNA degradation interferes in the measurement of gene expression, and in this context, microRNA quantification can lead to an incorrect estimation. In the present study, two different RNA isolation methods were used to perform micro...

  3. Topology and prediction of RNA pseudoknots

    DEFF Research Database (Denmark)

    Reidys, Christian; Huang, Fenix; Andersen, Jørgen Ellegaard

    2011-01-01

    Motivation: Several dynamic programming algorithms for predicting RNA structures with pseudoknots have been proposed that differ dramatically from one another in the classes of structures considered. Results: Here, we use the natural topological classification of RNA structures in terms...

  4. RNA Structural Alignments, Part I

    DEFF Research Database (Denmark)

    Havgaard, Jakob Hull; Gorodkin, Jan

    2014-01-01

    Simultaneous alignment and secondary structure prediction of RNA sequences is often referred to as "RNA structural alignment." A class of the methods for structural alignment is based on the principles proposed by Sankoff more than 25 years ago. The Sankoff algorithm simultaneously folds and aligns...... is so high that it took more than a decade before the first implementation of a Sankoff style algorithm was published. However, with the faster computers available today and the improved heuristics used in the implementations the Sankoff-based methods have become practical. This chapter describes...... the methods based on the Sankoff algorithm. All the practical implementations of the algorithm use heuristics to make them run in reasonable time and memory. These heuristics are also described in this chapter....

  5. Fatgraph models of RNA structure

    Directory of Open Access Journals (Sweden)

    Huang Fenix

    2017-01-01

    Full Text Available In this review paper we discuss fatgraphs as a conceptual framework for RNA structures. We discuss various notions of coarse-grained RNA structures and relate them to fatgraphs.We motivate and discuss the main intuition behind the fatgraph model and showcase its applicability to canonical as well as noncanonical base pairs. Recent discoveries regarding novel recursions of pseudoknotted (pk configurations as well as their translation into context-free grammars for pk-structures are discussed. This is shown to allow for extending the concept of partition functions of sequences w.r.t. a fixed structure having non-crossing arcs to pk-structures. We discuss minimum free energy folding of pk-structures and combine these above results outlining how to obtain an inverse folding algorithm for PK structures.

  6. RNA

    African Journals Online (AJOL)

    SARAH

    30 nov. 2013 ... Keywords: FMNR, mode of management, re-greening, leadership, evolutionary trend. INTRODUCTION .... régénération : L'évolution de la densité des ligneux entre. 2005 et 2012 ..... la production et la qualité fourragères de la.

  7. Nonradioactive RNA mobility shift with chemiluminescent detection ...

    African Journals Online (AJOL)

    hesham

    RNA mobility shift is one among many procedures used to study RNA-protein interaction. Yet, there are some limitations for the radioactive RNA mobility shift including; 1) the risk of using radiolabeled nucleotides, 2) the long time to get the results; this could range from days to weeks, and 3) its high cost as compared to ...

  8. Optimization of chemiluminescent detection of mitochondrial RNA ...

    African Journals Online (AJOL)

    RNA mobility shift is one among many procedures used to study RNA-protein interaction. Yet, there are some limitations for the radioactive RNA mobility shift including; 1) the risk of using radiolabeled nucleotides, 2) the long time to get the results; this could range from days to weeks, and 3) its high cost as compared to ...

  9. RNA polymerase activity of Ustilago maydis virus

    Energy Technology Data Exchange (ETDEWEB)

    Yie, S.W.

    1986-01-01

    Ustilago maydis virus has an RNA polymerase enzyme which is associated with virion capsids. In the presence of Mg/sup 2 +/ ion and ribonucleotide triphosphate, the enzyme catalyzes the in vitro synthesis of mRNA by using dsRNA as a template. The products of the UmV RNA polymerase were both ssRNA and dsRNA. The dsRNA was determined by characteristic mobilities in gel electrophoresis, lack of sensitivity to RNase, and specific hybridization tests. The ssRNAs were identified by elution from a CF-11 column and by their RNase sensitivity. On the basis of the size of ssRNAs, it was concluded that partial transcripts were produced from H dsRNA segments, and full length transcripts were produced from M and L dsRNA segments. The following observations indicates that transcription occurs by strand displacement; (1) Only the positive strand of M2 dsRNA was labeled by the in vitro reaction. (2) The M2 dsRNA which had been labeled with /sup 32/''P-UTP in vitro could be chased from dsRNA with unlabeled UTP. The transcription products of three UmV strains were compared, and the overall pattern of transcription was very similar among them.

  10. Analysis of RNA metabolism in fission yeast

    DEFF Research Database (Denmark)

    Wise, Jo Ann; Nielsen, Olaf

    2017-01-01

    Here we focus on the biogenesis and function of messenger RNA (mRNA) in fission yeast cells. Following a general introduction that also briefly touches on other classes of RNA, we provide an overview of methods used to analyze mRNAs throughout their life cycles....

  11. Tospovirus : induction and suppression of RNA silencing

    NARCIS (Netherlands)

    Hedil, Marcio

    2016-01-01

    While infecting their hosts, viruses must deal with host immunity. In plants the antiviral RNA silencing pathway is an important part of plant innate immunity. Tospoviruses are segmented negative-stranded RNA viruses of plants. To counteract the antiviral RNA silencing response in plants,

  12. Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins

    Directory of Open Access Journals (Sweden)

    Gayani N. P. Dedduwa-Mudalige

    2015-09-01

    Full Text Available Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA including siRNA, spliceosomal RNAs, tRNA, and rRNA. All of these RNAs play vital roles in the cell, such as catalysis of protein synthesis by rRNA, and therefore serve as potential drug targets. This work focused on platination of two highly conserved RNA hairpins from E. coli ribosomes, namely pseudouridine-modified helix 69 from 23S rRNA and the 790 loop of helix 24 from 16S rRNA. RNase T1 probing, MALDI mass spectrometry, and dimethyl sulfate mapping revealed platination at GpG sites. Chemical probing results also showed platination-induced RNA structural changes. These findings reveal solvent and structural accessibility of sites within bacterial RNA secondary structures that are functionally significant and therefore viable targets for cisplatin as well as other classes of small molecules. Identifying target preferences at the nucleotide level, as well as determining cisplatin-induced RNA conformational changes, is important for the design of more potent drug molecules. Furthermore, the knowledge gained through studies of RNA-targeting by cisplatin is applicable to a broad range of organisms from bacteria to human.

  13. Small catalytic RNA: Structure, function and application

    Energy Technology Data Exchange (ETDEWEB)

    Monforte, Joseph Albert [Univ. of California, Berkeley, CA (United States)

    1991-04-01

    We have utilized a combination of photochemical cross-linking techniques and site-directed mutagenesis to obtain secondary and tertiary structure information for the self-cleaving, self-ligating subsequence of RNA from the negative strand of Satellite Tobacco Ringspot Virus. We have found that the helical regions fold about a hinge to promoting four different possible tertiary interactions, creating a molecular of similar shape to a paperclip. A model suggesting that the ``paperclip`` and ``hammerhead`` RNAs share a similar three dimensional structure is proposed. We have used a self-cleaving RNA molecule related to a subsequence of plant viroids, a ``hammerhead,`` to study the length-dependent folding of RNA produced during transcription by RNA polymerase. We have used this method to determine the length of RNA sequestered within elongating E. coli and T7 RNA polymerase complexes. The data show that for E. coli RNA polymerase 121±s are sequestered within the ternary complex, which is consistent with the presence of an RNA-DNA hybrid within the transcription bubble, as proposed by others. The result for T7 RNA polymerase differs from E. coli RNA polymerase, with only 10{plus_minus}1 nucleotides sequestered within the ternary complex, setting a new upper limit for the minimum RNA-DNA required for a stable elongating complex. Comparisons between E. coli and T7 RNA polymerase are made. The relevance of the results to models or transcription termination, abortive initiation, and initiation to elongation mode transitions are discussed.

  14. Supplementary data: Materials and methods RNA expression ...

    Indian Academy of Sciences (India)

    ritt8

    Supplementary data: Materials and methods. RNA expression analysis. Freshly collected tissue was taken in TRIzol reagent for total RNA isolation according to the manufacturer's protocol. The cDNA synthesis was carried out in 1 μg total RNA using Random hexamer (Invitrogen, Carlsbad, USA) and Superscript III ...

  15. Regulatory RNAs derived from transfer RNA?

    Science.gov (United States)

    Pederson, Thoru

    2010-10-01

    Four recent studies suggest that cleavages of transfer RNAs generate products with microRNA-like features, with some evidence of function. If their regulatory functions were to be confirmed, these newly revealed RNAs would add to the expanding repertoire of small noncoding RNAs and would also provide new perspectives on the coevolution of transfer RNA and messenger RNA.

  16. Regulatory BC1 RNA in Cognitive Control

    Science.gov (United States)

    Iacoangeli, Anna; Dosunmu, Aderemi; Eom, Taesun; Stefanov, Dimitre G.; Tiedge, Henri

    2017-01-01

    Dendritic regulatory BC1 RNA is a non-protein-coding (npc) RNA that operates in the translational control of gene expression. The absence of BC1 RNA in BC1 knockout (KO) animals causes translational dysregulation that entails neuronal phenotypic alterations including prolonged epileptiform discharges, audiogenic seizure activity in vivo, and…

  17. Primer-dependent and primer-independent initiation of double stranded RNA synthesis by purified arabidopsis RNA-dependent RNA polymerases RDR2 and RDR6

    DEFF Research Database (Denmark)

    Devert, Anthony; Fabre, Nicolas; Floris, Maina Huguette Joséphine

    2015-01-01

    ) targeted by RNA silencing. The dsRNA is subsequently cleaved by the ribonuclease DICER-like into secondary small interfering RNAs (siRNAs) that reinforce and/or maintain the silenced state of the target RNA. Models of RNA silencing propose that RDRs could use primer-independent and primer......Cellular RNA-dependent RNA polymerases (RDRs) are fundamental components of RNA silencing in plants and many other eukaryotes. In Arabidopsis thaliana genetic studies have demonstrated that RDR2 and RDR6 are involved in the synthesis of double stranded RNA (dsRNA) from single stranded RNA (ssRNA......-dependent initiation to generate dsRNA from a transcript targeted by primary siRNA or microRNA (miRNA). However, the biochemical activities of RDR proteins are still partly understood. Here, we obtained active recombinant RDR2 and RDR6 in a purified form. We demonstrate that RDR2 and RDR6 have primer...

  18. Effective Anti-miRNA Oligonucleotides Show High Releasing Rate of MicroRNA from RNA-Induced Silencing Complex.

    Science.gov (United States)

    Ariyoshi, Jumpei; Matsuyama, Yohei; Kobori, Akio; Murakami, Akira; Sugiyama, Hiroshi; Yamayoshi, Asako

    2017-10-01

    MicroRNAs (miRNAs) regulate gene expression by forming RNA-induced silencing complexes (RISCs) and have been considered as promising therapeutic targets. MiRNA is an essential component of RISC for the modulation of gene expression. Therefore, the release of miRNA from RISC is considered as an effective method for the inhibition of miRNA functions. In our previous study, we reported that anti-miRNA oligonucleotides (AMOs), which are composed of the 2'-O-methyl (2'-OMe) RNA, could induce the release of miRNA from RISC. However, the mechanisms underlying the miRNA-releasing effects of chemically modified AMOs, which are conventionally used as anti-cancer drugs, are still unclear. In this study, we investigated the relationship between the miRNA releasing rate from RISC and the inhibitory effect on RISC activity (IC 50 ) using conventional chemically modified AMOs. We demonstrated that the miRNA-releasing effects of AMOs are directly proportional to the IC 50 values, and AMOs, which have an ability to promote the release of miRNA from RISC, can effectively inhibit RISC activity in living cells.

  19. Diverging affinity of tospovirus RNA silencing suppressor proteins, NSs, for various RNA duplex molecules.

    Science.gov (United States)

    Schnettler, Esther; Hemmes, Hans; Huismann, Rik; Goldbach, Rob; Prins, Marcel; Kormelink, Richard

    2010-11-01

    The tospovirus NSs protein was previously shown to suppress the antiviral RNA silencing mechanism in plants. Here the biochemical analysis of NSs proteins from different tospoviruses, using purified NSs or NSs containing cell extracts, is described. The results showed that all tospoviral NSs proteins analyzed exhibited affinity to small double-stranded RNA molecules, i.e., small interfering RNAs (siRNAs) and micro-RNA (miRNA)/miRNA* duplexes. Interestingly, the NSs proteins from tomato spotted wilt virus (TSWV), impatiens necrotic spot virus (INSV), and groundnut ringspot virus (GRSV) also showed affinity to long double-stranded RNA (dsRNA), whereas tomato yellow ring virus (TYRV) NSs did not. The TSWV NSs protein was shown to be capable of inhibiting Dicer-mediated cleavage of long dsRNA in vitro. In addition, it suppressed the accumulation of green fluorescent protein (GFP)-specific siRNAs during coinfiltration with an inverted-repeat-GFP RNA construct in Nicotiana benthamiana. In vivo interference of TSWV NSs in the miRNA pathway was shown by suppression of an enhanced GFP (eGFP) miRNA sensor construct. The ability to stabilize miRNA/miRNA* by different tospovirus NSs proteins in vivo was demonstrated by increased accumulation and detection of both miRNA171c and miRNA171c* in tospovirus-infected N. benthamiana. All together, these data suggest that tospoviruses interfere in the RNA silencing pathway by sequestering siRNA and miRNA/miRNA* molecules before they are uploaded into their respective RNA-induced silencing complexes. The observed affinity to long dsRNA for only a subset of the tospoviruses studied is discussed in light of evolutional divergence and their ancestral relation to the animal-infecting members of the Bunyaviridae.

  20. Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing.

    Science.gov (United States)

    Goldfarb, Katherine C; Cech, Thomas R

    2017-01-01

    MRP RNA is an abundant, essential noncoding RNA whose functions have been proposed in yeast but are incompletely understood in humans. Mutations in the genomic locus for MRP RNA cause pleiotropic human diseases, including cartilage hair hypoplasia (CHH). Here we applied CRISPR-Cas9 genome editing to disrupt the endogenous human MRP RNA locus, thereby attaining what has eluded RNAi and RNase H experiments: elimination of MRP RNA in the majority of cells. The resulting accumulation of ribosomal RNA (rRNA) precursor-analyzed by RNA fluorescent in situ hybridization (FISH), Northern blots, and RNA sequencing-implicates MRP RNA in pre-rRNA processing. Amelioration of pre-rRNA imbalance is achieved through rescue of MRP RNA levels by ectopic expression. Furthermore, affinity-purified MRP ribonucleoprotein (RNP) from HeLa cells cleaves the human pre-rRNA in vitro at at least one site used in cells, while RNP isolated from cells with CRISPR-edited MRP loci loses this activity, and ectopic MRP RNA expression restores cleavage activity. Thus, a role for RNase MRP in human pre-rRNA processing is established. As demonstrated here, targeted CRISPR disruption is a valuable tool for functional studies of essential noncoding RNAs that are resistant to RNAi and RNase H-based degradation. © 2017 Goldfarb and Cech; Published by Cold Spring Harbor Laboratory Press.

  1. The early history of tRNA recognition by aminoacyl-tRNA synthetases

    Indian Academy of Sciences (India)

    Madhu

    2006-10-04

    Oct 4, 2006 ... Discovery of aminoacyl-tRNA synthetases and importance ... The pioneering work of Fritz Lipmann on the high-energy ... the peculiar structural and functional relationships tRNAs ... a bulk of only 20 families of tRNA molecules in contrast ...... balance of tRNA and aminoacyl-tRNA synthetase; Science 242.

  2. Cooperation of an RNA Packaging Signal and a Viral Envelope Protein in Coronavirus RNA Packaging

    OpenAIRE

    Narayanan, Krishna; Makino, Shinji

    2001-01-01

    Murine coronavirus mouse hepatitis virus (MHV) produces a genome-length mRNA, mRNA 1, and six or seven species of subgenomic mRNAs in infected cells. Among these mRNAs, only mRNA 1 is efficiently packaged into MHV particles. MHV N protein binds to all MHV mRNAs, whereas envelope M protein interacts only with mRNA 1. This M protein-mRNA 1 interaction most probably determines the selective packaging of mRNA 1 into MHV particles. A short cis-acting MHV RNA packaging signal is necessary and suffi...

  3. Sequence analysis of RNase MRP RNA reveals its origination from eukaryotic RNase P RNA

    Science.gov (United States)

    Zhu, Yanglong; Stribinskis, Vilius; Ramos, Kenneth S.; Li, Yong

    2006-01-01

    RNase MRP is a eukaryote-specific endoribonuclease that generates RNA primers for mitochondrial DNA replication and processes precursor rRNA. RNase P is a ubiquitous endoribonuclease that cleaves precursor tRNA transcripts to produce their mature 5′ termini. We found extensive sequence homology of catalytic domains and specificity domains between their RNA subunits in many organisms. In Candida glabrata, the internal loop of helix P3 is 100% conserved between MRP and P RNAs. The helix P8 of MRP RNA from microsporidia Encephalitozoon cuniculi is identical to that of P RNA. Sequence homology can be widely spread over the whole molecule of MRP RNA and P RNA, such as those from Dictyostelium discoideum. These conserved nucleotides between the MRP and P RNAs strongly support the hypothesis that the MRP RNA is derived from the P RNA molecule in early eukaryote evolution. PMID:16540690

  4. RNA polymerase II mediated transcription from the polymerase III promoters in short hairpin RNA expression vector

    International Nuclear Information System (INIS)

    Rumi, Mohammad; Ishihara, Shunji; Aziz, Monowar; Kazumori, Hideaki; Ishimura, Norihisa; Yuki, Takafumi; Kadota, Chikara; Kadowaki, Yasunori; Kinoshita, Yoshikazu

    2006-01-01

    RNA polymerase III promoters of human ribonuclease P RNA component H1, human U6, and mouse U6 small nuclear RNA genes are commonly used in short hairpin RNA (shRNA) expression vectors due their precise initiation and termination sites. During transient transfection of shRNA vectors, we observed that H1 or U6 promoters also express longer transcripts enough to express several reporter genes including firefly luciferase, green fluorescent protein EGFP, and red fluorescent protein JRed. Expression of such longer transcripts was augmented by upstream RNA polymerase II enhancers and completely inhibited by downstream polyA signal sequences. Moreover, the transcription of firefly luciferase from human H1 promoter was sensitive to RNA polymerase II inhibitor α-amanitin. Our findings suggest that commonly used polymerase III promoters in shRNA vectors are also prone to RNA polymerase II mediated transcription, which may have negative impacts on their targeted use

  5. Using RNA Interference to Study Protein Function

    OpenAIRE

    Curtis, Carol D.; Nardulli, Ann M.

    2009-01-01

    RNA interference can be extremely useful in determining the function of an endogenously-expressed protein in its normal cellular environment. In this chapter, we describe a method that uses small interfering RNA (siRNA) to knock down mRNA and protein expression in cultured cells so that the effect of a putative regulatory protein on gene expression can be delineated. Methods of assessing the effectiveness of the siRNA procedure using real time quantitative PCR and Western analysis are also in...

  6. Analysis of extracellular RNA by digital PCR

    Directory of Open Access Journals (Sweden)

    Kenji eTakahashi

    2014-06-01

    Full Text Available The transfer of extracellular RNA is emerging as an important mechanism for intracellular communication. The ability for the transfer of functionally active RNA molecules from one cell to another within vesicles such as exosomes enables a cell to modulate cellular signaling and biological processes within recipient cells. The study of extracellular RNA requires sensitive methods for the detection of these molecules. In this methods article, we will describe protocols for the detection of such extracellular RNA using sensitive detection technologies such as digital PCR. These protocols should be valuable to researchers interested in the role and contribution of extracellular RNA to tumor cell biology.

  7. Characteristics and Prediction of RNA Structure

    Directory of Open Access Journals (Sweden)

    Hengwu Li

    2014-01-01

    Full Text Available RNA secondary structures with pseudoknots are often predicted by minimizing free energy, which is NP-hard. Most RNAs fold during transcription from DNA into RNA through a hierarchical pathway wherein secondary structures form prior to tertiary structures. Real RNA secondary structures often have local instead of global optimization because of kinetic reasons. The performance of RNA structure prediction may be improved by considering dynamic and hierarchical folding mechanisms. This study is a novel report on RNA folding that accords with the golden mean characteristic based on the statistical analysis of the real RNA secondary structures of all 480 sequences from RNA STRAND, which are validated by NMR or X-ray. The length ratios of domains in these sequences are approximately 0.382L, 0.5L, 0.618L, and L, where L is the sequence length. These points are just the important golden sections of sequence. With this characteristic, an algorithm is designed to predict RNA hierarchical structures and simulate RNA folding by dynamically folding RNA structures according to the above golden section points. The sensitivity and number of predicted pseudoknots of our algorithm are better than those of the Mfold, HotKnots, McQfold, ProbKnot, and Lhw-Zhu algorithms. Experimental results reflect the folding rules of RNA from a new angle that is close to natural folding.

  8. siRNA and innate immunity.

    Science.gov (United States)

    Robbins, Marjorie; Judge, Adam; MacLachlan, Ian

    2009-06-01

    Canonical small interfering RNA (siRNA) duplexes are potent activators of the mammalian innate immune system. The induction of innate immunity by siRNA is dependent on siRNA structure and sequence, method of delivery, and cell type. Synthetic siRNA in delivery vehicles that facilitate cellular uptake can induce high levels of inflammatory cytokines and interferons after systemic administration in mammals and in primary human blood cell cultures. This activation is predominantly mediated by immune cells, normally via a Toll-like receptor (TLR) pathway. The siRNA sequence dependency of these pathways varies with the type and location of the TLR involved. Alternatively nonimmune cell activation may also occur, typically resulting from siRNA interaction with cytoplasmic RNA sensors such as RIG1. As immune activation by siRNA-based drugs represents an undesirable side effect due to the considerable toxicities associated with excessive cytokine release in humans, understanding and abrogating this activity will be a critical component in the development of safe and effective therapeutics. This review describes the intracellular mechanisms of innate immune activation by siRNA, the design of appropriate sequences and chemical modification approaches, and suitable experimental methods for studying their effects, with a view toward reducing siRNA-mediated off-target effects.

  9. TruSeq Stranded mRNA and Total RNA Sample Preparation Kits

    Science.gov (United States)

    Total RNA-Seq enabled by ribosomal RNA (rRNA) reduction is compatible with formalin-fixed paraffin embedded (FFPE) samples, which contain potentially critical biological information. The family of TruSeq Stranded Total RNA sample preparation kits provides a unique combination of unmatched data quality for both mRNA and whole-transcriptome analyses, robust interrogation of both standard and low-quality samples and workflows compatible with a wide range of study designs.

  10. MysiRNA-designer: a workflow for efficient siRNA design.

    Directory of Open Access Journals (Sweden)

    Mohamed Mysara

    Full Text Available The design of small interfering RNA (siRNA is a multi factorial problem that has gained the attention of many researchers in the area of therapeutic and functional genomics. MysiRNA score was previously introduced that improves the correlation of siRNA activity prediction considering state of the art algorithms. In this paper, a new program, MysiRNA-Designer, is described which integrates several factors in an automated work-flow considering mRNA transcripts variations, siRNA and mRNA target accessibility, and both near-perfect and partial off-target matches. It also features the MysiRNA score, a highly ranked correlated siRNA efficacy prediction score for ranking the designed siRNAs, in addition to top scoring models Biopredsi, DISR, Thermocomposition21 and i-Score, and integrates them in a unique siRNA score-filtration technique. This multi-score filtration layer filters siRNA that passes the 90% thresholds calculated from experimental dataset features. MysiRNA-Designer takes an accession, finds conserved regions among its transcript space, finds accessible regions within the mRNA, designs all possible siRNAs for these regions, filters them based on multi-scores thresholds, and then performs SNP and off-target filtration. These strict selection criteria were tested against human genes in which at least one active siRNA was designed from 95.7% of total genes. In addition, when tested against an experimental dataset, MysiRNA-Designer was found capable of rejecting 98% of the false positive siRNAs, showing superiority over three state of the art siRNA design programs. MysiRNA is a freely accessible (Microsoft Windows based desktop application that can be used to design siRNA with a high accuracy and specificity. We believe that MysiRNA-Designer has the potential to play an important role in this area.

  11. 5S rRNA and ribosome.

    Science.gov (United States)

    Gongadze, G M

    2011-12-01

    5S rRNA is an integral component of the ribosome of all living organisms. It is known that the ribosome without 5S rRNA is functionally inactive. However, the question about the specific role of this RNA in functioning of the translation apparatus is still open. This review presents a brief history of the discovery of 5S rRNA and studies of its origin and localization in the ribosome. The previously expressed hypotheses about the role of this RNA in the functioning of the ribosome are discussed considering the unique location of 5S rRNA in the ribosome and its intermolecular contacts. Based on analysis of the current data on ribosome structure and its functional complexes, the role of 5S rRNA as an intermediary between ribosome functional domains is discussed.

  12. Kin Selection in the RNA World.

    Science.gov (United States)

    Levin, Samuel R; West, Stuart A

    2017-12-05

    Various steps in the RNA world required cooperation. Why did life's first inhabitants, from polymerases to synthetases, cooperate? We develop kin selection models of the RNA world to answer these questions. We develop a very simple model of RNA cooperation and then elaborate it to model three relevant issues in RNA biology: (1) whether cooperative RNAs receive the benefits of cooperation; (2) the scale of competition in RNA populations; and (3) explicit replicator diffusion and survival. We show: (1) that RNAs are likely to express partial cooperation; (2) that RNAs will need mechanisms for overcoming local competition; and (3) in a specific example of RNA cooperation, persistence after replication and offspring diffusion allow for cooperation to overcome competition. More generally, we show how kin selection can unify previously disparate answers to the question of RNA world cooperation.

  13. MicroRNA and cancer

    DEFF Research Database (Denmark)

    Jansson, Martin D; Lund, Anders H

    2012-01-01

    biological phenomena and pathologies. The best characterized non-coding RNA family consists in humans of about 1400 microRNAs for which abundant evidence have demonstrated fundamental importance in normal development, differentiation, growth control and in human diseases such as cancer. In this review, we...... summarize the current knowledge and concepts concerning the involvement of microRNAs in cancer, which have emerged from the study of cell culture and animal model systems, including the regulation of key cancer-related pathways, such as cell cycle control and the DNA damage response. Importantly, micro...

  14. RNA2DMut: a web tool for the design and analysis of RNA structure mutations.

    Science.gov (United States)

    Moss, Walter N

    2018-03-01

    With the widespread application of high-throughput sequencing, novel RNA sequences are being discovered at an astonishing rate. The analysis of function, however, lags behind. In both the cis - and trans -regulatory functions of RNA, secondary structure (2D base-pairing) plays essential regulatory roles. In order to test RNA function, it is essential to be able to design and analyze mutations that can affect structure. This was the motivation for the creation of the RNA2DMut web tool. With RNA2DMut, users can enter in RNA sequences to analyze, constrain mutations to specific residues, or limit changes to purines/pyrimidines. The sequence is analyzed at each base to determine the effect of every possible point mutation on 2D structure. The metrics used in RNA2DMut rely on the calculation of the Boltzmann structure ensemble and do not require a robust 2D model of RNA structure for designing mutations. This tool can facilitate a wide array of uses involving RNA: for example, in designing and evaluating mutants for biological assays, interrogating RNA-protein interactions, identifying key regions to alter in SELEX experiments, and improving RNA folding and crystallization properties for structural biology. Additional tools are available to help users introduce other mutations (e.g., indels and substitutions) and evaluate their effects on RNA structure. Example calculations are shown for five RNAs that require 2D structure for their function: the MALAT1 mascRNA, an influenza virus splicing regulatory motif, the EBER2 viral noncoding RNA, the Xist lncRNA repA region, and human Y RNA 5. RNA2DMut can be accessed at https://rna2dmut.bb.iastate.edu/. © 2018 Moss; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  15. RNA versatility, flexibility, and thermostability for practice in RNA nanotechnology and biomedical applications.

    Science.gov (United States)

    Haque, Farzin; Pi, Fengmei; Zhao, Zhengyi; Gu, Shanqing; Hu, Haibo; Yu, Hang; Guo, Peixuan

    2018-01-01

    In recent years, RNA has attracted widespread attention as a unique biomaterial with distinct biophysical properties for designing sophisticated architectures in the nanometer scale. RNA is much more versatile in structure and function with higher thermodynamic stability compared to its nucleic acid counterpart DNA. Larger RNA molecules can be viewed as a modular structure built from a combination of many 'Lego' building blocks connected via different linker sequences. By exploiting the diversity of RNA motifs and flexibility of structure, varieties of RNA architectures can be fabricated with precise control of shape, size, and stoichiometry. Many structural motifs have been discovered and characterized over the years and the crystal structures of many of these motifs are available for nanoparticle construction. For example, using the flexibility and versatility of RNA structure, RNA triangles, squares, pentagons, and hexagons can be constructed from phi29 pRNA three-way-junction (3WJ) building block. This review will focus on 2D RNA triangles, squares, and hexamers; 3D and 4D structures built from basic RNA building blocks; and their prospective applications in vivo as imaging or therapeutic agents via specific delivery and targeting. Methods for intracellular cloning and expression of RNA molecules and the in vivo assembly of RNA nanoparticles will also be reviewed. WIREs RNA 2018, 9:e1452. doi: 10.1002/wrna.1452 This article is categorized under: RNA Methods > RNA Nanotechnology RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs. © 2017 Wiley Periodicals, Inc.

  16. Evaluation of microRNA alignment techniques

    Science.gov (United States)

    Kaspi, Antony; El-Osta, Assam

    2016-01-01

    Genomic alignment of small RNA (smRNA) sequences such as microRNAs poses considerable challenges due to their short length (∼21 nucleotides [nt]) as well as the large size and complexity of plant and animal genomes. While several tools have been developed for high-throughput mapping of longer mRNA-seq reads (>30 nt), there are few that are specifically designed for mapping of smRNA reads including microRNAs. The accuracy of these mappers has not been systematically determined in the case of smRNA-seq. In addition, it is unknown whether these aligners accurately map smRNA reads containing sequence errors and polymorphisms. By using simulated read sets, we determine the alignment sensitivity and accuracy of 16 short-read mappers and quantify their robustness to mismatches, indels, and nontemplated nucleotide additions. These were explored in the context of a plant genome (Oryza sativa, ∼500 Mbp) and a mammalian genome (Homo sapiens, ∼3.1 Gbp). Analysis of simulated and real smRNA-seq data demonstrates that mapper selection impacts differential expression results and interpretation. These results will inform on best practice for smRNA mapping and enable more accurate smRNA detection and quantification of expression and RNA editing. PMID:27284164

  17. MicroRNA mimicry blocks pulmonary fibrosis

    Science.gov (United States)

    Montgomery, Rusty L; Yu, Guoying; Latimer, Paul A; Stack, Christianna; Robinson, Kathryn; Dalby, Christina M; Kaminski, Naftali; van Rooij, Eva

    2014-01-01

    Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis. PMID:25239947

  18. Modulation of RNA function by aminoglycoside antibiotics.

    Science.gov (United States)

    Schroeder, R; Waldsich, C; Wank, H

    2000-01-04

    One of the most important families of antibiotics are the aminoglycosides, including drugs such as neomycin B, paromomycin, gentamicin and streptomycin. With the discovery of the catalytic potential of RNA, these antibiotics became very popular due to their RNA-binding capacity. They serve for the analysis of RNA function as well as for the study of RNA as a potential therapeutic target. Improvements in RNA structure determination recently provided first insights into the decoding site of the ribosome at high resolution and how aminoglycosides might induce misreading of the genetic code. In addition to inhibiting prokaryotic translation, aminoglycosides inhibit several catalytic RNAs such as self-splicing group I introns, RNase P and small ribozymes in vitro. Furthermore, these antibiotics interfere with human immunodeficiency virus (HIV) replication by disrupting essential RNA-protein contacts. Most exciting is the potential of many RNA-binding antibiotics to stimulate RNA activities, conceiving small-molecule partners for the hypothesis of an ancient RNA world. SELEX (systematic evolution of ligands by exponential enrichment) has been used in this evolutionary game leading to small synthetic RNAs, whose NMR structures gave valuable information on how aminoglycosides interact with RNA, which could possibly be used in applied science.

  19. Movement of regulatory RNA between animal cells.

    Science.gov (United States)

    Jose, Antony M

    2015-07-01

    Recent studies suggest that RNA can move from one cell to another and regulate genes through specific base-pairing. Mechanisms that modify or select RNA for secretion from a cell are unclear. Secreted RNA can be stable enough to be detected in the extracellular environment and can enter the cytosol of distant cells to regulate genes. Mechanisms that import RNA into the cytosol of an animal cell can enable uptake of RNA from many sources including other organisms. This role of RNA is akin to that of steroid hormones, which cross cell membranes to regulate genes. The potential diagnostic use of RNA in human extracellular fluids has ignited interest in understanding mechanisms that enable the movement of RNA between animal cells. Genetic model systems will be essential to gain more confidence in proposed mechanisms of RNA transport and to connect an extracellular RNA with a specific biological function. Studies in the worm C. elegans and in other animals have begun to reveal parts of this novel mechanism of cell-to-cell communication. Here, I summarize the current state of this nascent field, highlight the many unknowns, and suggest future directions. © 2015 Wiley Periodicals, Inc.

  20. Comparison of protocols and RNA carriers for plasma miRNA isolation. Unraveling RNA carrier influence on miRNA isolation

    Science.gov (United States)

    Martos, Laura; Fernández-Pardo, Álvaro; Oto, Julia; Medina, Pilar; España, Francisco; Navarro, Silvia

    2017-01-01

    microRNAs are promising biomarkers in biological fluids in several diseases. Different plasma RNA isolation protocols and carriers are available, but their efficiencies have been scarcely compared. Plasma microRNAs were isolated using a phenol and column-based procedure and a column-based procedure, in the presence or absence of two RNA carriers (yeast RNA and MS2 RNA). We evaluated the presence of PCR inhibitors and the relative abundance of certain microRNAs by qRT-PCR. Furthermore, we analyzed the association between different isolation protocols, the relative abundance of the miRNAs in the sample, the GC content and the free energy of microRNAs. In all microRNAs analyzed, the addition of yeast RNA as a carrier in the different isolation protocols used gave lower raw Cq values, indicating higher microRNA recovery. Moreover, this increase in microRNAs recovery was dependent on their own relative abundance in the sample, their GC content and the free-energy of their own most stable secondary structure. Furthermore, the normalization of microRNA levels by an endogenous microRNA is more reliable than the normalization by plasma volume, as it reduced the difference in microRNA fold abundance between the different isolation protocols evaluated. Our thorough study indicates that a standardization of pre- and analytical conditions is necessary to obtain reproducible inter-laboratory results in plasma microRNA studies. PMID:29077772

  1. Henipavirus RNA in African bats.

    Directory of Open Access Journals (Sweden)

    Jan Felix Drexler

    Full Text Available BACKGROUND: Henipaviruses (Hendra and Nipah virus are highly pathogenic members of the family Paramyxoviridae. Fruit-eating bats of the Pteropus genus have been suggested as their natural reservoir. Human Henipavirus infections have been reported in a region extending from Australia via Malaysia into Bangladesh, compatible with the geographic range of Pteropus. These bats do not occur in continental Africa, but a whole range of other fruit bats is encountered. One of the most abundant is Eidolon helvum, the African Straw-coloured fruit bat. METHODOLOGY/PRINCIPAL FINDINGS: Feces from E. helvum roosting in an urban setting in Kumasi/Ghana were tested for Henipavirus RNA. Sequences of three novel viruses in phylogenetic relationship to known Henipaviruses were detected. Virus RNA concentrations in feces were low. CONCLUSIONS/SIGNIFICANCE: The finding of novel putative Henipaviruses outside Australia and Asia contributes a significant extension of the region of potential endemicity of one of the most pathogenic virus genera known in humans.

  2. REDIdb: the RNA editing database.

    Science.gov (United States)

    Picardi, Ernesto; Regina, Teresa Maria Rosaria; Brennicke, Axel; Quagliariello, Carla

    2007-01-01

    The RNA Editing Database (REDIdb) is an interactive, web-based database created and designed with the aim to allocate RNA editing events such as substitutions, insertions and deletions occurring in a wide range of organisms. The database contains both fully and partially sequenced DNA molecules for which editing information is available either by experimental inspection (in vitro) or by computational detection (in silico). Each record of REDIdb is organized in a specific flat-file containing a description of the main characteristics of the entry, a feature table with the editing events and related details and a sequence zone with both the genomic sequence and the corresponding edited transcript. REDIdb is a relational database in which the browsing and identification of editing sites has been simplified by means of two facilities to either graphically display genomic or cDNA sequences or to show the corresponding alignment. In both cases, all editing sites are highlighted in colour and their relative positions are detailed by mousing over. New editing positions can be directly submitted to REDIdb after a user-specific registration to obtain authorized secure access. This first version of REDIdb database stores 9964 editing events and can be freely queried at http://biologia.unical.it/py_script/search.html.

  3. 5S rRNA-derived and tRNA-derived SINEs in fruit bats.

    Science.gov (United States)

    Gogolevsky, Konstantin P; Vassetzky, Nikita S; Kramerov, Dmitri A

    2009-05-01

    Most short retroposons (SINEs) descend from cellular tRNA of 7SL RNA. Here, four new SINEs were found in megabats (Megachiroptera) but neither in microbats nor in other mammals. Two of them, MEG-RS and MEG-RL, descend from another cellular RNA, 5S rRNA; one (MEG-T2) is a tRNA-derived SINE; and MEG-TR is a hybrid tRNA/5S rRNA SINE. Insertion locus analysis suggests that these SINEs were active in the recent fruit bat evolution. Analysis of MEG-RS and MEG-RL in comparison with other few 5S rRNA-derived SINEs demonstrates that the internal RNA polymerase III promoter is their most invariant region, while the secondary structure is more variable. The mechanisms underlying the modular structure of these and other SINEs as well as their variation are discussed. The scenario of evolution of MEG SINEs is proposed.

  4. RNA-Binding Proteins Revisited – The Emerging Arabidopsis mRNA Interactome

    KAUST Repository

    Kö ster, Tino; Marondedze, Claudius; Meyer, Katja; Staiger, Dorothee

    2017-01-01

    RNA–protein interaction is an important checkpoint to tune gene expression at the RNA level. Global identification of proteins binding in vivo to mRNA has been possible through interactome capture – where proteins are fixed to target RNAs by UV crosslinking and purified through affinity capture of polyadenylated RNA. In Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked samples have been identified. As in mammals and yeast, the mRNA interactomes came with a few surprises. For example, a plethora of the proteins caught on RNA had not previously been linked to RNA-mediated processes, for example proteins of intermediary metabolism. Thus, the studies provide unprecedented insights into the composition of the mRNA interactome, highlighting the complexity of RNA-mediated processes.

  5. RNA-Binding Proteins Revisited – The Emerging Arabidopsis mRNA Interactome

    KAUST Repository

    Köster, Tino

    2017-04-13

    RNA–protein interaction is an important checkpoint to tune gene expression at the RNA level. Global identification of proteins binding in vivo to mRNA has been possible through interactome capture – where proteins are fixed to target RNAs by UV crosslinking and purified through affinity capture of polyadenylated RNA. In Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked samples have been identified. As in mammals and yeast, the mRNA interactomes came with a few surprises. For example, a plethora of the proteins caught on RNA had not previously been linked to RNA-mediated processes, for example proteins of intermediary metabolism. Thus, the studies provide unprecedented insights into the composition of the mRNA interactome, highlighting the complexity of RNA-mediated processes.

  6. Construction of RNA nanocages by re-engineering the packaging RNA of Phi29 bacteriophage

    Science.gov (United States)

    Hao, Chenhui; Li, Xiang; Tian, Cheng; Jiang, Wen; Wang, Guansong; Mao, Chengde

    2014-05-01

    RNA nanotechnology promises rational design of RNA nanostructures with wide array of structural diversities and functionalities. Such nanostructures could be used in applications such as small interfering RNA delivery and organization of in vivo chemical reactions. Though having impressive development in recent years, RNA nanotechnology is still quite limited and its programmability and complexity could not rival the degree of its closely related cousin: DNA nanotechnology. Novel strategies are needed for programmed RNA self-assembly. Here, we have assembled RNA nanocages by re-engineering a natural, biological RNA motif: the packaging RNA of phi29 bacteriophage. The resulting RNA nanostructures have been thoroughly characterized by gel electrophoresis, cryogenic electron microscopy imaging and dynamic light scattering.

  7. Role of RNase MRP in viral RNA degradation and RNA recombination.

    Science.gov (United States)

    Jaag, Hannah M; Lu, Qiasheng; Schmitt, Mark E; Nagy, Peter D

    2011-01-01

    RNA degradation, together with RNA synthesis, controls the steady-state level of viral RNAs in infected cells. The endoribonucleolytic cleavage of viral RNA is important not only for viral RNA degradation but for RNA recombination as well, due to the participation of some RNA degradation products in the RNA recombination process. To identify host endoribonucleases involved in degradation of Tomato bushy stunt virus (TBSV) in a Saccharomyces cerevisiae model host, we tested eight known endoribonucleases. Here we report that downregulation of SNM1, encoding a component of the RNase MRP, and a temperature-sensitive mutation in the NME1 gene, coding for the RNA component of RNase MRP, lead to reduced production of the endoribonucleolytically cleaved TBSV RNA in yeast. We also show that the highly purified yeast RNase MRP cleaves the TBSV RNA in vitro, resulting in TBSV RNA degradation products similar in size to those observed in yeast cells. Knocking down the NME1 homolog in Nicotiana benthamiana also led to decreased production of the cleaved TBSV RNA, suggesting that in plants, RNase MRP is involved in TBSV RNA degradation. Altogether, this work suggests a role for the host endoribonuclease RNase MRP in viral RNA degradation and recombination.

  8. The use of 125iodine-labeled RNA for detection of the RNA binding to ribosomes

    International Nuclear Information System (INIS)

    Mori, Tomohiko; Fukuda, Mitsuru

    1975-01-01

    The in vitro labeling of RNA with radioactive iodine is the efficient method to obtain the RNA with high specific activity. The present paper reports on the application of this technique to the production of iodine-labeled RNA for use in the experiment of binding RNA to ribosomes. Tobacco mosaic virus (TMV) RNA was used as natural mRNA, and E. coli S-30 preparation was used as a source of ribosomes. The TMV-RNA was prepared by bentonite-phenol extraction from TMV, and the method used for the iodation of RNA was based on the procedure described by Getz et al. The iodine-labeled RNA was incubated in a cell-free protein synthesizing system (S-30) prepared from E. coli K-12. After the incubation, the reaction mixture was layered onto sucrose gradient, centrifuged, and fractionated into 18 fractions. Optical density at 260 nm was measured, and radioactivity was counted, for each fraction. The binding of mRNA to ribosomes occurred even at 0 deg C, and the occurrence of the nonspecific binding was also shown. Consequently, the specific binding, i.e. the formation of the initiation complex being involved in amino acid incorporation, may be estimated by subtracting the radioactivity associated with monosomes in the presence of both rRNA and ATA from that in the presence of rRNA only. It was shown that the iodine-labeled RNA can be used for the studies of binding RNA to ribosomes. (Kako, I.)

  9. Deep Sequencing Insights in Therapeutic shRNA Processing and siRNA Target Cleavage Precision.

    Science.gov (United States)

    Denise, Hubert; Moschos, Sterghios A; Sidders, Benjamin; Burden, Frances; Perkins, Hannah; Carter, Nikki; Stroud, Tim; Kennedy, Michael; Fancy, Sally-Ann; Lapthorn, Cris; Lavender, Helen; Kinloch, Ross; Suhy, David; Corbau, Romu

    2014-02-04

    TT-034 (PF-05095808) is a recombinant adeno-associated virus serotype 8 (AAV8) agent expressing three short hairpin RNA (shRNA) pro-drugs that target the hepatitis C virus (HCV) RNA genome. The cytosolic enzyme Dicer cleaves each shRNA into multiple, potentially active small interfering RNA (siRNA) drugs. Using next-generation sequencing (NGS) to identify and characterize active shRNAs maturation products, we observed that each TT-034-encoded shRNA could be processed into as many as 95 separate siRNA strands. Few of these appeared active as determined by Sanger 5' RNA Ligase-Mediated Rapid Amplification of cDNA Ends (5-RACE) and through synthetic shRNA and siRNA analogue studies. Moreover, NGS scrutiny applied on 5-RACE products (RACE-seq) suggested that synthetic siRNAs could direct cleavage in not one, but up to five separate positions on targeted RNA, in a sequence-dependent manner. These data support an on-target mechanism of action for TT-034 without cytotoxicity and question the accepted precision of substrate processing by the key RNA interference (RNAi) enzymes Dicer and siRNA-induced silencing complex (siRISC).Molecular Therapy-Nucleic Acids (2014) 3, e145; doi:10.1038/mtna.2013.73; published online 4 February 2014.

  10. Disruption of Specific RNA-RNA Interactions in a Double-Stranded RNA Virus Inhibits Genome Packaging and Virus Infectivity.

    Science.gov (United States)

    Fajardo, Teodoro; Sung, Po-Yu; Roy, Polly

    2015-12-01

    Bluetongue virus (BTV) causes hemorrhagic disease in economically important livestock. The BTV genome is organized into ten discrete double-stranded RNA molecules (S1-S10) which have been suggested to follow a sequential packaging pathway from smallest to largest segment during virus capsid assembly. To substantiate and extend these studies, we have investigated the RNA sorting and packaging mechanisms with a new experimental approach using inhibitory oligonucleotides. Putative packaging signals present in the 3'untranslated regions of BTV segments were targeted by a number of nuclease resistant oligoribonucleotides (ORNs) and their effects on virus replication in cell culture were assessed. ORNs complementary to the 3' UTR of BTV RNAs significantly inhibited virus replication without affecting protein synthesis. Same ORNs were found to inhibit complex formation when added to a novel RNA-RNA interaction assay which measured the formation of supramolecular complexes between and among different RNA segments. ORNs targeting the 3'UTR of BTV segment 10, the smallest RNA segment, were shown to be the most potent and deletions or substitution mutations of the targeted sequences diminished the RNA complexes and abolished the recovery of viable viruses using reverse genetics. Cell-free capsid assembly/RNA packaging assay also confirmed that the inhibitory ORNs could interfere with RNA packaging and further substitution mutations within the putative RNA packaging sequence have identified the recognition sequence concerned. Exchange of 3'UTR between segments have further demonstrated that RNA recognition was segment specific, most likely acting as part of the secondary structure of the entire genomic segment. Our data confirm that genome packaging in this segmented dsRNA virus occurs via the formation of supramolecular complexes formed by the interaction of specific sequences located in the 3' UTRs. Additionally, the inhibition of packaging in-trans with inhibitory ORNs

  11. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element.

    Science.gov (United States)

    Fukunaga, Junichi; Nomura, Yusuke; Tanaka, Yoichiro; Amano, Ryo; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Sakamoto, Taiichi; Kozu, Tomoko

    2013-07-01

    AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5'-NNCCAC-3' and 5'-GCGMGN'N'-3' (M:A or C; N and N' form Watson-Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.

  12. Argonaute: The executor of small RNA function.

    Science.gov (United States)

    Azlan, Azali; Dzaki, Najat; Azzam, Ghows

    2016-08-20

    The discovery of small non-coding RNAs - microRNA (miRNA), short interfering RNA (siRNA) and PIWI-interacting RNA (piRNA) - represents one of the most exciting frontiers in biology specifically on the mechanism of gene regulation. In order to execute their functions, these small RNAs require physical interactions with their protein partners, the Argonaute (AGO) family proteins. Over the years, numerous studies have made tremendous progress on understanding the roles of AGO in gene silencing in various organisms. In this review, we summarize recent progress of AGO-mediated gene silencing and other cellular processes in which AGO proteins have been implicated with a particular focus on progress made in flies, humans and other model organisms as compliment. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  13. Designing synthetic RNA for delivery by nanoparticles

    International Nuclear Information System (INIS)

    Jedrzejczyk, Dominika; Pawlowska, Roza; Chworos, Arkadiusz; Gendaszewska-Darmach, Edyta

    2017-01-01

    The rapid development of synthetic biology and nanobiotechnology has led to the construction of various synthetic RNA nanoparticles of different functionalities and potential applications. As they occur naturally, nucleic acids are an attractive construction material for biocompatible nanoscaffold and nanomachine design. In this review, we provide an overview of the types of RNA and nucleic acid’s nanoparticle design, with the focus on relevant nanostructures utilized for gene-expression regulation in cellular models. Structural analysis and modeling is addressed along with the tools available for RNA structural prediction. The functionalization of RNA-based nanoparticles leading to prospective applications of such constructs in potential therapies is shown. The route from the nanoparticle design and modeling through synthesis and functionalization to cellular application is also described. For a better understanding of the fate of targeted RNA after delivery, an overview of RNA processing inside the cell is also provided. (topical review)

  14. Predicting RNA Structure Using Mutual Information

    DEFF Research Database (Denmark)

    Freyhult, E.; Moulton, V.; Gardner, P. P.

    2005-01-01

    , to display and predict conserved RNA secondary structure (including pseudoknots) from an alignment. Results: We show that MIfold can be used to predict simple pseudoknots, and that the performance can be adjusted to make it either more sensitive or more selective. We also demonstrate that the overall...... package. Conclusion: MIfold provides a useful supplementary tool to programs such as RNA Structure Logo, RNAalifold and COVE, and should be useful for automatically generating structural predictions for databases such as Rfam. Availability: MIfold is freely available from http......Background: With the ever-increasing number of sequenced RNAs and the establishment of new RNA databases, such as the Comparative RNA Web Site and Rfam, there is a growing need for accurately and automatically predicting RNA structures from multiple alignments. Since RNA secondary structure...

  15. Preparation of Total RNA from Fission Yeast.

    Science.gov (United States)

    Bähler, Jürg; Wise, Jo Ann

    2017-04-03

    Treatment with hot phenol breaks open fission yeast cells and begins to strip away bound proteins from RNA. Deproteinization is completed by multiple extractions with chloroform/isoamyl alcohol and separation of the aqueous and organic phases using MaXtract gel, an inert material that acts as a physical barrier between the phases. The final step is concentration of the RNA by ethanol precipitation. The protocol can be used to prepare RNA from several cultures grown in parallel, but it is important not to process too many samples at once because delays can be detrimental to RNA quality. A reasonable number of samples to process at once would be three to four for microarray or RNA sequencing analyses and six for preliminary investigations of mutants implicated in RNA metabolism. © 2017 Cold Spring Harbor Laboratory Press.

  16. A probabilistic model of RNA conformational space

    DEFF Research Database (Denmark)

    Frellsen, Jes; Moltke, Ida; Thiim, Martin

    2009-01-01

    efficient sampling of RNA conformations in continuous space, and with associated probabilities. We show that the model captures several key features of RNA structure, such as its rotameric nature and the distribution of the helix lengths. Furthermore, the model readily generates native-like 3-D......, the discrete nature of the fragments necessitates the use of carefully tuned, unphysical energy functions, and their non-probabilistic nature impairs unbiased sampling. We offer a solution to the sampling problem that removes these important limitations: a probabilistic model of RNA structure that allows......The increasing importance of non-coding RNA in biology and medicine has led to a growing interest in the problem of RNA 3-D structure prediction. As is the case for proteins, RNA 3-D structure prediction methods require two key ingredients: an accurate energy function and a conformational sampling...

  17. RNA-Binding Proteins in Plant Immunity

    Directory of Open Access Journals (Sweden)

    Virginia Woloshen

    2011-01-01

    Full Text Available Plant defence responses against pathogen infection are crucial to plant survival. The high degree of regulation of plant immunity occurs both transcriptionally and posttranscriptionally. Once transcribed, target gene RNA must be processed prior to translation. This includes polyadenylation, 5′capping, editing, splicing, and mRNA export. RNA-binding proteins (RBPs have been implicated at each level of RNA processing. Previous research has primarily focused on structural RNA-binding proteins of yeast and mammals; however, more recent work has characterized a number of plant RBPs and revealed their roles in plant immune responses. This paper provides an update on the known functions of RBPs in plant immune response regulation. Future in-depth analysis of RBPs and other related players will unveil the sophisticated regulatory mechanisms of RNA processing during plant immune responses.

  18. A phylogenetic framework for root lesion nematodes of the genus Pratylenchus (Nematoda): Evidence from 18S and D2-D3 expansion segments of 28S ribosomal RNA genes and morphological characters.

    Science.gov (United States)

    Subbotin, Sergei A; Ragsdale, Erik J; Mullens, Teresa; Roberts, Philip A; Mundo-Ocampo, Manuel; Baldwin, James G

    2008-08-01

    The root lesion nematodes of the genus Pratylenchus Filipjev, 1936 are migratory endoparasites of plant roots, considered among the most widespread and important nematode parasites in a variety of crops. We obtained gene sequences from the D2 and D3 expansion segments of 28S rRNA partial and 18S rRNA from 31 populations belonging to 11 valid and two unidentified species of root lesion nematodes and five outgroup taxa. These datasets were analyzed using maximum parsimony and Bayesian inference. The alignments were generated using the secondary structure models for these molecules and analyzed with Bayesian inference under the standard models and the complex model, considering helices under the doublet model and loops and bulges under the general time reversible model. The phylogenetic informativeness of morphological characters is tested by reconstruction of their histories on rRNA based trees using parallel parsimony and Bayesian approaches. Phylogenetic and sequence analyses of the 28S D2-D3 dataset with 145 accessions for 28 species and 18S dataset with 68 accessions for 15 species confirmed among large numbers of geographical diverse isolates that most classical morphospecies are monophyletic. Phylogenetic analyses revealed at least six distinct major clades of examined Pratylenchus species and these clades are generally congruent with those defined by characters derived from lip patterns, numbers of lip annules, and spermatheca shape. Morphological results suggest the need for sophisticated character discovery and analysis for morphology based phylogenetics in nematodes.

  19. The Old and New RNA World

    Directory of Open Access Journals (Sweden)

    Zofia Szweykowska-Kulińska

    2014-12-01

    Full Text Available Among the numerous hypotheses offering a scenario for the origin of life on Earth, the one called “The RNA World” has gained the most attention. According to this hypothesis RNA acted as a genetic information storage material, as a catalyst of all metabolic reactions, and as a regulator of all processes in the primordial world. Various experiments show that RNA molecules could have been synthesized abiotically, with the potential to mediate a whole repertoire of metabolic reactions. Ribozymes carrying out aminoacyl-tRNA reactions have been found in SELEX (systematic evolution of ligands by exponential enrichment approaches and the development of a ribosome from a RNA-built protoribosome is easy to imagine. Transfer RNA aminoacylation, protoribosome origin, and the availability of amino acids on early Earth allowed the genetic code to evolve. Encoded proteins most likely stabilized RNA molecules and were able to create channels across membranes. In the modern cell, DNA replaced RNA as the main depositor of genetic information and proteins carry out almost all metabolic reactions. However, RNA is still playing versatile, crucial roles in the cell. Apart from its classical functions in the cell, a huge small RNA world is controlling gene expression, chromatin condensation, response to environmental cues, and protecting the cell against the invasion of various nucleic acids forms. Long non-coding RNAs act as crucial gene expression regulators. Riboswitches act at the level of transcription, splicing or translation and mediate feedback regulation on biosynthesis and transport of the ligand they sense. Alternative splicing generates genetic variability and increases the protein repertoire in response to developmental or environmental changes. All these regulatory functions are essential in shaping cell plasticity in the changing milieu. Recent discoveries of new, unexpected and important functions of RNA molecules support the hypothesis that we

  20. Small catalytic RNA: Structure, function and application

    Energy Technology Data Exchange (ETDEWEB)

    Monforte, J.A.

    1991-04-01

    We have utilized a combination of photochemical cross-linking techniques and site-directed mutagenesis to obtain secondary and tertiary structure information for the self-cleaving, self-ligating subsequence of RNA from the negative strand of Satellite Tobacco Ringspot Virus. We have found that the helical regions fold about a hinge to promoting four different possible tertiary interactions, creating a molecular of similar shape to a paperclip. A model suggesting that the paperclip'' and hammerhead'' RNAs share a similar three dimensional structure is proposed. We have used a self-cleaving RNA molecule related to a subsequence of plant viroids, a hammerhead,'' to study the length-dependent folding of RNA produced during transcription by RNA polymerase. We have used this method to determine the length of RNA sequestered within elongating E. coli and T7 RNA polymerase complexes. The data show that for E. coli RNA polymerase 12{plus minus}1 nucleotides are sequestered within the ternary complex, which is consistent with the presence of an RNA-DNA hybrid within the transcription bubble, as proposed by others. The result for T7 RNA polymerase differs from E. coli RNA polymerase, with only 10{plus minus}1 nucleotides sequestered within the ternary complex, setting a new upper limit for the minimum RNA-DNA required for a stable elongating complex. Comparisons between E. coli and T7 RNA polymerase are made. The relevance of the results to models or transcription termination, abortive initiation, and initiation to elongation mode transitions are discussed.

  1. Inverse folding of RNA pseudoknot structures

    Directory of Open Access Journals (Sweden)

    Li Linda YM

    2010-06-01

    Full Text Available Abstract Background RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and G-U-base pairings (secondary structure and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, RNAinverse, RNA-SSD as well as INFO-RNA are limited to RNA secondary structures, we present in this paper the inverse folding algorithm Inv which can deal with 3-noncrossing, canonical pseudoknot structures. Results In this paper we present the inverse folding algorithm Inv. We give a detailed analysis of Inv, including pseudocodes. We show that Inv allows to design in particular 3-noncrossing nonplanar RNA pseudoknot 3-noncrossing RNA structures-a class which is difficult to construct via dynamic programming routines. Inv is freely available at http://www.combinatorics.cn/cbpc/inv.html. Conclusions The algorithm Inv extends inverse folding capabilities to RNA pseudoknot structures. In comparison with RNAinverse it uses new ideas, for instance by considering sets of competing structures. As a result, Inv is not only able to find novel sequences even for RNA secondary structures, it does so in the context of competing structures that potentially exhibit cross-serial interactions.

  2. Functional characterization of the Drosophila MRP (mitochondrial RNA processing) RNA gene.

    Science.gov (United States)

    Schneider, Mary D; Bains, Anupinder K; Rajendra, T K; Dominski, Zbigniew; Matera, A Gregory; Simmonds, Andrew J

    2010-11-01

    MRP RNA is a noncoding RNA component of RNase mitochondrial RNA processing (MRP), a multi-protein eukaryotic endoribonuclease reported to function in multiple cellular processes, including ribosomal RNA processing, mitochondrial DNA replication, and cell cycle regulation. A recent study predicted a potential Drosophila ortholog of MRP RNA (CR33682) by computer-based genome analysis. We have confirmed the expression of this gene and characterized the phenotype associated with this locus. Flies with mutations that specifically affect MRP RNA show defects in growth and development that begin in the early larval period and end in larval death during the second instar stage. We present several lines of evidence demonstrating a role for Drosophila MRP RNA in rRNA processing. The nuclear fraction of Drosophila MRP RNA localizes to the nucleolus. Further, a mutant strain shows defects in rRNA processing that include a defect in 5.8S rRNA processing, typical of MRP RNA mutants in other species, as well as defects in early stages of rRNA processing.

  3. RAID: a comprehensive resource for human RNA-associated (RNA–RNA/RNA–protein) interaction

    Science.gov (United States)

    Zhang, Xiaomeng; Wu, Deng; Chen, Liqun; Li, Xiang; Yang, Jinxurong; Fan, Dandan; Dong, Tingting; Liu, Mingyue; Tan, Puwen; Xu, Jintian; Yi, Ying; Wang, Yuting; Zou, Hua; Hu, Yongfei; Fan, Kaili; Kang, Juanjuan; Huang, Yan; Miao, Zhengqiang; Bi, Miaoman; Jin, Nana; Li, Kongning; Li, Xia; Xu, Jianzhen; Wang, Dong

    2014-01-01

    Transcriptomic analyses have revealed an unexpected complexity in the eukaryote transcriptome, which includes not only protein-coding transcripts but also an expanding catalog of noncoding RNAs (ncRNAs). Diverse coding and noncoding RNAs (ncRNAs) perform functions through interaction with each other in various cellular processes. In this project, we have developed RAID (http://www.rna-society.org/raid), an RNA-associated (RNA–RNA/RNA–protein) interaction database. RAID intends to provide the scientific community with all-in-one resources for efficient browsing and extraction of the RNA-associated interactions in human. This version of RAID contains more than 6100 RNA-associated interactions obtained by manually reviewing more than 2100 published papers, including 4493 RNA–RNA interactions and 1619 RNA–protein interactions. Each entry contains detailed information on an RNA-associated interaction, including RAID ID, RNA/protein symbol, RNA/protein categories, validated method, expressing tissue, literature references (Pubmed IDs), and detailed functional description. Users can query, browse, analyze, and manipulate RNA-associated (RNA–RNA/RNA–protein) interaction. RAID provides a comprehensive resource of human RNA-associated (RNA–RNA/RNA–protein) interaction network. Furthermore, this resource will help in uncovering the generic organizing principles of cellular function network. PMID:24803509

  4. Peptides as catalysts in the RNA world

    DEFF Research Database (Denmark)

    Wieczorek, Rafal; Dörr, Mark; Luisi, Pier Luigi

    The emergence of RNA chains from prebiotic soup is considered a stumbling block in the RNA world theory (Orgel 2004). Both the activation of RNA monomers and their subsequent oligomerization is hard to achieve in accepted early Earth conditions, thus putting doubt on the prebiotic plausibility...... chemistry and the RNA world. Prebiotic soup likely contained complex mixtures of various molecules. Interaction of peptides and nucleotides shows that we should give more consideration to systems chemistry approach in the origin-of-life research. Gorlero M, Wieczorek R, Adamala K, Giorgi A, Schininà ME...

  5. Emerging connections between RNA and autophagy

    DEFF Research Database (Denmark)

    Frankel, Lisa B; Lubas, Michal; Lund, Anders H

    2017-01-01

    in yeast, plants and animals, reviewing the molecular mechanisms and biological importance in normal physiology, stress and disease. In addition, we explore emerging evidence of core autophagy regulation mediated by RNA-binding proteins and noncoding RNAs, and point to gaps in our current knowledge......Macroautophagy/autophagy is a key catabolic process, essential for maintaining cellular homeostasis and survival through the removal and recycling of unwanted cellular material. Emerging evidence has revealed intricate connections between the RNA and autophagy research fields. While a majority...... of the connection between RNA and autophagy. Finally, we discuss the pathological implications of RNA-protein aggregation, primarily in the context of neurodegenerative disease....

  6. MiRNA Biogenesis and Intersecting Pathways

    DEFF Research Database (Denmark)

    Ben Chaabane, Samir

    MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Plant miRNAs are critical for plant growth, development and stress response, and are processed in Arabidopsis from primary miRNA transcripts (pri-miRNAs) by the endonuclease activity of the DICER-LIKE1...... questions need to be addressed to establish a valid link, we provide encouraging evidence of the involvement of chromatin remodeling factors FAS1 and FAS2 in miRNA biogenesis. Together, we have expanded our understanding of the intersections between miRNA biogenesis and other pathways....

  7. Personalized RNA Medicine for Pancreatic Cancer.

    Science.gov (United States)

    Gilles, Maud-Emmanuelle; Hao, Liangliang; Huang, Ling; Rupaimoole, Rajesha; Lopez-Casas, Pedro P; Pulver, Emilia; Jeong, Jong Cheol; Muthuswamy, Senthil K; Hidalgo, Manuel; Bhatia, Sangeeta N; Slack, Frank J

    2018-04-01

    Purpose: Since drug responses vary between patients, it is crucial to develop pre-clinical or co-clinical strategies that forecast patient response. In this study, we tested whether RNA-based therapeutics were suitable for personalized medicine by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX) models. Experimental Design: We performed microRNA (miRNA) profiling of PDX samples to determine the status of miRNA deregulation in individual pancreatic ductal adenocarcinoma (PDAC) patients. To deliver personalized RNA-based-therapy targeting oncogenic miRNAs that form part of this common PDAC miRNA over-expression signature, we packaged antimiR oligonucleotides against one of these miRNAs in tumor-penetrating nanocomplexes (TPN) targeting cell surface proteins on PDAC tumors. Results: As a validation for our pre-clinical strategy, the therapeutic potential of one of our nano-drugs, TPN-21, was first shown to decrease tumor cell growth and survival in PDO avatars for individual patients, then in their PDX avatars. Conclusions: This general approach appears suitable for co-clinical validation of personalized RNA medicine and paves the way to prospectively identify patients with eligible miRNA profiles for personalized RNA-based therapy. Clin Cancer Res; 24(7); 1734-47. ©2018 AACR . ©2018 American Association for Cancer Research.

  8. mRNA processing in yeast

    International Nuclear Information System (INIS)

    Stevens, A.

    1982-01-01

    Investigations in this laboratory center on basic enzymatic reactions of RNA. Still undefined are reactions involved in the conversion of precursors of mRA (pre-mRNA) to mRNA in eukaryotes. The pre-mRNA is called heterogeneous nuclear RNA and is 2 to 6 times larger than mRNA. The conversion, called splicing, involves a removal of internal sequences called introns by endoribonuclease action followed by a rejoining of the 3'- and 5'-end fragments, called exons, by ligating activity. It has not been possible yet to study the enzymes involved in vitro. Also undefined are reactions involved in the turnover or discarding of certain of the pre-mRNA molecules. Yeast is a simple eukaryote and may be expected to have the same, but perhaps simpler, processing reactions as the higher eukaryotes. Two enzymes involved in the processing of pre-mRNA and mRNA in yeast are under investigation. Both enzymes have been partially purified from ribonucleoprotein particles of yeast. The first is a unique decapping enzyme which cleaves [ 3 H]m 7 Gppp [ 14 C]RNA-poly (A) of yeast, yielding [ 3 H]m 7 GDP and is suggested by the finding that the diphosphate product, m 7 GpppA(G), and UDP-glucose are not hydrolyzed. The second enzyme is an endoribonuclease which converts both the [ 3 H] and [ 14 C] labels of [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) from an oligo(dT)-cellulose bound form to an unbound, acid-insoluble form. Results show that the stimulation involves an interaction of the labeled RNA with the small nuclear RNA. The inhibition of the enzyme by ethidium bromide and its stimulation by small nuclear RNA suggest that it may be a processing ribonuclease, requiring specific double-stranded features in its substrate. The characterization of the unique decapping enzyme and endoribonuclease may help to understand reactions involved in the processing of pre-mRNA and mRNA in eukaryotes

  9. MicroRNA delivery for regenerative medicine.

    Science.gov (United States)

    Peng, Bo; Chen, Yongming; Leong, Kam W

    2015-07-01

    MicroRNA (miRNA) directs post-transcriptional regulation of a network of genes by targeting mRNA. Although relatively recent in development, many miRNAs direct differentiation of various stem cells including induced pluripotent stem cells (iPSCs), a major player in regenerative medicine. An effective and safe delivery of miRNA holds the key to translating miRNA technologies. Both viral and nonviral delivery systems have seen success in miRNA delivery, and each approach possesses advantages and disadvantages. A number of studies have demonstrated success in augmenting osteogenesis, improving cardiogenesis, and reducing fibrosis among many other tissue engineering applications. A scaffold-based approach with the possibility of local and sustained delivery of miRNA is particularly attractive since the physical cues provided by the scaffold may synergize with the biochemical cues induced by miRNA therapy. Herein, we first briefly cover the application of miRNA to direct stem cell fate via replacement and inhibition therapies, followed by the discussion of the promising viral and nonviral delivery systems. Next we present the unique advantages of a scaffold-based delivery in achieving lineage-specific differentiation and tissue development. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Messenger RNA 3' end formation in plants.

    Science.gov (United States)

    Hunt, A G

    2008-01-01

    Messenger RNA 3' end formation is an integral step in the process that gives rise to mature, translated messenger RNAs in eukaryotes. With this step, a pre-messenger RNA is processed and polyadenylated, giving rise to a mature mRNA bearing the characteristic poly(A) tract. The poly(A) tract is a fundamental feature of mRNAs, participating in the process of translation initiation and being the focus of control mechanisms that define the lifetime of mRNAs. Thus messenger RNA 3' end formation impacts two steps in mRNA biogenesis and function. Moreover, mRNA 3' end formation is something of a bridge that integrates numerous other steps in mRNA biogenesis and function. While the process is essential for the expression of most genes, it is also one that is subject to various forms of regulation, such that both quantitative and qualitative aspects of gene expression may be modulated via the polyadenylation complex. In this review, the current status of understanding of mRNA 3' end formation in plants is discussed. In particular, the nature of mRNA 3' ends in plants is reviewed, as are recent studies that are beginning to yield insight into the functioning and regulation of plant polyadenylation factor subunits.

  11. Exploring RNA structure by integrative molecular modelling

    DEFF Research Database (Denmark)

    Masquida, Benoît; Beckert, Bertrand; Jossinet, Fabrice

    2010-01-01

    RNA molecular modelling is adequate to rapidly tackle the structure of RNA molecules. With new structured RNAs constituting a central class of cellular regulators discovered every year, the need for swift and reliable modelling methods is more crucial than ever. The pragmatic method based...... on interactive all-atom molecular modelling relies on the observation that specific structural motifs are recurrently found in RNA sequences. Once identified by a combination of comparative sequence analysis and biochemical data, the motifs composing the secondary structure of a given RNA can be extruded...

  12. The modification of siRNA with 3' cholesterol to increase nuclease protection and suppression of native mRNA by select siRNA polyplexes.

    Science.gov (United States)

    Ambardekar, Vishakha V; Han, Huai-Yun; Varney, Michelle L; Vinogradov, Serguei V; Singh, Rakesh K; Vetro, Joseph A

    2011-02-01

    Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3' cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. The Modification of siRNA with 3′ Cholesterol to Increase Nuclease Protection and Suppression of Native mRNA by Select siRNA Polyplexes

    Science.gov (United States)

    Ambardekar, Vishakha V.; Han, Huai-Yun; Varney, Michelle L.; Vinogradov, Serguei V.; Singh, Rakesh K.; Vetro, Joseph A.

    2010-01-01

    Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3′ cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. PMID:21047680

  14. RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II

    Directory of Open Access Journals (Sweden)

    Isabel X. Wang

    2014-03-01

    Full Text Available RNA sequences are expected to be identical to their corresponding DNA sequences. Here, we found all 12 types of RNA-DNA sequence differences (RDDs in nascent RNA. Our results show that RDDs begin to occur in RNA chains ∼55 nt from the RNA polymerase II (Pol II active site. These RDDs occur so soon after transcription that they are incompatible with known deaminase-mediated RNA-editing mechanisms. Moreover, the 55 nt delay in appearance indicates that they do not arise during RNA synthesis by Pol II or as a direct consequence of modified base incorporation. Preliminary data suggest that RDD and R-loop formations may be coupled. These findings identify sequence substitution as an early step in cotranscriptional RNA processing.

  15. RNA three-way junctions can act as flexible RNA structural elements in large RNA molecules: a molecular simulation analysis

    Czech Academy of Sciences Publication Activity Database

    Beššeová, Ivana; Réblová, Kamila; Leontis, N.B.; Šponer, Jiří

    2009-01-01

    Roč. 26, č. 6 (2009), s. 830-831 ISSN 0739-1102. [The 17th Conversation . 16.06.2009-20.06.2009, Albany] Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : RNA three-way junctions * RNA Subject RIV: BO - Biophysics

  16. The HIV-1 leader RNA conformational switch regulates RNA dimerization but does not regulate mRNA translation

    NARCIS (Netherlands)

    Abbink, Truus E. M.; Ooms, Marcel; Haasnoot, P. C. Joost; Berkhout, Ben

    2005-01-01

    The untranslated leader RNA is the most conserved part of the human immunodeficiency virus type I (HIV-1) genome. It contains many regulatory motifs that mediate a variety of steps in the viral life cycle. Previous work showed that the full-length leader RNA can adopt two alternative structures: a

  17. In vitro transcrip