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Sample records for human spliceosomal u1

  1. Therapeutic activity of modified U1 core spliceosomal particles

    PubMed Central

    Rogalska, Malgorzata Ewa; Tajnik, Mojca; Licastro, Danilo; Bussani, Erica; Camparini, Luca; Mattioli, Chiara; Pagani, Franco

    2016-01-01

    Modified U1 snRNAs bound to intronic sequences downstream of the 5′ splice site correct exon skipping caused by different types of mutations. Here we evaluate the therapeutic activity and structural requirements of these exon-specific U1 snRNA (ExSpeU1) particles. In a severe spinal muscular atrophy, mouse model, ExSpeU1, introduced by germline transgenesis, increases SMN2 exon 7 inclusion, SMN protein production and extends life span. In vitro, RNA mutant analysis and silencing experiments show that while U1A protein is dispensable, the 70K and stem loop IV elements mediate most of the splicing rescue activity through improvement of exon and intron definition. Our findings indicate that precise engineering of the U1 core spliceosomal RNA particle has therapeutic potential in pathologies associated with exon-skipping mutations. PMID:27041075

  2. Therapeutic activity of modified U1 core spliceosomal particles.

    PubMed

    Rogalska, Malgorzata Ewa; Tajnik, Mojca; Licastro, Danilo; Bussani, Erica; Camparini, Luca; Mattioli, Chiara; Pagani, Franco

    2016-01-01

    Modified U1 snRNAs bound to intronic sequences downstream of the 5' splice site correct exon skipping caused by different types of mutations. Here we evaluate the therapeutic activity and structural requirements of these exon-specific U1 snRNA (ExSpeU1) particles. In a severe spinal muscular atrophy, mouse model, ExSpeU1, introduced by germline transgenesis, increases SMN2 exon 7 inclusion, SMN protein production and extends life span. In vitro, RNA mutant analysis and silencing experiments show that while U1A protein is dispensable, the 70K and stem loop IV elements mediate most of the splicing rescue activity through improvement of exon and intron definition. Our findings indicate that precise engineering of the U1 core spliceosomal RNA particle has therapeutic potential in pathologies associated with exon-skipping mutations. PMID:27041075

  3. U1 small nuclear RNA and spliceosomal introns in Euglena gracilis

    PubMed Central

    Breckenridge, David G.; Watanabe, Yoh-ichi; Greenwood, Spencer J.; Gray, Michael W.; Schnare, Murray N.

    1999-01-01

    In the flagellated protozoon Euglena gracilis, characterized nuclear genes harbor atypical introns that usually are flanked by short repeats, adopt complex secondary structures in pre-mRNA, and do not obey the GT-AG rule of conventional cis-spliced introns. In the nuclear fibrillarin gene of E. gracilis, we have identified three spliceosomal-type introns that have GT-AG consensus borders. Furthermore, we have isolated a small RNA from E. gracilis and propose, on the basis of primary and secondary structure comparisons, that it is a homolog of U1 small nuclear RNA, an essential component of the cis-spliceosome in higher eukaryotes. Conserved sequences at the 5′ splice sites of the fibrillarin introns can potentially base pair with Euglena U1 small nuclear RNA. Our observations demonstrate that spliceosomal GT-AG cis-splicing occurs in Euglena, in addition to the nonconventional cis-splicing and spliced leader trans-splicing previously recognized in this early diverging unicellular eukaryote. PMID:9927657

  4. Comprehensive proteomic analysis of the human spliceosome

    NASA Astrophysics Data System (ADS)

    Zhou, Zhaolan; Licklider, Lawrence J.; Gygi, Steven P.; Reed, Robin

    2002-09-01

    The precise excision of introns from pre-messenger RNA is performed by the spliceosome, a macromolecular machine containing five small nuclear RNAs and numerous proteins. Much has been learned about the protein components of the spliceosome from analysis of individual purified small nuclear ribonucleoproteins and salt-stable spliceosome `core' particles. However, the complete set of proteins that constitutes intact functional spliceosomes has yet to be identified. Here we use maltose-binding protein affinity chromatography to isolate spliceosomes in highly purified and functional form. Using nanoscale microcapillary liquid chromatography tandem mass spectrometry, we identify ~145 distinct spliceosomal proteins, making the spliceosome the most complex cellular machine so far characterized. Our spliceosomes comprise all previously known splicing factors and 58 newly identified components. The spliceosome contains at least 30 proteins with known or putative roles in gene expression steps other than splicing. This complexity may be required not only for splicing multi-intronic metazoan pre-messenger RNAs, but also for mediating the extensive coupling between splicing and other steps in gene expression.

  5. Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis

    PubMed Central

    Bessonov, Sergey; Anokhina, Maria; Krasauskas, Andrius; Golas, Monika M.; Sander, Bjoern; Will, Cindy L.; Urlaub, Henning; Stark, Holger; Lührmann, Reinhard

    2010-01-01

    To better understand the compositional and structural dynamics of the human spliceosome during its activation, we set out to isolate spliceosomal complexes formed after precatalytic B but prior to catalytically active C complexes. By shortening the polypyrimidine tract of the PM5 pre-mRNA, which lacks a 3′ splice site and 3′ exon, we stalled spliceosome assembly at the activation stage. We subsequently affinity purified human Bact complexes under the same conditions previously used to isolate B and C complexes, and analyzed their protein composition by mass spectrometry. A comparison of the protein composition of these complexes allowed a fine dissection of compositional changes during the B to Bact and Bact to C transitions, and comparisons with the Saccharomyces cerevisiae Bact complex revealed that the compositional dynamics of the spliceosome during activation are largely conserved between lower and higher eukaryotes. Human SF3b155 and CDC5L were shown to be phosphorylated specifically during the B to Bact and Bact to C transition, respectively, suggesting these modifications function at these stages of splicing. The two-dimensional structure of the human Bact complex was determined by electron microscopy, and a comparison with the B complex revealed that the morphology of the human spliceosome changes significantly during its activation. The overall architecture of the human and S. cerevisiae Bact complex is similar, suggesting that many of the higher order interactions among spliceosomal components, as well as their dynamics, are also largely conserved. PMID:20980672

  6. Structural and functional analysis of the human spliceosomal DEAD-box helicase Prp28

    SciTech Connect

    Möhlmann, Sina; Mathew, Rebecca; Neumann, Piotr; Schmitt, Andreas; Lührmann, Reinhard; Ficner, Ralf

    2014-06-01

    The crystal structure of the helicase domain of the human spliceosomal DEAD-box protein Prp28 was solved by SAD. The binding of ADP and ATP by Prp28 was studied biochemically and analysed with regard to the crystal structure. The DEAD-box protein Prp28 is essential for pre-mRNA splicing as it plays a key role in the formation of an active spliceosome. Prp28 participates in the release of the U1 snRNP from the 5′-splice site during association of the U5·U4/U6 tri-snRNP, which is a crucial step in the transition from a pre-catalytic spliceosome to an activated spliceosome. Here, it is demonstrated that the purified helicase domain of human Prp28 (hPrp28ΔN) binds ADP, whereas binding of ATP and ATPase activity could not be detected. ATP binding could not be observed for purified full-length hPrp28 either, but within an assembled spliceosomal complex hPrp28 gains ATP-binding activity. In order to understand the structural basis for the ATP-binding deficiency of isolated hPrp28, the crystal structure of hPrp28ΔN was determined at 2.0 Å resolution. In the crystal the helicase domain adopts a wide-open conformation, as the two RecA-like domains are extraordinarily displaced from the productive ATPase conformation. Binding of ATP is hindered by a closed conformation of the P-loop, which occupies the space required for the γ-phosphate of ATP.

  7. Crystallization and biochemical characterization of the human spliceosomal Aar2-Prp8(RNaseH) complex.

    PubMed

    Santos, Karine; Preussner, Marco; Heroven, Anna Christina; Weber, Gert

    2015-11-01

    In eukaryotes, the removal of nuclear noncoding sequences (pre-mRNA splicing) is catalyzed by the spliceosome, which consists of five ribonucleoprotein particles (U1, U2, U4, U5 and U6 snRNPs, each with a respective snRNA) and a plethora of protein factors that aid spliceosomal maturation, assembly, activation and disassembly. Recently, the U5 snRNP maturation factor Aar2p from baker's yeast has been characterized structurally and biochemically. Aar2p binds to the RNaseH (RH) and Jab1/MPN domains of the highly conserved U5-specific Prp8p, which forms a framework for the spliceosomal catalytic centre. Thereby, Aar2p sterically excludes Brr2p, a helicase essential for the catalytic activation of the spliceosome, from Prp8p binding. At the same time, Aar2p blocks U4/U6 di-snRNA binding to Prp8p. Aar2p therefore prevents premature spliceosome activation and its functions are regulated by reversible phosphorylation. To date, little is known about the hypothetical human Aar2 (hsAar2) orthologue C20ORF4. This study identifies C20ORF4 (i) as part of the HeLa proteome by Western blotting and (ii) as a true Aar2 orthologue which binds to the RH domain (hsRH) of Prp8 and corroborates an evolutionary link between yeast and human Aar2 function. An elaborate strategy was devised to crystallize hsAar2 in complex with hsRH. The analysis of initial weakly diffracting crystals obtained by in situ proteolysis and homology modelling guided the design of an hsAar2 construct in which an internal loop was replaced by three serines (hsAar2(Δloop)). A complex of hsAar2(Δloop) and hsRH crystallized in space group C2; the crystals diffracted to 2.35 Å resolution and were suitable for structure determination by molecular-replacement approaches. The study presented here suggests a connection between Aar2 and the spliceosome in human cells and paves the way for structural studies of human Aar2. PMID:26527271

  8. Members of a family of proteins (the RD family) detected by a U1 70K monoclonal antibody are present in spliceosomal complexes.

    PubMed Central

    Staknis, D; Reed, R

    1995-01-01

    We have characterized a monoclonal antibody (mAb) to the U1 snRNP component U1 70K. We find that this antibody recognizes several proteins, in addition to U1 70K, in purified spliceosomal complexes and in total HeLa cell nuclear extract preparations. The novel mAb U1 70K antigens can also be specifically immunoprecipitated by the antibody. Similarly to U1 70K, many of the mAb U1 70K antigens can be phosphorylated by a co-purifying kinase activity. The epitope recognized by mAb U1 70K was previously shown to be a repeating arginine/aspartate (RD) dipeptide. Thus we have designated the novel mAb U1 70K antigens the RD family. Comparison of mAb U1 70K with a recently characterized antibody, mAb 16H3, whose epitope is a repeating R/D or R/E motif, showed that a large subset of the antigens are common. In contrast, most of the mAb U1 70K antigens are distinct from the proteins detected by mAb 104, an antibody to the SR family of splicing factors. Images PMID:7479068

  9. Spliceosomal Immunophilins

    PubMed Central

    Mesa, Annia; Somarelli, Jason A.; Herrera, Rene J.

    2008-01-01

    The spliceosome is a dynamic, macromolecular complex, which removes non-protein-coding introns from pre-mRNA to form mature mRNA in a process known as splicing. This ribonucleoprotein assembly is comprised of five uridine-rich small nuclear RNAs (snRNAs) as well as over 300 proteins. In humans, several of the known splicing factors are members of the immunophilin superfamily. Immunophilins are peptidyl-prolyl cis-trans isomerases that catalyze the conversion of proteins from cis to trans at Xaa-Pro bonds. Our review of the data portrays a picture of this protein family as activators of spliceosomal proteins by way of folding and transport. PMID:18544344

  10. SPF30 is an essential human splicing factor required for assembly of the U4/U5/U6 tri-small nuclear ribonucleoprotein into the spliceosome.

    PubMed

    Rappsilber, J; Ajuh, P; Lamond, A I; Mann, M

    2001-08-17

    Spliceosome assembly involves the sequential recruitment of small nuclear ribonucleoproteins (snRNPs) onto a pre-mRNA substrate. Although several non-snRNP proteins function during the binding of U1 and U2 snRNPs, little is known about the subsequent binding of the U4/U5/U6 tri-snRNP. A recent proteomic analysis of the human spliceosome identified SPF30 (Neubauer, G., King, A., Rappsilber, J., Calvio, C., Watson, M., Ajuh, P., Sleeman, J., Lamond, A., and Mann, M. (1998) Nat. Genet. 20, 46-50), a homolog of the survival of motor neurons (SMN) protein, as a spliceosome factor. We show here that SPF30 is a nuclear protein that associates with both U4/U5/U6 and U2 snRNP components. In the absence of SPF30, the preformed tri-snRNP fails to assemble into the spliceosome. Mass spectrometric analysis shows that a recombinant glutathione S-transferase-SPF30 fusion protein associates with complexes containing core Sm and U4/U5/U6 tri-snRNP proteins when added to HeLa nuclear extract, most strongly to U4/U6-90. The data indicate that SPF30 is an essential human splicing factor that may act to dock the U4/U5/U6 tri-snRNP to the A complex during spliceosome assembly or, alternatively, may act as a late assembly factor in both the tri-snRNP and the A-complex. PMID:11331295

  11. Conservation of the Protein Composition and Electron Microscopy Structure of Drosophila melanogaster and Human Spliceosomal Complexes▿ †

    PubMed Central

    Herold, Nadine; Will, Cindy L.; Wolf, Elmar; Kastner, Berthold; Urlaub, Henning; Lührmann, Reinhard

    2009-01-01

    Comprehensive proteomics analyses of spliceosomal complexes are currently limited to those in humans, and thus, it is unclear to what extent the spliceosome's highly complex composition and compositional dynamics are conserved among metazoans. Here we affinity purified Drosophila melanogaster spliceosomal B and C complexes formed in Kc cell nuclear extract. Mass spectrometry revealed that their composition is highly similar to that of human B and C complexes. Nonetheless, a number of Drosophila-specific proteins were identified, suggesting that there may be novel factors contributing specifically to splicing in flies. Protein recruitment and release events during the B-to-C transition were also very similar in both organisms. Electron microscopy of Drosophila B complexes revealed a high degree of structural similarity with human B complexes, indicating that higher-order interactions are also largely conserved. A comparison of Drosophila spliceosomes formed on a short versus long intron revealed only small differences in protein composition but, nonetheless, clear structural differences under the electron microscope. Finally, the characterization of affinity-purified Drosophila mRNPs indicated that exon junction complex proteins are recruited in a splicing-dependent manner during C complex formation. These studies provide insights into the evolutionarily conserved composition and structure of the metazoan spliceosome, as well as its compositional dynamics during catalytic activation. PMID:18981222

  12. Target discrimination by RNA-binding proteins: role of the ancillary protein U2A' and a critical leucine residue in differentiating the RNA-binding specificity of spliceosomal proteins U1A and U2B".

    PubMed Central

    Rimmele, M E; Belasco, J G

    1998-01-01

    The spliceosomal proteins U1A and U2B" each use a homologous RRM domain to bind specifically to their respective snRNA targets, U1hpll and U2hpIV, two stem-loops that are similar yet distinct in sequence. Previous studies have shown that binding of U2B" to U2hpIV is facilitated by the ancillary protein U2A', whereas specific binding of U1A to U1hpll requires no cofactor. Here we report that U2A' enables U2B" to distinguish the loop sequence of U2hpIV from that of U1hpll but plays no role in stem sequence discrimination. Although U2A' can also promote heterospecific binding of U1A to U2hpIV, a much higher concentration of the ancillary protein is required due to the approximately 500-fold greater affinity of U2A' for U2B". Additional experiments have identified a single leucine residue in U1A(Leu-44) that is critical for the intrinsic specificity of this protein for the loop sequence of U1 hpll in preference to that of U2hpIV. Our data suggest that most of the difference in RNA-binding specificity between U1A and U2B" can be accounted for by this leucine residue and by the contribution of the ancillary protein U2A' to the specificity of U2B". PMID:9814759

  13. Functional organization of the Sm core in the crystal structure of human U1 snRNP

    PubMed Central

    Weber, Gert; Trowitzsch, Simon; Kastner, Berthold; Lührmann, Reinhard; Wahl, Markus C

    2010-01-01

    U1 small nuclear ribonucleoprotein (snRNP) recognizes the 5′-splice site early during spliceosome assembly. It represents a prototype spliceosomal subunit containing a paradigmatic Sm core RNP. The crystal structure of human U1 snRNP obtained from natively purified material by in situ limited proteolysis at 4.4 Å resolution reveals how the seven Sm proteins, each recognize one nucleotide of the Sm site RNA using their Sm1 and Sm2 motifs. Proteins D1 and D2 guide the snRNA into and out of the Sm ring, and proteins F and E mediate a direct interaction between the Sm site termini. Terminal extensions of proteins D1, D2 and B/B′, and extended internal loops in D2 and B/B′ support a four-way RNA junction and a 3′-terminal stem-loop on opposite sides of the Sm core RNP, respectively. On a higher organizational level, the core RNP presents multiple attachment sites for the U1-specific 70K protein. The intricate, multi-layered interplay of proteins and RNA rationalizes the hierarchical assembly of U snRNPs in vitro and in vivo. PMID:21113136

  14. Multiple protein-protein interactions converging on the Prp38 protein during activation of the human spliceosome.

    PubMed

    Schütze, Tonio; Ulrich, Alexander K C; Apelt, Luise; Will, Cindy L; Bartlick, Natascha; Seeger, Martin; Weber, Gert; Lührmann, Reinhard; Stelzl, Ulrich; Wahl, Markus C

    2016-02-01

    Spliceosomal Prp38 proteins contain a conserved amino-terminal domain, but only higher eukaryotic orthologs also harbor a carboxy-terminal RS domain, a hallmark of splicing regulatory SR proteins. We show by crystal structure analysis that the amino-terminal domain of human Prp38 is organized around three pairs of antiparallel α-helices and lacks similarities to RNA-binding domains found in canonical SR proteins. Instead, yeast two-hybrid analyses suggest that the amino-terminal domain is a versatile protein-protein interaction hub that possibly binds 12 other spliceosomal proteins, most of which are recruited at the same stage as Prp38. By quantitative, alanine surface-scanning two-hybrid screens and biochemical analyses we delineated four distinct interfaces on the Prp38 amino-terminal domain. In vitro interaction assays using recombinant proteins showed that Prp38 can bind at least two proteins simultaneously via two different interfaces. Addition of excess Prp38 amino-terminal domain to in vitro splicing assays, but not of an interaction-deficient mutant, stalled splicing at a precatalytic stage. Our results show that human Prp38 is an unusual SR protein, whose amino-terminal domain is a multi-interface protein-protein interaction platform that might organize the relative positioning of other proteins during splicing. PMID:26673105

  15. Primary structure of a human arginine-rich nuclear protein that colocalizes with spliceosome components

    SciTech Connect

    Chaudhary, N.; McMahon, C.; Blobel, G. )

    1991-09-15

    The cDNA for a 54-kDa nuclear protein (p54) has been cloned from a human hepatoma expression library. Contained within p54 is an arginine/serine-rich region similar to segments of several proteins that participate in pre-mRNA splicing including the 70-kDa component of U1 small nuclear ribonucleoprotein particle (snRNP) and the Drosophila transformer and suppressor-of-white-apricot proteins. The arginine/serine-rich region is dominated by a series of 8-amino acid imperfect repetitive motifs (consensus sequence, Arg-Arg-Ser-Arg-Ser-Arg-Ser-Arg). Antibodies raised against synthetic peptides of p54 react with an {approximately}70-kDa protein on immunoblots of HeLa cell and rat liver nuclear proteins. This apparent discrepancy in mass is also observed when p54 mRNA is translated in vitro. Indirect immunofluorescence studies in HeLa cells show that p54 is distributed throughout the nucleus in a speckled pattern, with an additional diffuse labeling of the nucleus excluding the nucleoli. Double immunofluorescence experiments indicate that these punctate regions are coincident with the speckles seen in cells stained with antibodies against several constituents of the pre-mRNA splicing machinery. Sedimentation analysis of HeLa cell extracts on sucrose gradients showed that p54 migrates at 4-6 S, indicating that the protein is not a tightly associated component of snRNPs. Although the function of p54 is not yet known, the structure and immunolocalization data suggest that this protein may have a role in pre-mRNA processing.

  16. Spliceosome Database: a tool for tracking components of the spliceosome

    PubMed Central

    Cvitkovic, Ivan; Jurica, Melissa S.

    2013-01-01

    The spliceosome is the extremely complex macromolecular machine responsible for pre-mRNA splicing. It assembles from five U-rich small nuclear RNAs (snRNAs) and over 200 proteins in a highly dynamic fashion. One important challenge to studying the spliceosome is simply keeping track of all these proteins, a situation further complicated by the variety of names and identifiers that exist in the literature for them. To facilitate studies of the spliceosome and its components, we created a database of spliceosome-associated proteins and snRNAs, which is available at http://spliceosomedb.ucsc.edu and can be queried through a simple browser interface. In the database, we cataloged the various names, orthologs and gene identifiers of spliceosome proteins to navigate the complex nomenclature of spliceosome proteins. We also provide links to gene and protein records for the spliceosome components in other databases. To navigate spliceosome assembly dynamics, we created tools to compare the association of spliceosome proteins with complexes that form at specific stages of spliceosome assembly based on a compendium of mass spectrometry experiments that identified proteins in purified splicing complexes. Together, the information in the database provides an easy reference for spliceosome components and will support future modeling of spliceosome structure and dynamics. PMID:23118483

  17. CryoEM structures of two spliceosomal complexes: starter and dessert at the spliceosome feast

    PubMed Central

    Nguyen, Thi Hoang Duong; Galej, Wojciech P; Fica, Sebastian M; Lin, Pei-Chun; Newman, Andrew J; Nagai, Kiyoshi

    2016-01-01

    The spliceosome is formed on pre-mRNA substrates from five small nuclear ribonucleoprotein particles (U1, U2, U4/U6 and U5 snRNPs), and numerous non-snRNP factors. Saccharomyces cerevisiae U4/U6.U5 tri-snRNP comprises U5 snRNA, U4/U6 snRNA duplex and approximately 30 proteins and represents a substantial part of the spliceosome before activation. Schizosaccharomyces pombe U2.U6.U5 spliceosomal complex is a post-catalytic intron lariat spliceosome containing U2 and U5 snRNPs, NTC (nineteen complex), NTC-related proteins (NTR), U6 snRNA, and an RNA intron lariat. Two recent papers describe near-complete atomic structures of these complexes based on cryoEM single-particle analysis. The U4/U6.U5 tri-snRNP structure provides crucial insight into the activation mechanism of the spliceosome. The U2.U6.U5 complex reveals the striking architecture of NTC and NTR and important features of the group II intron-like catalytic RNA core remaining after spliced mRNA is released. These two structures greatly advance our understanding of the mechanism of pre-mRNA splicing. PMID:26803803

  18. Physical and genetic interactions of yeast Cwc21p, an ortholog of human SRm300/SRRM2, suggest a role at the catalytic center of the spliceosome.

    PubMed

    Grainger, Richard J; Barrass, J David; Jacquier, Alain; Rain, Jean-Christophe; Beggs, Jean D

    2009-12-01

    In Saccharomyces cerevisiae, Cwc21p is a protein of unknown function that is associated with the NineTeen Complex (NTC), a group of proteins involved in activating the spliceosome to promote the pre-mRNA splicing reaction. Here, we show that Cwc21p binds directly to two key splicing factors-namely, Prp8p and Snu114p-and becomes the first NTC-related protein known to dock directly to U5 snRNP proteins. Using a combination of proteomic techniques we show that the N-terminus of Prp8p contains an intramolecular fold that is a Snu114p and Cwc21p interacting domain (SCwid). Cwc21p also binds directly to the C-terminus of Snu114p. Complementary chemical cross-linking experiments reveal reciprocal protein footprints between the interacting Prp8 and Cwc21 proteins, identifying the conserved cwf21 domain in Cwc21p as a Prp8p binding site. Genetic and functional interactions between Cwc21p and Isy1p indicate that they have related functions at or prior to the first catalytic step of splicing, and suggest that Cwc21p functions at the catalytic center of the spliceosome, possibly in response to environmental or metabolic changes. We demonstrate that SRm300, the only SR-related protein known to be at the core of human catalytic spliceosomes, is a functional ortholog of Cwc21p, also interacting directly with Prp8p and Snu114p. Thus, the function of Cwc21p is likely conserved from yeast to humans.

  19. Splicing diversity revealed by reduced spliceosomes in C. merolae and other organisms

    PubMed Central

    Hudson, Andrew J; Stark, Martha R; Fast, Naomi M; Russell, Anthony G; Rader, Stephen D

    2015-01-01

    Pre-mRNA splicing has been considered one of the hallmarks of eukaryotes, yet its diversity is astonishing: the number of substrate introns for splicing ranges from hundreds of thousands in humans to a mere handful in certain parasites. The catalytic machinery that carries out splicing, the spliceosome, is similarly diverse, with over 300 associated proteins in humans to a few tens in other organisms. In this Point of View, we discuss recent work characterizing the reduced spliceosome of the acidophilic red alga Cyanidioschyzon merolae, which further highlights the diversity of splicing in that it does not possess the U1 snRNP that is characteristically responsible for 5′ splice site recognition. Comparisons to other organisms with reduced spliceosomes, such as microsporidia, trypanosomes, and Giardia, help to identify the most highly conserved splicing factors, pointing to the essential core of this complex machine. These observations argue for increased exploration of important biochemical processes through study of a wider ranger of organisms. PMID:26400738

  20. The Arabidopsis homolog of human minor spliceosomal protein U11-48K plays a crucial role in U12 intron splicing and plant development.

    PubMed

    Xu, Tao; Kim, Bo Mi; Kwak, Kyung Jin; Jung, Hyun Ju; Kang, Hunseung

    2016-05-01

    The minor U12 introns are removed from precursor mRNAs by the U12 intron-specific minor spliceosome. Among the seven ribonucleoproteins unique to the minor spliceosome, denoted as U11/U12-20K, U11/U12-25K, U11/U12-31K, U11/U12-65K, U11-35K, U11-48K, and U11-59K, the roles of only U11/U12-31K and U11/U12-65K have been demonstrated in U12 intron splicing and plant development. Here, the functional role of the Arabidopsis homolog of human U11-48K in U12 intron splicing and the development of Arabidopsis thaliana was examined using transgenic knockdown plants. The u11-48k mutants exhibited several defects in growth and development, such as severely arrested primary inflorescence stems, formation of serrated leaves, production of many rosette leaves after bolting, and delayed senescence. The splicing of most U12 introns analyzed was impaired in the u11-48k mutants. Comparative analysis of the splicing defects and phenotypes among the u11/u12-31k, u11-48k, and u11/12-65k mutants showed that the severity of abnormal development was closely correlated with the degree of impairment in U12 intron splicing. Taken together, these results provide compelling evidence that the Arabidopsis homolog of human U11-48K protein, as well as U11/U12-31K and U11/U12-65K proteins, is necessary for correct splicing of U12 introns and normal plant growth and development. PMID:27091878

  1. RNAtomy of the Spliceosome's heart

    PubMed Central

    Bonnal, Sophie; Valcárcel, Juan

    2013-01-01

    The EMBO J 32: 2804–2818 10.1038/emboj.2013.198; published online 09032013 In his 1543 monumental work De humanis corpori fabrica, Andreas Vesalius used rigorous dissection practices and a mechanistic view of the organ's function to provide the first accurate anatomical description of a human heart. Guided by similar principles of meticulous structural probing and mechanistic explanatory potential, Anokhina and colleagues in this issue of The EMBO Journal dissect the molecular topology of the RNA heart of the Spliceosome, the ribonucleoprotein machinery in charge of intron removal. Their findings reveal key structural features with important implications for understanding the mechanisms of pre-mRNA splicing catalysis. PMID:24065126

  2. U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer’s disease

    PubMed Central

    Bai, Bing; Hales, Chadwick M.; Chen, Ping-Chung; Gozal, Yair; Dammer, Eric B.; Fritz, Jason J.; Wang, Xusheng; Xia, Qiangwei; Duong, Duc M.; Street, Craig; Cantero, Gloria; Cheng, Dongmei; Jones, Drew R.; Wu, Zhiping; Li, Yuxin; Diner, Ian; Heilman, Craig J.; Rees, Howard D.; Wu, Hao; Lin, Li; Szulwach, Keith E.; Gearing, Marla; Mufson, Elliott J.; Bennett, David A.; Montine, Thomas J.; Seyfried, Nicholas T.; Wingo, Thomas S.; Sun, Yi E.; Jin, Peng; Hanfelt, John; Willcock, Donna M.; Levey, Allan; Lah, James J.; Peng, Junmin

    2013-01-01

    Deposition of insoluble protein aggregates is a hallmark of neurodegenerative diseases. The universal presence of β-amyloid and tau in Alzheimer’s disease (AD) has facilitated advancement of the amyloid cascade and tau hypotheses that have dominated AD pathogenesis research and therapeutic development. However, the underlying etiology of the disease remains to be fully elucidated. Here we report a comprehensive study of the human brain-insoluble proteome in AD by mass spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate in the disease, including U1-70K and other U1 small nuclear ribonucleoprotein (U1 snRNP) spliceosome components. Similar accumulations in mild cognitive impairment cases indicate that spliceosome changes occur in early stages of AD. Multiple U1 snRNP subunits form cytoplasmic tangle-like structures in AD but not in other examined neurodegenerative disorders, including Parkinson disease and frontotemporal lobar degeneration. Comparison of RNA from AD and control brains reveals dysregulated RNA processing with accumulation of unspliced RNA species in AD, including myc box-dependent-interacting protein 1, clusterin, and presenilin-1. U1-70K knockdown or antisense oligonucleotide inhibition of U1 snRNP increases the protein level of amyloid precursor protein. Thus, our results demonstrate unique U1 snRNP pathology and implicate abnormal RNA splicing in AD pathogenesis. PMID:24023061

  3. A day in the life of the spliceosome

    PubMed Central

    Matera, A. Gregory; Wang, Zefeng

    2014-01-01

    One of the most amazing findings in molecular biology was the discovery that eukaryotic genes are discontinuous, interrupted by stretches of non-coding sequence. The subsequent realization that the intervening regions are removed from pre-mRNA transcripts via the activity of a common set of small nuclear RNAs (snRNAs), which assemble together with associated proteins into a spliceosome, was equally surprising. How do cells orchestrate the assembly of this molecular machine? And how does the spliceosome accurately recognize exons and introns to carry out the splicing reaction? Insights into these questions have been gained by studying the life cycle of spliceosomal snRNAs from their transcription, nuclear export and reimport, all the way through to their dynamic assembly into the spliceosome. This assembly process can also affect the regulation of alternative splicing and has implications for human disease. PMID:24452469

  4. The spliceosome as a transposon sensor

    PubMed Central

    Dumesic, Phillip A; Madhani, Hiten D

    2013-01-01

    The ability to distinguish self from non-self nucleic acids enables eukaryotes to suppress mobile elements and maintain genome integrity. In organisms from protist to human, this function is performed by RNA silencing pathways. There have been major advances in our understanding of the RNA silencing machinery, but the mechanisms by which these pathways distinguish self from non-self remain unclear. Recent studies in the yeast C. neoformans indicate that transposon-derived transcripts encode suboptimal introns and tend to stall in spliceosomes, which promotes the biogenesis of siRNA that targets these transcripts. These findings identify gene expression signal strength as a metric by which a foreign element can be distinguished from a host gene, and reveal a new function for introns and the spliceosome in genome defense. Anticipating that these principles may apply to RNA silencing in other systems, we discuss strong hints in the literature suggesting that the spliceosome may guide small RNA biogenesis in the siRNA and piRNA pathways of plants and animals. PMID:24418889

  5. Endogenous U2·U5·U6 snRNA complexes in S. pombe are intron lariat spliceosomes

    PubMed Central

    Chen, Weijun; Shulha, Hennady P.; Ashar-Patel, Ami; Yan, Jing; Green, Karin M.; Query, Charles C.; Rhind, Nick; Weng, Zhiping; Moore, Melissa J.

    2014-01-01

    Excision of introns from pre-mRNAs is mediated by the spliceosome, a multi-megadalton complex consisting of U1, U2, U4/U6, and U5 snRNPs plus scores of associated proteins. Spliceosome assembly and disassembly are highly dynamic processes involving multiple stable intermediates. In this study, we utilized a split TAP-tag approach for large-scale purification of an abundant endogenous U2·U5·U6 complex from Schizosaccharomyces pombe. RNAseq revealed this complex to largely contain excised introns, indicating that it is primarily ILS (intron lariat spliceosome) complexes. These endogenous ILS complexes are remarkably resistant to both high-salt and nuclease digestion. Mass spectrometry analysis identified 68, 45, and 43 proteins in low-salt-, high-salt-, and micrococcal nuclease-treated preps, respectively. The protein content of a S. pombe ILS complex strongly resembles that previously reported for human spliced product (P) and Saccharomyces cerevisiae ILS complexes assembled on single pre-mRNAs in vitro. However, the ATP-dependent RNA helicase Brr2 was either substoichiometric in low-salt preps or completely absent from high-salt and MNase preps. Because Brr2 facilitates spliceosome disassembly, its relative absence may explain why the ILS complex accumulates logarithmically growing cultures and the inability of S. pombe extracts to support in vitro splicing. PMID:24442611

  6. The spliceosomal proteome: at the heart of the largest cellular ribonucleoprotein machine.

    PubMed

    Valadkhan, Saba; Jaladat, Yasaman

    2010-11-01

    Almost all primary transcripts in higher eukaryotes undergo several splicing events and alternative splicing is a major factor in generating proteomic diversity. Thus, the spliceosome, the ribonucleoprotein assembly that performs splicing, is a highly critical cellular machine and as expected, a very complex one. Indeed, the spliceosome is one of the largest, if not the largest, molecular machine in the cell with over 150 different components in human. A large fraction of the spliceosomal proteome is organized into small nuclear ribonucleoprotein particles by associating with one of the small nuclear RNAs, and the function of many spliceosomal proteins revolve around their association or interaction with the spliceosomal RNAs or the substrate pre-messenger RNAs. In addition to the complex web of protein-RNA interactions, an equally complex network of protein-protein interactions exists in the spliceosome, which includes a number of large, conserved proteins with critical functions in the spliceosomal catalytic core. These include the largest conserved nuclear protein, Prp8, which plays a critical role in spliceosomal function in a hitherto unknown manner. Taken together, the large spliceosomal proteome and its dynamic nature has made it a highly challenging system to study, and at the same time, provides an exciting example of the evolution of a proteome around a backbone of primordial RNAs likely dating from the RNA World.

  7. Purification of Drosophila snRNPs and characterization of two populations of functional U1 particles.

    PubMed Central

    Labourier, E; Rio, D C

    2001-01-01

    U1 snRNP is required at an early stage during assembly of the spliceosome, the dynamic ribonucleoprotein (RNP) complex that performs nuclear pre-mRNA splicing. Here, we report the purification of U1 snRNP particles from Drosophila nuclear extracts and the characterization of their biochemical properties, polypeptide contents, and splicing activities. On the basis of their antigenicity, apparent molecular weight, and by peptide sequencing, the Drosophila 70K, SNF, B, U1-C, D1, D2, D3, E, F, and G proteins are shown to be integral components of these particles. Sequence database searches revealed that both the U1-specific and the Sm proteins are extensively conserved between human and Drosophila snRNPs. Furthermore, both species possess a conserved intrinsic U1-associated kinase activity with identical substrate specificity in vitro. Finally, our results demonstrate that a second type of functional U1 particle, completely lacking the U1/U2-specific protein SNF and the associated protein kinase activity, can be isolated from cultured Kc cell or Canton S embryonic nuclear extracts. This work describes the first characterization of a purified Drosophila snRNP particle and reinforces the view that their activity and composition, with the exception of the atypical bifunctional U1-A/U2-B" SNF protein, are highly conserved in metazoans. PMID:11333025

  8. Nuclear cyclophilins affect spliceosome assembly and function in vitro.

    PubMed

    Adams, B M; Coates, Miranda N; Jackson, S RaElle; Jurica, Melissa S; Davis, Tara L

    2015-07-15

    Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.

  9. A review of craniofacial disorders caused by spliceosomal defects.

    PubMed

    Lehalle, D; Wieczorek, D; Zechi-Ceide, R M; Passos-Bueno, M R; Lyonnet, S; Amiel, J; Gordon, C T

    2015-11-01

    The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.

  10. Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis.

    PubMed Central

    Jurica, Melissa S; Licklider, Lawrence J; Gygi, Steven R; Grigorieff, Nikolaus; Moore, Melissa J

    2002-01-01

    We describe characterization of spliceosomes affinity purified under native conditions. These spliceosomes consist largely of C complex containing splicing intermediates. After C complex assembly on an MS2 affinity-tagged pre-mRNA substrate containing a 3' splice site mutation, followed by RNase H digestion of earlier complexes, spliceosomes were purified by size exclusion and affinity selection. This protocol yielded 40S C complexes in sufficient quantities to visualize in negative stain by electron microscopy. Complexes purified in this way contain U2, U5, and U6 snRNAs, but very little U1 or U4 snRNA. Analysis by tandem mass spectrometry confirmed the presence of core snRNP proteins (SM and LSM), U2 and U5 snRNP-specific proteins, and the second step factors Prp16, Prp17, Slu7, and Prp22. In contrast, proteins specific to earlier splicing complexes, such as U2AF and U1 snRNP components, were not detected in C complex, but were present in similarly purified H complex. Images of these spliceosomes revealed single particles with dimensions of approximately 270 x 240 A that assort into well-defined classes. These images represent an important first step toward attaining a comprehensive three-dimensional understanding of pre-mRNA splicing. PMID:11991638

  11. Origin of Spliceosomal Introns and Alternative Splicing

    PubMed Central

    Irimia, Manuel; Roy, Scott William

    2014-01-01

    In this work we review the current knowledge on the prehistory, origins, and evolution of spliceosomal introns. First, we briefly outline the major features of the different types of introns, with particular emphasis on the nonspliceosomal self-splicing group II introns, which are widely thought to be the ancestors of spliceosomal introns. Next, we discuss the main scenarios proposed for the origin and proliferation of spliceosomal introns, an event intimately linked to eukaryogenesis. We then summarize the evidence that suggests that the last eukaryotic common ancestor (LECA) had remarkably high intron densities and many associated characteristics resembling modern intron-rich genomes. From this intron-rich LECA, the different eukaryotic lineages have taken very distinct evolutionary paths leading to profoundly diverged modern genome structures. Finally, we discuss the origins of alternative splicing and the qualitative differences in alternative splicing forms and functions across lineages. PMID:24890509

  12. The spliceosome: a flexible, reversible macromolecular machine.

    PubMed

    Hoskins, Aaron A; Moore, Melissa J

    2012-05-01

    With more than a hundred individual RNA and protein parts and a highly dynamic assembly and disassembly pathway, the spliceosome is arguably the most complicated macromolecular machine in the eukaryotic cell. This complexity has made kinetic and mechanistic analysis of splicing incredibly challenging. Yet, recent technological advances are now providing tools for understanding this process in much greater detail. Ranging from genome-wide analyses of splicing and creation of an orthogonal spliceosome in vivo, to purification of active spliceosomes and observation of single molecules in vitro, such new experimental approaches are yielding significant insight into the inner workings of this remarkable machine. These experiments are rewriting the textbooks, with a new picture emerging of a dynamic, malleable machine heavily influenced by the identity of its pre-mRNA substrate.

  13. Spliceosome twin introns in fungal nuclear transcripts.

    PubMed

    Flipphi, Michel; Fekete, Erzsébet; Ag, Norbert; Scazzocchio, Claudio; Karaffa, Levente

    2013-08-01

    The spliceosome is an RNA/protein complex, responsible for intron excision from eukaryotic nuclear transcripts. In bacteria, mitochondria and plastids, intron excision does not involve the spliceosome, but occurs through mechanisms dependent on intron RNA secondary and tertiary structure. For group II/III chloroplast introns, "twintrons" (introns within introns) have been described. The excision of the external intron, and thus proper RNA maturation, necessitates prior removal of the internal intron, which interrupts crucial sequences of the former. We have here predicted analogous instances of spliceosomal twintrons ("stwintrons") in filamentous fungi. In two specific cases, where the internal intron interrupts the donor of the external intron after the first or after the second nucleotide, respectively, we show that intermediates with the sequence predicted by the "stwintron" hypothesis, are produced in the splicing process. This implies that two successive rounds of RNA scanning by the spliceosome are necessary to produce the mature mRNA. The phylogenetic distributions of the stwintrons we have identified suggest that they derive from "late" events, subsequent to the appearance of the host intron. They may well not be limited to fungal nuclear transcripts, and their generation and eventual disappearance in the evolutionary process are relevant to hypotheses of intron origin and alternative splicing.

  14. The spliceosomal PRP19 complex of trypanosomes

    PubMed Central

    Ambrósio, Daniela L.; Badjatia, Nitika; Günzl, Arthur

    2015-01-01

    Summary In trypanosomes, mRNAs are processed by spliced leader (SL) trans splicing, in which a capped SL, derived from SL RNA, is spliced onto the 5′ end of each mRNA. This process is mediated by the spliceosome, a large and dynamic RNA-protein machinery consisting of small nuclear ribonucleoproteins (snRNPs) and non-snRNP proteins. Due to early evolutionary divergence, the amino acid sequences of trypanosome splicing factors exhibit limited similarity to those of their eukaryotic orthologs making their bioinformatic identification challenging. Most of the ~ 60 protein components that have been characterized thus far are snRNP proteins because, in contrast to individual snRNPs, purification of intact spliceosomes has not been achieved yet. Here, we characterize the non-snRNP PRP19 complex of Trypanosoma brucei. We identified a complex that contained the core subunits PRP19, CDC5, PRL1, and SPF27, as well as PRP17, SKIP and PPIL1. Three of these proteins were newly annotated. The PRP19 complex was associated primarily with the activated spliceosome and, accordingly, SPF27 silencing blocked the first splicing step. Interestingly, SPF27 silencing caused an accumulation of SL RNA with a hypomethylated cap that closely resembled the defect observed previously upon depletion of the cyclin-dependent kinase CRK9, indicating that both proteins may function in spliceosome activation. PMID:25524563

  15. A spliceosomal intron in Giardia lamblia.

    PubMed

    Nixon, Julie E J; Wang, Amy; Morrison, Hilary G; McArthur, Andrew G; Sogin, Mitchell L; Loftus, Brendan J; Samuelson, John

    2002-03-19

    Short introns occur in numerous protist lineages, but there are no reports of intervening sequences in the protists Giardia lamblia and Trichomonas vaginalis, which may represent the deepest known branches in the eukaryotic line of descent. We have discovered a 35-bp spliceosomal intron in a gene encoding a putative [2Fe-2S] ferredoxin of G. lamblia. The Giardia intron contains a canonical splice site at its 3' end (AG), a noncanonical splice site at its 5' end (CT), and a branch point sequence that fits the yeast consensus sequence of TACTAAC except for the first nucleotide (AACTAAC). We have also identified several G. lamblia genes with spliceosomal peptides, including homologues of eukaryote-specific spliceosomal peptides (Prp8 and Prp11), several DExH-box RNA-helicases that have homologues in eubacteria, but serve essential functions in the splicing of introns in eukaryotes, and 11 predicted archaebacteria-like Sm and like-Sm core peptides, which coat small nuclear RNAs. Phylogenetic analyses show the Giardia Sm core peptides are the products of multiple, ancestral gene duplications followed by divergence, but they retain strong similarity to Sm and like-Sm peptides of other eukaryotes. Although we have documented only a single intron in Giardia, it likely has other introns and fully functional, spliceosomal machinery. If introns were added during eukaryotic evolution (the introns-late hypothesis), then these results push back the date of this event before the branching of G. lamblia.

  16. Detailed close-ups and the big picture of spliceosomes

    PubMed Central

    Jurica, Melissa S.

    2008-01-01

    Summary The spliceosome is the huge macromolecular assembly responsible for the removal of introns from pre-mRNA transcripts. The size and complexity of this dynamic cellular machine dictates that structural analysis of the spliceosome is best served by a combination of techniques. Electron microscopy is providing a more global, albeit less detailed, view of spliceosome assemblies. X-ray crystallographers and NMR spectroscopists are steadily reporting more atomic resolution structures of individual spliceosome components and fragments. Increasingly, structures of these individual pieces in complex with binding partners are yielding insights into the interfaces that hold the entire spliceosome assembly together. Although the information arising from the various structural studies of splicing machinery has not yet fully converged into a complete model, we can expect that a detailed understanding of spliceosome structure will arise at the juncture of structural and computational modeling methods. PMID:18550358

  17. Spliceosomal snRNA modifications and their function

    PubMed Central

    Karijolich, John; Yu, Yi-Tao

    2014-01-01

    Spliceosomal snRNAs are extensively 2'-O-methylated and pseudouridylated. The modified nucleotides are relatively highly conserved across species, and are often clustered in regions of functional importance in pre-mRNA splicing. Over the past decade, the study of the mechanisms and functions of spliceosomal snRNA modifications has intensified. Two independent mechanisms behind these modifications, RNA-independent (protein-only) and RNA-dependent (RNA-guided), have been discovered. The role of spliceosomal snRNA modifications in snRNP biogenesis and spliceosome assembly has also been verified. PMID:20215871

  18. The architecture of the spliceosomal U4/U6.U5 tri-snRNP

    PubMed Central

    Nguyen, Thi Hoang Duong; Galej, Wojciech P.; Bai, Xiao-chen; Savva, Christos G.; Newman, Andrew J.; Scheres, Sjors H. W.; Nagai, Kiyoshi

    2015-01-01

    U4/U6.U5 tri-snRNP is a 1.5 MDa pre-assembled spliceosomal complex comprising U5 snRNA, extensively base-paired U4/U6 snRNAs and >30 proteins, including the key components Prp8, Brr2 and Snu114. The tri-snRNP combines with a pre-mRNA substrate bound to U1 and U2 snRNPs and transforms into a catalytically active spliceosome following extensive compositional and conformational changes triggered by unwinding of the U4/U6 snRNAs. CryoEM single-particle reconstruction of yeast tri-snRNP at 5.9Å resolution reveals the essentially complete organization of its RNA and protein components. The single-stranded region of U4 snRNA between its 3′-stem-loop and the U4/U6 snRNA stem I is loaded into the Brr2 helicase active site ready for unwinding. Snu114 and the N-terminal domain of Prp8 position U5 snRNA to insert its Loop I, which aligns the exons for splicing, into the Prp8 active site cavity. The structure provides crucial insights into the activation process and the active site of the spliceosome. PMID:26106855

  19. Co-evolution of SNF spliceosomal proteins with their RNA targets in trans-splicing nematodes.

    PubMed

    Strange, Rex Meade; Russelburg, L Peyton; Delaney, Kimberly J

    2016-08-01

    Although the mechanism of pre-mRNA splicing has been well characterized, the evolution of spliceosomal proteins is poorly understood. The U1A/U2B″/SNF family (hereafter referred to as the SNF family) of RNA binding spliceosomal proteins participates in both the U1 and U2 small interacting nuclear ribonucleoproteins (snRNPs). The highly constrained nature of this system has inhibited an analysis of co-evolutionary trends between the proteins and their RNA binding targets. Here we report accelerated sequence evolution in the SNF protein family in Phylum Nematoda, which has allowed an analysis of protein:RNA co-evolution. In a comparison of SNF genes from ecdysozoan species, we found a correlation between trans-splicing species (nematodes) and increased phylogenetic branch lengths of the SNF protein family, with respect to their sister clade Arthropoda. In particular, we found that nematodes (~70-80 % of pre-mRNAs are trans-spliced) have experienced higher rates of SNF sequence evolution than arthropods (predominantly cis-spliced) at both the nucleotide and amino acid levels. Interestingly, this increased evolutionary rate correlates with the reliance on trans-splicing by nematodes, which would alter the role of the SNF family of spliceosomal proteins. We mapped amino acid substitutions to functionally important regions of the SNF protein, specifically to sites that are predicted to disrupt protein:RNA and protein:protein interactions. Finally, we investigated SNF's RNA targets: the U1 and U2 snRNAs. Both are more divergent in nematodes than arthropods, suggesting the RNAs have co-evolved with SNF in order to maintain the necessarily high affinity interaction that has been characterized in other species. PMID:27450547

  20. Co-evolution of SNF spliceosomal proteins with their RNA targets in trans-splicing nematodes.

    PubMed

    Strange, Rex Meade; Russelburg, L Peyton; Delaney, Kimberly J

    2016-08-01

    Although the mechanism of pre-mRNA splicing has been well characterized, the evolution of spliceosomal proteins is poorly understood. The U1A/U2B″/SNF family (hereafter referred to as the SNF family) of RNA binding spliceosomal proteins participates in both the U1 and U2 small interacting nuclear ribonucleoproteins (snRNPs). The highly constrained nature of this system has inhibited an analysis of co-evolutionary trends between the proteins and their RNA binding targets. Here we report accelerated sequence evolution in the SNF protein family in Phylum Nematoda, which has allowed an analysis of protein:RNA co-evolution. In a comparison of SNF genes from ecdysozoan species, we found a correlation between trans-splicing species (nematodes) and increased phylogenetic branch lengths of the SNF protein family, with respect to their sister clade Arthropoda. In particular, we found that nematodes (~70-80 % of pre-mRNAs are trans-spliced) have experienced higher rates of SNF sequence evolution than arthropods (predominantly cis-spliced) at both the nucleotide and amino acid levels. Interestingly, this increased evolutionary rate correlates with the reliance on trans-splicing by nematodes, which would alter the role of the SNF family of spliceosomal proteins. We mapped amino acid substitutions to functionally important regions of the SNF protein, specifically to sites that are predicted to disrupt protein:RNA and protein:protein interactions. Finally, we investigated SNF's RNA targets: the U1 and U2 snRNAs. Both are more divergent in nematodes than arthropods, suggesting the RNAs have co-evolved with SNF in order to maintain the necessarily high affinity interaction that has been characterized in other species.

  1. The human U1-70K snRNP protein: cDNA cloning, chromosomal localization, expression, alternative splicing and RNA-binding.

    PubMed Central

    Spritz, R A; Strunk, K; Surowy, C S; Hoch, S O; Barton, D E; Francke, U

    1987-01-01

    We have isolated and sequenced cDNA clones encoding the human U1-70K snRNP protein, and have mapped this locus (U1AP1) to human chromosome 19. The gene produces two size classes of RNA, a major 1.7-kb RNA and a minor 3.9-kb RNA. The 1.7-kb species appears to be the functional mRNA; the role of the 3.9-kb RNA, which extends further in the 5' direction, is unclear. The actual size of the hU1-70K protein is probably 52 kd, rather than 70 kd. The protein contains three regions similar to known nucleic acid-binding proteins, and it binds RNA in an in vitro assay. Comparison of the cDNA sequences indicates that there are multiple subclasses of mRNA that arise by alternative pre-mRNA splicing of at least four alternative exon segments. This suggests that multiple forms of the hU1-70K protein may exist, possibly with different functions in vivo. Images PMID:2447561

  2. Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD-895 and pladienolide-B.

    PubMed

    Kashyap, Manoj K; Kumar, Deepak; Villa, Reymundo; La Clair, James J; Benner, Chris; Sasik, Roman; Jones, Harrison; Ghia, Emanuela M; Rassenti, Laura Z; Kipps, Thomas J; Burkart, Michael D; Castro, Januario E

    2015-07-01

    RNA splicing plays a fundamental role in human biology. Its relevance in cancer is rapidly emerging as demonstrated by spliceosome mutations that determine the prognosis of patients with hematologic malignancies. We report studies using FD-895 and pladienolide-B in primary leukemia cells derived from patients with chronic lymphocytic leukemia and leukemia-lymphoma cell lines. We found that FD-895 and pladienolide-B induce an early pattern of mRNA intron retention - spliceosome modulation. This process was associated with apoptosis preferentially in cancer cells as compared to normal lymphocytes. The pro-apoptotic activity of these compounds was observed regardless of poor prognostic factors such as Del(17p), TP53 or SF3B1 mutations and was able to overcome the protective effect of culture conditions that resemble the tumor microenvironment. In addition, the activity of these compounds was observed not only in vitro but also in vivo using the A20 lymphoma murine model. Overall, these findings give evidence for the first time that spliceosome modulation is a valid target in chronic lymphocytic leukemia and provide an additional rationale for the development of spliceosome modulators for cancer therapy.

  3. A spliceosome intermediate with loosely associated tri-snRNP accumulates in the absence of Prp28 ATPase activity

    PubMed Central

    Boesler, Carsten; Rigo, Norbert; Anokhina, Maria M.; Tauchert, Marcel J.; Agafonov, Dmitry E.; Kastner, Berthold; Urlaub, Henning; Ficner, Ralf; Will, Cindy L.; Lührmann, Reinhard

    2016-01-01

    The precise role of the spliceosomal DEAD-box protein Prp28 in higher eukaryotes remains unclear. We show that stable tri-snRNP association during pre-catalytic spliceosomal B complex formation is blocked by a dominant-negative hPrp28 mutant lacking ATPase activity. Complexes formed in the presence of ATPase-deficient hPrp28 represent a novel assembly intermediate, the pre-B complex, that contains U1, U2 and loosely associated tri-snRNP and is stalled before disruption of the U1/5′ss base pairing interaction, consistent with a role for hPrp28 in the latter. Pre-B and B complexes differ structurally, indicating that stable tri-snRNP integration is accompanied by substantial rearrangements in the spliceosome. Disruption of the U1/5′ss interaction alone is not sufficient to bypass the block by ATPase-deficient hPrp28, suggesting hPrp28 has an additional function at this stage of splicing. Our data provide new insights into the function of Prp28 in higher eukaryotes, and the requirements for stable tri-snRNP binding during B complex formation. PMID:27377154

  4. An early evolutionary origin for the minor spliceosome.

    PubMed

    Russell, Anthony G; Charette, J Michael; Spencer, David F; Gray, Michael W

    2006-10-19

    The minor spliceosome is a ribonucleoprotein complex that catalyses the removal of an atypical class of spliceosomal introns (U12-type) from eukaryotic messenger RNAs. It was first identified and characterized in animals, where it was found to contain several unique RNA constituents that share structural similarity with and seem to be functionally analogous to the small nuclear RNAs (snRNAs) contained in the major spliceosome. Subsequently, minor spliceosomal components and U12-type introns have been found in plants but not in fungi. Unlike that of the major spliceosome, which arose early in the eukaryotic lineage, the evolutionary history of the minor spliceosome is unclear because there is evidence of it in so few organisms. Here we report the identification of homologues of minor-spliceosome-specific proteins and snRNAs, and U12-type introns, in distantly related eukaryotic microbes (protists) and in a fungus (Rhizopus oryzae). Cumulatively, our results indicate that the minor spliceosome had an early origin: several of its characteristic constituents are present in representative organisms from all eukaryotic supergroups for which there is any substantial genome sequence information. In addition, our results reveal marked evolutionary conservation of functionally important sequence elements contained within U12-type introns and snRNAs.

  5. Autoimmune response to U1 small nuclear ribonucleoprotein (U1 snRNP) associated with cytomegalovirus infection.

    PubMed

    Newkirk, M M; van Venrooij, W J; Marshall, G S

    2001-01-01

    The induction of autoantibodies to U1 small nuclear ribonucleoprotein (U1 snRNP) complexes is not well understood. We present evidence that healthy individuals with cytomegalovirus (CMV) infection have an increased frequency and quantity of antibodies to ribonucleoprotein, directed primarily against the U1-70k protein. A significant association between the presence of antibodies to CMV and antibodies to the total RNP targeted by the immune response to the spliceosome (to both the Sm and RNP; Sm/RNP) was found for patients with systemic lupus erythematosus (SLE) but not those with mixed connective-tissue disease. CMV thus may play a role in inducing autoimmune responses in a subset of patients with systemic lupus erythematosus.

  6. Autoimmune response to U1 small nuclear ribonucleoprotein (U1 snRNP) associated with cytomegalovirus infection.

    PubMed

    Newkirk, M M; van Venrooij, W J; Marshall, G S

    2001-01-01

    The induction of autoantibodies to U1 small nuclear ribonucleoprotein (U1 snRNP) complexes is not well understood. We present evidence that healthy individuals with cytomegalovirus (CMV) infection have an increased frequency and quantity of antibodies to ribonucleoprotein, directed primarily against the U1-70k protein. A significant association between the presence of antibodies to CMV and antibodies to the total RNP targeted by the immune response to the spliceosome (to both the Sm and RNP; Sm/RNP) was found for patients with systemic lupus erythematosus (SLE) but not those with mixed connective-tissue disease. CMV thus may play a role in inducing autoimmune responses in a subset of patients with systemic lupus erythematosus. PMID:11438044

  7. Dark U (1)

    NASA Astrophysics Data System (ADS)

    Chang, Chia-Feng; Ma, Ernest; Yuan, Tzu-Chiang

    2015-06-01

    In this talk we will explore the possibility of adding a local U(1) dark sector to the standard model with the Higgs boson as a portal connecting the visible standard model sector and the dark one. We will discuss existing experimental constraint on the model parameters from the invisible width of Higgs decay. Implications of such a dark U(1) sector on phenomenology at the Large Hardon Collider will be addressed. In particular, detailed results for the non-standard signals of multi-lepton-jets that arise from this simple dark sector will be presented.

  8. U1A Complex

    ScienceCinema

    None

    2016-07-12

    Some of the most sophisticated experiments in the stockpile stewardship program are conducted in an environmentally safe manner, nearly 1000 feet below the ground at the site. The U1a complex a sprawling underground laboratory and tunnel complex is home to a number of unique capabilities.

  9. U1A Complex

    SciTech Connect

    2014-10-28

    Some of the most sophisticated experiments in the stockpile stewardship program are conducted in an environmentally safe manner, nearly 1000 feet below the ground at the site. The U1a complex a sprawling underground laboratory and tunnel complex is home to a number of unique capabilities.

  10. Analyses of in vivo interaction and mobility of two spliceosomal proteins using FRAP and BiFC.

    PubMed

    Ali, Gul Shad; Prasad, K V S K; Hanumappa, M; Reddy, A S N

    2008-01-01

    U1-70K, a U1 snRNP-specific protein, and serine/arginine-rich (SR) proteins are components of the spliceosome and play critical roles in both constitutive and alternative pre-mRNA splicing. However, the mobility properties of U1-70K, its in vivo interaction with SR proteins, and the mobility of the U1-70K-SR protein complex have not been studied in any system. Here, we studied the in vivo interaction of U1-70K with an SR protein (SR45) and the mobility of the U1-70K/SR protein complex using bimolecular fluorescence complementation (BiFC) and fluorescence recovery after photobleaching (FRAP). Our results show that U1-70K exchanges between speckles and the nucleoplasmic pool very rapidly and that this exchange is sensitive to ongoing transcription and phosphorylation. BiFC analyses showed that U1-70K and SR45 interacted primarily in speckles and that this interaction is mediated by the RS1 or RS2 domain of SR45. FRAP analyses showed considerably slower recovery of the SR45/U1-70K complex than either protein alone indicating that SR45/U1-70K complexes remain in the speckles for a longer duration. Furthermore, FRAP analyses with SR45/U1-70K complex in the presence of inhibitors of phosphorylation did not reveal any significant change compared to control cells, suggesting that the mobility of the complex is not affected by the status of protein phosphorylation. These results indicate that U1-70K, like SR splicing factors, moves rapidly in the nucleus ensuring its availability at various sites of splicing. Furthermore, although it appears that U1-70K moves by diffusion its mobility is regulated by phosphorylation and transcription. PMID:18414657

  11. Origin and evolution of spliceosomal introns.

    PubMed

    Rogozin, Igor B; Carmel, Liran; Csuros, Miklos; Koonin, Eugene V

    2012-04-16

    Evolution of exon-intron structure of eukaryotic genes has been a matter of long-standing, intensive debate. The introns-early concept, later rebranded 'introns first' held that protein-coding genes were interrupted by numerous introns even at the earliest stages of life's evolution and that introns played a major role in the origin of proteins by facilitating recombination of sequences coding for small protein/peptide modules. The introns-late concept held that introns emerged only in eukaryotes and new introns have been accumulating continuously throughout eukaryotic evolution. Analysis of orthologous genes from completely sequenced eukaryotic genomes revealed numerous shared intron positions in orthologous genes from animals and plants and even between animals, plants and protists, suggesting that many ancestral introns have persisted since the last eukaryotic common ancestor (LECA). Reconstructions of intron gain and loss using the growing collection of genomes of diverse eukaryotes and increasingly advanced probabilistic models convincingly show that the LECA and the ancestors of each eukaryotic supergroup had intron-rich genes, with intron densities comparable to those in the most intron-rich modern genomes such as those of vertebrates. The subsequent evolution in most lineages of eukaryotes involved primarily loss of introns, with only a few episodes of substantial intron gain that might have accompanied major evolutionary innovations such as the origin of metazoa. The original invasion of self-splicing Group II introns, presumably originating from the mitochondrial endosymbiont, into the genome of the emerging eukaryote might have been a key factor of eukaryogenesis that in particular triggered the origin of endomembranes and the nucleus. Conversely, splicing errors gave rise to alternative splicing, a major contribution to the biological complexity of multicellular eukaryotes. There is no indication that any prokaryote has ever possessed a spliceosome or

  12. Origin and evolution of spliceosomal introns

    PubMed Central

    2012-01-01

    Evolution of exon-intron structure of eukaryotic genes has been a matter of long-standing, intensive debate. The introns-early concept, later rebranded ‘introns first’ held that protein-coding genes were interrupted by numerous introns even at the earliest stages of life's evolution and that introns played a major role in the origin of proteins by facilitating recombination of sequences coding for small protein/peptide modules. The introns-late concept held that introns emerged only in eukaryotes and new introns have been accumulating continuously throughout eukaryotic evolution. Analysis of orthologous genes from completely sequenced eukaryotic genomes revealed numerous shared intron positions in orthologous genes from animals and plants and even between animals, plants and protists, suggesting that many ancestral introns have persisted since the last eukaryotic common ancestor (LECA). Reconstructions of intron gain and loss using the growing collection of genomes of diverse eukaryotes and increasingly advanced probabilistic models convincingly show that the LECA and the ancestors of each eukaryotic supergroup had intron-rich genes, with intron densities comparable to those in the most intron-rich modern genomes such as those of vertebrates. The subsequent evolution in most lineages of eukaryotes involved primarily loss of introns, with only a few episodes of substantial intron gain that might have accompanied major evolutionary innovations such as the origin of metazoa. The original invasion of self-splicing Group II introns, presumably originating from the mitochondrial endosymbiont, into the genome of the emerging eukaryote might have been a key factor of eukaryogenesis that in particular triggered the origin of endomembranes and the nucleus. Conversely, splicing errors gave rise to alternative splicing, a major contribution to the biological complexity of multicellular eukaryotes. There is no indication that any prokaryote has ever possessed a spliceosome

  13. The significance of spliceosome mutations in chronic lymphocytic leukemia.

    PubMed

    Rozovski, Uri; Keating, Michael; Estrov, Zeev

    2013-07-01

    Cellular proteins produced via alternative splicing provide neoplastic cells with survival advantage and/or promote neoplastic cell proliferation. Pre-mRNA is spliced by the spliceosome consisting of large complexes of small nuclear RNA (snRNA) and protein subunits. Spliceosome gene mutations were detected in 40-80% of patients with myelodysplastic syndrome (MDS), particularly in those with ringed sideroblasts. Recently, two large whole-genome sequencing studies identified mutations in the spliceosome gene SF3B1 in approximately 10% of patients with chronic lymphocytic leukemia (CLL). Intrigued by these findings, we performed a pathway enrichment analysis and found that, unlike in MDS, in CLL spliceosome mutations exist almost exclusively in SF3B1. Patients with CLL with an SF3B1 gene mutation are characterized by a short progression-free survival and a low 10-year survival rate. Furthermore, the frequency of SF3B1 mutations is significantly higher in chemotherapy treated than in untreated patients with CLL, suggesting that chemotherapy induces SF3B1 gene mutations or selects a population of mutated cells. Whether SF3B1 gene mutations have a role in leukemogenesis, either because of altered splicing or other splicing-unrelated functions such as ectopic expression of Homeobox (Hox) genes previously reported in SF3B1+(/-) mice, remains to be determined.

  14. Organellar maturases: A window into the evolution of the spliceosome.

    PubMed

    Schmitz-Linneweber, Christian; Lampe, Marie-Kristin; Sultan, Laure D; Ostersetzer-Biran, Oren

    2015-09-01

    During the evolution of eukaryotic genomes, many genes have been interrupted by intervening sequences (introns) that must be removed post-transcriptionally from RNA precursors to form mRNAs ready for translation. The origin of nuclear introns is still under debate, but one hypothesis is that the spliceosome and the intron-exon structure of genes have evolved from bacterial-type group II introns that invaded the eukaryotic genomes. The group II introns were most likely introduced into the eukaryotic genome from an α-proteobacterial predecessor of mitochondria early during the endosymbiosis event. These self-splicing and mobile introns spread through the eukaryotic genome and later degenerated. Pieces of introns became part of the general splicing machinery we know today as the spliceosome. In addition, group II introns likely brought intron maturases with them to the nucleus. Maturases are found in most bacterial introns, where they act as highly specific splicing factors for group II introns. In the spliceosome, the core protein Prp8 shows homology to group II intron-encoded maturases. While maturases are entirely intron specific, their descendant of the spliceosomal machinery, the Prp8 protein, is an extremely versatile splicing factor with multiple interacting proteins and RNAs. How could such a general player in spliceosomal splicing evolve from the monospecific bacterial maturases? Analysis of the organellar splicing machinery in plants may give clues on the evolution of nuclear splicing. Plants encode various proteins which are closely related to bacterial maturases. The organellar genomes contain one maturase each, named MatK in chloroplasts and MatR in mitochondria. In addition, several maturase genes have been found in the nucleus as well, which are acting on mitochondrial pre-RNAs. All plant maturases show sequence deviation from their progenitor bacterial maturases, and interestingly are all acting on multiple organellar group II intron targets. Moreover

  15. U1h Superstructure

    SciTech Connect

    Glen Sykes

    2000-11-01

    The U1H Shaft Project is a design build subcontract to supply the U. S. Department of Energy (DOE) a 1,045 ft. deep, 20 ft. diameter, concrete lined shaft for unspecified purposes. The subcontract awarded to Atkinson Construction by Bechtel Nevada to design and construct the shaft for the DOE has been split into phases with portions of the work being released as dictated by available funding. The first portion released included the design for the shaft, permanent hoist, headframe, and collar arrangement. The second release consisted of constructing the shaft collar to a depth of 110 ft., the service entry, utility trenches, and installation of the temporary sinking plant. The temporary sinking plant included the installation of the sinking headframe, the sinking hoist, two deck winches, the shaft form, the sinking work deck, and temporary utilities required to sink the shaft. Both the design and collar construction were completed on schedule. The third release consisted of excavating and lining the shaft to the station depth of approximately 950 feet. Work is currently proceeding on this production sinking phase. At a depth of approximately 600 feet, Atkinson has surpassed production expectation and is more than 3 months ahead of schedule. Atkinson has employed the use of a Bobcat 331 excavator as the primary means of excavation. the shaft is being excavated entirely in an alluvial deposit with varying degrees of calcium carbonate cementation. Several more work packages are expected to be released in the near future. The remaining work packages include, construction of the shaft station a depth of 975 ft. and construction of the shaft sump to a depth of 1,045 ft., installation of the loading pocket and station steel and equipment, installation of the shaft steel and guides, installation of the shaft utilities, and installation of the permanent headframe, hoist, collar utilities, and facilities.

  16. New Insights into the Spliceosome by Single Molecule Fluorescence Microscopy

    PubMed Central

    Hoskins, Aaron A.; Gelles, Jeff; Moore, Melissa J.

    2011-01-01

    Splicing is an essential eukaryotic process in which introns are excised from precursors to messenger RNAs and exons ligated together. This reaction is catalyzed by a multi-MegaDalton machine called the spliceosome, composed of 5 small nuclear RNAs (snRNAs) and a core set of ~100 proteins minimally required for activity. Due to the spliceosome’s size, its low abundance in cellular extracts, and its highly dynamic assembly pathway, analysis of the kinetics of splicing and the conformational rearrangements occurring during spliceosome assembly and disassembly has proven extraordinarily challenging. Here, we review recent progress in combining chemical biology methodologies with single molecule fluorescence techniques to provide a window into splicing in real time. These methods complement ensemble measurements of splicing in vivo and in vitro to facilitate kinetic dissection of pre-mRNA splicing. PMID:22057211

  17. A unique spatial arrangement of the snRNPs within the native spliceosome emerges from in silico studies.

    PubMed

    Frankenstein, Ziv; Sperling, Joseph; Sperling, Ruth; Eisenstein, Miriam

    2012-06-01

    The spliceosome is a mega-Dalton ribonucleoprotein (RNP) assembly that processes primary RNA transcripts, producing functional mRNA. The electron microscopy structures of the native spliceosome and of several spliceosomal subcomplexes are available; however, the spatial arrangement of the latter within the native spliceosome is not known. We designed a computational procedure to efficiently fit thousands of conformers into the spliceosome envelope. Despite the low resolution limitations, we obtained only one model that complies with the available biochemical data. Our model localizes the five small nuclear RNPs (snRNPs) mostly within the large subunit of the native spliceosome, requiring only minor conformation changes. The remaining free volume presumably accommodates additional spliceosomal components. The constituents of the active core of the spliceosome are juxtaposed, forming a continuous surface deep within the large spliceosomal cavity, which provides a sheltered environment for the splicing reaction. PMID:22578543

  18. A unique spatial arrangement of the snRNPs within the native spliceosome emerges from in silico studies.

    PubMed

    Frankenstein, Ziv; Sperling, Joseph; Sperling, Ruth; Eisenstein, Miriam

    2012-06-01

    The spliceosome is a mega-Dalton ribonucleoprotein (RNP) assembly that processes primary RNA transcripts, producing functional mRNA. The electron microscopy structures of the native spliceosome and of several spliceosomal subcomplexes are available; however, the spatial arrangement of the latter within the native spliceosome is not known. We designed a computational procedure to efficiently fit thousands of conformers into the spliceosome envelope. Despite the low resolution limitations, we obtained only one model that complies with the available biochemical data. Our model localizes the five small nuclear RNPs (snRNPs) mostly within the large subunit of the native spliceosome, requiring only minor conformation changes. The remaining free volume presumably accommodates additional spliceosomal components. The constituents of the active core of the spliceosome are juxtaposed, forming a continuous surface deep within the large spliceosomal cavity, which provides a sheltered environment for the splicing reaction.

  19. U1 small nuclear ribonucleoprotein particle-specific proteins interact with the first and second stem-loops of U1 RNA, with the A protein binding directly to the RNA independently of the 70K and Sm proteins.

    PubMed Central

    Patton, J R; Habets, W; van Venrooij, W J; Pederson, T

    1989-01-01

    The U1 small nuclear ribonucleoprotein particle (U1 snRNP), a cofactor in pre-mRNA splicing, contains three proteins, termed 70K, A, and C, that are not present in the other spliceosome-associated snRNPs. We studied the binding of the A and C proteins to U1 RNA, using a U1 snRNP reconstitution system and an antibody-induced nuclease protection technique. Antibodies that reacted with the A and C proteins induced nuclease protection of the first two stem-loops of U1 RNA in reconstituted U1 snRNP. Detailed analysis of the antibody-induced nuclease protection patterns indicated the existence of relatively long-range protein-protein interactions in the U1 snRNP, with the 5' end of U1 RNA and its associated specific proteins interacting with proteins bound to the Sm domain near the 3' end. UV cross-linking experiments in conjunction with an A-protein-specific antibody demonstrated that the A protein bound directly to the U1 RNA rather than assembling in the U1 snRNP exclusively via protein-protein interactions. This conclusion was supported by additional experiments revealing that the A protein could bind to U1 RNA in the absence of bound 70K and Sm core proteins. Images PMID:2529425

  20. The nuclear cap-binding complex interacts with the U4/U6·U5 tri-snRNP and promotes spliceosome assembly in mammalian cells.

    PubMed

    Pabis, Marta; Neufeld, Noa; Steiner, Michaela C; Bojic, Teodora; Shav-Tal, Yaron; Neugebauer, Karla M

    2013-08-01

    The nuclear cap-binding complex (CBC) binds to the 7-methyl guanosine cap present on every RNA polymerase II transcript. CBC has been implicated in many aspects of RNA biogenesis; in addition to roles in miRNA biogenesis, nonsense-mediated decay, 3'-end formation, and snRNA export from the nucleus, CBC promotes pre-mRNA splicing. An unresolved question is how CBC participates in splicing. To investigate CBC's role in splicing, we used mass spectrometry to identify proteins that copurify with mammalian CBC. Numerous components of spliceosomal snRNPs were specifically detected. Among these, three U4/U6·U5 snRNP proteins (hBrr2, hPrp4, and hPrp31) copurified with CBC in an RNA-independent fashion, suggesting that a significant fraction of CBC forms a complex with the U4/U6·U5 snRNP and that the activity of CBC might be associated with snRNP recruitment to pre-mRNA. To test this possibility, CBC was depleted from HeLa cells by RNAi. Chromatin immunoprecipitation and live-cell imaging assays revealed decreased cotranscriptional accumulation of U4/U6·U5 snRNPs on active transcription units, consistent with a requirement for CBC in cotranscriptional spliceosome assembly. Surprisingly, recruitment of U1 and U2 snRNPs was also affected, indicating that RNA-mediated interactions between CBC and snRNPs contribute to splicing. On the other hand, CBC depletion did not impair snRNP biogenesis, ruling out the possibility that decreased snRNP recruitment was due to changes in nuclear snRNP concentration. Taken together, the data support a model whereby CBC promotes pre-mRNA splicing through a network of interactions with and among spliceosomal snRNPs during cotranscriptional spliceosome assembly.

  1. Plant-specific SR-related protein atSR45a interacts with spliceosomal proteins in plant nucleus.

    PubMed

    Tanabe, Noriaki; Kimura, Ayako; Yoshimura, Kazuya; Shigeoka, Shigeru

    2009-06-01

    Serine/arginine-rich (SR) protein and its homologues (SR-related proteins) are important regulators of constitutive and/or alternative splicing and other aspects of mRNA metabolism. To clarify the contribution of a plant-specific and stress-responsive SR-related protein, atSR45a, to splicing events, here we analyzed the interaction of atSR45a with the other splicing factors by conducting a yeast two-hybrid assay and a bimolecular fluorescence complementation analysis. The atSR45a-1a and -2 proteins, the presumed mature forms produced by alternative splicing of atSR45a, interacted with U1-70K and U2AF(35)b, splicing factors for the initial definition of 5' and 3' splice sites, respectively, in the early stage of spliceosome assembly. Both proteins also interacted with themselves, other SR proteins (atSR45 and atSCL28), and PRP38-like protein, a homologue of the splicing factor essential for cleavage of the 5' splice site. The mapping of deletion mutants of atSR45a proteins revealed that the C-terminal arginine/serine-rich (RS) domain of atSR45a proteins are required for the interaction with U1-70K, U2AF(35)b, atSR45, atSCL28, PRP38-like protein, and themselves, and the N-terminal RS domain enhances the interaction efficiency. Interestingly, the distinctive N-terminal extension in atSR45a-1a protein, but not atSR45a-2 protein, inhibited the interaction with these splicing factors. These findings suggest that the atSR45a proteins help to form the bridge between 5' and 3' splice sites in the spliceosome assembly and the efficiency of spliceosome formation is affected by the expression ratio of atSR45a-1a and atSR45a-2. PMID:19238562

  2. U1 snDNA clusters in grasshoppers: chromosomal dynamics and genomic organization

    PubMed Central

    Anjos, A; Ruiz-Ruano, F J; Camacho, J P M; Loreto, V; Cabrero, J; de Souza, M J; Cabral-de-Mello, D C

    2015-01-01

    The spliceosome, constituted by a protein set associated with small nuclear RNA (snRNA), is responsible for mRNA maturation through intron removal. Among snRNA genes, U1 is generally a conserved repetitive sequence. To unveil the chromosomal/genomic dynamics of this multigene family in grasshoppers, we mapped U1 genes by fluorescence in situ hybridization in 70 species belonging to the families Proscopiidae, Pyrgomorphidae, Ommexechidae, Romaleidae and Acrididae. Evident clusters were observed in all species, indicating that, at least, some U1 repeats are tandemly arrayed. High conservation was observed in the first four families, with most species carrying a single U1 cluster, frequently located in the third or fourth longest autosome. By contrast, extensive variation was observed among Acrididae, from a single chromosome pair carrying U1 to all chromosome pairs carrying it, with occasional occurrence of two or more clusters in the same chromosome. DNA sequence analysis in Eyprepocnemis plorans (species carrying U1 clusters on seven different chromosome pairs) and Locusta migratoria (carrying U1 in a single chromosome pair) supported the coexistence of functional and pseudogenic lineages. One of these pseudogenic lineages was truncated in the same nucleotide position in both species, suggesting that it was present in a common ancestor to both species. At least in E. plorans, this U1 snDNA pseudogenic lineage was associated with 5S rDNA and short interspersed elements (SINE)-like mobile elements. Given that we conclude in grasshoppers that the U1 snDNA had evolved under the birth-and-death model and that its intragenomic spread might be related with mobile elements. PMID:25248465

  3. Exon 45 skipping through U1-snRNA antisense molecules recovers the Dys-nNOS pathway and muscle differentiation in human DMD myoblasts.

    PubMed

    Cazzella, Valentina; Martone, Julie; Pinnarò, Chiara; Santini, Tiziana; Twayana, Shyam Sundar; Sthandier, Olga; D'Amico, Adele; Ricotti, Valeria; Bertini, Enrico; Muntoni, Francesco; Bozzoni, Irene

    2012-11-01

    Exon skipping has been demonstrated to be a successful strategy for the gene therapy of Duchenne muscular dystrophy (DMD): the rational being to convert severe Duchenne forms into milder Becker ones. Here, we show the selection of U1 snRNA-antisense constructs able to confer effective rescue of dystrophin synthesis in a Δ44 Duchenne genetic background, through skipping of exon 45; moreover, we demonstrate that the resulting dystrophin is able to recover timing of myogenic marker expression, to relocalize neuronal nitric oxide synthase (nNOS) and to rescue expression of miRNAs previously shown to be sensitive to the Dystrophin-nNOS-HDAC2 pathway. Becker mutations display different phenotypes, likely depending on whether the shorter protein is able to reconstitute the wide range of wild-type functions. Among them, efficient assembly of the dystrophin-associated protein complex (DAPC) and nNOS localization are important. Comparing different Becker deletions we demonstrate the correlation between the ability of the mutant dystrophin to relocalize nNOS and the expression levels of two miRNAs, miR-1 and miR29c, known to be involved in muscle homeostasis and to be controlled by the Dys-nNOS-HDAC2 pathway.

  4. A unique U5-->A substitution in the Physarum polycephalum U1 snRNA: evidence at the RNA and gene levels.

    PubMed

    Szkukalek, A; Mougin, A; Grégoire, A; Solymosy, F; Branlant, C

    1996-01-01

    The 5' terminal sequence of U1 snRNA that base-pairs with the intron 5' splice site in the course of spliceosome assembly was considered to be universally conserved. A study of the P polycephalum U1 snRNA at both RNA and gene levels shows that there are exceptions to this rule: the P polycephalum U1 snRNA has a U to A substitution at position 5, that is partially compensated by a high frequency of T residue at position +4 of introns. In contrast to the yeast genome, the P polycephalum genome contains several U1 snRNA coding sequences (about 20). They either encode the U1A snRNA expressed in microplasmodia or correspond to the previously cloned U1B coding sequence. Both coding sequences show the U5A substitution. The ratio of U1A versus U1B coding sequences is of about 3. A U1A gene was cloned. The 60 nt region upstream of the coding sequence has the same sequence as in the U1B gene. The U1B gene is probably expressed at another stage of the P polycephalum life cycle.

  5. The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome.

    PubMed

    Fabrizio, Patrizia; Dannenberg, Julia; Dube, Prakash; Kastner, Berthold; Stark, Holger; Urlaub, Henning; Lührmann, Reinhard

    2009-11-25

    Metazoan spliceosomes exhibit an elaborate protein composition required for canonical and alternative splicing. Thus, the minimal set of proteins essential for activation and catalysis remains elusive. We therefore purified in vitro assembled, precatalytic spliceosomal complex B, activated B(act), and step 1 complex C from the simple eukaryote Saccharomyces cerevisiae. Mass spectrometry revealed that yeast spliceosomes contain fewer proteins than metazoans and that each functional stage is very homogeneous. Dramatic compositional changes convert B to B(act), which is composed of approximately 40 evolutionarily conserved proteins that organize the catalytic core. Additional remodeling occurs concomitant with step 1, during which nine proteins are recruited to form complex C. The moderate number of proteins recruited to complex C will allow investigations of the chemical reactions in a fully defined system. Electron microscopy reveals high-quality images of yeast spliceosomes at defined functional stages, indicating that they are well-suited for three-dimensional structure analyses.

  6. The spliceosome catalyzes debranching in competition with reverse of the first chemical reaction.

    PubMed

    Tseng, Chi-Kang; Cheng, Soo-Chen

    2013-07-01

    Splicing of nuclear pre-mRNA occurs via two steps of the transesterification reaction, forming a lariat intermediate and product. The reactions are catalyzed by the spliceosome, a large ribonucleoprotein complex composed of five small nuclear RNAs and numerous protein factors. The spliceosome shares a similar catalytic core structure with that of fungal group II introns, which can self-splice using the same chemical mechanism. Like group II introns, both catalytic steps of pre-mRNA splicing can efficiently reverse on the affinity-purified spliceosome. The spliceosome also catalyzes a hydrolytic spliced-exon reopening reaction as observed in group II introns, indicating a strong link in their evolutionary relationship. We show here that, by arresting splicing after the first catalytic step, the purified spliceosome can catalyze debranching of lariat-intron-exon 2. The debranching reaction, although not observed in group II introns, has similar monovalent cation preferences as those for splicing catalysis of group II introns. The debranching reaction is in competition with the reverse Step 1 reaction influenced by the ionic environment and the structure of components binding near the catalytic center, suggesting that the catalytic center of the spliceosome can switch between different conformations to direct different chemical reactions.

  7. Yeast ortholog of the Drosophila crooked neck protein promotes spliceosome assembly through stable U4/U6.U5 snRNP addition.

    PubMed Central

    Chung, S; McLean, M R; Rymond, B C

    1999-01-01

    Mutants in the Drosophila crooked neck (crn) gene show an embryonic lethal phenotype with severe developmental defects. The unusual crn protein consists of sixteen tandem repeats of the 34 amino acid tetratricopeptide (TPR) protein recognition domain. Crn-like TPR elements are found in several RNA processing proteins, although it is unknown how the TPR repeats or the crn protein contribute to Drosophila development. We have isolated a Saccharomyces cerevisiae gene, CLF1, that encodes a crooked neck-like factor. CLF1 is an essential gene but the lethal phenotype of a clf1::HIS3 chromosomal null mutant can be rescued by plasmid-based expression of CLF1 or the Drosophila crn open reading frame. Clf1p is required in vivo and in vitro for pre-mRNA 5' splice site cleavage. Extracts depleted of Clf1p arrest spliceosome assembly after U2 snRNP addition but prior to productive U4/U6.U5 association. Yeast two-hybrid analyses and in vitro binding studies show that Clf1p interacts specifically and differentially with the U1 snRNP-Prp40p protein and the yeast U2AF65 homolog, Mud2p. Intriguingly, Prp40p and Mud2p also bind the phylogenetically conserved branchpoint binding protein (BBP/SF1). Our results indicate that Clf1p acts as a scaffolding protein in spliceosome assembly and suggest that Clf1p may support the cross-intron bridge during the prespliceosome-to-spliceosome transition. PMID:10445879

  8. SKIP Is a Component of the Spliceosome Linking Alternative Splicing and the Circadian Clock in Arabidopsis[W

    PubMed Central

    Wang, Xiaoxue; Wu, Fangming; Xie, Qiguang; Wang, Huamei; Wang, Ying; Yue, Yanling; Gahura, Ondrej; Ma, Shuangshuang; Liu, Lei; Cao, Ying; Jiao, Yuling; Puta, Frantisek; McClung, C. Robertson; Xu, Xiaodong; Ma, Ligeng

    2012-01-01

    Circadian clocks generate endogenous rhythms in most organisms from cyanobacteria to humans and facilitate entrainment to environmental diurnal cycles, thus conferring a fitness advantage. Both transcriptional and posttranslational mechanisms are prominent in the basic network architecture of circadian systems. Posttranscriptional regulation, including mRNA processing, is emerging as a critical step for clock function. However, little is known about the molecular mechanisms linking RNA metabolism to the circadian clock network. Here, we report that a conserved SNW/Ski-interacting protein (SKIP) domain protein, SKIP, a splicing factor and component of the spliceosome, is involved in posttranscriptional regulation of circadian clock genes in Arabidopsis thaliana. Mutation in SKIP lengthens the circadian period in a temperature-sensitive manner and affects light input and the sensitivity of the clock to light resetting. SKIP physically interacts with the spliceosomal splicing factor Ser/Arg-rich protein45 and associates with the pre-mRNA of clock genes, such as PSEUDORESPONSE REGULATOR7 (PRR7) and PRR9, and is necessary for the regulation of their alternative splicing and mRNA maturation. Genome-wide investigations reveal that SKIP functions in regulating alternative splicing of many genes, presumably through modulating recognition or cleavage of 5′ and 3′ splice donor and acceptor sites. Our study addresses a fundamental question on how the mRNA splicing machinery contributes to circadian clock function at a posttranscriptional level. PMID:22942380

  9. The conserved central domain of yeast U6 snRNA: importance of U2-U6 helix Ia in spliceosome assembly.

    PubMed Central

    Ryan, Daniel E; Abelson, John

    2002-01-01

    In the pre-mRNA processing machinery of eukaryotic cells, U6 snRNA is located at or near the active site for pre-mRNA splicing catalysis, and U6 is involved in catalyzing the first chemical step of splicing. We have further defined the roles of key features of yeast U6 snRNA in the splicing process. By assaying spliceosome assembly and splicing in yeast extracts, we found that mutations of yeast U6 nt 56 and 57 are similar to previously reported deletions of U2 nt 27 or 28, all within yeast U2-U6 helix Ia. These mutations lead to the accumulation of yeast A1 spliceosomes, which form just prior to the Prp2 ATPase step and the first chemical step of splicing. These results strongly suggest that, at a late stage of spliceosome assembly, the presence of U2-U6 helix Ia is important for promoting the first chemical step of splicing, presumably by bringing together the 5' splice site region of pre-mRNA, which is base paired to U6 snRNA, and the branchsite region of the intron, which is base paired to U2 snRNA, for activation of the first chemical step of splicing, as previously proposed by Madhani and Guthrie [Cell, 1992, 71: 803-817]. In the 3' intramolecular stem-loop of U6, mutation G81C causes an allele-specific accumulation of U6 snRNP. Base pairing of the U6 3' stem-loop in yeast spliceosomes does not extend as far as to include the U6 sequence of U2-U6 helix Ib, in contrast to the human U6 3' stem-loop structure. PMID:12212854

  10. Interactions of SR45, an SR-like protein, with spliceosomal proteins and an intronic sequence: insights into regulated splicing.

    PubMed

    Day, Irene S; Golovkin, Maxim; Palusa, Saiprasad G; Link, Alicia; Ali, Gul S; Thomas, Julie; Richardson, Dale N; Reddy, Anireddy S N

    2012-09-01

    SR45 is a serine/arginine-rich (SR)-like protein with two arginine/serine-rich (RS) domains. We have previously shown that SR45 regulates alternative splicing (AS) by differential selection of 5' and 3' splice sites. However, it is unknown how SR45 regulates AS. To gain mechanistic insights into the roles of SR45 in splicing, we screened a yeast two-hybrid library with SR45. This screening resulted in the isolation of two spliceosomal proteins, U1-70K and U2AF(35) b that are known to function in 5' and 3' splice site selection, respectively. This screen not only confirmed our prior observation that U1-70K and SR45 interact, but also helped to identify an additional interacting partner (U2AF(35) ). In vitro and in vivo analyses revealed an interaction of SR45 with both paralogs of U2AF(35) . Furthermore, we show that the RS1 and RS2 domains of SR45, and not the RNA recognition motif (RRM) domain, associate independently with both U2AF(35) proteins. Interaction studies among U2AF(35) paralogs and between U2AF(35) and U1-70K revealed that U2AF(35) can form homo- or heterodimers and that U2AF(35) proteins can associate with U1-70K. Using RNA probes from SR30 intron 10, whose splicing is altered in the sr45 mutant, we show that SR45 and U2AF(35) b bind to different parts of the intron, with a binding site for SR45 in the 5' region and two binding regions, each ending with a known 3' splice site, for U2AF(35) b. These results suggest that SR45 recruits U1snRNP and U2AF to 5' and 3' splice sites, respectively, by interacting with pre-mRNA, U1-70K and U2AF(35) and modulates AS. PMID:22563826

  11. The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells.

    PubMed

    Page, Nicolas; Schall, Nicolas; Strub, Jean-Marc; Quinternet, Marc; Chaloin, Olivier; Décossas, Marion; Cung, Manh Thong; Van Dorsselaer, Alain; Briand, Jean-Paul; Muller, Sylviane

    2009-01-01

    The phosphopeptide P140 issued from the spliceosomal U1-70K snRNP protein is recognized by lupus CD4(+) T cells, transiently abolishes T cell reactivity to other spliceosomal peptides in P140-treated MRL/lpr mice, and ameliorates their clinical features. P140 modulates lupus patients' T cell response ex vivo and is currently included in phase IIb clinical trials. Its underlying mechanism of action remains elusive. Here we show that P140 peptide binds a unique cell-surface receptor, the constitutively-expressed chaperone HSC70 protein, known as a presenting-protein. P140 induces apoptosis of activated MRL/lpr CD4(+) T cells. In P140-treated mice, it increases peripheral blood lymphocyte apoptosis and decreases B cell, activated T cell, and CD4(-)CD8(-)B220(+) T cell counts via a specific mechanism strictly depending on gammadelta T cells. Expression of inflammation-linked genes is rapidly regulated in CD4(+) T cells. This work led us to identify a powerful pathway taken by a newly-designed therapeutic peptide to immunomodulate lupus autoimmunity.

  12. Alternatively spliced, spliceosomal twin introns in Helminthosporium solani.

    PubMed

    Ág, Norbert; Flipphi, Michel; Karaffa, Levente; Scazzocchio, Claudio; Fekete, Erzsébet

    2015-12-01

    Spliceosomal twin introns, "stwintrons", have been defined as complex intervening sequences that carry a second intron ("internal intron") interrupting one of the conserved sequence domains necessary for their correct splicing via consecutive excision events. Previously, we have described and experimentally verified stwintrons in species of Sordariomycetes, where an "internal intron" interrupted the donor sequence of an "external intron". Here we describe and experimentally verify two novel stwintrons of the potato pathogen Helminthosporium solani. One instance involves alternative splicing of an internal intron interrupting the donor domain of an external intron and a second one interrupting the acceptor domain of an overlapping external intron, both events leading to identical mature mRNAs. In the second case, an internal intron interrupts the donor domain of the external intron, while an alternatively spliced intron leads to an mRNA carrying a premature chain termination codon. We thus extend the stwintron concept to the acceptor domain and establish a link of the occurrence of stwintrons with that of alternative splicing.

  13. Alternatively spliced, spliceosomal twin introns in Helminthosporium solani.

    PubMed

    Ág, Norbert; Flipphi, Michel; Karaffa, Levente; Scazzocchio, Claudio; Fekete, Erzsébet

    2015-12-01

    Spliceosomal twin introns, "stwintrons", have been defined as complex intervening sequences that carry a second intron ("internal intron") interrupting one of the conserved sequence domains necessary for their correct splicing via consecutive excision events. Previously, we have described and experimentally verified stwintrons in species of Sordariomycetes, where an "internal intron" interrupted the donor sequence of an "external intron". Here we describe and experimentally verify two novel stwintrons of the potato pathogen Helminthosporium solani. One instance involves alternative splicing of an internal intron interrupting the donor domain of an external intron and a second one interrupting the acceptor domain of an overlapping external intron, both events leading to identical mature mRNAs. In the second case, an internal intron interrupts the donor domain of the external intron, while an alternatively spliced intron leads to an mRNA carrying a premature chain termination codon. We thus extend the stwintron concept to the acceptor domain and establish a link of the occurrence of stwintrons with that of alternative splicing. PMID:26514742

  14. Association of the 72/74-kDa proteins, members of the heterogeneous nuclear ribonucleoprotein M group, with the pre-mRNA at early stages of spliceosome assembly.

    PubMed Central

    Kafasla, Panayiota; Patrinou-Georgoula, Meropi; Lewis, Joe D; Guialis, Apostolia

    2002-01-01

    We have investigated the role played in precursor mRNA (pre-mRNA) splicing by the protein pair of molecular size 72/74 kDa, which are integral components of a discrete subset of heterogeneous nuclear (hn) ribonucleoproteins (RNPs) named large heterogeneous nuclear RNP (LH-nRNP). This 72/74 kDa pair of proteins has been shown to belong to the hnRNP M group, and are referred to as 72/74(M). By applying specific immunoprecipitation assays in a consecutive series of splicing reactions in vitro, the antigenic 72/74(M) protein species were found to associate with the pre-mRNA and not the intermediate or final products of splicing. Kinetic studies, combined with isolation of pre-spliceosomal and spliceosomal complexes from the splicing reaction, indicated a loose association of 72/74(M) with both the initially formed H assembly and the first splicing-committed E complex. Stable binding was seen at a later stage of the reaction, well in advance of the appearance of the first intermediate products of RNA splicing. Evidence is provided that supports the almost exclusive association of 72/74(M) with pre-mRNA within the pre-spliceosomal A complex. This dynamic binding appeared to involve pre-mRNA sites similar to those of spliceosomal U1 and U2 small nuclear RNP complexes. Moreover, a preferential binding to a truncated RNA containing the 5' exon-intron part, rather than the intron-3' exon part, of pre-mRNA was observed. PMID:11964181

  15. Complex role of the beta 2-beta 3 loop in the interaction of U1A with U1 hairpin II RNA.

    PubMed

    Katsamba, Phinikoula S; Bayramyan, Melina; Haworth, Ian S; Myszka, David G; Laird-Offringa, Ite A

    2002-09-01

    RNA recognition motifs (RRMs) are characterized by highly conserved regions located centrally on a beta-sheet, which forms the RNA binding surface. Variable flanking regions, such as the loop connecting beta-strands 2 and 3, are thought to be important in determining the RNA-binding specificities of individual RRMs. The N-terminal RRM of the spliceosomal U1A protein mediates binding to an RNA hairpin (U1hpII) in the U1 small nuclear RNA. In this complex, the beta(2)-beta(3) loop protrudes through the 10-nucleotide RNA loop. Shortening of the RNA loop strongly perturbs binding, suggesting that an optimal "fit" of the beta(2)-beta(3) loop into the RNA loop is an important factor in complexation. To understand this interaction further, we mutated or deleted loop residues Lys(50) and Met(51), which protrude centrally into the RNA loop but do not make any direct contacts to the bases. Using BIACORE, we analyzed the ability of these U1A mutants to bind to wild type RNAs, or RNAs with shortened loops. Alanine replacement mutations only modestly affected binding to wild type U1hpII. Interestingly, simultaneous replacement of Lys(50) and Met(51) with alanine appeared to alleviate the loss of binding caused by shortening of the RNA loop. Deletion of Lys(50) or Met(51) caused a dramatic loss in stability of the U1A.U1hpII complex. However, deletion of both residues simultaneously was much less deleterious. Simulated annealing molecular dynamics analyses suggest this is due to the ability of this mutant to rearrange flanking amino acids to substitute for the two deleted residues. The double deletion mutant also exhibited substantially reduced negative effects of RNA loop shortening, suggesting the rearranged loop is better able to accommodate a short RNA loop. Our results indicate that one of the roles of the beta(2)-beta(3) loop is to provide a steric fit into the RNA loop, thereby stabilizing the RNA.protein complex. PMID:12082087

  16. Spliceosomal gene mutations in myelodysplasia: molecular links to clonal abnormalities of hematopoiesis

    PubMed Central

    Inoue, Daichi; Bradley, Robert K.; Abdel-Wahab, Omar

    2016-01-01

    Genomic analyses of the myeloid malignancies and clonal disorders of hematopoiesis that may give rise to these disorders have identified that mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are among the most common targets of somatic mutations. These spliceosomal mutations often occur in a mutually exclusive manner with one another and, in aggregate, account for the most frequent class of mutations in patients with myelodysplastic syndromes (MDSs) in particular. Although substantial progress has been made in understanding the effects of several of these mutations on splicing and splice site recognition, functional connections linking the mechanistic changes in splicing induced by these mutations to the phenotypic consequences of clonal and aberrant hematopoiesis are not yet well defined. This review describes our current understanding of the mechanistic and biological effects of spliceosomal gene mutations in MDSs as well as the regulation of splicing throughout normal hematopoiesis. PMID:27151974

  17. Exhaustive analysis of the modular structure of the spliceosomal assembly network: a Petri net approach.

    PubMed

    Bortfeldt, Ralf H; Schuster, Stefan; Koch, Ina

    2010-01-01

    Spliceosomes are macro-complexes involving hundreds of proteins with many functional interactions. Spliceosome assembly belongs to the key processes that enable splicing of mRNA and modulate alternative splicing. A detailed list of factors involved in spliceosomal reactions has been assorted over the past decade, but, their functional interplay is often unknown and most of the present biological models cover only parts of the complete assembly process. It is a challenging task to build a computational model that integrates dispersed knowledge and combines a multitude of reaction schemes proposed earlier.Because for most reactions involved in spliceosome assembly kinetic parameters are not available, we propose a discrete modeling using Petri nets, through which we are enabled to get insights into the system's behavior via computation of structural and dynamic properties. In this paper, we compile and examine reactions from experimental reports that contribute to a functional spliceosome. All these reactions form a network, which describes the inventory and conditions necessary to perform the splicing process. The analysis is mainly based on system invariants. Transition invariants (T-invariants) can be interpreted as signaling routes through the network. Due to the huge number of T-invariants that arise with increasing network size and complexity, maximal common transition sets (MCTS) and T-clusters were used for further analysis. Additionally, we introduce a false color map representation, which allows a quick survey of network modules and the visual detection of single reactions or reaction sequences, which participate in more than one signaling route. We designed a structured model of spliceosome assembly, which combines the demands on a platform that i) can display involved factors and concurrent processes, ii) offers the possibility to run computational methods for knowledge extraction, and iii) is successively extendable as new insights into spliceosome

  18. The core spliceosome as target and effector of non-canonical ATM signaling

    PubMed Central

    Tresini, Maria; Warmerdam, Daniël O.; Kolovos, Petros; Snijder, Loes; Vrouwe, Mischa G.; Demmers, Jeroen A.A.; van IJcken, Wilfred F.J.; Grosveld, Frank G.; Medema, René H.; Hoeijmakers, Jan H.J.; Mullenders, Leon H.F.; Vermeulen, Wim; Marteijn, Jurgen A.

    2015-01-01

    In response to DNA damage tissue homoeostasis is ensured by protein networks promoting DNA repair, cell cycle arrest or apoptosis. DNA damage response signaling pathways coordinate these processes, partly by propagating gene expression-modulating signals. DNA damage influences not only abundance of mRNAs, but also their coding information through alternative splicing. Here we show that transcription-blocking DNA lesions promote chromatin displacement of late-stage spliceosomes and initiate a positive feedback loop centered on the signaling kinase ATM. We propose that initial spliceosome displacement and subsequent R-loop formation is triggered by pausing of RNA polymerase at DNA lesions. In turn, R-loops activate ATM which signals to further impede spliceosome organization and augment UV-triggered alternative splicing at genome-wide level. Our findings define the R-loop-dependent ATM activation by transcription-blocking lesions as an important event in the DNA damage response of non-replicating cells and highlight a key role for spliceosome displacement in this process. PMID:26106861

  19. Single molecule analysis reveals reversible and irreversible steps during spliceosome activation

    PubMed Central

    Hoskins, Aaron A; Rodgers, Margaret L; Friedman, Larry J; Gelles, Jeff; Moore, Melissa J

    2016-01-01

    The spliceosome is a complex machine composed of small nuclear ribonucleoproteins (snRNPs) and accessory proteins that excises introns from pre-mRNAs. After assembly the spliceosome is activated for catalysis by rearrangement of subunits to form an active site. How this rearrangement is coordinated is not well-understood. During activation, U4 must be released to allow U6 conformational change, while Prp19 complex (NTC) recruitment is essential for stabilizing the active site. We used multi-wavelength colocalization single molecule spectroscopy to directly observe the key events in Saccharomyces cerevisiae spliceosome activation. Following binding of the U4/U6.U5 tri-snRNP, the spliceosome either reverses assembly by discarding tri-snRNP or proceeds to activation by irreversible U4 loss. The major pathway for NTC recruitment occurs after U4 release. ATP stimulates both the competing U4 release and tri-snRNP discard processes. The data reveal the activation mechanism and show that overall splicing efficiency may be maintained through repeated rounds of disassembly and tri-snRNP reassociation. DOI: http://dx.doi.org/10.7554/eLife.14166.001 PMID:27244240

  20. Prevalent and distinct spliceosomal 3′-end processing mechanisms for fungal telomerase RNA

    PubMed Central

    Qi, Xiaodong; Rand, Dustin P.; Podlevsky, Joshua D.; Li, Yang; Mosig, Axel; Stadler, Peter F.; Chen, Julian J.-L.

    2015-01-01

    Telomerase RNA (TER) is an essential component of the telomerase ribonucleoprotein complex. The mechanism for TER 3′-end processing is highly divergent among different organisms. Here we report a unique spliceosome-mediated TER 3′-end cleavage mechanism in Neurospora crassa which is distinct from that found specifically in the fission yeast Schizosaccharomyces pombe. While the S. pombe TER intron contains the canonical 5′-splice site GUAUGU, the N. crassa TER intron contains a non-canonical 5′-splice site AUAAGU that alone prevents the second step of splicing and promotes spliceosomal cleavage. The unique N. crassa TER 5′-splice site sequence is evolutionarily conserved in TERs from Pezizomycotina and early branching Taphrinomycotina species. This suggests that the widespread and basal N. crassa-type spliceosomal cleavage mechanism is more ancestral than the S. pombe-type. The discovery of a prevalent, yet distinct, spliceosomal cleavage mechanism throughout diverse fungal clades furthers our understanding of TER evolution and non-coding RNA processing. PMID:25598218

  1. Spliceosome discards intermediates via the DEAH box ATPase Prp43p.

    PubMed

    Mayas, Rabiah M; Maita, Hiroshi; Semlow, Daniel R; Staley, Jonathan P

    2010-06-01

    To promote fidelity in nuclear pre-mRNA splicing, the spliceosome rejects and discards suboptimal substrates that have engaged the spliceosome. Whereas DExD/H box ATPases have been implicated in rejecting suboptimal substrates, the mechanism for discarding suboptimal substrates has remained obscure. Corroborating evidence that suboptimal, mutated lariat intermediates can be exported to the cytoplasm for turnover, we have found that the ribosome can translate mutated lariat intermediates. By glycerol gradient analysis, we have found that the spliceosome can dissociate mutated lariat intermediates in vivo in a manner that requires the DEAH box ATPase Prp43p. Through an in vitro assay, we demonstrate that Prp43p promotes the discard of suboptimal and optimal 5' exon and lariat intermediates indiscriminately. Finally, we demonstrate a requirement for Prp43p in repressing splicing at a cryptic splice site. We propose a model for the fidelity of exon ligation in which the DEAH box ATPase Prp22p slows the flow of suboptimal intermediates through exon ligation and Prp43p generally promotes discard of intermediates, thereby establishing a pathway for turnover of stalled intermediates. Because Prp43p also promotes spliceosome disassembly after exon ligation, this work establishes a parallel between the discard of suboptimal intermediates and the dissociation of a genuine excised intron product.

  2. Recruitment of the NineTeen Complex to the activated spliceosome requires AtPRMT5

    PubMed Central

    Deng, Xian; Lu, Tiancong; Wang, Lulu; Gu, Lianfeng; Sun, Jing; Kong, Xiangfeng; Liu, Chunyan; Cao, Xiaofeng

    2016-01-01

    Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is involved in a multitude of biological processes in eukaryotes. Symmetric arginine dimethylation mediated by PRMT5 modulates constitutive and alternative pre-mRNA splicing of diverse genes to regulate normal growth and development in multiple species; however, the underlying molecular mechanism remains largely unknown. A genetic screen for suppressors of an Arabidopsis symmetric arginine dimethyltransferase mutant, atprmt5, identified two gain-of-function alleles of pre-mRNA processing factor 8 gene (prp8-8 and prp8-9), the highly conserved core component of the U5 small nuclear ribonucleoprotein (snRNP) and the spliceosome. These two atprmt5 prp8 double mutants showed suppression of the developmental and splicing alterations of atprmt5 mutants. In atprmt5 mutants, the NineTeen complex failed to be assembled into the U5 snRNP to form an activated spliceosome; this phenotype was restored in the atprmt5 prp8-8 double mutants. We also found that loss of symmetric arginine dimethylation of Sm proteins prevents recruitment of the NineTeen complex and initiation of spliceosome activation. Together, our findings demonstrate that symmetric arginine dimethylation has important functions in spliceosome assembly and activation, and uncover a key molecular mechanism for arginine methylation in pre-mRNA splicing that impacts diverse developmental processes. PMID:27114555

  3. NOUGHT MAY ENDURE BUT MUTABILITY*: SPLICEOSOME DYNAMICS AND THE REGULATION OF SPLICING

    PubMed Central

    Smith, Duncan J.; Query, Charles C.; Konarska, Maria M.

    2008-01-01

    SUMMARY The spliceosome is both compositionally and conformationally dynamic. Each transition along the splicing pathway presents an opportunity for progression, pausing or discard, allowing splice site choice to be regulated throughout both the assembly and catalytic phases of the reaction. PMID:18570869

  4. Origin of a peculiar extra U(1)

    SciTech Connect

    Barr, S.M.; Dorsner, I.

    2005-07-01

    The origin of a family-independent ''extra U(1)'', discovered by Barr, Bednarz, and Benesh and independently by Ma, and whose phenomenology has recently been studied by Ma and Roy, is discussed. Even though it satisfies anomaly constraints in a highly economical way, with just a single extra triplet of leptons per family, this extra U(1) cannot come from four-dimensional grand unification. However, it is shown here that it can come from a Pati-Salam scheme with an extra U(1), which explains the otherwise surprising cancellation of anomalies.

  5. Spatial orientation and dynamics of the U1A proteins in the U1A-UTR complex.

    PubMed

    Clerte, C; Hall, K B

    2000-06-20

    The human U1A protein contains three distinct domains: the N-terminal RBD1 (amino acids 1-101), the C-terminal RBD2 (amino acids 195-282), and the linker region (amino acids 102-194). The RBD1 domains of two U1A proteins bind specifically to two internal loops in the 3' untranslated region (3' UTR) of its own pre-mRNA. Tryptophan fluorescence and fluorescence resonance energy transfer data show that the two RBD2 domains do not interact with any regions of the UTR complex and display an overall tumbling that is uncorrelated from the core of the complex (formed by RBD1-UTR), indicating that the linker regions of the two U1A proteins remain flexible. The two RBD2 domains are separated by an apparent distance greater than 74 A in the UTR complex. The linker region adjacent to the RBD1 domain (103-ERDRKREKRKPKSQETP-119) is supposedly involved in protein-protein interactions (12). A single cysteine, introduced at position 101 or 121 of the U1A protein, was used as a specific attachment site for the fluorophore pair IAEDANS [N'-iodoacetyl-N'-(1-sulfo-5-n-naphthyl)ethylenediamine]/DABMI [4-(dimethylamino)-phenylazophenyl-4'-maleimide]. In the U1A-UTR complex (2:1), the dyes at the 101 position are separated by = approximately 51 A, while the dyes at the 121 position are at an apparent distance = approximately 58 A. The 101-121 crossed distance on adjacent U1A proteins averages to = 55 A. These results suggest that the amino acid sequence 101-121 of the two U1A proteins in the complex are held in proximity to each other in a compact conformation.

  6. Structural/functional properties of a mammalian multi-component structure containing all major spliceosomal small nuclear ribonucleoprotein particles.

    PubMed Central

    Moraitou, M; Patrinou-Georgoula, M; Guialis, A

    1998-01-01

    An approx. 40 S multi-component structure, consisting of all major spliceosomal small nuclear ribonucleoprotein particles (snRNP) (U1, U2, U4/U6 and U5) in stable association with a large number of polypeptides, mainly in the range 50-210 kDa, has been reported to exist within rat liver nuclear extracts [Guialis, Moraitou, Patrinou-Georgoula and Dangli (1991) Nucleic Acids Res. 19, 287-296]. Using a new polyclonal antibody recognizing a 63 kDa protein component of the complex, this multi-snRNP assembly was detected within rat liver nuclear extracts as efficiently as with the antibody for the U2 snRNP-specific B' polypeptide. The 63 kDa protein was found to correspond to the 66 kDa subunit of the splicing factor SF3a, a known integral component of the HeLa 17 S U2 snRNP. Anti-2,2,7-trimethylguanosine affinity chromatography was an easy and efficient way of purifying the multi-snRNP complex from rat liver 40 S heterogeneous nuclear ribonucleoprotein particle (hnRNP)-containing sucrose gradient fractions. By subsequent glycerol-gradient sedimentation, all known snRNP forms active in RNA splicing were identified among its constituents. A complex structurally similar to the rat multi-snRNP was also identified in HeLa nuclear extracts. Preservation of hnRNP-snRNP interactions was observed within HeLa 40 S fractions. Moreover, these fractions were capable of restoring splicing activity when applied in reconstitution studies to supplement a micrococcal nuclease-treated splicing extract. PMID:9576861

  7. Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency

    PubMed Central

    Argente, Jesús; Flores, Raquel; Gutiérrez-Arumí, Armand; Verma, Bhupendra; Martos-Moreno, Gabriel Á; Cuscó, Ivon; Oghabian, Ali; Chowen, Julie A; Frilander, Mikko J; Pérez-Jurado, Luis A

    2014-01-01

    The molecular basis of a significant number of cases of isolated growth hormone deficiency remains unknown. We describe three sisters affected with severe isolated growth hormone deficiency and pituitary hypoplasia caused by biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein (snRNP) formation and splicing of U12-type introns. We found anomalies in U11/U12 di-snRNP formation and in splicing of multiple U12-type introns in patient cells. Defective transcripts include preprohormone convertases SPCS2 and SPCS3 and actin-related ARPC5L genes, which are candidates for the somatotroph-restricted dysfunction. The reported novel mechanism for familial growth hormone deficiency demonstrates that general mRNA processing defects of the minor spliceosome can lead to very narrow tissue-specific consequences. Subject Categories Genetics, Gene Therapy ' Genetic Disease; Metabolism PMID:24480542

  8. Phosphorylated SAP155, the spliceosomal component, is localized to chromatin in postnatal mouse testes

    SciTech Connect

    Eto, Ko; Sonoda, Yoshiyuki; Jin, Yuji; Abe, Shin-ichi

    2010-03-19

    SAP155 is an essential component of the spliceosome and its phosphorylation is required for splicing catalysis, but little is known concerning its expression and regulation during spermatogenesis in postnatal mouse testes. We report that SAP155 is ubiquitously expressed in nuclei of germ and Sertoli cells within the seminiferous tubules of 6- and 35-day postpartum (dpp) testes. Analyses by fractionation of testes revealed that (1) phosphorylated SAP155 was found in the fraction containing nuclear structures at 6 dpp in amounts much larger than that at other ages; (2) non-phosphorylated SAP155 was detected in the fraction containing nucleoplasm; and (3) phosphorylated SAP155 was preferentially associated with chromatin. Our findings suggest that the active spliceosome, containing phosphorylated SAP155, performs pre-mRNA splicing on chromatin concomitant with transcription during testicular development.

  9. Nuclear expression of a group II intron is consistent with spliceosomal intron ancestry.

    PubMed

    Chalamcharla, Venkata R; Curcio, M Joan; Belfort, Marlene

    2010-04-15

    Group II introns are self-splicing RNAs found in eubacteria, archaea, and eukaryotic organelles. They are mechanistically similar to the metazoan nuclear spliceosomal introns; therefore, group II introns have been invoked as the progenitors of the eukaryotic pre-mRNA introns. However, the ability of group II introns to function outside of the bacteria-derived organelles is debatable, since they are not found in the nuclear genomes of eukaryotes. Here, we show that the Lactococcus lactis Ll.LtrB group II intron splices accurately and efficiently from different pre-mRNAs in a eukaryote, Saccharomyces cerevisiae. However, a pre-mRNA harboring a group II intron is spliced predominantly in the cytoplasm and is subject to nonsense-mediated mRNA decay (NMD), and the mature mRNA from which the group II intron is spliced is poorly translated. In contrast, a pre-mRNA bearing the Tetrahymena group I intron or the yeast spliceosomal ACT1 intron at the same location is not subject to NMD, and the mature mRNA is translated efficiently. Thus, a group II intron can splice from a nuclear transcript, but RNA instability and translation defects would have favored intron loss or evolution into protein-dependent spliceosomal introns, consistent with the bacterial group II intron ancestry hypothesis.

  10. U (1U (1 ) symmetry-protected topological order in Gutzwiller wave functions

    NASA Astrophysics Data System (ADS)

    Liu, Zheng-Xin; Mei, Jia-Wei; Ye, Peng; Wen, Xiao-Gang

    2014-12-01

    Gutzwiller projection is a way to construct many-body wave functions that could carry topological order or symmetry-protected topological (SPT) order. However, an important issue is to determine whether or not a given Gutzwiller-projected wave function (GWF) carries a nontrivial SPT order, and which SPT order is carried by the wave function. In this paper, we numerically study the SPT order in a spin S =1 GWF on the kagome lattice. Using the standard Monte Carlo method, we directly confirm that the GWF has (1) gapped bulk with short-range correlations, (2) a trivial topological order via a nondegenerate ground state, and zero topological entanglement entropy, (3) a nontrivial U (1U (1 ) SPT order via the Hall conductances of the protecting U (1U (1 ) symmetry, and (4) a symmetry-protected gapless boundary. This represents numerical evidence of continuous symmetry-protected topological order in two-dimensional bosonic lattice systems.

  11. Spliceosome assembly in the absence of stable U4/U6 RNA pairing

    PubMed Central

    Burke, Jordan E.; Butcher, Samuel E.; Brow, David A.

    2015-01-01

    The cycle of spliceosome assembly, intron excision, and spliceosome disassembly involves large-scale structural rearrangements of U6 snRNA that are functionally important. U6 enters the splicing pathway bound to the Prp24 protein, which chaperones annealing of U6 to U4 RNA to form a U4/U6 di-snRNP. During catalytic activation of the assembled spliceosome, U4 snRNP is released and U6 is paired to U2 snRNA. Here we show that point mutations in U4 and U6 that decrease U4/U6 base-pairing in vivo are lethal in combination. However, this synthetic phenotype is rescued by a mutation in U6 that alters a U6–Prp24 contact and stabilizes U2/U6. Remarkably, the resulting viable triple mutant strain lacks detectable U4/U6 base-pairing and U4/U6 di-snRNP. Instead, this strain accumulates free U4 snRNP, protein-free U6 RNA, and a novel complex containing U2/U6 di-snRNP. Further mutational analysis indicates that disruption of the U6–Prp24 interaction rather than stabilization of U2/U6 renders stable U4/U6 di-snRNP assembly nonessential. We propose that an essential function of U4/U6 pairing is to displace Prp24 from U6 RNA, and thus a destabilized U6–Prp24 complex renders stable U4/U6 pairing nonessential. PMID:25762536

  12. Confined vortices in topologically massive U (1U (1 ) theory

    NASA Astrophysics Data System (ADS)

    Anber, Mohamed M.; Burnier, Yannis; Sabancilar, Eray; Shaposhnikov, Mikhail

    2015-09-01

    We report on a new topological vortex solution in U (1U (1 ) Maxwell-Chern-Simons theory. The existence of the vortex is envisaged by analytical means, and a numerical solution is obtained by integrating the equations of motion. These vortices have a long-range force because one of the U(1)'s remains unbroken in the infrared, which is guarded by the Coleman-Hill theorem. The sum of the winding numbers of an ensemble of vortices has to vanish; otherwise the system would have a logarithmically divergent energy. In turn, these vortices exhibit classical confinement. We investigate the rich parameter space of the solutions, and show that one recovers the Abrikosov-Nielsen-Olesen, U(1) Maxwell-Chern-Simons, U(1) pure Chern-Simons, and global vortices as various limiting cases. Unlike these limiting cases, the higher winding solutions of our vortices carry noninteger charges under the broken U(1). This is the first vortex solution exhibiting such behavior.

  13. CACTIN is an essential nuclear protein in Arabidopsis and may be associated with the eukaryotic spliceosome.

    PubMed

    Baldwin, Katherine L; Dinh, Elizabeth M; Hart, Brian M; Masson, Patrick H

    2013-04-01

    CACTIN is a conserved eukaryotic protein without known functional domains. Previous research revealed that CACTIN is essential in animals and protists and that it may function in inflammation pathways in animals; however, these pathways are not as broadly conserved as CACTIN. Therefore, the ancestral molecular function of CACTIN remains unknown. Our studies using Arabidopsis show that CACTIN is required for embryogenesis. Fluorescently tagged CACTIN localizes to nuclear speckles and colocalizes with known splicing proteins. In yeast-two-hybrid studies, we found that CACTIN binds to a putative component of the spliceosome. These findings support a possible role for CACTIN in splicing.

  14. Meta-analysis of gene expression profiles indicates genes in spliceosome pathway are up-regulated in hepatocellular carcinoma (HCC).

    PubMed

    Xu, Weijin; Huang, Huixing; Yu, Long; Cao, Lihuan

    2015-04-01

    Hepatocellular carcinoma (HCC) is among the commonest kind of malignant tumors, which accounts for more than 500,000 cases of newly diagnosed cancer annually. Many microarray studies for identifying differentially expressed genes (DEGs) in HCC have been conducted, but results have varied across different studies. Here, we performed a meta-analysis of publicly available microarray Gene Expression Omnibus datasets, which covers five independent studies, containing 753 HCC samples and 638 non-tumor liver samples. We identified 192 DEGs that were consistently up-regulated in HCC vs. normal liver tissue. For the 192 up-regulated genes, we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis. To our surprise, besides several cell growth-related pathways, spliceosome pathway was also up-regulated in HCC. For further exploring the relationship between spliceosome pathway and HCC, we investigated the expression data of spliceosome pathway genes in 15 independent studies in Nextbio database ( https://www.nextbio.com/b/nextbioCorp.nb ). It was found that many genes of spliceosome pathway such as HSPA1A, SNRPE, SF3B2, SF3B4 and TRA2A genes which we identified to be up-regulated in our meta-analysis were generally overexpressed in HCC. At last, using real-time PCR, we also found that BUD31, SF3B2, SF3B4, SNRPE, SPINK1, TPA2A and HSPA1A genes are significantly up-regulated in clinical HCC samples when compared to the corresponding non-tumorous liver tissues. Our study for the first time indicates that many genes of spliceosome pathway are up-regulated in HCC. This finding might put new insights for people's understanding about the relationship of spliceosome pathway and HCC.

  15. Spliceosome SNRNP200 Promotes Viral RNA Sensing and IRF3 Activation of Antiviral Response

    PubMed Central

    Tremblay, Nicolas; Baril, Martin; Chatel-Chaix, Laurent; Es-Saad, Salwa; Park, Alex Young; Koenekoop, Robert K.; Lamarre, Daniel

    2016-01-01

    Spliceosomal SNRNP200 is a Ski2-like RNA helicase that is associated with retinitis pigmentosa 33 (RP33). Here we found that SNRNP200 promotes viral RNA sensing and IRF3 activation through the ability of its amino-terminal Sec63 domain (Sec63-1) to bind RNA and to interact with TBK1. We show that SNRNP200 relocalizes into TBK1-containing cytoplasmic structures upon infection, in contrast to the RP33-associated S1087L mutant, which is also unable to rescue antiviral response of SNRNP200 knockdown cells. This functional rescue correlates with the Sec63-1-mediated binding of viral RNA. The hindered IFN-β production of knockdown cells was further confirmed in peripheral blood cells of RP33 patients bearing missense mutation in SNRNP200 upon infection with Sendai virus (SeV). This work identifies a novel immunoregulatory role of the spliceosomal SNRNP200 helicase as an RNA sensor and TBK1 adaptor for the activation of IRF3-mediated antiviral innate response. PMID:27454487

  16. Novel Introner-Like Elements in fungi Are Involved in Parallel Gains of Spliceosomal Introns.

    PubMed

    Collemare, Jérôme; Beenen, Henriek G; Crous, Pedro W; de Wit, Pierre J G M; van der Burgt, Ate

    2015-01-01

    Spliceosomal introns are key components of the eukaryotic gene structure. Although they contributed to the emergence of eukaryotes, their origin remains elusive. In fungi, they might originate from the multiplication of invasive introns named Introner-Like Elements (ILEs). However, so far ILEs have been observed in six fungal species only, including Fulvia fulva and Dothistroma septosporum (Dothideomycetes), arguing against ILE insertion as a general mechanism for intron gain. Here, we identified novel ILEs in eight additional fungal species that are phylogenetically related to F. fulva and D. septosporum using PCR amplification with primers derived from previously identified ILEs. The ILE content appeared unique to each species, suggesting independent multiplication events. Interestingly, we identified four genes each containing two gained ILEs. By analysing intron positions in orthologues of these four genes in Ascomycota, we found that three ILEs had inserted within a 15 bp window that contains regular spliceosomal introns in other fungal species. These three positions are not the result of intron sliding because ILEs are newly gained introns. Furthermore, the alternative hypothesis of an inferred ancestral gain followed by independent losses contradicts the observed degeneration of ILEs. These observations clearly indicate three parallel intron gains in four genes that were randomly identified. Our findings suggest that parallel intron gain is a phenomenon that has been highly underestimated in ILE-containing fungi, and likely in the whole fungal kingdom.

  17. Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing.

    PubMed

    Trochet, Delphine; Prudhon, Bernard; Jollet, Arnaud; Lorain, Stéphanie; Bitoun, Marc

    2016-01-01

    Dynamin 2 (DNM2) is a large GTPase, ubiquitously expressed, involved in membrane trafficking and regulation of actin and microtubule cytoskeletons. DNM2 mutations cause autosomal dominant centronuclear myopathy which is a rare congenital myopathy characterized by skeletal muscle weakness and histopathological features including nuclear centralization in absence of regeneration. No curative treatment is currently available for the DNM2-related autosomal dominant centronuclear myopathy. In order to develop therapeutic strategy, we evaluated here the potential of Spliceosome-Mediated RNA Trans-splicing technology to reprogram the Dnm2-mRNA in vitro and in vivo in mice. We show that classical 3'-trans-splicing strategy cannot be considered as accurate therapeutic strategy regarding toxicity of the pre-trans-splicing molecules leading to low rate of trans-splicing in vivo. Thus, we tested alternative strategies devoted to prevent this toxicity and enhance frequency of trans-splicing events. We succeeded to overcome the toxicity through a 5'-trans-splicing strategy which also allows detection of trans-splicing events at mRNA and protein levels in vitro and in vivo. These results suggest that the Spliceosome-Mediated RNA Trans-splicing strategy may be used to reprogram mutated Dnm2-mRNA but highlight the potential toxicity linked to the molecular tools which have to be carefully investigated during preclinical development. PMID:27623444

  18. The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing.

    PubMed

    De Maio, Federico A; Risso, Guillermo; Iglesias, Nestor G; Shah, Priya; Pozzi, Berta; Gebhard, Leopoldo G; Mammi, Pablo; Mancini, Estefania; Yanovsky, Marcelo J; Andino, Raul; Krogan, Nevan; Srebrow, Anabella; Gamarnik, Andrea V

    2016-08-01

    Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. PMID:27575636

  19. Cross talk between spliceosome and microprocessor defines the fate of pre-mRNA.

    PubMed

    Mattioli, Chiara; Pianigiani, Giulia; Pagani, Franco

    2014-01-01

    The spliceosome and the microprocessor complex (MPC) are two important processing machineries that act on precursor (pre)-mRNA. Both cleave the pre-mRNA to generate spliced mature transcripts and microRNAs (miRNAs), respectively. While spliceosomes identify in a complex manner correct splice sites, MPCs typically target RNA hairpins (pri-miRNA hairpins). In addition, pre-mRNA transcripts can contain pri-miRNA-like hairpins that are cleaved by the MPC without generating miRNAs. Recent evidence indicates that the position of hairpins on pre-mRNA, their distance from splice sites, and the relative efficiency of cropping and splicing contribute to determine the fate of a pre-mRNA. Depending on these factors, a pre-mRNA can be preferentially used to generate a miRNA, a constitutively or even an alternative spliced transcript. For example, competition between splicing and cropping on splice-site-overlapping miRNAs (SO miRNAs) results in alternative spliced isoforms and influences miRNA biogenesis. In several cases, the outcome of a pre-mRNA transcript and its final handling as miRNA or mRNA substrate can be frequently closely connected to the functional relationships between diverse pre-mRNA processing events. These events are influenced by both gene context and physiopathological conditions.

  20. The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing.

    PubMed

    De Maio, Federico A; Risso, Guillermo; Iglesias, Nestor G; Shah, Priya; Pozzi, Berta; Gebhard, Leopoldo G; Mammi, Pablo; Mancini, Estefania; Yanovsky, Marcelo J; Andino, Raul; Krogan, Nevan; Srebrow, Anabella; Gamarnik, Andrea V

    2016-08-01

    Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication.

  1. The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing

    PubMed Central

    Shah, Priya; Pozzi, Berta; Gebhard, Leopoldo G.; Mammi, Pablo; Yanovsky, Marcelo J.; Andino, Raul; Krogan, Nevan; Srebrow, Anabella; Gamarnik, Andrea V.

    2016-01-01

    Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. PMID:27575636

  2. Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing

    PubMed Central

    Trochet, Delphine; Prudhon, Bernard; Jollet, Arnaud; Lorain, Stéphanie; Bitoun, Marc

    2016-01-01

    Dynamin 2 (DNM2) is a large GTPase, ubiquitously expressed, involved in membrane trafficking and regulation of actin and microtubule cytoskeletons. DNM2 mutations cause autosomal dominant centronuclear myopathy which is a rare congenital myopathy characterized by skeletal muscle weakness and histopathological features including nuclear centralization in absence of regeneration. No curative treatment is currently available for the DNM2-related autosomal dominant centronuclear myopathy. In order to develop therapeutic strategy, we evaluated here the potential of Spliceosome-Mediated RNA Trans-splicing technology to reprogram the Dnm2-mRNA in vitro and in vivo in mice. We show that classical 3′-trans-splicing strategy cannot be considered as accurate therapeutic strategy regarding toxicity of the pre-trans-splicing molecules leading to low rate of trans-splicing in vivo. Thus, we tested alternative strategies devoted to prevent this toxicity and enhance frequency of trans-splicing events. We succeeded to overcome the toxicity through a 5′-trans-splicing strategy which also allows detection of trans-splicing events at mRNA and protein levels in vitro and in vivo. These results suggest that the Spliceosome-Mediated RNA Trans-splicing strategy may be used to reprogram mutated Dnm2-mRNA but highlight the potential toxicity linked to the molecular tools which have to be carefully investigated during preclinical development. PMID:27623444

  3. A quantitative high-throughput in vitro splicing assay identifies inhibitors of spliceosome catalysis.

    PubMed

    Berg, Michael G; Wan, Lili; Younis, Ihab; Diem, Michael D; Soo, Michael; Wang, Congli; Dreyfuss, Gideon

    2012-04-01

    Despite intensive research, there are very few reagents with which to modulate and dissect the mRNA splicing pathway. Here, we describe a novel approach to identify such tools, based on detection of the exon junction complex (EJC), a unique molecular signature that splicing leaves on mRNAs. We developed a high-throughput, splicing-dependent EJC immunoprecipitation (EJIPT) assay to quantitate mRNAs spliced from biotin-tagged pre-mRNAs in cell extracts, using antibodies to EJC components Y14 and eukaryotic translation initiation factor 4aIII (eIF4AIII). Deploying EJIPT we performed high-throughput screening (HTS) in conjunction with secondary assays to identify splicing inhibitors. We describe the identification of 1,4-naphthoquinones and 1,4-heterocyclic quinones with known anticancer activity as potent and selective splicing inhibitors. Interestingly, and unlike previously described small molecules, most of which target early steps, our inhibitors represented by the benzothiazole-4,7-dione, BN82685, block the second of two trans-esterification reactions in splicing, preventing the release of intron lariat and ligation of exons. We show that BN82685 inhibits activated spliceosomes' elaborate structural rearrangements that are required for second-step catalysis, allowing definition of spliceosomes stalled in midcatalysis. EJIPT provides a platform for characterization and discovery of splicing and EJC modulators. PMID:22252314

  4. Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells

    PubMed Central

    Sato, Naoki; Maeda, Masao; Sugiyama, Mai; Ito, Satoko; Hyodo, Toshinori; Masuda, Akio; Tsunoda, Nobuyuki; Kokuryo, Toshio; Hamaguchi, Michinari; Nagino, Masato; Senga, Takeshi

    2015-01-01

    RNA splicing is a fundamental process for protein synthesis. Recent studies have reported that drugs that inhibit splicing have cytotoxic effects on various tumor cell lines. In this report, we demonstrate that depletion of SNW1, a component of the spliceosome, induces apoptosis in breast cancer cells. Proteomics and biochemical analyses revealed that SNW1 directly associates with other spliceosome components, including EFTUD2 (Snu114) and SNRNP200 (Brr2). The SKIP region of SNW1 interacted with the N-terminus of EFTUD2 as well as two independent regions in the C-terminus of SNRNP200. Similar to SNW1 depletion, knockdown of EFTUD2 increased the numbers of apoptotic cells. Furthermore, we demonstrate that exogenous expression of either the SKIP region of SNW1 or the N-terminus region of EFTUD2 significantly promoted cellular apoptosis. Our results suggest that the inhibition of SNW1 or its associating proteins may be a novel therapeutic strategy for cancer treatment. PMID:25450007

  5. Novel Introner-Like Elements in fungi Are Involved in Parallel Gains of Spliceosomal Introns

    PubMed Central

    Crous, Pedro W.; de Wit, Pierre J. G. M.; van der Burgt, Ate

    2015-01-01

    Spliceosomal introns are key components of the eukaryotic gene structure. Although they contributed to the emergence of eukaryotes, their origin remains elusive. In fungi, they might originate from the multiplication of invasive introns named Introner-Like Elements (ILEs). However, so far ILEs have been observed in six fungal species only, including Fulvia fulva and Dothistroma septosporum (Dothideomycetes), arguing against ILE insertion as a general mechanism for intron gain. Here, we identified novel ILEs in eight additional fungal species that are phylogenetically related to F. fulva and D. septosporum using PCR amplification with primers derived from previously identified ILEs. The ILE content appeared unique to each species, suggesting independent multiplication events. Interestingly, we identified four genes each containing two gained ILEs. By analysing intron positions in orthologues of these four genes in Ascomycota, we found that three ILEs had inserted within a 15 bp window that contains regular spliceosomal introns in other fungal species. These three positions are not the result of intron sliding because ILEs are newly gained introns. Furthermore, the alternative hypothesis of an inferred ancestral gain followed by independent losses contradicts the observed degeneration of ILEs. These observations clearly indicate three parallel intron gains in four genes that were randomly identified. Our findings suggest that parallel intron gain is a phenomenon that has been highly underestimated in ILE-containing fungi, and likely in the whole fungal kingdom. PMID:26046656

  6. Anomalous Flavor U(1)_X for Everything

    SciTech Connect

    Dreiner, Herbi K.; Murayama, Hitoshi; Thormeier, Marc

    2003-12-01

    We present an ambitious model of flavor, based on an anomalous U(1)_X gauge symmetry with one flavon, only two right-handed neutrinos and only two mass scales: M_{grav} and m_{3/2}. In particular, there are no new scales introduced for right-handed neutrino masses. The X-charges of the matter fields are such that R-parity is conserved exactly, higher-dimensional operators are sufficiently suppressed to guarantee a proton lifetime in agreement with experiment, and the phenomenology is viable for quarks, charged leptons, as well as neutrinos. In our model one of the three light neutrinos automatically is massless. The price we have to pay for this very successful model are highly fractional X-charges which can likely be improved with less restrictive phenomenological ansatze for mass matrices.

  7. The network organization of protein interactions in the spliceosome is reproduced by the simple rules of food-web models

    PubMed Central

    Pires, Mathias M.; Cantor, Maurício; Guimarães, Paulo R.; de Aguiar, Marcus A. M.; dos Reis, Sérgio F.; Coltri, Patricia P.

    2015-01-01

    The network structure of biological systems provides information on the underlying processes shaping their organization and dynamics. Here we examined the structure of the network depicting protein interactions within the spliceosome, the macromolecular complex responsible for splicing in eukaryotic cells. We show the interactions of less connected spliceosome proteins are nested subsets of the connections of the highly connected proteins. At the same time, the network has a modular structure with groups of proteins sharing similar interaction patterns. We then investigated the role of affinity and specificity in shaping the spliceosome network by adapting a probabilistic model originally designed to reproduce food webs. This food-web model was as successful in reproducing the structure of protein interactions as it is in reproducing interactions among species. The good performance of the model suggests affinity and specificity, partially determined by protein size and the timing of association to the complex, may be determining network structure. Moreover, because network models allow building ensembles of realistic networks while encompassing uncertainty they can be useful to examine the dynamics and vulnerability of intracelullar processes. Unraveling the mechanisms organizing the spliceosome interactions is important to characterize the role of individual proteins on splicing catalysis and regulation. PMID:26443080

  8. The network organization of protein interactions in the spliceosome is reproduced by the simple rules of food-web models.

    PubMed

    Pires, Mathias M; Cantor, Maurício; Guimarães, Paulo R; de Aguiar, Marcus A M; Dos Reis, Sérgio F; Coltri, Patricia P

    2015-01-01

    The network structure of biological systems provides information on the underlying processes shaping their organization and dynamics. Here we examined the structure of the network depicting protein interactions within the spliceosome, the macromolecular complex responsible for splicing in eukaryotic cells. We show the interactions of less connected spliceosome proteins are nested subsets of the connections of the highly connected proteins. At the same time, the network has a modular structure with groups of proteins sharing similar interaction patterns. We then investigated the role of affinity and specificity in shaping the spliceosome network by adapting a probabilistic model originally designed to reproduce food webs. This food-web model was as successful in reproducing the structure of protein interactions as it is in reproducing interactions among species. The good performance of the model suggests affinity and specificity, partially determined by protein size and the timing of association to the complex, may be determining network structure. Moreover, because network models allow building ensembles of realistic networks while encompassing uncertainty they can be useful to examine the dynamics and vulnerability of intracelullar processes. Unraveling the mechanisms organizing the spliceosome interactions is important to characterize the role of individual proteins on splicing catalysis and regulation.

  9. Spliceosome mutations exhibit specific associations with epigenetic modifiers and proto-oncogenes mutated in myelodysplastic syndrome.

    PubMed

    Mian, Syed A; Smith, Alexander E; Kulasekararaj, Austin G; Kizilors, Aytug; Mohamedali, Azim M; Lea, Nicholas C; Mitsopoulos, Konstantinos; Ford, Kevin; Nasser, Erick; Seidl, Thomas; Mufti, Ghulam J

    2013-07-01

    The recent identification of acquired mutations in key components of the spliceosome machinery strongly implicates abnormalities of mRNA splicing in the pathogenesis of myelodysplastic syndromes. However, questions remain as to how these aberrations functionally combine with the growing list of mutations in genes involved in epigenetic modification and cell signaling/transcription regulation identified in these diseases. In this study, amplicon sequencing was used to perform a mutation screen in 154 myelodysplastic syndrome patients using a 22-gene panel, including commonly mutated spliceosome components (SF3B1, SRSF2, U2AF1, ZRSR2), and a further 18 genes known to be mutated in myeloid cancers. Sequencing of the 22-gene panel revealed that 76% (n=117) of the patients had mutations in at least one of the genes, with 38% (n=59) having splicing gene mutations and 49% (n=75) patients harboring more than one gene mutation. Interestingly, single and specific epigenetic modifier mutations tended to coexist with SF3B1 and SRSF2 mutations (P<0.03). Furthermore, mutations in SF3B1 and SRSF2 were mutually exclusive to TP53 mutations both at diagnosis and at the time of disease transformation. Moreover, mutations in FLT3, NRAS, RUNX1, CCBL and C-KIT were more likely to co-occur with splicing factor mutations generally (P<0.02), and SRSF2 mutants in particular (P<0.003) and were significantly associated with disease transformation (P<0.02). SF3B1 and TP53 mutations had varying impacts on overall survival with hazard ratios of 0.2 (P<0.03, 95% CI, 0.1-0.8) and 2.1 (P<0.04, 95% CI, 1.1-4.4), respectively. Moreover, patients with splicing factor mutations alone had a better overall survival than those with epigenetic modifier mutations, or cell signaling/transcription regulator mutations with and without coexisting mutations of splicing factor genes, with worsening prognosis (P<0.001). These findings suggest that splicing factor mutations are maintained throughout disease

  10. Calabi-Yau manifolds from noncommutative Hermitian U (1 ) instantons

    NASA Astrophysics Data System (ADS)

    Yang, Hyun Seok

    2015-05-01

    We show that Calabi-Yau manifolds are emergent from the commutative limit of six-dimensional noncommutative Hermitian U (1 ) instantons. Therefore, we argue that the noncommutative Hermitian U (1 ) instantons correspond to quantized Calabi-Yau manifolds.

  11. Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome.

    PubMed

    Lynch, Danielle C; Revil, Timothée; Schwartzentruber, Jeremy; Bhoj, Elizabeth J; Innes, A Micheil; Lamont, Ryan E; Lemire, Edmond G; Chodirker, Bernard N; Taylor, Juliet P; Zackai, Elaine H; McLeod, D Ross; Kirk, Edwin P; Hoover-Fong, Julie; Fleming, Leah; Savarirayan, Ravi; Majewski, Jacek; Jerome-Majewska, Loydie A; Parboosingh, Jillian S; Bernier, Francois P

    2014-07-22

    Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-costo-mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development.

  12. The target of the DEAH-box NTP triphosphatase Prp43 in Saccharomyces cerevisiae spliceosomes is the U2 snRNP-intron interaction

    PubMed Central

    Fourmann, Jean-Baptiste; Dybkov, Olexandr; Agafonov, Dmitry E; Tauchert, Marcel J; Urlaub, Henning; Ficner, Ralf; Fabrizio, Patrizia; Lührmann, Reinhard

    2016-01-01

    The DEAH-box NTPase Prp43 and its cofactors Ntr1 and Ntr2 form the NTR complex and are required for disassembling intron-lariat spliceosomes (ILS) and defective earlier spliceosomes. However, the Prp43 binding site in the spliceosome and its target(s) are unknown. We show that Prp43 fused to Ntr1's G-patch motif (Prp43_Ntr1GP) is as efficient as the NTR in ILS disassembly, yielding identical dissociation products and recognizing its natural ILS target even in the absence of Ntr1’s C-terminal-domain (CTD) and Ntr2. Unlike the NTR, Prp43_Ntr1GP disassembles earlier spliceosomal complexes (A, B, Bact), indicating that Ntr2/Ntr1-CTD prevents NTR from disrupting properly assembled spliceosomes other than the ILS. The U2 snRNP-intron interaction is disrupted in all complexes by Prp43_Ntr1GP, and in the spliceosome contacts U2 proteins and the pre-mRNA, indicating that the U2 snRNP-intron interaction is Prp43’s major target. DOI: http://dx.doi.org/10.7554/eLife.15564.001 PMID:27115347

  13. A 25-bp ancient spliceosomal intron in the TvRab1a gene of Trichomonas vaginalis.

    PubMed

    Deng, Xiao-Ling; Xu, Ming-Yan; Xu, Xiao-Yuan; Ba-Thein, William; Zhang, Ren-Li; Fu, Yu-Cai

    2009-02-01

    Spliceosomal introns play a key role in eukaryotic genome evolution and protein diversity. A large Rab GTPase family has been identified in a unicellular eukaryote Trichomonas vaginalis. However, the characteristics of introns in Rab genes of T. vaginalis have not been investigated previously. In this study, we identified a 25-bp spliceosomal intron in the T. vaginalis Rab1a (TvRab1a) gene, the smallest intron in T. vaginalis to be characterized to date. This intron contains a canonical splice site at both 5' (GT) and 3' (AG) ends, and a putative branch-point sequence (TCTAAC) that matches the Trichomonad consensus sequence of ACTAAC except for the first nucleotide. The position and phase of the TvRab1a intron are evolutionarily conserved in Rab1 homologous genes across at least five eukaryotic supergroups, including Opisthokonta, Amoebozoa, Excavata, Chromalveolata, and Plantae. These results strongly suggest that the TvRab1a intron is likely to be an ancient spliceosomal intron, and it can therefore be used as a phylogenetic marker to evaluate particular eukaryotic groupings. Identification and characterization of the TvRabla intron may provide an insight into the evolution of the large Rab repertoire in T. vaginalis. PMID:18926921

  14. Unique genome of dicyemid mesozoan: highly shortened spliceosomal introns in conservative exon/intron structure.

    PubMed

    Ogino, Kazutoyo; Tsuneki, Kazuhiko; Furuya, Hidetaka

    2010-01-01

    Dicyemids are enigmatic endoparasites, or endosymbionts, living in the renal sac of benthic cephalopod molluscs. The body of dicyemids consists of only 9-41 cells, with neither extracellular matrices nor differentiated tissues. Due to the unusually simple body organization, dicyemids have long been the subject of phylogenetic controversy. Molecular evidences suggest dicyemids are lophotrochozoans that have secondarily lost many morphological characters. We studied 40 genes of the dicyemid Dicyema japonicum and found that their spliceosomal introns are very short (mean length=26 bp). This size was shorter than that of introns of animals, such as Fugu rubripes and Oikopleura dioica which possess compact genome and introns. In the intron size, the dicyemid was nearly equal to the chlorarachniophyte Bigelowiella natans nucleomorph (18-21 bp) which has the shortest introns of any known eukaryote. Despite the short introns, the intron density (5.3 introns/gene) of the dicyemid is similar to that in model invertebrates. In addition, the exon/intron structure of the dicyemid is more similar to vertebrates than to the model invertebrates. These results suggest that the positions of the introns are possibly conserved under functional constraints.

  15. Tempo and mode of spliceosomal intron evolution in actin of foraminifera.

    PubMed

    Flakowski, Jérôme; Bolivar, Ignacio; Fahrni, José; Pawlowski, Jan

    2006-07-01

    Spliceosomal introns are present in almost all eukaryotic genes, yet little is known about their origin and turnover in the majority of eukaryotic phyla. There is no agreement whether most introns are ancestral and have been lost in some lineage or have been gained recently. We addressed this question by analyzing the spatial and temporal distribution of introns in actins of foraminifera, a group of testate protists whose exceptionally rich fossil record permits the calibration of molecular phylogenies to date intron origins. We identified 24 introns dispersed along the sequence of two foraminiferan actin paralogues and actin deviating proteins, an unconventional type of fast-evolving actin found in some foraminifera. Comparison of intron positions indicates that 20 of 24 introns are specific to foraminifera. Four introns shared between foraminifera and other eukaryotes were interpreted as parallel gains because they have been found only in single species belonging to phylogenetically distinctive lineages. Moreover, additional recent intron gain due to the transfer between the actin paralogues was observed in two cultured species. Based on a relaxed molecular clock timescale, we conclude that intron gains in actin took place throughout the evolution of foraminifera, with the oldest introns inserted between 550 and 500 million years ago and the youngest ones acquired less than 100 million years ago.

  16. Proteomic Analysis Reveals CACN-1 Is a Component of the Spliceosome in Caenorhabditis elegans

    PubMed Central

    Doherty, Michael F.; Adelmant, Guillaume; Cecchetelli, Alyssa D.; Marto, Jarrod A.; Cram, Erin J.

    2014-01-01

    Cell migration is essential for embryonic development and tissue formation in all animals. cacn-1 is a conserved gene of unknown molecular function identified in a genome-wide screen for genes that regulate distal tip cell migration in the nematode worm Caenorhabditis elegans. In this study we take a proteomics approach to understand CACN-1 function. To isolate CACN-1−interacting proteins, we used an in vivo tandem-affinity purification strategy. Tandem-affinity purification−tagged CACN-1 complexes were isolated from C. elegans lysate, analyzed by mass spectrometry, and characterized bioinformatically. Results suggest significant interaction of CACN-1 with the C. elegans spliceosome. All of the identified interactors were screened for distal tip cell migration phenotypes using RNAi. Depletion of many of these factors led to distal tip cell migration defects, particularly a failure to stop migrating, a phenotype commonly seen in cacn-1 deficient animals. The results of this screen identify eight novel regulators of cell migration and suggest CACN-1 may participate in a protein network dedicated to high-fidelity gonad development. The composition of proteins comprising the CACN-1 network suggests that this critical developmental module may exert its influence through alternative splicing or other post-transcriptional gene regulation. PMID:24948787

  17. A pseudouridine residue in the spliceosome core is part of the filamentous growth program in yeast

    PubMed Central

    Basak, Anindita; Query, Charles C.

    2014-01-01

    SUMMARY Pseudouridine nucleobases, while abundant in tRNAs, rRNAs, and snRNAs, are not known to have physiologic roles in cell differentiation. We have identified a novel pseudouridine residue (Ψ28) on spliceosomal U6 snRNA that is induced during filamentous growth of Saccharomyces cerevisiae. Pus1p catalyzes this modification and is up-regulated during filamentation. Several U6 snRNA mutants are strongly pseudouridylated at Ψ28; remarkably, these U6 mutants activate pseudo-hyphal growth, dependent upon Pus1p, arguing that U6-Ψ28 per se can initiate at least part of the filamentous growth program, a conclusion confirmed using a designer snoRNA targeting U6-U28 pseudouridylation. Conversely, mutants that block U6-U28 pseudouridylation inhibit pseudo-hyphal growth. U6-U28 pseudouridylation changes the efficiency of splicing of suboptimal introns; thus, Pus1p-dependent pseudouridylation of U6 snRNA contributes to the filamentation growth program. PMID:25127136

  18. Molecular dynamics studies of U1A-RNA complexes.

    PubMed Central

    Reyes, C M; Kollman, P A

    1999-01-01

    The U1A protein binds to a hairpin RNA and an internal-loop RNA with picomolar affinities. To probe the molecular basis of U1A binding, we performed state-of-the-art nanosecond molecular dynamics simulations on both complexes. The good agreement with experimental structures supports the protocols used in the simulations. We compare the dynamics, hydrogen-bonding occupancies, and interfacial flexibility of both complexes and also describe a rigid-body motion in the U1A-internal loop complex that is not observed in the U1A-hairpin simulation. We relate these observations to experimental mutational studies and highlight their significance in U1A binding affinity and specificity. PMID:10024175

  19. Repair of rhodopsin mRNA by spliceosome-mediated RNA trans-splicing: a new approach for autosomal dominant retinitis pigmentosa.

    PubMed

    Berger, Adeline; Lorain, Stéphanie; Joséphine, Charlène; Desrosiers, Melissa; Peccate, Cécile; Voit, Thomas; Garcia, Luis; Sahel, José-Alain; Bemelmans, Alexis-Pierre

    2015-05-01

    The promising clinical results obtained for ocular gene therapy in recent years have paved the way for gene supplementation to treat recessively inherited forms of retinal degeneration. The situation is more complex for dominant mutations, as the toxic mutant gene product must be removed. We used spliceosome-mediated RNA trans-splicing as a strategy for repairing the transcript of the rhodopsin gene, the gene most frequently mutated in autosomal dominant retinitis pigmentosa. We tested 17 different molecules targeting the pre-mRNA intron 1, by transient transfection of HEK-293T cells, with subsequent trans-splicing quantification at the transcript level. We found that the targeting of some parts of the intron promoted trans-splicing more efficiently than the targeting of other areas, and that trans-splicing rate could be increased by modifying the replacement sequence. We then developed cell lines stably expressing the rhodopsin gene, for the assessment of phenotypic criteria relevant to the pathogenesis of retinitis pigmentosa. Using this model, we showed that trans-splicing restored the correct localization of the protein to the plasma membrane. Finally, we tested our best candidate by AAV gene transfer in a mouse model of retinitis pigmentosa that expresses a mutant allele of the human rhodopsin gene, and demonstrated the feasibility of trans-splicing in vivo. This work paves the way for trans-splicing gene therapy to treat retinitis pigmentosa due to rhodopsin gene mutation and, more generally, for the treatment of genetic diseases with dominant transmission.

  20. Structural Basis of Brr2-Prp8 Interactions and Implications for U5 snRNP Biogenesis and the Spliceosome Active Site

    PubMed Central

    Nguyen, Thi Hoang Duong; Li, Jade; Galej, Wojciech P.; Oshikane, Hiroyuki; Newman, Andrew J.; Nagai, Kiyoshi

    2013-01-01

    Summary The U5 small nuclear ribonucleoprotein particle (snRNP) helicase Brr2 disrupts the U4/U6 small nuclear RNA (snRNA) duplex and allows U6 snRNA to engage in an intricate RNA network at the active center of the spliceosome. Here, we present the structure of yeast Brr2 in complex with the Jab1/MPN domain of Prp8, which stimulates Brr2 activity. Contrary to previous reports, our crystal structure and mutagenesis data show that the Jab1/MPN domain binds exclusively to the N-terminal helicase cassette. The residues in the Jab1/MPN domain, whose mutations in human Prp8 cause the degenerative eye disease retinitis pigmentosa, are found at or near the interface with Brr2, clarifying its molecular pathology. In the cytoplasm, Prp8 forms a precursor complex with U5 snRNA, seven Sm proteins, Snu114, and Aar2, but after nuclear import, Brr2 replaces Aar2 to form mature U5 snRNP. Our structure explains why Aar2 and Brr2 are mutually exclusive and provides important insights into the assembly of U5 snRNP. PMID:23727230

  1. An SC35-like protein and a novel serine/arginine-rich protein interact with Arabidopsis U1-70K protein.

    PubMed

    Golovkin, M; Reddy, A S

    1999-12-17

    The U1 small nuclear ribonucleoprotein 70-kDa protein, a U1 small nuclear ribonucleoprotein-specific protein, has been shown to have multiple roles in nuclear precursor mRNA processing in animals. By using the C-terminal arginine-rich region of Arabidopsis U1-70K protein in the yeast two-hybrid system, we have identified an SC35-like (SR33) and a novel plant serine/arginine-rich (SR) protein (SR45) that interact with the plant U1-70K. The SR33 and SR45 proteins share several features with SR proteins including modular domains typical of splicing factors in the SR family of proteins. However, both plant SR proteins are rich in proline, and SR45, unlike most animal SR proteins, has two distinct arginine/serine-rich domains separated by an RNA recognition motif. By using coprecipitation assays we confirmed the interaction of plant U1-70K with SR33 and SR45 proteins. Furthermore, in vivo and in vitro protein-protein interaction experiments have shown that SR33 protein interacts with itself and with SR45 protein but not with two other members (SRZ21 and SRZ22) of the SR family that are known to interact with the Arabidopsis full-length U-70K only. A Clk/Sty protein kinase (AFC-2) from Arabidopsis phosphorylated four SR proteins (SR33, SR45, SRZ21, and SRZ22). Coprecipitation studies have confirmed the interaction of SR proteins with AFC2 kinase, and the interaction between AFC2 and SR33 is modulated by the phosphorylation status of these proteins. These and our previous results suggest that the plant U1-70K interacts with at least four distinct members of the SR family including SR45 with its two arginine/serine-rich domains, and the interaction between the SR proteins and AFC2 is modulated by phosphorylation. The interaction of plant U1-70K with a novel set of proteins suggests the early stages of spliceosome assembly, and intron recognition in plants is likely to be different from animals. PMID:10593939

  2. Gauge U(1) dark symmetry and radiative light fermion masses

    NASA Astrophysics Data System (ADS)

    Kownacki, Corey; Ma, Ernest

    2016-09-01

    A gauge U (1) family symmetry is proposed, spanning the quarks and leptons as well as particles of the dark sector. The breaking of U (1) to Z2 divides the two sectors and generates one-loop radiative masses for the first two families of quarks and leptons, as well as all three neutrinos. We study the phenomenological implications of this new connection between family symmetry and dark matter. In particular, a scalar or pseudoscalar particle associated with this U (1) breaking may be identified with the 750 GeV diphoton resonance recently observed at the Large Hadron Collider (LHC).

  3. F-GUTs with Mordell-Weil U (1)'s

    NASA Astrophysics Data System (ADS)

    Antoniadis, I.; Leontaris, G. K.

    2014-07-01

    In this note we study the constraints on F-theory GUTs with extra U (1)'s in the context of elliptic fibrations with rational sections. We consider the simplest case of one abelian factor (Mordell-Weil rank one) and investigate the conditions that are induced on the coefficients of its Tate form. Converting the equation representing the generic hypersurface P112 to this Tate's form we find that the presence of a U (1), already in this local description, is consistent with the exceptional E6 and E7 non-abelian singularities. We briefly comment on a viable E6 × U (1) effective F-theory model.

  4. Efficient expression of protein coding genes from the murine U1 small nuclear RNA promoters.

    PubMed Central

    Bartlett, J S; Sethna, M; Ramamurthy, L; Gowen, S A; Samulski, R J; Marzluff, W F

    1996-01-01

    Few promoters are active at high levels in all cells. Of these, the majority encode structural RNAs transcribed by RNA polymerases I or III and are not accessible for the expression of proteins. An exception are the small nuclear RNAs (snRNAs) transcribed by RNA polymerase II. Although snRNA biosynthesis is unique and thought not to be compatible with synthesis of functional mRNA, we have tested these promoters for their ability to express functional mRNAs. We have used the murine U1a and U1b snRNA gene promoters to express the Escherichia coli lacZ gene and the human alpha-globin gene from either episomal or integrated templates by transfection, or infection into a variety of mammalian cell types. Equivalent expression of beta-galactosidase was obtained from < 250 nucleotides of 5'-flanking sequence containing the complete promoter of either U1 snRNA gene or from the 750-nt cytomegalovirus promoter and enhancer regions. The mRNA was accurately initiated at the U1 start site, efficiently spliced and polyadenylylated, and localized to polyribosomes. Recombinant adenovirus containing the U1b-lacZ chimeric gene transduced and expressed beta-galactosidase efficiently in human 293 cells and airway epithelial cells in culture. Viral vectors containing U1 snRNA promoters may be an attractive alternative to vectors containing viral promoters for persistent high-level expression of therapeutic genes or proteins. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8799116

  5. The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation

    PubMed Central

    Absmeier, Eva; Wollenhaupt, Jan; Mozaffari-Jovin, Sina; Becke, Christian; Lee, Chung-Tien; Preussner, Marco; Heyd, Florian; Urlaub, Henning; Lührmann, Reinhard; Santos, Karine F.; Wahl, Markus C.

    2015-01-01

    The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6•U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 di-snRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation. PMID:26637280

  6. Alternative pre-mRNA splicing in Drosophila spliceosomal assembly factor RNP-4F during development.

    PubMed

    Fetherson, Rebecca A; Strock, Stephen B; White, Kristen N; Vaughn, Jack C

    2006-04-26

    The 5'- and 3'-UTR regions in pre-mRNAs play a variety of roles in controlling eukaryotic gene expression, including translational modulation. Here we report the results of a systematic study of alternative splicing in rnp-4f, which encodes a Drosophila spliceosomal assembly factor. We show that most of the nine introns are constitutively spliced, but several patterns of alternative splicing are observed in two pre-mRNA regions including the 5'-UTR. Intron V is shown to be of recent evolutionary origin and is infrequently spliced, resulting in generation of an in-frame stop codon and a predicted truncated protein lacking a nuclear localization signal, so that alternative splicing regulates its subcellular localization. Intron 0, located in the 5'-UTR, is subject to three different splicing decisions in D. melanogaster. Northern analysis of poly(A+) mRNAs reveals two differently sized rnp-4f mRNA isoforms in this species. A switch in relative isoform abundance occurs during mid-embryo stages, when the larger isoform becomes more abundant. This isoform is shown to represent intron 0 unspliced mRNA, whereas the smaller transcript represents the product of alternative splicing. Comparative genomic analysis predicts that intron 0 is present in diverse Drosophila species. Intron 0 splicing results in loss of an evolutionarily conserved stem-loop constituting a potential cis-regulatory element at the 3'-splice site. A model is proposed for the role of this element both in 5'-UTR alternative splicing decisions and in RNP-4F translational modulation. Preliminary evidences in support of our model are discussed.

  7. Simple U (1 ) gauge theory explanation of the diphoton excess

    NASA Astrophysics Data System (ADS)

    Chang, Spencer

    2016-03-01

    The recent ATLAS and CMS diphoton resonance excesses are explored in a simple U (1 ) gauge theory extension of the Standard Model where the resonance is the Higgs boson of the U (1 ) symmetry breaking, ϕ . This particle couples to exotic quarks which, through loops, can produce a large enough rate to explain the excess. Due to the choice of U (1 ) charges, flavor constraints are naturally suppressed, allowing arbitrary flavor violation in the decays of the new quarks to up-type quarks, modifying their signal topologies. An additional heavy quark in the model decays to the lighter exotic quark by emitting either ϕ or the U (1 ) gauge boson Ax, giving extra signals containing diphoton and digluon resonances. Finally, the new Higgs can decay into γ Ax and Z Ax, followed by Ax decaying into Standard Model fermions through kinetic mixing. Thus, this model gives interesting modified signals to the general class of exotic quark models explaining the diphoton resonance.

  8. Underground storage tank 291-D1U1: Closure plan

    SciTech Connect

    Mancieri, S.; Giuntoli, N.

    1993-09-01

    The 291-D1U1 tank system was installed in 1983 on the north side of Building 291. It supplies diesel fuel to the Building 291 emergency generator and air compressor. The emergency generator and air compressor are located southwest and southeast, respectively, of the tank (see Appendix B, Figure 2). The tank system consists of a single-walled, 2,000- gallon, fiberglass tank and a fuel pump system, fill pipe, vent pipe, electrical conduit, and fuel supply and return piping. The area to be excavated is paved with asphalt and concrete. It is not known whether a concrete anchor pad is associated with this tank. Additionally, this closure plan assumes that the diesel tank is below the fill pad. The emergency generator and air compressor for Building 291 and its associated UST, 291-D1U1, are currently in use. The generator and air compressor will be supplied by a temporary above-ground fuel tank prior to the removal of 291-D1U1. An above-ground fuel tank will be installed as a permanent replacement for 291-D1U1. The system was registered with the State Water Resources Control Board on June 27, 1984, as 291-41D and has subsequently been renamed 291-D1U1. Figure 1 (see Appendix B) shows the location of the 291-D1U1 tank system in relation to the Lawrence Livermore National Laboratory (LLNL). Figure 2 (see Appendix B) shows the 291-D1U1 tank system in relation to Building 291. Figure 3 (see Appendix B) shows a plan view of the 291-D1U1 tank system.

  9. Cloning of the cDNA for U1 small nuclear ribonucleoprotein particle 70K protein from Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Reddy, A. S.; Czernik, A. J.; An, G.; Poovaiah, B. W.

    1992-01-01

    We cloned and sequenced a plant cDNA that encodes U1 small nuclear ribonucleoprotein (snRNP) 70K protein. The plant U1 snRNP 70K protein cDNA is not full length and lacks the coding region for 68 amino acids in the amino-terminal region as compared to human U1 snRNP 70K protein. Comparison of the deduced amino acid sequence of the plant U1 snRNP 70K protein with the amino acid sequence of animal and yeast U1 snRNP 70K protein showed a high degree of homology. The plant U1 snRNP 70K protein is more closely related to the human counter part than to the yeast 70K protein. The carboxy-terminal half is less well conserved but, like the vertebrate 70K proteins, is rich in charged amino acids. Northern analysis with the RNA isolated from different parts of the plant indicates that the snRNP 70K gene is expressed in all of the parts tested. Southern blotting of genomic DNA using the cDNA indicates that the U1 snRNP 70K protein is coded by a single gene.

  10. Dirac-fermionic dark matter in U(1)X models

    NASA Astrophysics Data System (ADS)

    Alves, Alexandre; Berlin, Asher; Profumo, Stefano; Queiroz, Farinaldo S.

    2015-10-01

    We study a number of U(1)X models featuring a Dirac fermion dark matter particle. We perform a comprehensive analysis which includes the study of corrections to the muon magnetic moment, dilepton searches with LHC data, as well as direct and indirect dark matter detection constraints. We consider four different coupling structures, namely U(1) B-L , U(1) d-u , U(1)universal, and U{(1)}_{10+overline{5}} , all motivated by compelling extensions to the standard model. We outline the viable and excluded regions of parameter space using a large set of probes. Our key findings are that (i) the combination of direct detection and collider constraints rule out dark matter particle masses lighter than ˜ 1 TeV, unless rather suppressed Z '-fermion couplings exist, and that (ii) for several of the models under consideration, collider constraints rule out Z ' masses up to ˜ 3 TeV. Lastly, we show that we can accommodate the recent Diboson excess reported by ATLAS collaboration within the U(1) d- u model.

  11. Effective string action for the /U(1U(1) dual Ginzburg-Landau theory beyond the London limit

    NASA Astrophysics Data System (ADS)

    Koma, Yoshiaki; Koma, Miho; Ebert, Dietmar; Toki, Hiroshi

    2003-01-01

    The effective string action of the color-electric flux tube in the U(1U(1) dual Ginzburg-Landau (DGL) theory is studied by performing a path-integral analysis by taking into account the finite thickness of the flux tube. The DGL theory, corresponding to the low-energy effective theory of Abelian-projected SU(3) gluodynamics, can be expressed as a [U(1)] 3 dual Abelian Higgs (DAH) model with a certain constraint in the Weyl symmetric formulation. This formulation allows us to adopt quite similar path-integral techniques as in the U(1) DAH model, and therefore, the resulting effective string action in the U(1U(1) DGL theory has also quite a similar structure except the number of color degrees of freedom. A modified Yukawa interaction appears as a boundary contribution, which is completely due to the finite thickness of the flux tube, and is reduced into the ordinary Yukawa interaction in the deep type-II (London) limit.

  12. Haploinsufficiency of SF3B4, a Component of the Pre-mRNA Spliceosomal Complex, Causes Nager Syndrome

    PubMed Central

    Bernier, Francois P.; Caluseriu, Oana; Ng, Sarah; Schwartzentruber, Jeremy; Buckingham, Kati J.; Innes, A. Micheil; Jabs, Ethylin Wang; Innis, Jeffrey W.; Schuette, Jane L.; Gorski, Jerome L.; Byers, Peter H.; Andelfinger, Gregor; Siu, Victoria; Lauzon, Julie; Fernandez, Bridget A.; McMillin, Margaret; Scott, Richard H.; Racher, Hilary; Majewski, Jacek; Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael J.; Parboosingh, Jillian S.

    2012-01-01

    Nager syndrome, first described more than 60 years ago, is the archetype of a class of disorders called the acrofacial dysostoses, which are characterized by craniofacial and limb malformations. Despite intensive efforts, no gene for Nager syndrome has yet been identified. In an international collaboration, FORGE Canada and the National Institutes of Health Centers for Mendelian Genomics used exome sequencing as a discovery tool and found that mutations in SF3B4, a component of the U2 pre-mRNA spliceosomal complex, cause Nager syndrome. After Sanger sequencing of SF3B4 in a validation cohort, 20 of 35 (57%) families affected by Nager syndrome had 1 of 18 different mutations, nearly all of which were frameshifts. These results suggest that most cases of Nager syndrome are caused by haploinsufficiency of SF3B4. Our findings add Nager syndrome to a growing list of disorders caused by mutations in genes that encode major components of the spliceosome and also highlight the synergistic potential of international collaboration when exome sequencing is applied in the search for genes responsible for rare Mendelian phenotypes. PMID:22541558

  13. RNA11 protein is associated with the yeast spliceosome and is localized in the periphery of the cell nucleus.

    PubMed Central

    Chang, T H; Clark, M W; Lustig, A J; Cusick, M E; Abelson, J

    1988-01-01

    The yeast rna mutations (rna2 through rna10/11) are a set of temperature-sensitive mutations that result in the accumulation of pre-mRNAs at the nonpermissive temperature. Most of the yeast RNA gene products are involved in and essential for mRNA splicing in vitro, suggesting that they code for components of the splicing machinery. We tested this proposal by using an in vitro-synthesized RNA11 protein to complement the temperature-sensitive defect of the rna11 extract. During the in vitro complementation, the input RNA11 protein was associated with the 40S spliceosome and a 30S complex, suggesting that the RNA11 protein is indeed a component of the spliceosome. The formation of the RNA11-associated 30S complex did not require any exogenous RNA substrate, suggesting that this 30S particle is likely to be a preassembled complex involved in splicing. The RNA11-specific antibody inhibited the mRNA splicing in vitro, confirming the essential role of the RNA11 protein in mRNA splicing. Finally, using the anti-RNA11 antibody, we localized the RNA11 protein to the periphery of the yeast nucleus. Images PMID:3043176

  14. Genetic interaction mapping reveals a role for the SWI/SNF nucleosome remodeler in spliceosome activation in fission yeast.

    PubMed

    Patrick, Kristin L; Ryan, Colm J; Xu, Jiewei; Lipp, Jesse J; Nissen, Kelly E; Roguev, Assen; Shales, Michael; Krogan, Nevan J; Guthrie, Christine

    2015-03-01

    Although numerous regulatory connections between pre-mRNA splicing and chromatin have been demonstrated, the precise mechanisms by which chromatin factors influence spliceosome assembly and/or catalysis remain unclear. To probe the genetic network of pre-mRNA splicing in the fission yeast Schizosaccharomyces pombe, we constructed an epistatic mini-array profile (E-MAP) and discovered many new connections between chromatin and splicing. Notably, the nucleosome remodeler SWI/SNF had strong genetic interactions with components of the U2 snRNP SF3 complex. Overexpression of SF3 components in ΔSWI/SNF cells led to inefficient splicing of many fission yeast introns, predominantly those with non-consensus splice sites. Deletion of SWI/SNF decreased recruitment of the splicing ATPase Prp2, suggesting that SWI/SNF promotes co-transcriptional spliceosome assembly prior to first step catalysis. Importantly, defects in SWI/SNF as well as SF3 overexpression each altered nucleosome occupancy along intron-containing genes, illustrating that the chromatin landscape both affects--and is affected by--co-transcriptional splicing.

  15. Phenomenological implications of supersymmetric family nonuniversal U(1){sup '} models

    SciTech Connect

    Everett, Lisa L.; Jiang Jing; Langacker, Paul G.; Liu Tao

    2010-11-01

    We construct a class of anomaly-free supersymmetric U(1){sup '} models that are characterized by family nonuniversal U(1){sup '} charges motivated from E{sub 6} embeddings. The family nonuniversality arises from an interchange of the standard roles of the two SU(5) 5{sup *} representations within the 27 of E{sub 6} for the third generation. We analyze U(1){sup '} and electroweak symmetry breaking and present the particle mass spectrum. The models, which include additional Higgs multiplets and exotic quarks at the TeV scale, result in specific patterns of flavor-changing neutral currents in the b{yields}s transitions that can accommodate the presently observed deviations in this sector from the standard model predictions.

  16. Inflationary magnetogenesis with broken local U(1) symmetry

    NASA Astrophysics Data System (ADS)

    Domènech, Guillem; Lin, Chunshan; Sasaki, Misao

    2016-07-01

    We point out that a successful inflationary magnetogenesis could be realised if we break the local U(1) gauge symmetry during inflation. The effective electric charge is fixed as a fundamental constant, which allows us to obtain an almost scale-invariant magnetic spectrum avoiding both the strong coupling and back reaction problems. We examine the corrections to the primordial curvature perturbation due to these stochastic electromagnetic fields and find that, at both linear and non-linear orders, the contributions from the electromagnetic field are negligible compared to those created from vacuum fluctuations. Finally, the U(1) gauge symmetry is restored at the end of inflation.

  17. Strong Phase Transition within the U(1)-extended MSSM

    SciTech Connect

    Ahriche, Amine

    2010-10-31

    In this work, the electroweak phase transition (EWPT) strength has been investigated within the U(1) extended Minimal Supersymmetric Standard Model (UMSSM) without introducing any exotic fields. We found that the EWPT could be strongly first order for reasonable values of the lightest Higgs and neutralino masses.

  18. Progressive gauge U(1) family symmetry for quarks and leptons

    NASA Astrophysics Data System (ADS)

    Ma, Ernest

    2016-08-01

    The pattern of quark and lepton mass matrices is unexplained in the standard model of particle interactions. I propose the novel idea of a progressive gauge U (1 ) symmetry where it is a reflection of the regressive electroweak symmetry breaking pattern, caused by an extended Higgs scalar sector. Phenomenological implications of this new hypothesis are discussed.

  19. Underground storage tank 511-D1U1 closure plan

    SciTech Connect

    Mancieri, S.; Giuntoli, N.

    1993-09-01

    This document contains the closure plan for diesel fuel underground storage tank 511-D1U1 and appendices containing supplemental information such as staff training certification and task summaries. Precision tank test data, a site health and safety plan, and material safety data sheets are also included.

  20. Time-Reversal Symmetric U (1 ) Quantum Spin Liquids

    NASA Astrophysics Data System (ADS)

    Wang, Chong; Senthil, T.

    2016-01-01

    We study possible quantum U (1 ) spin liquids in three dimensions with time-reversal symmetry. We find a total of seven families of such U (1 ) spin liquids, distinguished by the properties of their emergent electric or magnetic charges. We show how these spin liquids are related to each other. Two of these classes admit nontrivial protected surface states which we describe. We show how to access all of the seven spin liquids through slave particle (parton) constructions. We also provide intuitive loop gas descriptions of their ground-state wave functions. One of these phases is the "topological Mott insulator," conventionally described as a topological insulator of an emergent fermionic "spinon." We show that this phase admits a remarkable dual description as a topological insulator of emergent fermionic magnetic monopoles. This results in a new (possibly natural) surface phase for the topological Mott insulator and a new slave particle construction. We describe some of the continuous quantum phase transitions between the different U (1 ) spin liquids. Each of these seven families of states admits a finer distinction in terms of their surface properties, which we determine by combining these spin liquids with symmetry-protected topological phases. We discuss lessons for materials such as pyrochlore quantum spin ices which may harbor a U (1 ) spin liquid. We suggest the topological Mott insulator as a possible ground state in some range of parameters for the quantum spin ice Hamiltonian.

  1. Underground storage tank 431-D1U1, Closure Plan

    SciTech Connect

    Mancieri, S.

    1993-09-01

    This document contains information about the decommissioning of Tank 431-D1U1. This tank was installed in 1965 for diesel fuel storage. This tank will remain in active usage until closure procedures begin. Soils and ground water around the tank will be sampled to check for leakage. Appendices include; proof of proper training for workers, health and safety briefing record, task hazard analysis summary, and emergency plans.

  2. Fermions in the U(1) Y hypercharge theory

    NASA Astrophysics Data System (ADS)

    Lee, I.-Hsiu

    1991-05-01

    The U(1) Y hypercharge sector of the standard electroweak theory is studied on the lattice. It is shown that, for fermions with both nonsinglet ψL and ψR, the doubler modes can be removed in the continuum limit while the masses of the physical fermions can be tuned appropriately. Data from simulations will be discussed and compared with recent analytic calculations.

  3. Compact F-theory GUTs with U(1)PQ

    NASA Astrophysics Data System (ADS)

    Marsano, Joseph; Saulina, Natalia; Schäfer-Nameki, Sakura

    2010-04-01

    We construct semi-local and global realizations of SU(5) GUTs in F-theory that utilize a U(1)PQ symmetry to protect against dimension four proton decay. Symmetries of this type, which assign charges to H u and H d that forbid a tree level μ term, play an important role in scenarios for neutrino physics and gauge mediation that have been proposed in local F-theory model building. As demonstrated in [1], the presence of such a symmetry implies the existence of non-GUT exotics in the spectrum, when hypercharge flux is used to break the GUT group and to give rise to doublet-triplet splitting. These exotics are of precisely the right type to solve the unification problem in such F-theory models and might also comprise a non-standard messenger sector for gauge mediation. We present a detailed description of models with U(1)PQ in the semi-local regime, which does not depend on details of any specific Calabi-Yau four-fold, and then specialize to the geometry of [2] to construct three-generation examples with the minimal allowed number of non-GUT exotics. Among these, we find a handful of models in which the D3-tadpole constraint can be satisfied without requiring the introduction of anti-D3-branes, though this analysis does not incorporate contributions from additional fluxes that will ultimately be needed for moduli stabilization. Finally, because SU(5) singlets that carry U(1)PQ charge may serve as candidate right-handed neutrinos or can be used to lift the exotics, we study their origin in compact models and motivate a conjecture for how to count their zero modes in a semi-local setting.

  4. Entanglement entropy of U (1) quantum spin liquids

    NASA Astrophysics Data System (ADS)

    Pretko, Michael; Senthil, T.

    2016-09-01

    We here investigate the entanglement structure of the ground state of a (3 +1 )-dimensional U (1 ) quantum spin liquid, which is described by the deconfined phase of a compact U (1 ) gauge theory. A gapless photon is the only low-energy excitation, with matter existing as deconfined but gapped excitations of the system. It is found that, for a given bipartition of the system, the elements of the entanglement spectrum can be grouped according to the electric flux between the two regions, leading to a useful interpretation of the entanglement spectrum in terms of electric charges living on the boundary. The entanglement spectrum is also given additional structure due to the presence of the gapless photon. Making use of the Bisognano-Wichmann theorem and a local thermal approximation, these two contributions to the entanglement (particle and photon) are recast in terms of boundary and bulk contributions, respectively. Both pieces of the entanglement structure give rise to universal subleading terms (relative to the area law) in the entanglement entropy, which are logarithmic in the system size (logL ), as opposed to the subleading constant term in gapped topologically ordered systems. The photon subleading logarithm arises from the low-energy conformal field theory and is essentially local in character. The particle subleading logarithm arises due to the constraint of closed electric loops in the wave function and is shown to be the natural generalization of topological entanglement entropy to the U (1 ) spin liquid. This contribution to the entanglement entropy can be isolated by means of the Grover-Turner-Vishwanath construction (which generalizes the Kitaev-Preskill scheme to three dimensions).

  5. At the origin of spliceosomal introns: Is multiplication of introner-like elements the main mechanism of intron gain in fungi?

    PubMed

    Collemare, Jérôme; van der Burgt, Ate; de Wit, Pierre J G M

    2013-03-01

    The recent discovery of introner-like elements (ILEs) in six fungal species shed new light on the origin of regular spliceosomal introns (RSIs) and the mechanism of intron gains. These novel spliceosomal introns are found in hundreds of copies, are longer than RSIs and harbor stable predicted secondary structures. Yet, they are prone to degeneration in sequence and length to become undistinguishable from RSIs, suggesting that ILEs are predecessors of most RSIs. In most fungi, other near-identical introns were found duplicated in lower numbers in the same gene or in unrelated genes, indicating that intron duplication is a widespread phenomenon. However, ILEs are associated with the majority of intron gains, suggesting that the other types of duplication are of minor importance to the overall gains of introns. Our data support the hypothesis that ILEs' multiplication corresponds to the main mechanism of intron gain in fungi.

  6. Electroweak phase transition in the U(1)' MSSM

    NASA Astrophysics Data System (ADS)

    Ahriche, Amine; Nasri, Salah

    2011-02-01

    In this work, we have investigated the nature of the electroweak phase transition in the U(1) extended minimal supersymmetric standard model without introducing any exotic fields. The effective potential has been estimated exactly at finite temperature taking into account the whole particle spectrum. For reasonable values of the lightest Higgs and neutralino, we found that the electroweak phase transition could be strongly first order due to: (1) the interactions of the singlet with the doublets in the effective potential, and (2) the evolution of the wrong vacuum that delays the transition.

  7. Higgs Bosons in the NMSSM and its U(1) Extensions

    SciTech Connect

    Gunion, John F.

    2008-11-23

    I specify the characteristics of a Higgs boson that would be 'ideal' in the light of current data and theoretical attractiveness. I then review why it is that the Higgs bosons of the Standard Model and the Minimal Supersymmetric Model cannot be ideal whereas the lightest Higgs boson of the Next to Minimal Supersymmetric Model can be ideal. Experimental consequences for Higgs and supersymmetry discovery are then reviewed. I then examine the alternatives to the NMSSM in which the MSSM is extended via an extra U(1) symmetry.

  8. Electroweak phase transition in the U(1){sup '} MSSM

    SciTech Connect

    Ahriche, Amine; Nasri, Salah

    2011-02-15

    In this work, we have investigated the nature of the electroweak phase transition in the U(1) extended minimal supersymmetric standard model without introducing any exotic fields. The effective potential has been estimated exactly at finite temperature taking into account the whole particle spectrum. For reasonable values of the lightest Higgs and neutralino, we found that the electroweak phase transition could be strongly first order due to: (1) the interactions of the singlet with the doublets in the effective potential, and (2) the evolution of the wrong vacuum that delays the transition.

  9. Regular spliceosomal introns are invasive in Chlamydomonas reinhardtii: 15 introns in the recently relocated mitochondrial cox2 and cox3 genes.

    PubMed

    Watanabe, K I; Ohama, T

    2001-01-01

    In the unicellular green alga, Chlamydomonas reinhardtii, cytochrome oxidase subunit 2 (cox2) and 3 (cox3) genes are missing from the mitochondrial genome. We isolated and sequenced a BAC clone that carries the whole cox3 gene and its corresponding cDNA. Almost the entire cox2 gene and its cDNA were also determined. Comparison of the genomic and the corresponding cDNA sequences revealed that the cox3 gene contains as many as nine spliceosomal introns and that cox2 bears six introns. Putative mitochondria targeting signals were predicted at each N terminal of the cox genes. These spliceosomal introns were typical GT-AG-type introns, which are very common not only in Chlamydomonas nuclear genes but also in diverse eukaryotic taxa. We found no particular distinguishing features in the cox introns. Comparative analysis of these genes with the various mitochondrial genes showed that 8 of the 15 introns were interrupting the conserved mature protein coding segments, while the other 7 introns were located in the N-terminal target peptide regions. Phylogenetic analysis of the evolutionary position of C. reinhardtii in Chlorophyta was carried out and the existence of the cox2 and cox3 genes in the mitochondrial genome was superimposed in the tree. This analysis clearly shows that these cox genes were relocated during the evolution of Chlorophyceae. It is apparent that long before the estimated period of relocation of these mitochondrial genes, the cytosol had lost the splicing ability for group II introns. Therefore, at least eight introns located in the mature protein coding region cannot be the direct descendant of group II introns. Here, we conclude that the presence of these introns is due to the invasion of spliceosomal introns, which occurred during the evolution of Chlorophyceae. This finding provides concrete evidence supporting the "intron-late" model, which rests largely on the mobility of spliceosomal introns. PMID:11675593

  10. Supersymmetric U(1){sup '} model with multiple dark matters

    SciTech Connect

    Hur, Taeil; Lee, Hye-Sung; Nasri, Salah

    2008-01-01

    We consider a scenario where a supersymmetric model has multiple dark matter particles. Adding a U(1){sup '} gauge symmetry is a well-motivated extension of the minimal supersymmetric standard model (MSSM). It can cure the problems of the MSSM such as the {mu} problem or the proton decay problem with high-dimensional lepton number and baryon number violating operators which R parity allows. An extra parity (U parity) may arise as a residual discrete symmetry after U(1){sup '} gauge symmetry is spontaneously broken. The lightest U-parity particle (LUP) is stable under the new parity becoming a new dark matter candidate. Up to three massive particles can be stable in the presence of the R parity and the U parity. We numerically illustrate that multiple stable particles in our model can satisfy both constraints from the relic density and the direct detection, thus providing a specific scenario where a supersymmetric model has well-motivated multiple dark matters consistent with experimental constraints. The scenario provides new possibilities in the present and upcoming dark matter searches in the direct detection and collider experiments.

  11. Wilson loops in noncompact U(1) gauge theories at criticality

    SciTech Connect

    Metlitski, Max A.

    2008-04-15

    We study the properties of Wilson loops in three-dimensional noncompact U(1) gauge theories with global Abelian symmetries. We use duality in the continuum and on the lattice to argue that, close to the critical point between the Higgs and Coulomb phases, all correlators of the Wilson loops are periodic functions of the Wilson loop charge, Q. The period depends on the global symmetry of the theory, which determines the magnetic flux carried by the dual particles. For single flavor scalar electrodynamics, the emergent period is Q=1. In the general case of N complex scalars with a U(1){sup N-1} global symmetry, the period is Q=N. We also give some arguments why this phenomenon does not generalize to theories with a full non-Abelian SU(N) symmetry, where no periodicity in Q is expected. Implications for lattice simulations, as well as for physical systems, such as easy-plane antiferromagnets and disordered superfluids, are noted.

  12. Littlest Seesaw model from S 4 × U(1)

    NASA Astrophysics Data System (ADS)

    King, Stephen F.; Luhn, Christoph

    2016-09-01

    We show how a minimal (littlest) seesaw model involving two right-handed neutrinos and a very constrained Dirac mass matrix, with one texture zero and two independent Dirac masses, may arise from S 4 ×U(1) symmetry in a semi-direct supersymmetric model. The resulting CSD3 form of neutrino mass matrix only depends on two real mass parameters plus one undetermined phase. We show how the phase may be fixed to be one of the cube roots of unity by extending the S 4 × U(1) symmetry to include a product of Z 3 factors together with a CP symmetry, which is spontaneously broken leaving a single residual Z 3 in the charged lepton sector and a residual Z 2 in the neutrino sector, with suppressed higher order corrections. With the phase chosen from the cube roots of unity to be -2π /3, the model predicts a normal neutrino mass hierarchy with m 1 = 0, reactor angle θ 13 = 8 .7°, solar angle θ 12 = 34°, atmospheric angle θ 23 = 44°, and CP violating oscillation phase δ CP = -93°, depending on the fit of the model to the neutrino masses.

  13. Cooperative binding of TIA-1 and U1 snRNP in K-SAM exon splicing activation

    SciTech Connect

    Gesnel, Marie-Claude; Theoleyre, Sandrine; Del Gatto-Konczak, Fabienne; Breathnach, Richard . E-mail: breathna@nantes.inserm.fr

    2007-07-13

    In 293 cells, splicing of the human fibroblast growth factor receptor-2 K-SAM alternative exon is inefficient, but can be made efficient by provoking TIA-1 binding to the U-rich IAS1 sequence downstream from the exon's 5' splice site. We show here that TIA-1 domains known to interact with U1 snRNP and to recruit it to 5' splice sites in vitro are required for TIA-1 activation of K-SAM exon splicing in vivo. We further show that tethering downstream from the K-SAM exon a fusion between the U1 snRNP component U1C and the bacteriophage MS2 coat protein provokes IAS1-dependent exon splicing, and present evidence that the fusion functions after its incorporation into U1 snRNP. Our in vivo data, taken together with previous in vitro results, show that K-SAM splicing activation involves cooperative binding of TIA-1 and U1 snRNP to the exon's 5' splice site region.

  14. A dominant negative mutation in the conserved RNA helicase motif 'SAT' causes splicing factor PRP2 to stall in spliceosomes.

    PubMed Central

    Plumpton, M; McGarvey, M; Beggs, J D

    1994-01-01

    To characterize sequences in the RNA helicase-like PRP2 protein of Saccharomyces cerevisiae that are essential for its function in pre-mRNA splicing, a pool of random PRP2 mutants was generated. A dominant negative allele was isolated which, when overexpressed in a wild-type yeast strain, inhibited cell growth by causing a defect in pre-mRNA splicing. This defect was partially alleviated by simultaneous co-overexpression of wild-type PRP2. The dominant negative PRP2 protein inhibited splicing in vitro and caused the accumulation of stalled splicing complexes. Immunoprecipitation with anti-PRP2 antibodies confirmed that dominant negative PRP2 protein competed with its wild-type counterpart for interaction with spliceosomes, with which the mutant protein remained associated. The PRP2-dn1 mutation led to a single amino acid change within the conserved SAT motif that in the prototype helicase eIF-4A is required for RNA unwinding. Purified dominant negative PRP2 protein had approximately 40% of the wild-type level of RNA-stimulated ATPase activity. As ATPase activity was reduced only slightly, but splicing activity was abolished, we propose that the dominant negative phenotype is due primarily to a defect in the putative RNA helicase activity of PRP2 protein. Images PMID:8112301

  15. Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis.

    PubMed

    Herold, Tobias; Metzeler, Klaus H; Vosberg, Sebastian; Hartmann, Luise; Röllig, Christoph; Stölzel, Friedrich; Schneider, Stephanie; Hubmann, Max; Zellmeier, Evelyn; Ksienzyk, Bianka; Jurinovic, Vindi; Pasalic, Zlatana; Kakadia, Purvi M; Dufour, Annika; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Sauerland, Maria Cristina; Büchner, Thomas; Berdel, Wolfgang E; Woermann, Bernhard J; Bornhäuser, Martin; Ehninger, Gerhard; Mansmann, Ulrich; Hiddemann, Wolfgang; Bohlander, Stefan K; Spiekermann, Karsten; Greif, Philipp A

    2014-08-21

    In acute myeloid leukemia (AML), isolated trisomy 13 (AML+13) is a rare chromosomal abnormality whose prognostic relevance is poorly characterized. We analyzed the clinical course of 34 AML+13 patients enrolled in the German AMLCG-1999 and SAL trials and performed exome sequencing, targeted candidate gene sequencing and gene expression profiling. Relapse-free (RFS) and overall survival (OS) of AML+13 patients were inferior compared to other ELN Intermediate-II patients (n=855) (median RFS, 7.8 vs 14.1 months, P = .006; median OS 9.3 vs. 14.8 months, P = .004). Besides the known high frequency of RUNX1 mutations (75%), we identified mutations in spliceosome components in 88%, including SRSF2 codon 95 mutations in 81%. Recurring mutations were detected in ASXL1 (44%) and BCOR (25%). Two patients carried mutations in CEBPZ, suggesting that CEBPZ is a novel recurrently mutated gene in AML. Gene expression analysis revealed a homogeneous expression profile including upregulation of FOXO1 and FLT3 and downregulation of SPRY2. This is the most comprehensive clinical and biological characterization of AML+13 to date, and reveals a striking clustering of lesions in a few genes, defining AML+13 as a genetically homogeneous subgroup with alterations in a few critical cellular pathways. Clinicaltrials.gov identifiers: AMLCG-1999: NCT00266136; AML96: NCT00180115; AML2003: NCT00180102; and AML60+: NCT00893373. PMID:24923295

  16. Pseudouridines in U2 snRNA stimulate the ATPase activity of Prp5 during spliceosome assembly.

    PubMed

    Wu, Guowei; Adachi, Hironori; Ge, Junhui; Stephenson, David; Query, Charles C; Yu, Yi-Tao

    2016-03-15

    Pseudouridine (Ψ) is the most abundant internal modification identified in RNA, and yet little is understood of its effects on downstream reactions. Yeast U2 snRNA contains three conserved Ψs (Ψ35, Ψ42, and Ψ44) in the branch site recognition region (BSRR), which base pairs with the pre-mRNA branch site during splicing. Here, we show that blocks to pseudouridylation at these positions reduce the efficiency of pre-mRNA splicing, leading to growth-deficient phenotypes. Restoration of pseudouridylation at these positions using designer snoRNAs results in near complete rescue of splicing and cell growth. These Ψs interact genetically with Prp5, an RNA-dependent ATPase involved in monitoring the U2 BSRR-branch site base-pairing interaction. Biochemical analysis indicates that Prp5 has reduced affinity for U2 snRNA that lacks Ψ42 and Ψ44 and that Prp5 ATPase activity is reduced when stimulated by U2 lacking Ψ42 or Ψ44 relative to wild type, resulting in inefficient spliceosome assembly. Furthermore, in vivo DMS probing analysis reveals that pseudouridylated U2, compared to U2 lacking Ψ42 and Ψ44, adopts a slightly different structure in the branch site recognition region. Taken together, our results indicate that the Ψs in U2 snRNA contribute to pre-mRNA splicing by directly altering the binding/ATPase activity of Prp5. PMID:26873591

  17. Minimal anomalous U(1){sup '} extension of the MSSM

    SciTech Connect

    Anastasopoulos, Pascal; Fucito, Francesco; Lionetto, Andrea; Pradisi, Gianfranco; Racioppi, Antonio; Stanev, Yassen S.

    2008-10-15

    We study an extension of the minimal supersymmetric standard model by an anomalous Abelian vector multiplet and a Stueckelberg multiplet. The anomalies are cancelled by the Green-Schwarz mechanism and the addition of Chern-Simons terms. The advantage of this choice over the standard one is that it allows for arbitrary values of the quantum numbers of the extra U(1). As a first step toward the study of hadron annihilations producing four leptons in the final state (a clean signal which might be studied at LHC), we then compute the decays Z{sup '}{yields}Z{sub 0}{gamma} and Z{sup '}{yields}Z{sub 0}Z{sub 0}. We find that the largest values of the decay rate are {approx}10{sup -4} GeV, while the expected number of events per year at LHC is at most of the order of 10.

  18. U(1) prime dark matter and R-parity violation

    SciTech Connect

    Brahm, D.E.

    1990-04-01

    Attempts to understand physics beyond the Standard Model must face many phenomenological constraint, from recent Z{sup {degree}} data, neutral current measurements, cosmology and astrophysics, neutrino experiments, tests of lepton-and baryon-number conservation and CP violation, and many other ongoing experiments. The most interesting models are those which are allowed by current data, but offer predictions which can soon be experimentally confirmed or refuted. Two classes of such models are explored in this dissertation. The first, containing an extra U(1){prime} gauge group, has a dark matter candidate which could soon be detected. The second, incorporating supersymmetry with R-parity violation, predicts rare Z{sup {degree}} decays at LEP; some of these models can already be ruled out by LEP data and gluino searches at the Tevatron. 54 refs., 31 figs.

  19. Gauge Invariant U(1) Field Theories with Magnetic Monopole Symmetry.

    NASA Astrophysics Data System (ADS)

    Goldman, Neil

    1982-03-01

    A quantum field theory of a magnetically and electrically charged fermion field is developed. This is done for an abelian duet of vector boson fields in a U(1), gauge invariant manner. The U(1) symmetry is maintained through a scalar field interacting with the boson fields. The gauge invariance is preserved by extending the Mandelstam path dependent method for electromagnetism. This is done without recourse to Dirac strings or solitons. Further, the energy momentum and angular momentum tensor operators are found explicitly in terms of path dependent variables. A two dimensional charge space is coupled invariantly with the vector boson duet preserving the symmetry of the fermion monopole interactions with the use of the axial vector current, avoiding explicit use of the dual field tensor terms. It is found that if the postulated symmetries are not broken, only part of the Lorentz force law's dual tensor interaction term emerges in the low energy first order in the coupling constant limit. If the mediating scalar field is in the Higg's gauge, the following constraint is found:. 2(pi)n = SQRT.(2m(,0)(lamda)/f, where n = 0, (+OR -)1, (+OR-)2...,. and m(,0) and f are the Higg's model parameters and (lamda) is the coupling constant for the vector boson fields with the scalar fields. The Feynman diagrams are found for the Green's functions in a path dependent, gauge invariant formulation. This situation leads to a specific model for studying the scalar mediating field from a vacuum point of view, and for future work, by breaking the symmetry with the fermion field interaction.

  20. U(1U(1)⋊Z2 Chern-Simons theory and Z4 parafermion fractional quantum Hall states

    NASA Astrophysics Data System (ADS)

    Barkeshli, Maissam; Wen, Xiao-Gang

    2010-01-01

    We study U(1U(1)⋊Z2 Chern-Simons theory with integral coupling constants (k,l) and its relation to certain non-Abelian fractional quantum Hall (FQH) states. For the U(1U(1)⋊Z2 Chern-Simons theory, we show how to compute the dimension of its Hilbert space on genus g surfaces and how this yields the quantum dimensions of topologically distinct excitations. We find that Z2 vortices in the U(1U(1)⋊Z2 Chern-Simons theory carry non-Abelian statistics and we show how to compute the dimension of the Hilbert space in the presence of n pairs of Z2 vortices on a sphere. These results allow us to show that l=3 U(1U(1)⋊Z2 Chern-Simons theory is the low-energy effective theory for the Z4 parafermion (Read-Rezayi) fractional quantum Hall states, which occur at filling fraction ν=(2)/(2k-3) . The U(1U(1)⋊Z2 theory is more useful than an alternative SU(2)4×U(1)/U(1) Chern-Simons theory because the fields are more closely related to physical degrees of freedom of the electron fluid and to an Abelian bilayer phase on the other side of a two-component to single-component quantum phase transition. We discuss the possibility of using this theory to understand further phase transitions in FQH systems, especially the ν=2/3 phase diagram.

  1. Aggregation Properties of the Small Nuclear Ribonucleoprotein U1-70K in Alzheimer Disease*

    PubMed Central

    Diner, Ian; Hales, Chadwick M.; Bishof, Isaac; Rabenold, Lake; Duong, Duc M.; Yi, Hong; Laur, Oskar; Gearing, Marla; Troncoso, Juan; Thambisetty, Madhav; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.

    2014-01-01

    Recent evidence indicates that U1-70K and other U1 small nuclear ribonucleoproteins are Sarkosyl-insoluble and associate with Tau neurofibrillary tangles selectively in Alzheimer disease (AD). Currently, the mechanisms underlying the conversion of soluble nuclear U1 small nuclear ribonucleoproteins into insoluble cytoplasmic aggregates remain elusive. Based on the biochemical and subcellular distribution properties of U1-70K in AD, we hypothesized that aggregated U1-70K itself or other biopolymers (e.g. proteins or nucleic acids) interact with and sequester natively folded soluble U1-70K into insoluble aggregates. Here, we demonstrate that total homogenates from AD brain induce soluble U1-70K from control brain or recombinant U1-70K to become Sarkosyl-insoluble. This effect was not dependent on RNA and did not correlate with detergent-insoluble Tau levels as AD homogenates with reduced levels of these components were still capable of inducing U1-70K aggregation. In contrast, proteinase K-treated AD homogenates and Sarkosyl-soluble AD fractions were unable to induce U1-70K aggregation, indicating that aggregated proteins in AD brain are responsible for inducing soluble U1-70K aggregation. It was determined that the C terminus of U1-70K, which harbors two disordered low complexity (LC) domains, is necessary for U1-70K aggregation. Moreover, both LC1 and LC2 domains were sufficient for aggregation. Finally, protein cross-linking and mass spectrometry studies demonstrated that a U1-70K fragment harboring the LC1 domain directly interacts with aggregated U1-70K in AD brain. Our results support a hypothesis that aberrant forms of U1-70K in AD can directly sequester soluble forms of U1-70K into insoluble aggregates. PMID:25355317

  2. SU(2) x U(1) vacuum and the Centauro events

    NASA Technical Reports Server (NTRS)

    Kazanas, D.; Balasubrahmanyan, V. K.; Streitmatter, R. E.

    1984-01-01

    It is proposed that the fireballs invoked to explain the Centauro events are bubbles of a metastable superdense state of nuclear matter, created in high energy (E is approximately 10 to the 15th power eV) cosmic ray collisions at the top of the atmosphere. If these bubbles are created with a Lorentz factor gamma approximately = 10 at their CM frame, the objections against the origin of these events in cosmic ray interactions are overcome. Assuming further, that the Centauro events are to the explosive decay of these metastable bubbles, a relationship between their lifetime, tau, and the threshold energy for bubble formation, E sub th, is derived. The minimum lifetime consistent with such an interpretation in tau is approximately 10 to the -8th power sec, while the E sub th appears to be insensitive to the value of tau and always close to E sub th is approximately 10 to the 15th power eV. Finally it is speculated that if the available CM energy is thermalized in such collisions, these bubbles might be manifestations of excitations of the SU(2) x U(1) false vacuum. The absence of neutral pions in the Centauro events is then explained by the decay of these excitations.

  3. Attractive inverse square potential, U(1) gauge, and winding transitions.

    PubMed

    Nisoli, Cristiano; Bishop, A R

    2014-02-21

    The inverse square potential arises in a variety of different quantum phenomena, yet notoriously it must be handled with care: it suffers from pathologies rooted in the mathematical foundations of quantum mechanics. We show that its recently studied conformality breaking corresponds to an infinitely smooth winding-unwinding topological transition for the classical statistical mechanics of a one-dimensional system: this describes the tangling or untangling of floppy polymers under a biasing torque. When the ratio between torque and temperature exceeds a critical value the polymer undergoes tangled oscillations, with an extensive winding number. At lower torque or higher temperature the winding number per unit length is zero. Approaching criticality, the correlation length of the order parameter-the extensive winding number-follows a Kosterlitz-Thouless-type law. The model is described by the Wilson line of a (0+1) U(1) gauge theory, and applies to the tangling or untangling of floppy polymers and to the winding or diffusing kinetics in diffusion-convection reactions. PMID:24579570

  4. Attractive Inverse Square Potential, U(1) Gauge, and Winding Transitions

    NASA Astrophysics Data System (ADS)

    Nisoli, Cristiano; Bishop, A. R.

    2014-02-01

    The inverse square potential arises in a variety of different quantum phenomena, yet notoriously it must be handled with care: it suffers from pathologies rooted in the mathematical foundations of quantum mechanics. We show that its recently studied conformality breaking corresponds to an infinitely smooth winding-unwinding topological transition for the classical statistical mechanics of a one-dimensional system: this describes the tangling or untangling of floppy polymers under a biasing torque. When the ratio between torque and temperature exceeds a critical value the polymer undergoes tangled oscillations, with an extensive winding number. At lower torque or higher temperature the winding number per unit length is zero. Approaching criticality, the correlation length of the order parameter—the extensive winding number—follows a Kosterlitz-Thouless-type law. The model is described by the Wilson line of a (0+1) U(1) gauge theory, and applies to the tangling or untangling of floppy polymers and to the winding or diffusing kinetics in diffusion-convection reactions.

  5. AAV-mediated in vivo knockdown of luciferase using combinatorial RNAi and U1i.

    PubMed

    Koornneef, A; van Logtenstein, R; Timmermans, E; Pisas, L; Blits, B; Abad, X; Fortes, P; Petry, H; Konstantinova, P; Ritsema, T

    2011-09-01

    RNA interference (RNAi) has been successfully employed for specific inhibition of gene expression; however, safety and delivery of RNAi remain critical issues. We investigated the combinatorial use of RNAi and U1 interference (U1i). U1i is a gene-silencing technique that acts on the pre-mRNA by preventing polyadenylation. RNAi and U1i have distinct mechanisms of action in different cellular compartments and their combined effect allows usage of minimal doses, thereby avoiding toxicity while retaining high target inhibition. As a proof of concept, we investigated knockdown of the firefly luciferase reporter gene by combinatorial use of RNAi and U1i, and evaluated their inhibitory potential both in vitro and in vivo. Co-transfection of RNAi and U1i constructs showed additive reduction of luciferase expression up to 95% in vitro. We attained similar knockdown when RNAi and U1i constructs were hydrodynamically transfected into murine liver, demonstrating for the first time successful in vivo application of U1i. Moreover, we demonstrated long-term gene silencing by AAV-mediated transduction of murine muscle with RNAi/U1i constructs targeting firefly luciferase. In conclusion, these results provide a proof of principle for the combinatorial use of RNAi and U1i to enhance target gene knockdown in vivo.

  6. Identification of a novel nuclear localization signal and speckle-targeting sequence of tuftelin-interacting protein 11, a splicing factor involved in spliceosome disassembly

    SciTech Connect

    Tannukit, Sissada; Crabb, Tara L.; Hertel, Klemens J.; Wen, Xin; Jans, David A.; Paine, Michael L.

    2009-12-18

    Tuftelin-interacting protein 11 (TFIP11) is a protein component of the spliceosome complex that promotes the release of the lariat-intron during late-stage splicing through a direct recruitment and interaction with DHX15/PRP43. Expression of TFIP11 is essential for cell and organismal survival. TFIP11 contains a G-patch domain, a signature motif of RNA-processing proteins that is responsible for TFIP11-DHX15 interactions. No other functional domains within TFIP11 have been described. TFIP11 is localized to distinct speckled regions within the cell nucleus, although excluded from the nucleolus. In this study sequential C-terminal deletions and mutational analyses have identified two novel protein elements in mouse TFIP11. The first domain covers amino acids 701-706 (VKDKFN) and is an atypical nuclear localization signal (NLS). The second domain is contained within amino acids 711-735 and defines TFIP11's distinct speckled nuclear localization. The identification of a novel TFIP11 nuclear speckle-targeting sequence (TFIP11-STS) suggests that this domain directly interacts with additional spliceosomal components. These data help define the mechanism of nuclear/nuclear speckle localization of the splicing factor TFIP11, with implications for it's function.

  7. FgPrp4 Kinase Is Important for Spliceosome B-Complex Activation and Splicing Efficiency in Fusarium graminearum.

    PubMed

    Gao, Xuli; Jin, Qiaojun; Jiang, Cong; Li, Yang; Li, Chaohui; Liu, Huiquan; Kang, Zhensheng; Xu, Jin-Rong

    2016-04-01

    PRP4 encodes the only kinase among the spliceosome components. Although it is an essential gene in the fission yeast and other eukaryotic organisms, the Fgprp4 mutant was viable in the wheat scab fungus Fusarium graminearum. Deletion of FgPRP4 did not block intron splicing but affected intron splicing efficiency in over 60% of the F. graminearum genes. The Fgprp4 mutant had severe growth defects and produced spontaneous suppressors that were recovered in growth rate. Suppressor mutations were identified in the PRP6, PRP31, BRR2, and PRP8 orthologs in nine suppressor strains by sequencing analysis with candidate tri-snRNP component genes. The Q86K mutation in FgMSL1 was identified by whole genome sequencing in suppressor mutant S3. Whereas two of the suppressor mutations in FgBrr2 and FgPrp8 were similar to those characterized in their orthologs in yeasts, suppressor mutations in Prp6 and Prp31 orthologs or FgMSL1 have not been reported. Interestingly, four and two suppressor mutations identified in FgPrp6 and FgPrp31, respectively, all are near the conserved Prp4-phosphorylation sites, suggesting that these mutations may have similar effects with phosphorylation by Prp4 kinase. In FgPrp31, the non-sense mutation at R464 resulted in the truncation of the C-terminal 130 aa region that contains all the conserved Prp4-phosphorylation sites. Deletion analysis showed that the N-terminal 310-aa rich in SR residues plays a critical role in the localization and functions of FgPrp4. We also conducted phosphoproteomics analysis with FgPrp4 and identified S289 as the phosphorylation site that is essential for its functions. These results indicated that FgPrp4 is critical for splicing efficiency but not essential for intron splicing, and FgPrp4 may regulate pre-mRNA splicing by phosphorylation of other components of the tri-snRNP although itself may be activated by phosphorylation at S289.

  8. Single field inflation in supergravity with a U(1) gauge symmetry

    SciTech Connect

    Heurtier, L.; Khalil, S.; Moursy, A.

    2015-10-19

    A single field inflation based on a supergravity model with a shift symmetry and U(1) extension of the MSSM is analyzed. We show that one of the real components of the two U(1) charged scalar fields plays the role of inflaton with an effective scalar potential similar to the “new chaotic inflation” scenario. Both non-anomalous and anomalous (with Fayet-Iliopoulos term) U(1) are studied. We show that the non-anomalous U(1) scenario is consistent with data of the cosmic microwave background and recent astrophysical measurements. A possible kinetic mixing between U(1) and U(1){sub B−L} is considered in order to allow for natural decay channels of the inflaton, leading to a reheating epoch. Upper limits on the reheating temperature thus turn out to favour an intermediate (∼O(10{sup 13}) GeV) scale B−L symmetry breaking.

  9. Single field inflation in supergravity with a U(1) gauge symmetry

    SciTech Connect

    Heurtier, L.; Khalil, S.; Moursy, A. E-mail: skhalil@zewailcity.edu.eg

    2015-10-01

    A single field inflation based on a supergravity model with a shift symmetry and U(1) extension of the MSSM is analyzed. We show that one of the real components of the two U(1) charged scalar fields plays the role of inflaton with an effective scalar potential similar to the ''new chaotic inflation'' scenario. Both non-anomalous and anomalous (with Fayet-Iliopoulos term) U(1) are studied. We show that the non-anomalous U(1) scenario is consistent with data of the cosmic microwave background and recent astrophysical measurements. A possible kinetic mixing between U(1) and U(1){sub B−L} is considered in order to allow for natural decay channels of the inflaton, leading to a reheating epoch. Upper limits on the reheating temperature thus turn out to favour an intermediate (∼ O(10{sup 13}) GeV) scale B−L symmetry breaking.

  10. General U(1U(1) F-theory compactifications and beyond: geometry of unHiggsings and novel matter structure

    NASA Astrophysics Data System (ADS)

    Cvetič, Mirjam; Klevers, Denis; Piragua, Hernan; Taylor, Washington

    2015-11-01

    We construct the general form of an F-theory compactification with two U(1) factors based on a general elliptically fibered Calabi-Yau manifold with Mordell-Weil group of rank two. This construction produces broad classes of models with diverse matter spectra, including many that are not realized in earlier F-theory constructions with U(1U(1) gauge symmetry. Generic U(1U(1) models can be related to a Higgsed non-Abelian model with gauge group SU(2)×SU(2)×SU(3), SU(2)3×SU(3), or a subgroup thereof. The nonlocal horizontal divisors of the Mordell-Weil group are replaced with local vertical divisors associated with the Cartan generators of non-Abelian gauge groups from Kodaira singularities. We give a global resolution of codimension two singularities of the Abelian model; we identify the full anomaly free matter content, and match it to the unHiggsed non-Abelian model. The non-Abelian Weierstrass model exhibits a new algebraic description of the singularities in the fibration that results in the first explicit construction of matter in the symmetric representation of SU(3). This matter is realized on double point singularities of the discriminant locus. The construction suggests a generalization to U(1) k factors with k > 2, which can be studied by Higgsing theories with larger non-Abelian gauge groups.

  11. Neutrino mixings and grand unification: SU(5) GUT with anomaly free U(1)F

    NASA Astrophysics Data System (ADS)

    Tavartkiladze, Zurab

    2013-05-01

    The model of supersymmetric SU(5) GUT augmented with anomaly free U(1)F flavor symmetry is presented. The field content and the U(1)F charge assignment is obtained by specific embedding of SU(5) × U(1)F in larger non-Abelian group. We focus on a particular case which gives very economical field content with the U(1)F charges fixed in such a way that for quarks and leptons appealing texture zero Yukawa couplings are generated. The model gives realistic fermion masses and mixings and predict inverted hierarchical neutrino mass scenario with interesting implications.

  12. Organization of core spliceosomal components U5 snRNA loop I and U4/U6 Di-snRNP within U4/U6.U5 Tri-snRNP as revealed by electron cryomicroscopy.

    PubMed

    Sander, Bjoern; Golas, Monika M; Makarov, Evgeny M; Brahms, Hero; Kastner, Berthold; Lührmann, Reinhard; Stark, Holger

    2006-10-20

    In eukaryotes, pre-mRNA exons are interrupted by large noncoding introns. Alternative selection of exons and nucleotide-exact removal of introns are performed by the spliceosome, a highly dynamic macromolecular machine. U4/U6.U5 tri-snRNP is the largest and most conserved building block of the spliceosome. By 3D electron cryomicroscopy and labeling, the exon-aligning U5 snRNA loop I is localized at the center of the tetrahedrally shaped tri-snRNP reconstructed to approximately 2.1 nm resolution in vitrified ice. Independent 3D reconstructions of its subunits, U4/U6 and U5 snRNPs, show how U4/U6 and U5 combine to form tri-snRNP and, together with labeling experiments, indicate a close proximity of the spliceosomal core components U5 snRNA loop I and U4/U6 at the center of tri-snRNP. We suggest that this central tri-snRNP region may be the site to which the prespliceosomal U2 snRNA has to approach closely during formation of the catalytic core of the spliceosome.

  13. F-theory compactifications with multiple U(1)-factors: constructing elliptic fibrations with rational sections

    NASA Astrophysics Data System (ADS)

    Cvetič, Mirjam; Klevers, Denis; Piragua, Hernan

    2013-06-01

    We study F-theory compactifications with U(1U(1) gauge symmetry on elliptically fibered Calabi-Yau manifolds with a rank two Mordell-Weil group. We find that the natural presentation of an elliptic curve {E} with two rational points and a zero point is the generic Calabi-Yau onefold in dP 2. We determine the birational map to its Tate and Weier- strass form and the coordinates of the two rational points in Weierstrass form. We discuss its resolved elliptic fibrations over a general base B and classify them in the case of B = {P} 2. A thorough analysis of the generic codimension two singularities of these elliptic Calabi-Yau manifolds is presented. This determines the general U(1U(1)-charges of matter in corresponding F-theory compactifications. The matter multiplicities for the fibration over {P} 2 are determined explicitly and shown to be consistent with anomaly cancellation. Explicit toric examples are constructed, both with U(1U(1) and SU(5)×U(1U(1) gauge symmetry. As a by-product, we prove the birational equivalence of the two elliptic fibrations with elliptic fibers in the two blow-ups Bl (1,0,0) {P} 2(1, 2, 3) and Bl (0,1,0) {P} 2(1, 1, 2) employing birational maps and extremal transitions.

  14. Phenomenological study on the wino radiative decay in anomalous U(1){sup '} models

    SciTech Connect

    Fucito, Francesco; Lionetto, Andrea; Pacifici, Daniel Ricci; Racioppi, Antonio

    2010-12-01

    An extension of the standard model by at least one extra U(1) gauge symmetry has been investigated by many authors. In this paper we explore the possibility that this extra U(1) is anomalous. One possible signature of this model could be given by the photons produced in the decays of the next to lightest supersymmetric particle into the lightest supersymmetric particle.

  15. Integrated Approaches for Analyzing U1-70K Cleavage in Alzheimer’s Disease

    PubMed Central

    2015-01-01

    The accumulation of pathologic protein fragments is common in neurodegenerative disorders. We have recently identified in Alzheimer’s disease (AD) the aggregation of the U1-70K splicing factor and abnormal RNA processing. Here, we present that U1-70K can be cleaved into an N-terminal truncation (N40K) in ∼50% of AD cases, and the N40K abundance is inversely proportional to the total level of U1-70K. To map the cleavage site, we compared tryptic peptides of N40K and stable isotope labeled U1-70K by liquid chromatography–tandem mass spectrometry (MS), revealing that the proteolysis site is located in a highly repetitive and hydrophilic domain of U1-70K. We then adapted Western blotting to map the cleavage site in two steps: (i) mass spectrometric analysis revealing that U1-70K and N40K share the same N-termini and contain no major modifications; (ii) matching N40K with a series of six recombinant U1-70K truncations to define the cleavage site within a small region (Arg300 ± 6 residues). Finally, N40K expression led to substantial degeneration of rat primary hippocampal neurons. In summary, we combined multiple approaches to identify the U1-70K proteolytic site and found that the N40K fragment might contribute to neuronal toxicity in Alzheimer’s disease. PMID:24902715

  16. Closure report for underground storage tank 141-R3U1 and its associated underground piping

    SciTech Connect

    Mallon, B.J.; Blake, R.G.

    1994-03-01

    Underground storage tank UST 141-R3U1 at Lawrence Livermore National Laboratory (LLNL), was registered with the State Water Resources Control Board on June 27, 1984. This tank system consisted of a concrete tank, lined with polyvinyl chloride, and approximately 100 feet of PVC underground piping. UST 141-R3U1 had a capacity of 450 gallons. The underground piping connected three floor drains and one sink inside Building 141 to UST 141-R3U1. The wastewater collected in UST 141-R3U1 contained organic solvents, metals, and inorganic acids. On November 30, 1987, the 141-R3U1 tank system failed a precision tank test. The 141-R3U1 tank system was subsequently emptied and removed from service pending further precision tests to determine the location of the leak within the tank system. A precision tank test on February 5, 1988, was performed to confirm the November 30, 1987 test. Four additional precision tests were performed on this tank system between February 25, 1988, and March 6, 1988. The leak was located where the inlet piping from Building 141 penetrates the concrete side of UST 141-R3U1. The volume of wastewater that entered the backfill and soil around and/or beneath UST 141-R3U1 is unknown. On December 13, 1989, the LLNL Environmental Restoration Division submitted a plan to close UST 141-R3U1 and its associated piping to the Alameda County Department of Environmental Health. UST 141-R3U1 was closed as an UST, and shall be used instead as additional secondary containment for two aboveground storage tanks.

  17. Splicing and spliceosome formation of the yeast MATa1 transcript require a minimum distance from the 5' splice site to the internal branch acceptor site.

    PubMed Central

    Köhrer, K; Domdey, H

    1988-01-01

    Small deletions of 6, 7, and 12 nucleotides introduced between the 5' splice site and the internal branch acceptor site of the first intron of the yeast MATa1 gene completely abolish accurate splicing in vitro in these constructs. Splicing only occurs at an alternative 5' splice site which was found in the first exon of the MATa1 gene and which is used both in vivo and in vitro. The splicing defect cannot be cured by expanding the distance from the branch point to the 3' splice site. If the alternative 5' splice site is deleted as well in these constructs, neither spliced products nor spliceosomes are formed. Our findings especially lead to the conclusion that a minimum distance between the 5' splice site and the internal branch acceptor site of the intron is required for the formation of splicing complexes and for accurate splicing. Images PMID:3054807

  18. An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses

    PubMed Central

    Schreiber, Claire A.; Sakuma, Toshie; Izumiya, Yoshihiro; Holditch, Sara J.; Hickey, Raymond D.; Bressin, Robert K.; Basu, Upamanyu; Koide, Kazunori; Asokan, Aravind; Ikeda, Yasuhiro

    2015-01-01

    Adeno-associated viruses (AAV) have evolved to exploit the dynamic reorganization of host cell machinery during co-infection by adenoviruses and other helper viruses. In the absence of helper viruses, host factors such as the proteasome and DNA damage response machinery have been shown to effectively inhibit AAV transduction by restricting processes ranging from nuclear entry to second-strand DNA synthesis. To identify host factors that might affect other key steps in AAV infection, we screened an siRNA library that revealed several candidate genes including the PHD finger-like domain protein 5A (PHF5A), a U2 snRNP-associated protein. Disruption of PHF5A expression selectively enhanced transgene expression from AAV by increasing transcript levels and appears to influence a step after second-strand synthesis in a serotype and cell type-independent manner. Genetic disruption of U2 snRNP and associated proteins, such as SF3B1 and U2AF1, also increased expression from AAV vector, suggesting the critical role of U2 snRNP spliceosome complex in this host-mediated restriction. Notably, adenoviral co-infection and U2 snRNP inhibition appeared to target a common pathway in increasing expression from AAV vectors. Moreover, pharmacological inhibition of U2 snRNP by meayamycin B, a potent SF3B1 inhibitor, substantially enhanced AAV vector transduction of clinically relevant cell types. Further analysis suggested that U2 snRNP proteins suppress AAV vector transgene expression through direct recognition of intact AAV capsids. In summary, we identify U2 snRNP and associated splicing factors, which are known to be affected during adenoviral infection, as novel host restriction factors that effectively limit AAV transgene expression. Concurrently, we postulate that pharmacological/genetic manipulation of components of the spliceosomal machinery might enable more effective gene transfer modalities with recombinant AAV vectors. PMID:26244496

  19. U(1) symmetries in F-theory GUTs with multiple sections

    NASA Astrophysics Data System (ADS)

    Mayrhofer, Christoph; Palti, Eran; Weigand, Timo

    2013-03-01

    We present a systematic construction of F-theory compactifications with Abelian gauge symmetries in addition to a non-Abelian gauge group G. The formalism is generally applicable to models in global Tate form but we focus on the phenomenologically interesting case of G = SU(5). The Abelian gauge factors arise due to extra global sections resulting from a specific factorisation of the Tate polynomial which describes the elliptic fibration. These constructions, which accommodate up to four different U(1) factors, are worked out in detail for the two possible embeddings of a single U(1) factor into E 8, usually denoted SU(5) × U(1) X and SU(5) × U(1) PQ . The resolved models can be understood either patchwise via a small resolution or in terms of a {{{P}}_{1,1,2 }} [4] description of the elliptic fibration. We derive the U(1) charges of the fields from the geometry, construct the U(1) gauge fluxes and exemplify the structure of the Yukawa interaction points. A particularly interesting result is that the global SU(5) × U(1) PQ model exhibits extra SU(5)-singlet states which are incompatible with a single global decomposition of the 248 of E 8. The states in turn lead to new Yukawa type couplings which have not been considered in local model building.

  20. U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer’s disease due to autosomal dominant genetic mutations and trisomy 21

    PubMed Central

    2014-01-01

    Background We recently identified U1 small nuclear ribonucleoprotein (snRNP) tangle-like aggregates and RNA splicing abnormalities in sporadic Alzheimer’s disease (AD). However little is known about snRNP biology in early onset AD due to autosomal dominant genetic mutations or trisomy 21 in Down syndrome. Therefore we investigated snRNP biochemical and pathologic features in these disorders. Findings We performed quantitative proteomics and immunohistochemistry in postmortem brain from genetic AD cases. Electron microscopy was used to characterize ultrastructural features of pathologic aggregates. U1-70k and other snRNPs were biochemically enriched in the insoluble fraction of human brain from subjects with presenilin 1 (PS1) mutations. Aggregates of U1 snRNP-immunoreactivity formed cytoplasmic tangle-like structures in cortex of AD subjects with PS1 and amyloid precursor protein (APP) mutations as well as trisomy 21. Ultrastructural analysis with electron microscopy in an APP mutation case demonstrated snRNP immunogold labeling of paired helical filaments (PHF). Conclusions These studies identify U1 snRNP pathologic changes in brain of early onset genetic forms of AD. Since dominant genetic mutations and trisomy 21 result in dysfunctional amyloid processing, the findings suggest that aberrant β-amyloid processing may influence U1 snRNP aggregate formation. PMID:24773620

  1. Baryon Triality And Neutrino Masses From An Anomalous FlavorU(1)

    SciTech Connect

    Dreiner, Herbi K.; Luhn, Christoph; Murayama, Hitoshi; Thormeier,Marc

    2007-08-15

    We construct a concise U(1){sub X} Froggatt-Nielsen model in which baryon triality, a discrete gauge Z{sub 3}-symmetry, arises from U(1){sub X} breaking. The proton is thus stable, however, R-parity is violated. With the proper choice of U(1){sub X} charges we can obtain neutrino masses and mixings consistent with an explanation of the atmospheric and solar neutrino anomalies in terms of neutrino oscillations, with no right-handed neutrinos required. The only mass scale apart from M{sub grav} is m{sub soft}.

  2. Functional analysis of U1-70K interacting SR proteins in pre-mRNA splicing in Arabidopsis

    SciTech Connect

    A.S.N. Reddy

    2008-11-25

    Proteins of a serine/arginine-rich (SR) family are part of the spliceosome and are implicated in both constitutive and alternative splicing of pre-mRNAs. With the funding from DOE we have been studying alternative of splicing of genes encoding serine/arginine-rich (SR) proteins and the roles of SR proteins that interact with U1-70K in regulating basic and alternative splicing. Alternative splicing of pre-mRNAs of Arabidopsis serine/arginine-rich proteins and its regulation by hormones and stresses: We analyzed the splicing of all 19 Arabidopsis genes in different tissues, during different seedling stages and in response to various hormonal and stress treatments. Remarkably, about 90 different transcripts are produced from 15 SR genes, thereby increasing the transcriptome complexity of SR genes by about five fold. Using the RNA isolated from polysomes we have shown that most of the splice variants are recruited for translation. Alternative splicing of some SR genes is controlled in a developmental and tissue-specific manner (Palusa et al., 2007). Interestingly, among the various hormones and abiotic stresses tested, temperature stress (cold and heat) and ultraviolet light dramatically altered alternative splicing of pre-mRNAs of several SR genes whereas hormones altered the splicing of only two SR genes (Palusa et al., 2007). Localization and dynamics of a novel serine/arginine-rich protein that interacts with U1-70K: We analyzed the intranuclear movement of SR45 fused to GFP by fluorescence recovery after photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP). We demonstrate that the movement of GFP-SR45 is ATP-dependent. Interestingly, inhibition of transcription or phosphorylation slowed the mobility of GFP-SR45 (Ali et al., 2006). Our studies have revealed that the nuclear localization signals are located in arg/ser-rich domains (RS) 1 and 2, whereas the speckle targeting signals are exclusively present in RS2 (Ali et al., 2006). The regulation of

  3. Tate's algorithm for F-theory GUTs with two U(1)s

    NASA Astrophysics Data System (ADS)

    Lawrie, Craig; Sacco, Damiano

    2015-03-01

    We present a systematic study of elliptic fibrations for F-theory realizations of gauge theories with two U(1) factors. In particular, we determine a new class of SU(5) × U(1)2 fibrations, which can be used to engineer Grand Unified Theories, with multiple, differently charged, 10 matter representations. To determine these models we apply Tate's algorithm to elliptic fibrations with two U(1) symmetries, which are realized in terms of a cubic in . In the process, we find fibers which are not characterized solely in terms of vanishing orders, but with some additional specialization, which plays a key role in the construction of these novel SU(5) models with multiple 10 matter. We also determine a table of Tate-like forms for Kodaira fibers with two U(1)s.

  4. Dark Matter and neutrino masses from global U(1) B - L symmetry breaking

    NASA Astrophysics Data System (ADS)

    Lindner, Manfred; Schmidt, Daniel; Schwetz, Thomas

    2011-11-01

    We present a scenario where neutrino masses and Dark Matter are related due to a global U(1) B - L symmetry. Specifically we consider neutrino mass generation via the Zee-Babu two-loop mechanism, augmented by a scalar singlet whose VEV breaks the global U(1) B - L symmetry. In order to obtain a Dark Matter candidate we introduce two Standard Model singlet fermions. They form a Dirac particle and are stable because of a remnant Z2 symmetry. Hence, in this model the stability of Dark Matter follows from the global U(1) B - L symmetry. We discuss the Dark Matter phenomenology of the model, and compare it to similar models based on gauged U(1) B - L. We argue that in contrast to the gauged versions, the model based on the global symmetry does not suffer from severe constraints from Z‧ searches.

  5. Shadow Higgs boson from a scale-invariant hidden U(1){sub s} model

    SciTech Connect

    Chang, W.-F.; Ng, John N.; Wu, Jackson M. S.

    2007-06-01

    We study a scale-invariant SU(2)xU(1){sub Y}xU(1){sub s} model which has only dimensionless couplings. The shadow U(1){sub s} is hidden, and it interacts with the standard model (SM) solely through mixing in the scalar sector and kinetic mixing of the U(1) gauge bosons. The gauge symmetries are broken radiatively by the Coleman-Weinberg mechanism. Lifting of the flat direction in the scalar potential gives rise to a light scalar, the scalon, or the shadow Higgs, and a heavier scalar which we identify as the SM Higgs boson. The phenomenology of this model is discussed. In particular, the constraints on the shadow Higgs in different mass ranges, and the possibility of discovering a shadow Higgs with a mass a few tens of GeV in precision t-quark studies at the LHC, are investigated.

  6. All exactly solvable U(1)-invariant quantum spin 1 chains from Hecke algebra

    SciTech Connect

    Alcarez, F.C. ); Koberle, R. ); Lima-Santos, A. )

    1992-12-10

    In this paper, the authors obtain all exactly integrable spin 1 quantum chains, which are U(1) invariant and satisfy the Hecke algebra. The authors present various generalizations for arbitrary spin S and discuss their solution via Bethe ansatz methods.

  7. Classically conformal U (1 )' extended standard model and Higgs vacuum stability

    NASA Astrophysics Data System (ADS)

    Oda, Satsuki; Okada, Nobuchika; Takahashi, Dai-suke

    2015-07-01

    We consider the minimal U (1 )' extension of the standard model (SM) with conformal invariance at the classical level, where in addition to the SM particle contents, three generations of right-handed neutrinos and a U (1 )' Higgs field are introduced. In the presence of the three right-handed neutrinos, which are responsible for the seesaw mechanism, this model is free from all the gauge and gravitational anomalies. The U (1 )' gauge symmetry is radiatively broken via the Coleman-Weinberg mechanism, by which the U (1 )' gauge boson (Z' boson) mass as well as the Majorana mass for the right-handed neutrinos are generated. The radiative U (1 )' symmetry breaking also induces a negative mass squared for the SM Higgs doublet to trigger the electroweak symmetry breaking. In this context, we investigate a possibility to solve the SM Higgs vacuum instability problem. The model includes only three free parameters (U (1 )' charge of the SM Higgs doublet, U (1 )' gauge coupling and Z' boson mass), for which we perform parameter scan, and identify a parameter region resolving the SM Higgs vacuum instability. We also examine naturalness of the model. The heavy states associated with the U (1 )' symmetry breaking contribute to the SM Higgs self-energy. We find an upper bound on Z' boson mass, mZ'≲6 TeV , in order to avoid a fine-tuning severer than 10% level. The Z' boson in this mass range can be discovered at the LHC Run-2 in the near future.

  8. 40 CFR Table U-1 to Subpart U of... - CO2 Emission Factors for Common Carbonates

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false CO2 Emission Factors for Common.... 98, Subpt. U, Table U-1 Table U-1 to Subpart U of Part 98—CO2 Emission Factors for Common Carbonates Mineral name—carbonate CO2 emission factor(tons CO2/ton carbonate) Limestone—CaCO3 0.43971...

  9. 40 CFR Table U-1 to Subpart U of... - CO2 Emission Factors for Common Carbonates

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false CO2 Emission Factors for Common.... 98, Subpt. U, Table U-1 Table U-1 to Subpart U of Part 98—CO2 Emission Factors for Common Carbonates Mineral name—carbonate CO2 emission factor(tons CO2/ton carbonate) Limestone—CaCO3 0.43971...

  10. 40 CFR Table U-1 to Subpart U of... - CO2 Emission Factors for Common Carbonates

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false CO2 Emission Factors for Common.... 98, Subpt. U, Table U-1 Table U-1 to Subpart U of Part 98—CO2 Emission Factors for Common Carbonates Mineral name—carbonate CO2 emission factor(tons CO2/ton carbonate) Limestone—CaCO3 0.43971...

  11. 40 CFR Table U-1 to Subpart U of... - CO2 Emission Factors for Common Carbonates

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false CO2 Emission Factors for Common.... 98, Subpt. U, Table U-1 Table U-1 to Subpart U of Part 98—CO2 Emission Factors for Common Carbonates Mineral name—carbonate CO2 emission factor(tons CO2/ton carbonate) Limestone—CaCO3 0.43971...

  12. Closure report for underground storage tank 161-R1U1 and its associated underground piping

    SciTech Connect

    Mallon, B.J.; Blake, R.G.

    1994-05-01

    Underground storage tank (UST) 161-31 R at the Lawrence Livermore National Laboratory (LLNL) was registered with the State Water Resources Control Board on June 27, 1984. UST 161-31R was subsequently renamed UST 161-R1U1 (Fig. A-1, Appendix A). UST 161-R1U1 was installed in 1976, and had a capacity of 383 gallons. This tank system consisted of a fiberglass reinforced plastic tank, approximately 320 feet of polyvinyl chloride (PVC) underground piping from Building 161, and approximately 40 feet of PVC underground piping from Building 160. The underground piping connected laboratory drains and sinks inside Buildings 160 and 161 to UST 161-R1U1. The wastewater collected in UST 161-R1U1, contained organic solvents, metals, inorganic acids, and radionuclides, most of which was produced within Building 161. On June 28, 1989, the UST 161-R1U1 piping system.around the perimeter of Building 161 failed a precision test performed by Gary Peters Enterprises (Appendix B). The 161-R1U1 tank system was removed from service after the precision test. In July 1989, additional hydrostatic tests and helium leak detection tests were performed (Appendix B) to determine the locations of the piping failures in the Building 161 piping system. The locations of the piping system failures are shown in Figure A-2 (Appendix A). On July 11, 1989, LLNL submitted an Unauthorized Release Report to Alameda County Department of Environmental Health (ACDEH), Appendix C.

  13. Hidden gauged U (1 ) model: Unifying scotogenic neutrino and flavor dark matter

    NASA Astrophysics Data System (ADS)

    Yu, Jiang-Hao

    2016-06-01

    In both scotogenic neutrino and flavor dark matter models, the dark sector communicates with the standard model fermions via Yukawa portal couplings. We propose an economic scenario where the scotogenic neutrino and a flavored mediator share the same inert Higgs doublet and all are charged under a hidden gauged U (1 ) symmetry. The dark Z2 symmetry in the dark sector is regarded as the remnant of this hidden U (1 ) symmetry breaking. In particular, we investigate a dark U (1 )D [and also U (1 )B-L] model which unifies the scotogenic neutrino and top-flavored mediator. Thus dark tops and dark neutrinos are the standard model fermion partners, and the dark matter could be the inert Higgs or the lightest dark neutrino. We note that this model has rich collider signatures on dark tops, the inert Higgs and the Z' gauge boson. Moreover, the scalar associated to the U (1 )D [and also U (1 )B -L ] symmetry breaking could explain the 750 GeV diphoton excess reported by ATLAS and CMS recently.

  14. The Arabidopsis U11/U12-65K is an indispensible component of minor spliceosome and plays a crucial role in U12 intron splicing and plant development.

    PubMed

    Jung, Hyun Ju; Kang, Hunseung

    2014-06-01

    The U12-dependent introns have been identified in a wide range of eukaryotes and are removed from precursor-mRNAs by U12 intron-specific minor spliceosome. Although several proteins unique to minor spliceosome have been identified, the nature of their effect on U12 intron splicing as well as plant growth and development remain largely unknown. Here, we characterized the functional role of an U12-type spliceosomal protein, U11/U12-65K in Arabidopsis thaliana. The transgenic knockdown plants generated by artificial miRNA-mediated silencing strategy exhibited severe defect in growth and development, such as severely arrested primary inflorescence stems, serrated leaves, and the formation of many rosette leaves after bolting. RNA sequencing and reverse transcription polymerase chain reaction (RT-PCR) analyses revealed that splicing of 198 out of the 234 previously predicted U12 intron-containing genes and 32 previously unidentified U12 introns was impaired in u11/u12-65k mutant. Moreover, the U11/U12-65K mutation affected alternative splicing, as well as U12 intron splicing, of many introns. Microarray analysis revealed that the genes involved in cell wall biogenesis and function, plant development, and metabolic processes are differentially expressed in the mutant plants. U11/U12-65K protein bound specifically to U12 small nuclear RNA (snRNA), which is necessary for branch-point site recognition. Taken together, these results provide clear evidence that U11/U12-65K is an indispensible component of minor spliceosome and involved in U12 intron splicing and alternative splicing of many introns, which is crucial for plant development.

  15. Cytochrome P450 107U1 is required for sporulation and antibiotic production in Streptomyces coelicolor

    PubMed Central

    Tian, Zhenghua; Cheng, Qian; Yoshimoto, Francis K.; Lei, Li; Lamb, David C.; Guengerich, F. Peter

    2013-01-01

    The filamentous bacterium Streptomyces coelicolor has a complex life cycle involving the formation of hair-like aerial mycelia on the colony surface, which differentiate into chains of spores. Genes required for the initiation of aerial mycelium formation have been termed ‘bld’ (bald), describing the smooth, undifferentiated colonies of mutant strains. We report the identification of a new bld gene designated as sco3099 and biochemical analysis of its encoded enzyme, cytochrome P450 (P450, or CYP) 107U1. Deletion of sco3099 resulted in a mutant defective in aerial hyphae sporulation and sensitive to heat shock, indicating that P450 107U1 plays a key role in growth and development of S. coelicolor. This is the first P450 reported to participate in a sporulation process in Streptomycetes. The substrate and catalytic properties of P450 107U1 were further investigated in mass spectrometry-based metabolomic studies. Glycocholic acid (from the medium) was identified as a substrate of P450 107U1 and was oxidized to glyco-7-oxo-deoxycholic acid. Although this reaction is apparently not relevant to the observed sporulation deficiency, it suggests that P450 107U1 might exert its physiological function by oxidizing other steroid-like molecules. PMID:23357279

  16. String Scale Gauge Coupling Unification with Vector-Like Exotics and Noncanonical U(1)Y Normalization

    NASA Astrophysics Data System (ADS)

    Barger, V.; Jiang, Jing; Langacker, Paul; Li, Tianjun

    We use a new approach to study string scale gauge coupling unification systematically, allowing both the possibility of noncanonical U(1)Y normalization and the existence of vector-like particles whose quantum numbers are the same as those of the Standard Model (SM) fermions and their Hermitian conjugates and the SM adjoint particles. We first give all the independent sets (Yi) of particles that can be employed to achieve SU(3)C and SU(2)L string scale gauge coupling unification and calculate their masses. Second, for a noncanonical U(1)Y normalization, we obtain string scale SU(3)C ×SU(2)L ×U(1)Y gauge coupling unification by choosing suitable U(1)Y normalizations for each of the Yi sets. Alternatively, for the canonical U(1)Y normalization, we achieve string scale gauge coupling unification by considering suitable combinations of the Yi sets or by introducing additional independent sets (Zi), that do not affect the SU(3)C ×SU(2)L unification at tree level, and then choosing suitable combinations, one from the Yi sets and one from the Zi sets. We also briefly discuss string scale gauge coupling unification in models with higher Kac-Moody levels for SU(2)L or SU(3)C.

  17. Cytochrome P450 107U1 is required for sporulation and antibiotic production in Streptomyces coelicolor.

    PubMed

    Tian, Zhenhua; Cheng, Qian; Yoshimoto, Francis K; Lei, Li; Lamb, David C; Guengerich, F Peter

    2013-02-15

    The filamentous bacterium Streptomyces coelicolor has a complex life cycle involving the formation of hair-like aerial mycelia on the colony surface, which differentiate into chains of spores. Genes required for the initiation of aerial mycelium formation have been termed 'bld' (bald), describing the smooth, undifferentiated colonies of mutant strains. We report the identification of a new bld gene designated as sco3099 and biochemical analysis of its encoded enzyme, cytochrome P450 (P450, or CYP) 107U1. Deletion of sco3099 resulted in a mutant defective in aerial hyphae sporulation and sensitive to heat shock, indicating that P450 107U1 plays a key role in growth and development of S. coelicolor. This is the first P450 reported to participate in a sporulation process in Streptomycetes. The substrate and catalytic properties of P450 107U1 were further investigated in mass spectrometry-based metabolomic studies. Glycocholic acid (from the medium) was identified as a substrate of P450 107U1 and was oxidized to glyco-7-oxo-deoxycholic acid. Although this reaction is apparently not relevant to the observed sporulation deficiency, it suggests that P450 107U1 might exert its physiological function by oxidizing other steroid-like molecules.

  18. Pigmentary degenerative maculopathy as prominent phenotype in an Italian SPG56/CYP2U1 family.

    PubMed

    Leonardi, Luca; Ziccardi, Lucia; Marcotulli, Christian; Rubegni, Anna; Longobardi, Antonino; Serrao, Mariano; Storti, Eugenia; Pierelli, Francesco; Tessa, Alessandra; Parisi, Vincenzo; Santorelli, Filippo M; Carlo, Casali

    2016-04-01

    SPG56 is an autosomal recessive form of hereditary spastic paraplegia (HSP) associated with mutations in CYP2U1. There is no clear documentation of visual impairment in the few reported cases of SPG56, although this form is complex on clinical ground and visual deficit are extremely frequent in complicated HSP. We report three patients in a consanguineous family harboring the novel homozygous c.1168C>T (p.R390*) in SPG56/CYP2U1, and showing a pigmentary degenerative maculopathy associated with progressive spastic paraplegia. Furthermore, we characterized precisely the ophthalmologic phenotype through indirect ophthalmoscopy, retinal optical coherence tomography and visual evoked potentials. This is the first formal report of pigmentary degenerative maculopathy associated with a CYP2U1 homozygous mutation. PMID:26914923

  19. Oscillating asymmetric sneutrino dark matter from the maximally U(1)L supersymmetric inverse seesaw

    NASA Astrophysics Data System (ADS)

    Chen, Shao-Long; Kang, Zhaofeng

    2016-10-01

    The inverse seesaw mechanism provides an attractive approach to generate small neutrino mass, which origins from a tiny U(1)L breaking. In this paper, we work in the supersymmetric version of this mechanism, where the singlet-like sneutrino could be an asymmetric dark matter (ADM) candidate in the maximally U(1)L symmetric limit. However, even a tiny δm, the mass splitting between sneutrino and anti-sneutrino as a result of the tiny U(1)L breaking effect, could lead to fast oscillation between sneutrino and anti-sneutrino and thus spoils the ADM scenario. We study the evolution of this oscillation and find that a weak scale sneutrino, which tolerates a relatively larger δm ∼10-5 eV, is strongly favored. We also investigate possible natural ways to realize that small δm in the model.

  20. Dim 6 nucleon decay in anomalous U(1){sub A} SUSY GUT

    SciTech Connect

    Muramatsu, Yu

    2012-07-27

    Anomalous U(1){sub A} SUSY GUT models are atractive because they can solve many difficulties in SUSY GUT models. In anomalous U(1){sub A} SUSY GUT models, nucleon decay amplitudes of dim 6 effective interactions are larger than that of dim 5 effective interactions. Then, I discuss dim 6 effective interactions in some models, and predict proton lifetimes for many decay modes by calculating interactions. First, I fix unitary matrices that make Yukawa coupling matrices diagonalize, and predict proton lifetimes. Second, I study uncertainties of these unitary matrices, and show these effects on proton lifetimes. From these results, I show that we can distinguish some models from by nucleon decay.

  1. Modular invariant gaugino condensation in the presence of ananomalous U(1)*

    SciTech Connect

    Gaillard, Mary K.; Giedt, Joel; Mints, Aleksey L.

    2003-12-10

    Starting from the previously constructed effective supergravity theory below the scale of U(1) breaking in orbifold compactifications of the weakly coupled heterotic string, we study the effective theory below the scale of supersymmetry breaking by gaugino and matter condensation in a hidden sector. Questions we address include vacuum stability and the masses of the various moduli fields, including those associated with flat directions at the U(1) breaking scale, and of their fermionic superpartners. The issue of soft supersymmetry-breaking masses in the observable sector presents a particularly serious challenge for this class of models.

  2. Nonlinear optical conductivity of U (1 ) spin liquids with large spinon Fermi surfaces

    NASA Astrophysics Data System (ADS)

    Ma, Yuan-Fei; Ng, Tai-Kai

    2016-06-01

    In this paper we study the nonlinear current response of U (1 ) spin liquids with large spinon Fermi surfaces under the perturbation of a time-dependent ac electric field E (t ) within the framework of an effective U (1 ) gauge theory. In particular, the third-order nonlinear current response to ac electric fields is derived. We show that as in the case of linear current response, an in-gap power-law (˜ωη ) response is found for the nonlinear current at low frequency. The nonlinear susceptibility may also induce through process of third harmonic generation propagating EM wave with frequency 3 ω inside the spin liquids.

  3. Approaching Minimal Flavour Violation from an SU(5) × S 4 × U(1) SUSY GUT

    NASA Astrophysics Data System (ADS)

    Dimou, Maria; King, Stephen F.; Luhn, Christoph

    2016-02-01

    We show how approximate Minimal Flavour Violation (MFV) can emerge from an SU(5) Supersymmetric Grand Unified Theory (SUSY GUT) supplemented by an S 4 × U(1) family symmetry, which provides a good description of all quark and lepton (including neutrino) masses, mixings and CP violation. Assuming a SUSY breaking mechanism which respects the family symmetry, we calculate in full explicit detail the low energy mass insertion parameters in the super-CKM basis, including the effects of canonical normalisation and renormalisation group running. We find that the very simple family symmetry S 4 ×U(1) is sufficient to approximately reproduce the effects of low energy MFV.

  4. Physiologic Expression of Sf3b1(K700E) Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation.

    PubMed

    Obeng, Esther A; Chappell, Ryan J; Seiler, Michael; Chen, Michelle C; Campagna, Dean R; Schmidt, Paul J; Schneider, Rebekka K; Lord, Allegra M; Wang, Lili; Gambe, Rutendo G; McConkey, Marie E; Ali, Abdullah M; Raza, Azra; Yu, Lihua; Buonamici, Silvia; Smith, Peter G; Mullally, Ann; Wu, Catherine J; Fleming, Mark D; Ebert, Benjamin L

    2016-09-12

    More than 80% of patients with the refractory anemia with ring sideroblasts subtype of myelodysplastic syndrome (MDS) have mutations in Splicing Factor 3B, Subunit 1 (SF3B1). We generated a conditional knockin mouse model of the most common SF3B1 mutation, Sf3b1(K700E). Sf3b1(K700E) mice develop macrocytic anemia due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell (LT-HSC) expansion. Sf3b1(K700E) myeloid progenitors and SF3B1-mutant MDS patient samples demonstrate aberrant 3' splice-site selection associated with increased nonsense-mediated decay. Tet2 loss cooperates with Sf3b1(K700E) to cause a more severe erythroid and LT-HSC phenotype. Furthermore, the spliceosome modulator, E7017, selectively kills SF3B1(K700E)-expressing cells. Thus, SF3B1(K700E) expression reflects the phenotype of the mutation in MDS and may be a therapeutic target in MDS. PMID:27622333

  5. The nuclear matrix protein p255 is a highly phosphorylated form of RNA polymerase II largest subunit which associates with spliceosomes.

    PubMed Central

    Vincent, M; Lauriault, P; Dubois, M F; Lavoie, S; Bensaude, O; Chabot, B

    1996-01-01

    The monoclonal antibody CC-3 recognizes a phosphodependent epitope on a 255 kDa nuclear matrix protein (p255) recently shown to associate with splicing complexes as part of the [U4/U6.U5] tri-snRNP particle [Chabot et al. (1995) Nucleic Acids Res. 23, 3206-3213]. In mouse and Drosophila cultured cells the electrophoretic mobility of p255, faster in the latter species, was identical to that of the hyperphosphorylated form of RNA polymerase II largest subunit (IIo). The CC-3 immunoreactivity of p255 was abolished by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, which is known to cause the dephosphorylation of the C-terminal domain of subunit IIo by inhibiting the TFIIH-associated kinase. The identity of p255 was confirmed by showing that CC-3-immunoprecipitated p255 was recognized by POL3/3 and 8WG16, two antibodies specific to RNA polymerase II largest subunit. Lastly, the recovery of RNA polymerase II largest subunit from HeLa splicing mixtures was compromised by EDTA, which prevents the interaction of p255 with splicing complexes and inhibits splicing. Our results indicate that p255 represents a highly phosphorylated form of RNA polymerase II largest subunit physically associated with spliceosomes and possibly involved in coupling transcription to RNA processing. PMID:8972849

  6. Dilatometric study of U1-xAmxO2±δ and U1-xCexO2±δ reactive sintering

    NASA Astrophysics Data System (ADS)

    Horlait, Denis; Feledziak, Alex; Lebreton, Florent; Clavier, Nicolas; Prieur, Damien; Dacheux, Nicolas; Delahaye, Thibaud

    2013-10-01

    In order to reduce the radiotoxicity of nuclear fuel waste, the transmutation of americium in U1-xAmxO2±δ dedicated fuels is considered. A convenient route to produce such fuels is reactive sintering from a UO2+δ/AmO2-δ green pellet, i.e., a single heat treatment during which both the densification and the formation of the U1-xAmxO2±δ solid solution occur. The mechanisms of such sintering are however barely known and require experimental data. In this aim, the densification through reactive sintering of a UO2+δ/AmO2-δ sample was monitored by dilatometry. The obtained results were compared to those reported for the formation of the U1-xAmxO2±δ solid solution monitored by in situ high-temperature X-ray diffraction. To assess the use of Ce as a substitute of Am, similar dilatometric studies were also carried out on UO2+δ/CeO2 pellets. Obtained results show that the use of a reactive sintering causes a delay in the densification process associated to the competition between solid solution formation and densification, which yields limitations in pellet final densities. The importance of redox behavior of Am (or Ce) on the achievement of solid solution formation and densification are also discussed, especially based on discrepancies in densification behavior between UO2+δ/AmO2-δ and UO2+δ/CeO2.

  7. Control of mouse U1 snRNA gene expression during in vitro differentiation of mouse embryonic stem cells.

    PubMed Central

    Cheng, Y; Lund, E; Kahan, B W; Dahlberg, J E

    1997-01-01

    Early in mouse development, two classes of U1 RNAs, mU1a and mU1b, are synthesized, but as development proceeds, transcription of the embryo-specific mU1b genes is selectively down-regulated to a barely detectable level. We show here that during in vitro differentiation of mouse embryonic stem (ES) cells, both exogenously introduced and endogenous U1b genes are subject to normal developmental regulation. Thus, ES cells represent a convenient isogenic system for studying the control of expression of developmentally regulated snRNA genes. Using this system, we have identified a region in the proximal 5'flanking region, located outside the PSE element, that is responsible for differential transcription of the mU1a and mU1b genes in both developing cells and transiently transfected NIH 3T3 cells. PMID:9153321

  8. Deletion of SNURF/SNRPN U1B and U1B* upstream exons in a child with developmental delay and excessive weight.

    PubMed

    Koufaris, Costas; Alexandrou, Angelos; Papaevripidou, Ioannis; Alexandrou, Ioanna; Christophidou-Anastasiadou, Violetta; Sismani, Carolina

    2016-09-01

    Prader-Willi syndrome is a rare syndrome characterized by hypotonia, developmental delay and excessive appetite. This syndrome is caused by the loss of function of paternally-expressed genes located in an imprinting centre in 15q11-q13. Here, we report the case of a patient who was referred to us with Prader-Willi syndrome-like symptoms including obesity and developmental delay. Examination of this patient revealed that he was a carrier of a paternally inherited deletion that affected the U1B and U1B* upstream exons of the SNURF-SNRNP gene within the 15q11-q13 imprinted region. Mutations localized within this genomic region have not been previously reported in Prader-Willi syndrome patients. It is possible that disruption of upstream exons of SNURF-SNRNP could contribute to Prader-Willi phenotype by disrupting brain-specific alternative transcripts, although, case reports from further patients with a comparable phenotype are required. PMID:27659333

  9. U(1)B-L symmetry restoration and effective neutrino species

    NASA Astrophysics Data System (ADS)

    Ishida, Hiroyuki; Takahashi, Fuminobu

    2014-06-01

    The U(1)B-L symmetry could be restored during inflation, since the BICEP2 results suggest a GUT-scale inflation with the Hubble parameter, Hinf≃1014 GeV, close to the U(1)B-L breaking scale. We consider a scenario in which the B-L Higgs field dominates the Universe after inflation, and mainly decays into the U(1)B-L gauge bosons, whose subsequent decays reheat the Universe. Interestingly, if one of the right-handed neutrinos is extremely light and behaves as dark radiation or hot dark matter, its abundance is determined by the B-L charge assignment and the relativistic degree of freedom in plasma. We find that ΔNeff takes discrete values between 0.188 and 0.220 in the standard model plus three right-handed neutrinos, depending on whether the decay into heavier right-handed neutrinos is kinematically accessible or not. In the fiveness U(1)5 case, we find that ΔNeff takes discrete values between 0.313 and 0.423. The tension between BICEP2 and Planck can be partially relaxed by dark radiation.

  10. Draft Genome Sequence of Erythromycin- and Oxytetracycline-Sensitive Nocardia seriolae Strain U-1 (NBRC 110359)

    PubMed Central

    Sukeda, Masaki; Shimizu, Masato; Yamane, Jin; Ohnishi, Kouhei; Oshima, Syun-ichirou

    2016-01-01

    In Japan, the emergence of macrolide- and oxytetracycline-resistant strains of Nocardia seriolae has previously been reported. Here, we describe the draft genome sequence of N. seriolae strain U-1, isolated in 2011 from a diseased yellowtail in Kagoshima Prefecture. The draft genome does not have any genes responsible for macrolide and tetracycline resistance. PMID:26798107

  11. Axionic domain wall number related to U(1)anom global symmetry

    NASA Astrophysics Data System (ADS)

    Kim, Jihn E.

    2016-08-01

    The QCD axion with fa at an intermediate scale, 109 GeV ∼1012 GeV, seems in conflict with the gravity spoil of global symmetries and may face the axionic domain wall problem. We point out that the string compactifications with an anomalous U(1) gauge symmetry, allowing desirable chiral matter spectra, circumvent these two problems simultaneously.

  12. Spontaneous SUSY breaking with anomalous U(1) symmetry by meta-stable vacuum

    SciTech Connect

    Nishino, Hiroyuki

    2008-11-23

    We will discuss a SUSY breaking model with anomalous U(1) symmetry. We discard R-symmetry and allow non-renormalizable terms for the model. It will be shown that certain class of models, where the number of positively charged fields is larger than that of negatively charged fields, can have meta-stable SUSY breaking vacuum.

  13. Geophysical investigation of the 216-U-1/2 pipeline, 200 west area

    SciTech Connect

    Fassett, J.W; Bergstrom, K.A., Westinghouse Hanford

    1996-08-22

    Ground-penetrating radar was used at three locations in an attempt to locate and determine the depth of the 216-U-1/2 pipeline. Many anomalies were found, all very useful to the project, but only some of which were identified with the pipeline.

  14. Construction of an SO(10) x U(1)-F model of the Yukawa interactions

    SciTech Connect

    Albright, Carl H.; Nandi, Satyanarayan

    1995-07-01

    We construct a supersymmetric SO(10) \\times U(1)_F model of the Yukawa interactions at the grand unification scale from knowledge of a phenomenological set of mass matrices obtained by a previous bottom-up approach. The U(1)_F family symmetry determines the textures for the Majorana and generic Dirac mass matrices, while the SO(10) symmetry relates each particular element of the up, down, neutrino and charged lepton Dirac matrices. The dominant second and third family contributions in the Dirac sector are renormalizable, while the remaining contributions to the Dirac mass matrices are of higher order, restricted by the U(1)_F family symmetry to a small set of tree diagrams, and mainly complex-symmetric. The tree diagrams for the Majorana mass matrix are all non-renormalizable and of progressively higher-order, leading to a nearly geometrical structure. Pairs of {\\bf 1, 45, 10} and {\\bf 126} Higgs representations enter with those having large vacuum expectation values breaking the symmetry down to SU(3)_c \\times SU(2)_L \\times U(1)_Y near the grand unification scale. In terms of 12 parameters expressed as the Yukawa couplings times vacuum expectation values for the Higgs representations employed, a realistic set of 15 quark and lepton masses (including those for the 3 heavy righthanded Majorana neutrinos) and 8 mixing parameters emerges for the neutrino scenario involving the non-adiabatic conversion of solar neutrinos and the depletion of atmospheric muon-neutrinos through oscillations into tau-neutrinos.

  15. Low scale nonuniversal, nonanomalous U(1){sub F}{sup '} in a minimal supersymmetric standard model

    SciTech Connect

    Chen Muchun; Huang Jinrui

    2010-10-01

    We propose a nonuniversal U(1){sub F}{sup '} symmetry combined with the minimal supersymmetric standard model. All anomaly cancellation conditions are satisfied without exotic fields other than three right-handed neutrinos. Because our model allows all three generations of chiral superfields to have different U(1){sub F}{sup '} charges, upon the breaking of the U(1){sub F}{sup '} symmetry at a low scale, realistic masses and mixing angles in both the quark and lepton sectors are obtained. In our model, neutrinos are predicted to be Dirac fermions and their mass ordering is of the inverted hierarchy type. The U(1){sub F}{sup '} charges of the chiral superfields also naturally suppress the {mu}-term and automatically forbid baryon number and lepton number violating operators. While all flavor-changing neutral current constraints in the down quark and charged-lepton sectors can be satisfied, we find that the constraint from D{sup 0}-D{sup 0} turns out to be much more stringent than the constraints from the precision electroweak data.

  16. 13. DETAIL, U1 JOINT, FROM BELOW AND SOUTH, SHOWING RIVETED ...

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

    13. DETAIL, U1 JOINT, FROM BELOW AND SOUTH, SHOWING RIVETED CONNECTION, AND INTERSECTION OF END POST, VERTICAL, DIAGONAL AND UPPER CHORD MEMBERS AND LATERAL BRACING - Glendale Road Bridge, Spanning Deep Creek Lake on Glendale Road, McHenry, Garrett County, MD

  17. Classically conformal U(1 ) ' extended standard model, electroweak vacuum stability, and LHC Run-2 bounds

    NASA Astrophysics Data System (ADS)

    Das, Arindam; Oda, Satsuki; Okada, Nobuchika; Takahashi, Dai-suke

    2016-06-01

    We consider the minimal U(1 ) ' extension of the standard model (SM) with the classically conformal invariance, where an anomaly-free U(1 ) ' gauge symmetry is introduced along with three generations of right-handed neutrinos and a U(1 ) ' Higgs field. Since the classically conformal symmetry forbids all dimensional parameters in the model, the U(1 ) ' gauge symmetry is broken by the Coleman-Weinberg mechanism, generating the mass terms of the U(1 ) ' gauge boson (Z' boson) and the right-handed neutrinos. Through a mixing quartic coupling between the U(1 ) ' Higgs field and the SM Higgs doublet field, the radiative U(1 ) ' gauge symmetry breaking also triggers the breaking of the electroweak symmetry. In this model context, we first investigate the electroweak vacuum instability problem in the SM. Employing the renormalization group equations at the two-loop level and the central values for the world average masses of the top quark (mt=173.34 GeV ) and the Higgs boson (mh=125.09 GeV ), we perform parameter scans to identify the parameter region for resolving the electroweak vacuum instability problem. Next we interpret the recent ATLAS and CMS search limits at the LHC Run-2 for the sequential Z' boson to constrain the parameter region in our model. Combining the constraints from the electroweak vacuum stability and the LHC Run-2 results, we find a bound on the Z' boson mass as mZ'≳3.5 TeV . We also calculate self-energy corrections to the SM Higgs doublet field through the heavy states, the right-handed neutrinos and the Z' boson, and find the naturalness bound as mZ'≲7 TeV , in order to reproduce the right electroweak scale for the fine-tuning level better than 10%. The resultant mass range of 3.5 TeV ≲mZ'≲7 TeV will be explored at the LHC Run-2 in the near future.

  18. Higgs phenomenology in the minimal S U (3 )L×U (1 )X model

    NASA Astrophysics Data System (ADS)

    Okada, Hiroshi; Okada, Nobuchika; Orikasa, Yuta; Yagyu, Kei

    2016-07-01

    We investigate the phenomenology of a model based on the S U (3 )c×S U (3 )L×U (1 )X gauge theory, the so-called 331 model. In particular, we focus on the Higgs sector of the model which is composed of three S U (3 )L triplet Higgs fields and is the minimal form for realizing a phenomenologically acceptable scenario. After the spontaneous symmetry breaking S U (3 )L×U (1 )X→S U (2 )L×U (1 )Y , our Higgs sector effectively becomes that with two S U (2 )L doublet scalar fields, in which the first- and the second-generation quarks couple to a different Higgs doublet from that which couples to the third-generation quarks. This structure causes the flavor-changing neutral current mediated by Higgs bosons at the tree level. By taking an alignment limit of the mass matrix for the C P -even Higgs bosons, which is naturally realized in the case with the breaking scale of S U (3 )L×U (1 )X much larger than that of S U (2 )L×U (1 )Y, we can avoid current constraints from flavor experiments such as the B0-B¯ 0 mixing even for the Higgs bosons masses that are O (100 ) GeV . In this allowed parameter space, we clarify that a characteristic deviation in quark Yukawa couplings of the Standard Model-like Higgs boson is predicted, which has a different pattern from that seen in two Higgs doublet models with a softly broken Z2 symmetry. We also find that the flavor-violating decay modes of the extra Higgs boson, e.g., H /A →t c and H±→t s , can be dominant, and they yield the important signature to distinguish our model from the two Higgs doublet models.

  19. Charged particles with electromagnetic interactions and U(1)-gauge theory: Hamiltonian and Lagrangian formalisms

    SciTech Connect

    Beckers, J.; Hussin, V.

    1984-06-15

    The motion of charged particles in external electromagnetic fields is reviewed with the purpose of determining the whole set of constants of motion. The Johnson-Lippmann results concerning the interaction with a constant magnetic field are taken as the starting point of the study. Our results are obtained through simple group-theoretical arguments based essentially on extended Lie algebras associated with the kinematical group of the (constant) electromagnetic field involved in the interaction. Nonrelativistic Schroedinger (or Pauli) and relativistic Dirac Hamiltonians are considered. The corresponding Lagrangian densities are then studied when the charged particles move in arbitrary electromagnetic fields. Through Noether's theorem, we get the constants of motion when coordinate and gauge transformations are combined. These results complete the U(1)-gauge theory and relate the works of Bacry, Combe, and Richard and of Jackiw and Manton when external gauge fields are considered. These developments enhance the minimal-coupling principle, the U(1)-gauge theory, and Noether's theorem.

  20. Diphoton resonances in a U (1 )B -L extension of the minimal supersymmetric standard model

    NASA Astrophysics Data System (ADS)

    Lazarides, G.; Shafi, Q.

    2016-06-01

    Inspired by the 750 GeV diphoton state recently reported by ATLAS and CMS, we propose a U (1 )B-L extension of the MSSM which predicts the existence of four spin zero resonance states that are degenerate in mass in the supersymmetric limit. Vectorlike fields, a gauge singlet field, as well as the MSSM Higgsinos are prevented from acquiring arbitrary large masses by a U (1 ) R symmetry. Indeed, these masses can be considerably lighter than the Z' gauge boson mass. Depending on kinematics, the resonance states could decay into right-handed neutrinos and sneutrinos, and/or MSSM Higgs fields and Higgsinos with total decay widths in the multi-GeV range.

  1. Minimal gauged U(1) B-L model with spontaneous R parity violation.

    PubMed

    Barger, Vernon; Pérez, Pavel Fileviez; Spinner, Sogee

    2009-05-01

    We study the minimal gauged U(1) B-L supersymmetric model and show that it provides an attractive theory for spontaneous R-parity violation. Both U(1) B-L and R parity are broken by the vacuum expectation value of the right-handed sneutrino (proportional to the soft supersymmetry masses), thereby linking the B-L and soft SUSY scales. In this context we find a consistent mechanism for generating neutrino masses and a realistic mass spectrum, all without extending the Higgs sector of the minimal supersymmetry standard model. We discuss the most relevant collider signals and the connection between the Z' gauge boson and R-parity violation. PMID:19518859

  2. G-flux, M5 instantons, and U(1) symmetries in F-theory

    NASA Astrophysics Data System (ADS)

    Marsano, Joseph; Saulina, Natalia; Schäfer-Nameki, Sakura

    2013-03-01

    Local aspects of singular F-theory compactifications for supersymmetric grand unified theory model building are fairly well understood in terms of Higgs bundles and their spectral data. Several global issues remain, however, including a description of G-fluxes, which are key to constructing chiral matter and stabilizing moduli, and the global realization of U(1) symmetries that can forbid phenomenologically unfavorable couplings. In this paper, we sharpen our earlier proposal for describing G-fluxes and U(1)s through a distinguished “Tate” divisor. As an application, we give a general discussion of M5-instanton contributions in the presence of G-flux and exemplify this in a concrete example, where we comment on the ability of instanton-induced superpotential couplings to stabilize Kähler moduli.

  3. Shaft Sinking at the Nevada Test Site, U1h Shaft Project

    SciTech Connect

    B. Briggs; R. Musick

    2001-03-01

    The U1h Shaft Project is a design/build subcontract to construct one 6.1 meter (m) (20 feet (ft)) finished diameter shaft to a depth of 321.6 m (1,055 ft.) at the Nevada Test Site. Atkinson Construction was subcontracted by Bechtel Nevada to construct the U1h Shaft for the U.S. Department of Energy. The project consists of furnishing and installing the sinking plant, construction of the 321.6 m (1,055 ft.) of concrete lined shaft, development of a shaft station at a depth of 297.5 m (976 ft.), and construction of a loading pocket at the station. The outfitting of the shaft and installation of a new hoist may be incorporated into the project at a later date. This paper will describe the design phase, the excavation and lining operation, shaft station construction and the contractual challenges encountered on this project.

  4. Kagome Chiral Spin Liquid as a Gauged U (1 ) Symmetry Protected Topological Phase

    NASA Astrophysics Data System (ADS)

    He, Yin-Chen; Bhattacharjee, Subhro; Pollmann, Frank; Moessner, R.

    2015-12-01

    While the existence of a chiral spin liquid (CSL) on a class of spin-1 /2 kagome antiferromagnets is by now well established numerically, a controlled theoretical path from the lattice model leading to a low-energy topological field theory is still lacking. This we provide via an explicit construction starting from reformulating a microscopic model for a CSL as a lattice gauge theory and deriving the low-energy form of its continuum limit. A crucial ingredient is the realization that the bosonic spinons of the gauge theory exhibit a U (1 ) symmetry protected topological (SPT) phase, which upon promoting its U (1 ) global symmetry to a local gauge structure ("gauging"), yields the CSL. We suggest that such an explicit lattice-based construction involving gauging of a SPT phase can be applied more generally to understand topological spin liquids.

  5. Kagome Chiral Spin Liquid as a Gauged U(1) Symmetry Protected Topological Phase.

    PubMed

    He, Yin-Chen; Bhattacharjee, Subhro; Pollmann, Frank; Moessner, R

    2015-12-31

    While the existence of a chiral spin liquid (CSL) on a class of spin-1/2 kagome antiferromagnets is by now well established numerically, a controlled theoretical path from the lattice model leading to a low-energy topological field theory is still lacking. This we provide via an explicit construction starting from reformulating a microscopic model for a CSL as a lattice gauge theory and deriving the low-energy form of its continuum limit. A crucial ingredient is the realization that the bosonic spinons of the gauge theory exhibit a U(1) symmetry protected topological (SPT) phase, which upon promoting its U(1) global symmetry to a local gauge structure ("gauging"), yields the CSL. We suggest that such an explicit lattice-based construction involving gauging of a SPT phase can be applied more generally to understand topological spin liquids.

  6. Thermochemical modeling of the U1-yGdyO2 x phase

    SciTech Connect

    McMurray, Jacob; Shin, Dongwon; Slone, Benjamin W; Besmann, Theodore M

    2013-01-01

    A thermodynamic model for the U1-yGdyO2 x phase was developed using the compound energy formalism (CEF) with a three sublattice approach and is an extension of the already successful CEF representation of the fluorite UO2 x phase. The Gibbs energies for the end-members created by the addition of Gd to the cation sublattice are estimated using the lattice stability of a fictive gadolinium oxide fluorite structure compound from density functional theory. The model interaction parameters are determined from reported oxygen potential-temperature-composition measurements. The calculated results are in good agreement with the experimental data and the trends are consistent. The CEF for the U1-yGdyO2 x solid solution can be combined with other representations of actinide and fission product containing fluorite UO2 phases to develop multi-component models within the CEF framework.

  7. Role of the U(1) ghost beyond leading order in a large-Nc expansion

    SciTech Connect

    Hrayr Matevosyan; Anthony Thomas

    2008-09-01

    The 1/Nc expansion is one of the very few methods we have for generating a systematic expansion of QCD at the energy scale relevant to hadron structure. The present formulation of this theory relies on 't Hooft's double-line notation for calculating the leading order of a diagram in the 1/Nc expansion, where the local SU(Nc) gauge symmetry is substituted by a U(Nc) symmetry and the associated U(1) ghost field is ignored. In the current work we demonstrate the insufficiency of this formulation for describing certain non-planar diagrams. We derive a more complete set of Feynman rules that include the U(1) ghost field and provide a useful tool for calculating both color factors and 1/Nc orders of given color-singlet diagrams.

  8. Diphoton excess from hidden U(1) gauge symmetry with large kinetic mixing

    NASA Astrophysics Data System (ADS)

    Takahashi, Fuminobu; Yamada, Masaki; Yokozaki, Norimi

    2016-09-01

    We show that the 750 GeV diphoton excess can be explained by introducing vector-like quarks and hidden fermions charged under a hidden U(1) gauge symmetry, which has a relatively large coupling constant as well as a significant kinetic mixing with U(1)Y. With the large kinetic mixing, the standard model gauge couplings unify around 1017 GeV, suggesting the grand unified theory without too rapid proton decay. Our scenario predicts events with a photon and missing transverse momentum, and its cross section is related to that for the diphoton excess through the kinetic mixing. We also discuss other possible collider signatures and cosmology, including various ways to evade constraints on exotic stable charged particles. In some cases where the 750 GeV diphoton excess is due to diaxion decays, our scenario also predicts triphoton and tetraphoton signals.

  9. CERN LEP indications for two light Higgs bosons and the U(1){sup '} model

    SciTech Connect

    Demir, Durmus A.; Solmaz, Levent; Solmaz, Saime

    2006-01-01

    Reanalyses of LEP data have shown preference to two light CP-even Higgs bosons. We discuss implications of such a Higgs boson spectrum for the minimal supersymmetric model extended by a standard model singlet chiral superfield and an additional Abelian gauge invariance [the U(1){sup '} model]. We, in particular, determine parameter regions that lead to two light CP-even Higgs bosons while satisfying existing bounds on the mass and mixings of the extra vector boson. In these parameter regions, the pseudoscalar Higgs is found to be nearly degenerate in mass with either the lightest or next-to-lightest Higgs boson. Certain parameters of the U(1){sup '} model such as the effective {mu} parameter are found to be significantly bounded by the LEP two light Higgs signal.

  10. D-branes and extended characters in SL(2,R)/U(1)

    NASA Astrophysics Data System (ADS)

    Fotopoulos, Angelos; Niarchos, Vasilis; Prezas, Nikolaos

    2005-03-01

    We present a detailed study of D-branes in the axially gauged SL(2/U(1) coset conformal field theory for integer level k. Our analysis is based on the modular bootstrap approach and utilizes the extended SL(2,R)/U(1) characters and the embedding of the parafermionic coset algebra in the N=2 superconformal algebra. We propose three basic classes of boundary states corresponding to D0-, D1- and D2-branes. We verify that these boundary states satisfy the Cardy consistency conditions and discuss their physical properties. The D0- and D1-branes agree with those found in earlier work by Ribault and Schomerus using different methods (descent from the Euclidean AdS model). The D2-branes are new. They are not, in general, space-filling but extend from the asymptotic circle at infinity up to a minimum distance ρ⩾0 from the tip of the cigar.

  11. A conserved intronic U1 snRNP-binding sequence promotes trans-splicing in Drosophila.

    PubMed

    Gao, Jun-Li; Fan, Yu-Jie; Wang, Xiu-Ye; Zhang, Yu; Pu, Jia; Li, Liang; Shao, Wei; Zhan, Shuai; Hao, Jianjiang; Xu, Yong-Zhen

    2015-04-01

    Unlike typical cis-splicing, trans-splicing joins exons from two separate transcripts to produce chimeric mRNA and has been detected in most eukaryotes. Trans-splicing in trypanosomes and nematodes has been characterized as a spliced leader RNA-facilitated reaction; in contrast, its mechanism in higher eukaryotes remains unclear. Here we investigate mod(mdg4), a classic trans-spliced gene in Drosophila, and report that two critical RNA sequences in the middle of the last 5' intron, TSA and TSB, promote trans-splicing of mod(mdg4). In TSA, a 13-nucleotide (nt) core motif is conserved across Drosophila species and is essential and sufficient for trans-splicing, which binds U1 small nuclear RNP (snRNP) through strong base-pairing with U1 snRNA. In TSB, a conserved secondary structure acts as an enhancer. Deletions of TSA and TSB using the CRISPR/Cas9 system result in developmental defects in flies. Although it is not clear how the 5' intron finds the 3' introns, compensatory changes in U1 snRNA rescue trans-splicing of TSA mutants, demonstrating that U1 recruitment is critical to promote trans-splicing in vivo. Furthermore, TSA core-like motifs are found in many other trans-spliced Drosophila genes, including lola. These findings represent a novel mechanism of trans-splicing, in which RNA motifs in the 5' intron are sufficient to bring separate transcripts into close proximity to promote trans-splicing. PMID:25838544

  12. A conserved intronic U1 snRNP-binding sequence promotes trans-splicing in Drosophila.

    PubMed

    Gao, Jun-Li; Fan, Yu-Jie; Wang, Xiu-Ye; Zhang, Yu; Pu, Jia; Li, Liang; Shao, Wei; Zhan, Shuai; Hao, Jianjiang; Xu, Yong-Zhen

    2015-04-01

    Unlike typical cis-splicing, trans-splicing joins exons from two separate transcripts to produce chimeric mRNA and has been detected in most eukaryotes. Trans-splicing in trypanosomes and nematodes has been characterized as a spliced leader RNA-facilitated reaction; in contrast, its mechanism in higher eukaryotes remains unclear. Here we investigate mod(mdg4), a classic trans-spliced gene in Drosophila, and report that two critical RNA sequences in the middle of the last 5' intron, TSA and TSB, promote trans-splicing of mod(mdg4). In TSA, a 13-nucleotide (nt) core motif is conserved across Drosophila species and is essential and sufficient for trans-splicing, which binds U1 small nuclear RNP (snRNP) through strong base-pairing with U1 snRNA. In TSB, a conserved secondary structure acts as an enhancer. Deletions of TSA and TSB using the CRISPR/Cas9 system result in developmental defects in flies. Although it is not clear how the 5' intron finds the 3' introns, compensatory changes in U1 snRNA rescue trans-splicing of TSA mutants, demonstrating that U1 recruitment is critical to promote trans-splicing in vivo. Furthermore, TSA core-like motifs are found in many other trans-spliced Drosophila genes, including lola. These findings represent a novel mechanism of trans-splicing, in which RNA motifs in the 5' intron are sufficient to bring separate transcripts into close proximity to promote trans-splicing.

  13. A conserved intronic U1 snRNP-binding sequence promotes trans-splicing in Drosophila

    PubMed Central

    Gao, Jun-Li; Fan, Yu-Jie; Wang, Xiu-Ye; Zhang, Yu; Pu, Jia; Li, Liang; Shao, Wei; Zhan, Shuai; Hao, Jianjiang

    2015-01-01

    Unlike typical cis-splicing, trans-splicing joins exons from two separate transcripts to produce chimeric mRNA and has been detected in most eukaryotes. Trans-splicing in trypanosomes and nematodes has been characterized as a spliced leader RNA-facilitated reaction; in contrast, its mechanism in higher eukaryotes remains unclear. Here we investigate mod(mdg4), a classic trans-spliced gene in Drosophila, and report that two critical RNA sequences in the middle of the last 5′ intron, TSA and TSB, promote trans-splicing of mod(mdg4). In TSA, a 13-nucleotide (nt) core motif is conserved across Drosophila species and is essential and sufficient for trans-splicing, which binds U1 small nuclear RNP (snRNP) through strong base-pairing with U1 snRNA. In TSB, a conserved secondary structure acts as an enhancer. Deletions of TSA and TSB using the CRISPR/Cas9 system result in developmental defects in flies. Although it is not clear how the 5′ intron finds the 3′ introns, compensatory changes in U1 snRNA rescue trans-splicing of TSA mutants, demonstrating that U1 recruitment is critical to promote trans-splicing in vivo. Furthermore, TSA core-like motifs are found in many other trans-spliced Drosophila genes, including lola. These findings represent a novel mechanism of trans-splicing, in which RNA motifs in the 5′ intron are sufficient to bring separate transcripts into close proximity to promote trans-splicing. PMID:25838544

  14. Minimal flavor violation in the minimal U(1)B-L model and resonant leptogenesis

    NASA Astrophysics Data System (ADS)

    Okada, Nobuchika; Orikasa, Yuta; Yamada, Toshifumi

    2012-10-01

    We investigate the resonant leptogenesis scenario in the minimally U(1)B-L extended standard model with minimal flavor violation. In our model, the U(1)B-L gauge symmetry is broken at the TeV scale and standard model singlet neutrinos gain Majorana masses of order TeV. In addition, we introduce a flavor symmetry on the singlet neutrinos at a scale higher than TeV. The flavor symmetry is explicitly broken by the neutrino Dirac Yukawa coupling, which induces splittings in the singlet neutrino Majorana masses at lower scales through renormalization group evolutions. We call this setup minimal flavor violation. The mass splittings are proportional to the tiny Dirac Yukawa coupling, and hence they automatically enhance the CP asymmetry parameter necessary for the resonant leptogenesis mechanism. In this paper, we calculate the baryon number yield by solving the Boltzmann equations, including the effects of U(1)B-L gauge boson that also has TeV scale mass and causes washing-out of the singlet neutrinos in the course of thermal leptogenesis. The Dirac Yukawa coupling for neutrinos is fixed in terms of neutrino oscillation data and an arbitrary 3×3 complex-valued orthogonal matrix. We show that the right amount of baryon number asymmetry can be achieved through thermal leptogenesis in the context of the minimal flavor violation with singlet neutrinos and U(1)B-L gauge boson at the TeV scale. These particles can be discovered at the LHC in the near future.

  15. Dark Matter in Supersymmetric U(1){sub B-L} Model

    SciTech Connect

    Khalil, S.; Okada, H.

    2009-04-17

    We analyze the dark matter problem in the context of supersymmetric, U(1){sub B-L} model. In this model, the lightest neutalino can be B-L gaugino Z-tilde{sub B-L} or Higgsinos {chi}-tilde{sub 1,2} dominated. We examine the thermal relic abundance of these particles and discuss the prospects for their direct detection if they form part of our galactic halo.

  16. Engineering assessment and certification of integrity of the 325-I1U1 tank system

    SciTech Connect

    Schwartz, W W; Graser, D A

    1991-12-01

    This Engineering Assessment and Certification of Integrity of retention tank 325-I1U1 of Lawrence Livermore Laboratory has been prepared in response to 40 CFR 265.191 for an existing tank system that stores hazardous waste and does not have secondary containment. This technical assessment has been reviewed by an independent, qualified, California-registered professional engineer, who has certified the tank system to be adequately designed and compatible with the stored waste so that it will not collapse, rupture, or fail. Certification of the 325-I1U1 tank system is qualified by the fact that 40 CFR 265-193 requires that a system be upgraded to include secondary containment when it reaches 15 years of age or within two years after January 12, 1987, whichever comes later. Tank 325-I1U1 was built in 1968 and required upgrading to secondary containment by January 12, 1989. This Engineering Assessment has been prepared as Best Management practice since this tank system was in service after January 12, 1989, but is not in use at this time. This document will be kept on file at the facility. Certification and documentation of the onground retention tank 325-I1O1, which is part of the 325-I1 retention tank system, is not included in this assessment. A discussion of tank 325-I1O1, however, is included in this report to provide a complete description of the 325-I1 retention tank system.

  17. Phase Transition Couplings in U(1) and SU(N) Regularized Gauge Theories

    NASA Astrophysics Data System (ADS)

    Laperashvili, L. V.; Ryzhikh, D. A.; Nielsen, H. B.

    Using a two-loop approximation for β functions, we have considered the corresponding renormalization group improved effective potential in the dual Abelian Higgs model (DAHM) of scalar monopoles and calculated the phase transition (critical) couplings in U(1) and SU(N) regularized gauge theories. In contrast to our previous result αcrit 0.17, obtained in the one-loop approximation with the DAHM effective potential (see Ref. 20), the critical value of the electric fine structure constant in the two-loop approximation, calculated in the present paper, is equal to αcrit 0.208 and coincides with the lattice result for compact QED10: α crit lat≈ 0.20+/- 0.015. Following the 't Hooft's idea of the ``Abelization'' of monopole vacuum in the Yang-Mills theories, we have obtained an estimation of the SU(N) triple point coupling constants, which is α {N, crit}-1= (N)/(2) √ {(N+1)/(N-1)} α { U(1),crit}-1. This relation was used for the description of the Planck scale values of the inverse running constants α i-1(μ ) (i= 1, 2, 3 correspond to U(1), SU(2) and SU(3) groups), according to the ideas of the multiple point model.16

  18. Hidden extra U(1) at the electroweak/TeV scale

    SciTech Connect

    Grossmann, B. N.; Rai, Santosh Kumar; McElrath, B.; Nandi, S.

    2010-09-01

    We propose a simple extension of the standard model (SM) by adding an extra U(1) symmetry which is hidden from the SM sector. Such a hidden U(1) has not been considered before, and its existence at the TeV scale can be explored at the LHC. This hidden U(1) does not couple directly to the SM particles, and couples only to new SU(2){sub L} singlet exotic quarks and singlet Higgs bosons, and is broken at the TeV scale. The dominant signals at the high-energy hadron colliders are multilepton and multi-b-jet final states with or without missing energy. We calculate the signal rates as well as the corresponding standard model background for these final states. A very distinctive signal is 6 high p{sub T} b-jets in the final state with no missing energy. For a wide range of the exotic quarks masses the signals are observable above the background at the LHC.

  19. Phenomenological implications of the flipped SU(5) × U(1) superstring model

    NASA Astrophysics Data System (ADS)

    Tamvakis, K.

    1991-07-01

    We study in detail gauge symmetry breaking in the SU(5)× U(1) 1× U(1) 4× SO(10)× SO(6) superstring model, solving the D and F-flatness conditions and taking into account quartic and quintic superpotential terms. We find that, to this order, the model describes two massive generations of quarks and leptons as well as a massless generation expected to receive naturally suppressed masses from higher order non-renormalizable terms. D and F-flatness restricts the number of massless isodoublets to four. We solve the coupled renormalization group equations for the gauge and Yukawa couplings in the two-loop approximation and obtain the top-quark mass as a function of two parameters of the model which could be chosen to be ratios of singlet v.e.v's associated with the surplu s ( U(1)) 4 breaking. We obtain a heavy top-quark with 150 GeV ≤ m1 < 200 GeV, for most part of the parameter space, while lower values are possible only in a very small extremal region. We also compute the allowed range of unification parameters ( Mx, sin2θω, α3( Mw)) in the presence of a heavy top quark.

  20. Galactic gamma ray excess and dark matter phenomenology in a U(1) B- L model

    NASA Astrophysics Data System (ADS)

    Biswas, Anirban; Choubey, Sandhya; Khan, Sarif

    2016-08-01

    In this work, we have considered a gauged U(1)B-L extension of the Standard Model (SM) with three right handed neutrinos for anomaly cancellation and two additional SM singlet complex scalars with nontrivial B-L charges. One of these is used to spontaneously break the U(1)B-L gauge symmetry, leading to Majorana masses for the neutrinos through the standard Type I seesaw mechanism, while the other becomes the dark matter (DM) candidate in the model. We test the viability of the model to simultaneously explain the DM relic density observed in the CMB data as well as the Galactic Centre (GC) γ-ray excess seen by Fermi-LAT. We show that for DM masses in the range 40-55 GeV and for a wide range of U(1)B-L gauge boson masses, one can satisfy both these constraints if the additional neutral Higgs scalar has a mass around the resonance region. In studying the dark matter phenomenology and GC excess, we have taken into account theoretical as well as experimental constraints coming from vacuum stability condition, Planck bound on DM relic density, LHC and LUX and present allowed areas in the model parameter space consistent with all relevant data, calculate the predicted gamma ray flux from the GC and discuss the related phenomenology.

  1. Cation and Vacancy Disorder in U1-yNdyO2.00-X Alloys

    DOE PAGES

    Barabash, Rozaliya I.; Voit, Stewart L.; Aidhy, Dilpuneet S.; Lee, Seung Min; Knight, Travis W.; Sprouster, David J.; Ecker, Lynne E.

    2015-09-14

    In this study, the intermixing and clustering of U/Nd, O, and vacancies were studied by both laboratory and synchrotron-based x-ray diffraction in U1-yNdyO2-X alloys. It was found that an increased holding time at the high experimental temperature during initial alloy preparation results in a lower disorder of the Nd distribution in the alloys. Adjustment of the oxygen concentration in the U1-yNdyO2-X alloys with different Nd concentrations was accompanied by the formation of vacancies on the oxygen sublattice and a nanocrystalline component. The lattice parameters in the U1-yNdyO2-X alloys were also found to deviate significantly from Vegard's law when the Ndmore » concentration was high (53%) and decreased with increasing oxygen concentration. Such changes indicate the formation of large vacancy concentrations during oxygen adjustment at these high temperatures. Finally, the change in the vacancy concentration after the oxygen adjustment was estimated relative to Nd concentration and oxygen stoichiometry.« less

  2. Non-holomorphic modular forms and SL(2,R)/U(1) superconformal field theory

    NASA Astrophysics Data System (ADS)

    Eguchi, Tohru; Sugawara, Yuji

    2011-03-01

    We study the torus partition function of the {{{{text{SL}}left( {2,mathbb{R}} right)}} left/ {{{text{U}}(1)}} right.} SUSY gauged WZW model coupled to mathcal{N} = 2 U(1) current. Starting from the path-integral formulation of the theory, we introduce an infra-red regularization which preserves good modular properties and discuss the decomposition of the partition function in terms of the mathcal{N} = 2 characters of discrete (BPS) and continuous (non-BPS) representations. Contrary to our naive expectation, we find a non-holomorphic dependence (dependence on bar{tau } ) in the expansion coefficients of continuous representations. This non-holomorphicity appears in such a way that the anomalous modular behaviors of the discrete (BPS) characters are compensated by the transformation law of the non-holomorphic coefficients of the continuous (non-BPS) characters. Discrete characters together with the non-holomorphic continuous characters combine into real analytic Jacobi forms and these combinations exactly agree with the "modular completion" of discrete characters known in the theory of Mock theta functions [11]. We consider this to be a general phenomenon: we expect to encounter "holomorphic anomaly" ( bar{tau } -dependence) in string partition function on non-compact target manifolds. The anomaly occurs due to the incompatibility of holomorphy and modular invariance of the theory. Appearance of non-holomorphicity in {{{{text{SL}}left( {2,mathbb{R}} right)}} left/ {{{text{U}}(1)}} right.} elliptic genus has recently been observed by Troost [12].

  3. Mixed-state form factors of U(1) twist fields in the Dirac theory

    NASA Astrophysics Data System (ADS)

    Chen, Yixiong

    2016-08-01

    Using the ‘Liouville space’ (the space of operators) of the massive Dirac theory, we define mixed-state form factors of U(1) twist fields. We consider mixed states with density matrices diagonal in the asymptotic particle basis. This includes the thermal Gibbs state as well as all generalized Gibbs ensembles of the Dirac theory. When the mixed state is specialized to a thermal Gibbs state, using a Riemann-Hilbert problem and low-temperature expansion, we obtain finite-temperature form factors of U(1) twist fields. We then propose the expression for form factors of U(1) twist fields in general diagonal mixed states. We verify that these form factors satisfy a system of nonlinear functional differential equations, which is derived from the trace definition of mixed-state form factors. At last, under weak analytic conditions on the eigenvalues of the density matrix, we write down the large distance form factor expansions of two-point correlation functions of these twist fields. Using the relation between the Dirac and Ising models, this provides the large-distance expansion of the Rényi entropy (for integer Rényi parameter) in the Ising model in diagonal mixed states.

  4. The PSI-U1 snRNP interaction regulates male mating behavior in Drosophila.

    PubMed

    Wang, Qingqing; Taliaferro, J Matthew; Klibaite, Ugne; Hilgers, Valérie; Shaevitz, Joshua W; Rio, Donald C

    2016-05-10

    Alternative pre-mRNA splicing (AS) is a critical regulatory mechanism that operates extensively in the nervous system to produce diverse protein isoforms. Fruitless AS isoforms have been shown to influence male courtship behavior, but the underlying mechanisms are unknown. Using genome-wide approaches and quantitative behavioral assays, we show that the P-element somatic inhibitor (PSI) and its interaction with the U1 small nuclear ribonucleoprotein complex (snRNP) control male courtship behavior. PSI mutants lacking the U1 snRNP-interacting domain (PSIΔAB mutant) exhibit extended but futile mating attempts. The PSIΔAB mutant results in significant changes in the AS patterns of ∼1,200 genes in the Drosophila brain, many of which have been implicated in the regulation of male courtship behavior. PSI directly regulates the AS of at least one-third of these transcripts, suggesting that PSI-U1 snRNP interactions coordinate the behavioral network underlying courtship behavior. Importantly, one of these direct targets is fruitless, the master regulator of courtship. Thus, PSI imposes a specific mode of regulatory control within the neuronal circuit controlling courtship, even though it is broadly expressed in the fly nervous system. This study reinforces the importance of AS in the control of gene activity in neurons and integrated neuronal circuits, and provides a surprising link between a pleiotropic pre-mRNA splicing pathway and the precise control of successful male mating behavior.

  5. 17 CFR 259.101 - Form U-1, application or declaration under the Public Utility Holding Company Act of 1935.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... prescribed. Editorial Note: For Federal Register citations affecting Form U-1, see the List of CFR Sections... declaration under the Public Utility Holding Company Act of 1935. 259.101 Section 259.101 Commodity and... HOLDING COMPANY ACT OF 1935 Forms for Applications and Declarations § 259.101 Form U-1, application...

  6. Extended quantum U(1)-liquid phase in a three-dimensional quantum dimer model

    SciTech Connect

    Sikora, Olga; Shannon, Nic; Pollmann, Frank; Penc, Karlo; Fulde, Peter

    2011-09-15

    Recently, quantum dimer models have attracted a great deal of interest as a paradigm for the study of exotic quantum phases. Much of this excitement has centered on the claim that a certain class of quantum dimer model can support a quantum U(1)-liquid phase with deconfined fractional excitations in three dimensions. These fractional monomer excitations are quantum analogs of the magnetic monopoles found in spin ice. In this paper, we use extensive quantum Monte Carlo simulations to establish the ground-state phase diagram of the quantum dimer model on the three-dimensional diamond lattice as a function of the ratio {mu} of the potential to kinetic-energy terms in the Hamiltonian. We find that, for {mu}{sub c}=0.75{+-}0.02, the model undergoes a first-order quantum phase transition from an ordered ''R state'' into an extended quantum U(1)-liquid phase, which terminates in a quantum critical Rokhsar-Kivelson (RK) point for {mu}=1. This confirms the published field-theoretical scenario. We present detailed evidence for the existence of the U(1)-liquid phase and indirect evidence for the existence of its photon and monopole excitations. Simulations are benchmarked against a variety of exact and perturbative results, and a comparison is made of different variational wave functions. We also explore the ergodicity of the quantum dimer model on a diamond lattice within a given flux sector, identifying a new conserved quantity related to transition graphs of dimer configurations. These results complete and extend the previous analysis of O. Sikora et al.[Phys. Rev. Lett. 103, 247001 (2009)].

  7. Systematic U(1 ) B - L extensions of loop-induced neutrino mass models with dark matter

    NASA Astrophysics Data System (ADS)

    Ho, Shu-Yu; Toma, Takashi; Tsumura, Koji

    2016-08-01

    We study the gauged U(1 ) B - L extensions of the models for neutrino masses and dark matter. In this class of models, tiny neutrino masses are radiatively induced through the loop diagrams, while the origin of the dark matter stability is guaranteed by the remnant of the gauge symmetry. Depending on how the lepton number conservation is violated, these models are systematically classified. We present complete lists for the one-loop Z2 and the two-loop Z3 radiative seesaw models as examples of the classification. The anomaly cancellation conditions in these models are also discussed.

  8. Thermodynamical Bethe Ansatz analysis in an SU(2)/×U(1) symmetric /σ-model

    NASA Astrophysics Data System (ADS)

    Balog, János; Forgács, Péter

    2000-03-01

    Four different types of free energies are computed by both thermodynamical Bethe Ansatz (TBA) techniques and by weak coupling perturbation theory in an integrable one-parameter deformation of the O(4) principal chiral σ-model (with SU(2)×U(1) symmetry). The model exhibits both `fermionic' and `bosonic' type free energies and in all cases the perturbative and the TBA results are in perfect agreement, strongly supporting the correctness of the proposed S matrix. The mass gap is also computed in terms of the Λ parameters of the modified minimal subtraction scheme and a lattice regularized version of the model.

  9. Probing hidden sectors with Stückelberg U(1) gauge fields.

    PubMed

    Feng, Wan-Zhe; Shiu, Gary; Soler, Pablo; Ye, Fang

    2014-08-01

    We propose a framework in which visible matter interacts with matter from a hidden sector through mass mixings of Stückelberg U(1) gauge fields. In contrast to other Z(') mediation scenarios, our setup has the added appealing features that (i) the choice of Z(')'s can be significantly broadened without necessarily introducing unwanted exotic matter and (ii) there can be sizable tree-level interactions between the visible and hidden sectors. String theory embeddings of this scenario and their phenomenological features are briefly discussed. PMID:25148316

  10. Proton hexality from an anomalous flavor U(1) and neutrino masses: Linking to the string scale

    NASA Astrophysics Data System (ADS)

    Dreiner, Herbi K.; Luhn, Christoph; Murayama, Hitoshi; Thormeier, Marc

    2008-05-01

    We devise minimalistic gauged U(1 Froggatt-Nielsen models which at low-energy give rise to the recently suggested discrete gauge Z-symmetry, proton hexality, thus stabilizing the proton. Assuming three generations of right-handed neutrinos, with the proper choice of X-charges, we obtain viable neutrino masses. Furthermore, we find scenarios such that no X-charged hidden sector superfields are needed, which from a bottom-up perspective allows the calculation of g, g and G's Kač-Moody levels. The only mass scale apart from M is m.

  11. Decaying neutralino dark matter in anomalous U(1){sub H} models

    SciTech Connect

    Sierra, D. Aristizabal; Restrepo, D.; Zapata, Oscar

    2009-09-01

    In supersymmetric models extended with an anomalous U(1){sub H} different R-parity violating couplings can yield an unstable neutralino. We show that in this context astrophysical and cosmological constraints on neutralino decaying dark matter forbid bilinear R-parity breaking neutralino decays and lead to a class of purely trilinear R-parity violating scenarios in which the neutralino is stable on cosmological scales. We have found that among the resulting models some of them become suitable to explain the observed anomalies in cosmic-ray electron/positron fluxes.

  12. A three-loop neutrino model with global U (1) symmetry

    NASA Astrophysics Data System (ADS)

    Hatanaka, Hisaki; Nishiwaki, Kenji; Okada, Hiroshi; Orikasa, Yuta

    2015-05-01

    We study a three-loop induced neutrino model with a global U (1) symmetry at TeV scale, in which we naturally accommodate a bosonic dark matter candidate. We discuss the allowed regions of masses and quartic couplings for charged scalar bosons as well as the dark matter mass on the analogy of the original Zee-Babu model, and show the difference between them. We also discuss that the possibility of the collider searches in a future like-sign electron liner collider could be promising.

  13. Critical exponents in U(1) lattice gauge theory with a monopole term

    NASA Astrophysics Data System (ADS)

    Damm, G.; Kerler, W.

    1998-04-01

    We investigate critical properties of the phase transition in the four-dimensional compact U(1) lattice gauge theory supplemented by a monopole term for values of the monopole coupling λ such that the transition is of second order. It has been previously shown that at λ = 0.9 the critical exponent is already characteristic of a second-order transition and that it is different from the one of the Gaussian case. In the present study we perform a finite size analysis at λ = 1.1 to get information wether the value of this exponent is universal.

  14. U(1){sub R} mediation from the flux compactification in six dimensions

    SciTech Connect

    Lee, Hyun Min

    2008-11-23

    We consider a supersymmetric completion of codimension-two branes with nonzero tension in a 6D gauged supergravity. As a consequence, we obtain the football solution with 4D Minkowski space as a new supersymmetric background that preserves 4D N = 1 SUSY. In the presence of brane multiplets, we derive the 4D effective supergravity action for the football background and show that the remaining modulus can be stabilized by a bulk non-perturbative correction with brane uplifting potentials at a zero vacuum energy. We find that the U(1){sub R} mediation can be a dominant source of SUSY breaking for a brane scalar with nonzero R charge.

  15. Gaussian effective potential for the standard model SU(2)xU(1) electroweak theory

    SciTech Connect

    Siringo, Fabio; Marotta, Luca

    2008-07-01

    The Gaussian effective potential is derived for the non-Abelian SU(2)xU(1) gauge theory of electroweak interactions. At variance with naive derivations, the Gaussian effective potential is proven to be a genuine variational tool in any gauge. The role of ghosts is discussed and the unitarity gauge is shown to be the only choice which allows calculability without insertion of further approximations. The full non-Abelian calculation confirms the existence of a light Higgs boson in the nonperturbative strong coupling regime of the Higgs sector.

  16. U(1)-invariant membranes: The geometric formulation, Abel, and pendulum differential equations

    SciTech Connect

    Zheltukhin, A. A.; Trzetrzelewski, M.

    2010-06-15

    The geometric approach to study the dynamics of U(1)-invariant membranes is developed. The approach reveals an important role of the Abel nonlinear differential equation of the first type with variable coefficients depending on time and one of the membrane extendedness parameters. The general solution of the Abel equation is constructed. Exact solutions of the whole system of membrane equations in the D=5 Minkowski space-time are found and classified. It is shown that if the radial component of the membrane world vector is only time dependent, then the dynamics is described by the pendulum equation.

  17. Deconfinement Phase Transition in a 3D Nonlocal U(1) Lattice Gauge Theory

    SciTech Connect

    Arakawa, Gaku; Ichinose, Ikuo; Matsui, Tetsuo; Sakakibara, Kazuhiko

    2005-06-03

    We introduce a 3D compact U(1) lattice gauge theory having nonlocal interactions in the temporal direction, and study its phase structure. The model is relevant for the compact QED{sub 3} and strongly correlated electron systems like the t-J model of cuprates. For a power-law decaying long-range interaction, which simulates the effect of gapless matter fields, a second-order phase transition takes place separating the confinement and deconfinement phases. For an exponentially decaying interaction simulating matter fields with gaps, the system exhibits no signals of a second-order transition.

  18. CYCLIN-DEPENDENT KINASE G1 is associated with the spliceosome to regulate CALLOSE SYNTHASE5 splicing and pollen wall formation in Arabidopsis.

    PubMed

    Huang, Xue-Yong; Niu, Jin; Sun, Ming-Xi; Zhu, Jun; Gao, Ju-Fang; Yang, Jun; Zhou, Que; Yang, Zhong-Nan

    2013-02-01

    Arabidopsis thaliana CYCLIN-DEPEDENT KINASE G1 (CDKG1) belongs to the family of cyclin-dependent protein kinases that were originally characterized as cell cycle regulators in eukaryotes. Here, we report that CDKG1 regulates pre-mRNA splicing of CALLOSE SYNTHASE5 (CalS5) and, therefore, pollen wall formation. The knockout mutant cdkg1 exhibits reduced male fertility with impaired callose synthesis and abnormal pollen wall formation. The sixth intron in CalS5 pre-mRNA, a rare type of intron with a GC 5' splice site, is abnormally spliced in cdkg1. RNA immunoprecipitation analysis suggests that CDKG1 is associated with this intron. CDKG1 contains N-terminal Ser/Arg (RS) motifs and interacts with splicing factor Arginine/Serine-Rich Zinc Knuckle-Containing Protein33 (RSZ33) through its RS region to regulate proper splicing. CDKG1 and RS-containing Zinc Finger Protein22 (SRZ22), a splicing factor interacting with RSZ33 and U1 small nuclear ribonucleoprotein particle (snRNP) component U1-70k, colocalize in nuclear speckles and reside in the same complex. We propose that CDKG1 is recruited to U1 snRNP through RSZ33 to facilitate the splicing of the sixth intron of CalS5.

  19. CYCLIN-DEPENDENT KINASE G1 Is Associated with the Spliceosome to Regulate CALLOSE SYNTHASE5 Splicing and Pollen Wall Formation in Arabidopsis[C][W][OA

    PubMed Central

    Huang, Xue-Yong; Niu, Jin; Sun, Ming-Xi; Zhu, Jun; Gao, Ju-Fang; Yang, Jun; Zhou, Que; Yang, Zhong-Nan

    2013-01-01

    Arabidopsis thaliana CYCLIN-DEPEDENT KINASE G1 (CDKG1) belongs to the family of cyclin-dependent protein kinases that were originally characterized as cell cycle regulators in eukaryotes. Here, we report that CDKG1 regulates pre-mRNA splicing of CALLOSE SYNTHASE5 (CalS5) and, therefore, pollen wall formation. The knockout mutant cdkg1 exhibits reduced male fertility with impaired callose synthesis and abnormal pollen wall formation. The sixth intron in CalS5 pre-mRNA, a rare type of intron with a GC 5′ splice site, is abnormally spliced in cdkg1. RNA immunoprecipitation analysis suggests that CDKG1 is associated with this intron. CDKG1 contains N-terminal Ser/Arg (RS) motifs and interacts with splicing factor Arginine/Serine-Rich Zinc Knuckle-Containing Protein33 (RSZ33) through its RS region to regulate proper splicing. CDKG1 and RS-containing Zinc Finger Protein22 (SRZ22), a splicing factor interacting with RSZ33 and U1 small nuclear ribonucleoprotein particle (snRNP) component U1-70k, colocalize in nuclear speckles and reside in the same complex. We propose that CDKG1 is recruited to U1 snRNP through RSZ33 to facilitate the splicing of the sixth intron of CalS5. PMID:23404887

  20. Z ', Higgses and heavy neutrinos in U(1)' models: from the LHC to the GUT scale

    NASA Astrophysics Data System (ADS)

    Accomando, Elena; Corianò, Claudio; Rose, Luigi Delle; Fiaschi, Juri; Marzo, Carlo; Moretti, Stefano

    2016-07-01

    We study a class of non-exotic minimal U(1)' extensions of the Standard Model, which includes all scenarios that are anomaly-free with the ordinary fermion content augmented by one Right-Handed neutrino per generation, wherein the new Abelian gauge group is spontaneously broken by the non-zero Vacuum Expectation Value of an additional Higgs singlet field, in turn providing mass to a Z ' state. By adopting the B - L example, whose results can be recast into those pertaining to the whole aforementioned class, and allowing for both scalar and gauge mixing, we first extract the surviving parameter space in presence of up-to-date theoretical and experimental constraints. Over the corresponding parameter configurations, we then delineate the high energy behaviour of such constructs in terms of their stability and perturbativity. Finally, we highlight key production and decay channels of the new states entering the spectra of this class of models, i.e., heavy neutrinos, a second Higgs state and the Z ', which are amenable to experimental investigation at the Large Hadron Collider. We therefore set the stage to establish a direct link between measurements obtainable at the Electro-Weak scale and the dynamics of the underlying model up to those where a Grand Unification Theory embedding a U(1)' can be realised.

  1. Nucleon decay via dimension-6 operators in anomalous U(1)A supersymmetric GUT

    NASA Astrophysics Data System (ADS)

    Maekawa, Nobuhiro; Muramatsu, Yu

    2013-11-01

    Nucleon lifetimes for various decay modes via dimension-6 operators are calculated in the anomalous U(1)A grand unified theory (GUT) scenario, in which the unification scale Λu becomes smaller than the usual supersymmetric (SUSY) unification scale ΛG=2×1016GeV in general. Since the predicted lifetime τ(p→π0+ec) falls around the experimental lower bound, though it is strongly dependent on the explicit models, the discovery of the this nucleon decay can be expected in the near future. We explain why the two ratios R1≡(Γn→π0+νc)/(Γp→π0+ec) and R2≡(Γp→K0+μc)/(Γp→π0+ec) are important in identifying the grand unification group, and we show that three anomalous U(1)A SUSY GUT models, with SU(5), SO(10) and E6 grand unification groups, can be identified by measuring the two ratios. If R1 is larger than 0.4, the grand unification group is not SU(5), and moreover, if R2 is larger than 0.3, the grand unification group is implied to be E6.

  2. Aligned natural inflation and moduli stabilization from anomalous U(1) gauge symmetries

    NASA Astrophysics Data System (ADS)

    Li, Tianjun; Li, Zhijin; Nanopoulos, Dimitri V.

    2014-11-01

    To obtain natural inflation with large tensor-to-scalar ratio in string framework, we need a special moduli stabilization mechanism which can separate the masses of real and imaginary components of Kähler moduli at different scales, and achieve a trans-Planckian axion decay constant from sub-Planckian axion decay constants. In this work, we stabilize the matter fields by F-terms and the real components of Kähler moduli by D-terms of two anomalous U(1)X × U(1)A symmetries strongly at high scales, while the corresponding axions remain light due to their independence on the Fayet-Iliopoulos (FI) term in moduli stabilization. The racetrack-type axion superpotential is obtained from gaugino condensations of the hidden gauge symmetries SU(n)×SU(m) with massive matter fields in the bi-fundamental respresentations. The axion alignment via Kim-Nilles-Pelroso (KNP) mechanism corresponds to an approximate S 2 exchange symmetry of two Kähler moduli in our model, and a slightly S 2 symmetry breaking leads to the natural inflation with super-Planckian decay constant.

  3. Cold-atom quantum simulation of U(1) lattice gauge-Higgs model

    NASA Astrophysics Data System (ADS)

    Kasamatsu, Kenichi; Kuno, Yoshihito; Takahashi, Yoshiro; Ichinose, Ikuo; Matsui, Tetsuo

    2015-03-01

    We discuss the possible methods to construct a quantum simulator of the U(1) lattice gauge-Higgs model using cold atoms in an optical lattice. These methods require no severe fine tunings of parameters of atomic-interactions in contrast with the other previous literature. We propose some realistic experimental setups to realize the atomic quantum simulator of the U(1) lattice gauge-Higgs model in a two-dimensional optical lattice. Our target gauge-Higgs model has a nontrivial phase structure, i.e., existence of the phase boundary between confinement and Higgs phases, and this phase boundary is to be observed by cold-atom experiments. As a reference to such experiments, we make numerical simulations of the time-dependent Gross-Pitaevskii equation and observe the real-time dynamics of the atomic simulators. Clarification of the dynamics of this gauge-Higgs model sheds some lights upon various unsolved problems including the inflation process of the early universe.

  4. 750 GeV resonance in the gauged U(1)‧-extended MSSM

    NASA Astrophysics Data System (ADS)

    Jiang, Yun; Li, Ying-Ying; Liu, Tao

    2016-08-01

    Recently the ATLAS and CMS Collaborations at the LHC announced their observation of a potential 750 GeV di-photon resonance, after analyzing the √{ s} = 13 TeV LHC data. This observation has significant implications for low-energy supersymmetry. Beyond the MSSM and the NMSSM, we study the MSSM-extensions with an extra U(1) ‧ gauge symmetry. The anomaly cancellation and the spontaneous breaking of the non-decoupled U(1) ‧ generally require introducing vector-like supermultiplets (both colored and color-neutral ones) and singlet supermultiplets, respectively. We illustrate that the potential 750 GeV resonance (Y) can be accommodated in various mechanisms, as a singlet-like scalar or pseudoscalar. Three benchmark scenarios are presented: (1) vector-like quarks (VLQ) mediated pp → Y → γγ; (2) scalar VLQ mediated pp → Y → γγ; (3) heavy scalar (pseudo-scalar) H / A associated production pp →H* /A* → YH / h. Additionally, we notice that the Z‧-mediated vector boson fusion production and Z‧-associated production pp → Yqq‧, if yielding a signal rate of the observed level, might have been excluded by the searches for Z‧ via Drell-Yan process at the LHC.

  5. Fermion mass hierarchy and nonhierarchical mass ratios in SU(5)xU(1){sub F}

    SciTech Connect

    Duque, Luis F.; Gutierrez, Diego A.; Nardi, Enrico; Norena, Jorge

    2008-08-01

    We consider a SU(5)xU(1){sub F} grand unified theory (GUT)-flavor model in which the number of effects that determine the charged fermions Yukawa matrices is much larger than the number of observables, resulting in a hierarchical fermion spectrum with no particular regularities. The GUT-flavor symmetry is broken by flavons in the adjoint of SU(5), realizing a variant of the Froggatt-Nielsen mechanism that gives rise to a large number of effective operators. By assuming a common mass for the heavy fields and universality of the fundamental Yukawa couplings, we reduce the number of free parameters to one. The observed fermion mass spectrum is reproduced thanks to selection rules that discriminate among various contributions. Bottom-tau Yukawa unification is preserved at leading order, but there is no unification for the first two families. Interestingly, U(1){sub F} charges alone do not determine the hierarchy, and can only give upper bounds on the parametric suppression of the Yukawa operators.

  6. Integrable spin chain for the SL(2,R)/U(1) black hole sigma model.

    PubMed

    Ikhlef, Yacine; Jacobsen, Jesper Lykke; Saleur, Hubert

    2012-02-24

    We introduce a spin chain based on finite-dimensional spin-1/2 SU(2) representations but with a non-Hermitian "Hamiltonian" and show, using mostly analytical techniques, that it is described at low energies by the SL(2,R)/U(1) Euclidian black hole conformal field theory. This identification goes beyond the appearance of a noncompact spectrum; we are also able to determine the density of states, and show that it agrees with the formulas in [J. Maldacena, H. Ooguri, and J. Son, J. Math. Phys. (N.Y.) 42, 2961 (2001)] and [A. Hanany, N. Prezas, and J. Troost, J. High Energy Phys. 04 (2002) 014], hence providing a direct "physical measurement" of the associated reflection amplitude. PMID:22463514

  7. Higgs boson production in the U(1)B‑L model at the ILC

    NASA Astrophysics Data System (ADS)

    Han, Jinzhong; Yang, Bingfang; Liu, Ning; Li, Jitao

    2016-06-01

    In the framework of the minimal U(1)B‑L extension of the Standard Model, we investigate the Higgs boson production processes e+e‑→ ZH, e+e‑→ ν eν¯eH, e+e‑→ tt¯H, e+e‑→ ZHH and e+e‑→ ν eν¯eHH at the International Linear Collider (ILC). We present the production cross-sections, the relative corrections and compare our results with the expected experimental accuracies for Higgs decay channel H → bb¯. In the allowed parameter space, we find that the effects of the three single Higgs boson production processes might approach the observable threshold of the ILC. But the Higgs signal strengths μbb¯ of the two double Higgs boson production processes are all out of the observable threshold so that these effects will be difficult to be observed at the ILC.

  8. Family nonuniversal U(1){sup '} gauge symmetries and b{yields}s transitions

    SciTech Connect

    Barger, Vernon; Everett, Lisa; Jiang Jing; Langacker, Paul; Liu Tao; Wagner, Carlos E. M.

    2009-09-01

    We present a correlated analysis for the {delta}B=1, 2 processes which occur via b{yields}s transitions within models with a family nonuniversal U(1){sup '}. We take a model-independent approach and only require family universal charges for the first and second generations and small fermion mixing angles. The results of our analysis show that within this class of models, the anomalies in B{sub s}-B{sub s} mixing and the time-dependent CP asymmetries of the penguin-dominated B{sub d}{yields}({pi},{phi},{eta}{sup '},{rho},{omega},f{sub 0})K{sub S} decays can be accommodated.

  9. Black rings in U(1)3 supergravity and their dual 2d CFT

    NASA Astrophysics Data System (ADS)

    Sadeghian, S.; Yavartanoo, H.

    2016-05-01

    We study the near-horizon geometry of black ring solutions in five-dimensional U(1)3 supergravity with three electric dipole charges and one angular momentum. We consider the extremal vanishing horizon (EVH) limit of these solutions and show that the near-horizon geometries develop AdS3 throats locally. At the near-EVH near horizon limit, the AdS3 factor turns into a BTZ black hole. By analysing the first law of thermodynamics for black rings we show that at the EVH limit, they reduce to the first law of thermodynamics for BTZ black holes. Using the AdS3/CFT2 duality, we propose a dual CFT to describe the near-horizon low energy dynamics of near-EVH black rings. We also discuss the connection between our CFT proposal and the Kerr/CFT correspondence in the cases where these two overlap.

  10. Density of states and Fisher's zeros in compact U(1) pure gauge theory

    NASA Astrophysics Data System (ADS)

    Bazavov, A.; Berg, B. A.; Du, Daping; Meurice, Y.

    2012-03-01

    We present high-accuracy calculations of the density of states using multicanonical methods for lattice gauge theory with a compact gauge group U(1) on 44, 64, and 84 lattices. We show that the results are consistent with weak and strong coupling expansions. We present methods based on Chebyshev interpolations and Cauchy theorem to find the (Fisher’s) zeros of the partition function in the complex β=1/g2 plane. The results are consistent with reweighting methods whenever the latter are accurate. We discuss the volume dependence of the imaginary part of the Fisher’s zeros, the width and depth of the plaquette distribution at the value of β where the two peaks have equal height. We discuss strategies to discriminate between first- and second-order transitions and explore them with data at larger volume but lower statistics. Higher statistics and even larger lattices are necessary to draw strong conclusions regarding the order of the transition.

  11. Engineering assessment and certification of integrity of the 141-R1U1 tank system

    SciTech Connect

    Graser, D.A. )

    1990-09-01

    This Engineering Assessment and Certification of Integrity of retention tank 141-R1U1 is in response to the requirements of 40 CFR 265.191 for an existing tank system that stores hazardous waste and does not have secondary containment. This technical assessment has been reviewed by an independent, qualified, California registered professional engineer, who has certified the tank system to be adequately designed and compatible with the stored waste so that it will not collapse rupture, or fail. This document will be kept on file at the facility. Onground retention tanks 141-R1O1 and 141-R1O2, which are also part of the 141-R1 retention tank system, do not have secondary containment; consequently, certification documentation for these tanks is not included in this assessment. A discussion of the onground tanks, however, is included in this report to provide a complete description of the 141-R1 retention tank system. 8 refs., 7 figs.

  12. Higgs portal dark matter in the minimal gauged U(1){sub B-L} model

    SciTech Connect

    Okada, Nobuchika; Seto, Osamu

    2010-07-15

    We propose a scenario of the right-handed neutrino dark matter in the context of the minimal gauged U(1){sub B-L} model by introducing an additional parity which ensures the stability of dark matter particle. The annihilation of this right-handed neutrino takes place dominantly through the s-channel Higgs boson exchange, so that this model can be called the Higgs portal dark matter model. We show that the thermal relic abundance of the right-handed neutrino dark matter with the help of Higgs resonance can match the observed dark matter abundance. In addition, we estimate the cross section with nucleon and show that the next generation direct dark matter search experiments can explore this model.

  13. b {r-arrow} s transitions in family-dependent U(1)' models.

    SciTech Connect

    Barger, V.; Everett, L.; Jiang, J.; Langacker, P.; Liu, T.; Wagner, C. E. M.; High Energy Physics; Univ. of Chicago; Univ. of Wisconsin; Inst. for Advanced Study

    2009-01-01

    We analyze flavor-changing-neutral-current (FCNC) effects in the b {yields} s transitions that are induced by family non-universal U(1){prime} gauge symmetries. After systematically developing the necessary formalism, we present a correlated analysis for the {Delta}B = 1,2 processes. We adopt a model-independent approach in which we only require family-universal charges for the first and second generations and small fermion mixing angles. We analyze the constraints on the resulting parameter space from B{sub s}-{bar B} mixing and the time-dependent CP asymmetries of the penguin-dominated B{sub d} {yields} ({pi},{phi}, {eta}{prime}, {rho},{omega},f0)K{sub S} decays. Our results indicate that the currently observed discrepancies in some of these modes with respect to the Standard Model predictions can be consistently accommodated within this general class of models.

  14. Family non-universal U(1)' gauge symmetries and b {r_arrow} s transitions.

    SciTech Connect

    Barger, V.; Everett, L.; Jiang, J.; Langacker, P.; Liu, T.; Wagner, C .E. M.; High Energy Physics; Univ. of Chicago; Univ. of Wisconsin at Madison; Inst. for Advanced Study

    2009-01-01

    We present a correlated analysis for the {Delta}B = 1, 2 processes which occur via b {yields} s transitions within models with a family nonuniversal U(1){prime}. We take a model-independent approach and only require family universal charges for the first and second generations and small fermion mixing angles. The results of our analysis show that within this class of models, the anomalies in B{sub s}-B{sub s}{sup -} mixing and the time-dependent CP asymmetries of the penguin-dominated B{sub d} {yields} ({pi},{psi},{eta}{prime},{rho},{omega},f{sub 0})K{sub S} decays can be accommodated.

  15. A Model of Fermion Masses and Flavor Mixings with Family Symmetry SU(3) otimes U(1)

    NASA Astrophysics Data System (ADS)

    Yang, Wei-Min; Wang, Qi; Zhong, Jin-Jin

    2012-01-01

    The family symmetry SU(3) otimes U(1) is proposed to solve flavor problems about fermion masses and flavor mixings. It is breaking is implemented by some flavon fields at the high-energy scale. In addition a discrete group Z2 is introduced to generate tiny neutrino masses, which is broken by a real singlet scalar field at the middle-energy scale. The low-energy effective theory is elegantly obtained after all of super-heavy fermions are integrated out and decoupling. All the fermion mass matrices are regularly characterized by four fundamental matrices and thirteen parameters. The model can perfectly fit and account for all the current experimental data about the fermion masses and flavor mixings, in particular, it finely predicts the first generation quark masses and the values of θl13 and JlCP in neutrino physics. All of the results are promising to be tested in the future experiments.

  16. Seismic evaluation of the U1a complex at the Nevada Test Site

    SciTech Connect

    McCamant, R R; Davito, A M; Hahn, K R; Murray, R C; Ng, D S; Sahni, V K; Schnechter, K M; Van Dyke, M

    1998-10-16

    As part of an overall safety evaluation of the Ula Complex, a seismic evaluation of structures, systems, and components (SSC) was conducted. A team of seismic, safety, and operation engineers from Los Alamos National Laboratory (LANL), Bechtel Nevada (BN) and Lawrence Livermore National Laboratory (LLNL) was chartered to perform the seismic evaluation. The UlA Complex is located in Area 1 of the Nevada Test Site (NTS) in Nevada. The complex is a test facility for physics experiments in support of the Science Based Stockpile Stewardship Program. The Ula Complex consists of surface and subsurface facilities. The subsurface facility is a tunnel complex located 963 feet below the surface. The seismic evaluation of U 1 a Complex is required to comply with the DOE Natural Phenomena Policy. This policy consists of an order, an implementing guide, and standards which provide guidance for design and evaluation of SSCs, categorization of SSCs, characterization of site, and hazard level definition.

  17. High intranuclear mobility and dynamic clustering of the splicing factor U1 snRNP observed by single particle tracking

    PubMed Central

    Kues, Thorsten; Dickmanns, Achim; Lührmann, Reinhard; Peters, Reiner; Kubitscheck, Ulrich

    2001-01-01

    Uridine-rich small nuclear ribonucleoproteins (U snRNPs) are components of the splicing machinery that removes introns from precursor mRNA. Like other splicing factors, U snRNPs are diffusely distributed throughout the nucleus and, in addition, are concentrated in distinct nuclear substructures referred to as speckles. We have examined the intranuclear distribution and mobility of the splicing factor U1 snRNP on a single-molecule level. Isolated U1 snRNPs were fluorescently labeled and incubated with digitonin-permeabilized 3T3 cells in the presence of Xenopus egg extract. By confocal microscopy, U1 snRNPs were found to be imported into nuclei, yielding a speckled intranuclear distribution. Employing a laser video-microscope optimized for high sensitivity and high speed, single U1 snRNPs were visualized and tracked at a spatial precision of 35 nm and a time resolution of 30 ms. The single-particle data revealed that U1 snRNPs occurred in small clusters that colocalized with speckles. In the clusters, U1 snRNPs resided for a mean decay time of 84 ms before leaving the optical slice in the direction of the optical axis, which corresponded to a mean effective diffusion coefficient of 1 μm2/s. An analysis of the trajectories of single U1 snRNPs revealed that at least three kinetic classes of low, medium, and high mobility were present. Moreover, the mean square displacements of these fractions were virtually independent of time, suggesting arrays of binding sites. The results substantiate the view that nuclear speckles are not rigid structures but highly dynamic domains characterized by a rapid turnover of U1 snRNPs and other splicing factors. PMID:11593012

  18. Effect of CO2 on the fermentation capacities of the acetogen Peptostreptococcus productus U-1.

    PubMed

    Misoph, M; Drake, H L

    1996-06-01

    The fermentative capacities of the acetogenic bacterium Peptostreptococcus productus U-1 (ATCC 35244) were examined. Although acetate was formed from all the substrates tested, additional products were produced in response to CO2 limitation. Under CO2-limited conditions, fructose-dependent growth yielded high levels of lactate as a reduced end product; lactate was also produced under CO2-enriched conditions when fructose concentrations were elevated. In the absence of supplemental CO2, xylose-dependent growth yielded lactate and succinate as major reduced end products. Although supplemental CO2 and acetogenesis stimulated cell yields on fructose, xylose-dependent cell yields were decreased in response to CO2 and acetogenesis. In contrast, glycerol-dependent growth yielded high levels of ethanol in the absence of supplemental CO2, and pyruvate was subject to only acetogenic utilization independent of CO2. CO2 pulsing during the growth of CO2-limited fructose cultures stopped lactate synthesis immediately, indicating that CO2-limited cells were nonetheless metabolically poised to respond quickly to exogenous CO2. Resting cells that were cultivated at the expense of fructose without supplemental CO2 readily consumed fructose in the absence of exogenous CO2 and formed only lactate. Although the specific activity of lactate dehydrogenase was not appreciably influenced by supplemental C02 during cultivation, cells cultivated on fructose under CO2-enriched conditions displayed minimal capacities to consume fructose in the absence of exogenous CO2. These results demonstrate that the utilization of alternative fermentations for the conservation of energy and growth of P. productus U-1 is augmented by the relative availability of CO2 and growth substrate.

  19. Kaposi's sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing.

    PubMed

    Majerciak, Vladimir; Yamanegi, Koji; Allemand, Eric; Kruhlak, Michael; Krainer, Adrian R; Zheng, Zhi-Ming

    2008-03-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 facilitates the expression of both intronless viral ORF59 genes and intron-containing viral K8 and K8.1 genes (V. Majerciak, N. Pripuzova, J. P. McCoy, S. J. Gao, and Z. M. Zheng, J. Virol. 81:1062-1071, 2007). In this study, we showed that disruption of ORF57 in a KSHV genome led to increased accumulation of ORF50 and K8 pre-mRNAs and reduced expression of ORF50 and K-bZIP proteins but had no effect on latency-associated nuclear antigen (LANA). Cotransfection of ORF57 and K8beta cDNA, which retains a suboptimal intron of K8 pre-mRNA due to alternative splicing, promoted RNA splicing of K8beta and production of K8alpha (K-bZIP). Although Epstein-Barr virus EB2, a closely related homolog of ORF57, had a similar activity in the cotransfection assays, herpes simplex virus type 1 ICP27 was inactive. This enhancement of RNA splicing by ORF57 correlates with the intact N-terminal nuclear localization signal motifs of ORF57 and takes place in the absence of other viral proteins. In activated KSHV-infected B cells, KSHV ORF57 partially colocalizes with splicing factors in nuclear speckles and assembles into spliceosomal complexes in association with low-abundance viral ORF50 and K8 pre-mRNAs and essential splicing components. The association of ORF57 with snRNAs occurs by ORF57-Sm protein interaction. We also found that ORF57 binds K8beta pre-mRNAs in vitro in the presence of nuclear extracts. Collectively our data indicate that KSHV ORF57 functions as a novel splicing factor in the spliceosome-mediated splicing of viral RNA transcripts.

  20. A compare-and-contrast NMR dynamics study of two related RRMs: U1A and SNF.

    PubMed

    DeKoster, Gregory T; Delaney, Kimberly J; Hall, Kathleen B

    2014-07-01

    The U1A/U2B″/SNF family of small nuclear ribonucleoproteins uses a phylogenetically conserved RNA recognition motif (RRM1) to bind RNA stemloops in U1 and/or U2 small nuclear RNA (snRNA). RRMs are characterized by their α/β sandwich topology, and these RRMs use their β-sheet as the RNA binding surface. Unique to this RRM family is the tyrosine-glutamine-phenylalanine (YQF) triad of solvent-exposed residues that are displayed on the β-sheet surface; the aromatic residues form a platform for RNA nucleobases to stack. U1A, U2B″, and SNF have very different patterns of RNA binding affinity and specificity, however, so here we ask how YQF in Drosophila SNF RRM1 contributes to RNA binding, as well as to domain stability and dynamics. Thermodynamic double-mutant cycles using tyrosine and phenylalanine substitutions probe the communication between those two residues in the free and bound states of the RRM. NMR experiments follow corresponding changes in the glutamine side-chain amide in both U1A and SNF, providing a physical picture of the RRM1 β-sheet surface. NMR relaxation and dispersion experiments compare fast (picosecond to nanosecond) and intermediate (microsecond-to-millisecond) dynamics of U1A and SNF RRM1. We conclude that there is a network of amino acid interactions involving Tyr-Gln-Phe in both SNF and U1A RRM1, but whereas mutations of the Tyr-Gln-Phe triad result in small local responses in U1A, they produce extensive microsecond-to-millisecond global motions throughout SNF that alter the conformational states of the RRM.

  1. Program package for multicanonical simulations of U(1) lattice gauge theory

    NASA Astrophysics Data System (ADS)

    Bazavov, Alexei; Berg, Bernd A.

    2009-11-01

    We document our Fortran 77 code for multicanonical simulations of 4D U(1) lattice gauge theory in the neighborhood of its phase transition. This includes programs and routines for canonical simulations using biased Metropolis heatbath updating and overrelaxation, determination of multicanonical weights via a Wang-Landau recursion, and multicanonical simulations with fixed weights supplemented by overrelaxation sweeps. Measurements are performed for the action, Polyakov loops and some of their structure factors. Many features of the code transcend the particular application and are expected to be useful for other lattice gauge theory models as well as for systems in statistical physics. Catalogue identifier: AEET_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEET_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 18 376 No. of bytes in distributed program, including test data, etc.: 205 183 Distribution format: tar.gz Programming language: Fortran 77 Computer: Any capable of compiling and executing Fortran code Operating system: Any capable of compiling and executing Fortran code Classification: 11.5 Nature of problem: Efficient Markov chain Monte Carlo simulation of U(1) lattice gauge theory close to its phase transition. Measurements and analysis of the action per plaquette, the specific heat, Polyakov loops and their structure factors. Solution method: Multicanonical simulations with an initial Wang-Landau recursion to determine suitable weight

  2. The Chiral and U(1)A Symmetries of the QCD Phase Transition using Chiral Lattice Fermions

    NASA Astrophysics Data System (ADS)

    Lin, Zhongjie

    With regard to the nature of the finite-temperature QCD phase transition and the fate of the chiral and anomalous axial symmetries associated with it, we present in this thesis two parallel sets of investigations into the QCD phase transition region between 139 and 195 MeV. Both studies adopt the Iwasaki gauge action augmented with the dislocation suppression determinant ratio with 2+1 flavors of chiral fermions. This choice of lattice action accurately reproduces the SU(2)L x SU(2)R and U (1)A symmtries of the continuum. The first study simulates QCD thermodynamics on a line of constant physics that represents 200 MeV pions and physical kaons using domain wall fermions (DWF) at three space-time volumes: 163 x 8, 24 3 x 8, and 323 x 8, where the largest volume varies in linear size between 5.6 fm (at T = 139 MeV) and 4.0 fm (at T = 195 MeV). The chiral condensates, connected and disconnected susceptibilities and the Dirac eigenvalue spectrum are reported and compared between different volumes as well as with the staggered results. We find a pseudo-critical temperature, Tc, of approximately 165 MeV and strong finite volume dependence below T c. Clear evidence is seen for U(1)A symmetry breaking above Tc which is quantitatively explained by the measured density of near-zero modes in accordance with the dilute instanton gas approximation. The second study targets on a line of constant physics with pions of physical mass, which is the very first study using a chiral lattice fermion formulaation. We continue to use the basic setup from the m pi ≈ 200 MeV simulations, except that we use a generalized form of domain wall fermions, known as the Mobius fermions, to further reduce the residual chiral symmetry breaking present in the domain wall formulation with finite extent in the fifth dimension. Preliminary results including the chiral condensates and the susceptibilities are reported for two space-time volumes of 323 x 8 and 643 x 8. We observe a dramatic increase in

  3. Suppression of mammalian 5' splice-site defects by U1 small nuclear RNAs from a distance.

    PubMed

    Cohen, J B; Snow, J E; Spencer, S D; Levinson, A D

    1994-10-25

    One of the earliest events in the process of intron removal from mRNA precursors is the establishment of a base-pairing interaction between U1 small nuclear (sn) RNA and the 5' splice site. Mutations at the 5' splice site that prevent splicing can often be suppressed by coexpression of U1 snRNAs with compensatory changes, but in yeast, accurate splicing is not restored when the universally conserved first intron base is changed. In our mammalian system as well, such a mutation could not be suppressed, but the complementary U1 caused aberrant splicing 12 bases downstream. This result is reminiscent of observations in yeast that aberrant 5' splice sites can be activated by U1 snRNA from a distance. Using a rapid, qualitative protein expression assay, we provide evidence that 5' splice-site mutations can be suppressed in mammalian cells by U1 snRNAs with complementarity to a range of sequences upstream or downstream of the site. Our approach uncouples in vivo the commitment-activation step of mammalian splicing from the process of 5' splice-site definition and as such will facilitate the genetic characterization of both.

  4. A 4 × U(1)PQ model for the lepton flavor structure and the strong CP problem

    NASA Astrophysics Data System (ADS)

    Nomura, Takaaki; Shimizu, Yusuke; Yamada, Toshifumi

    2016-06-01

    We present a model with A 4 × U(1)PQ lepton flavor symmetry which explains the origin of the lepton flavor structure and also solves the strong CP problem. Standard model gauge singlet fields, so-called "flavons", charged under the A 4 × U(1)PQ symmetry are introduced and are coupled with the lepton and the Higgs sectors. The flavon vacuum expectation values (VEVs) trigger spontaneous breaking of the A 4 × U(1)PQ symmetry. The breaking pattern of the A 4 accounts for the tri-bimaximal neutrino mixing and the deviation from it due to the non-zero θ 13 angle, and the breaking of the U(1)PQ gives rise to a pseudo-Nambu-Goldstone boson, axion, whose VEV cancels the QCD θ term. We investigate the breaking of the A 4 × U(1)PQ symmetry through an analysis on the scalar potential and further discuss the properties of the axion in the model, including its decay constant, mass and coupling with photons. It is shown that the axion decay constant is related with the right-handed neutrino mass through the flavon VEVs. Experimental constraints on the axion and their implications are also studied.

  5. Description of work for 216-U-1 and 216-U-2 stainless steel pipeline integrity testing

    SciTech Connect

    Wasemiller, M.A.

    1994-06-30

    The objectives of this integrity test are to (1) inspect the interior of this pipeline by in-line camera survey and (2) if required, conduct a pressure test on a section of the pipeline. The U-1 and U-2 Cribs were constructed in 1951. From March 1952 to June 1967, the site received cell drainage from Tank 5-2 in the 221-U Building nd waste from the 224-U Building via the overflow from the 241-U-361 Settling Tank. From June 1957 to July 1957, the site received waste from the 224-U Building via the overflow from the 241-U-361 Settling Tank and contaminated solvent from the 276-U Settling Tank solvent storage area. The discharge of 221-U waste was discontinued during shutdown of production operations. From July 1957 to May 1967, the site received waste from the 224-U Building and equipment decontamination and reclamation wastes from operations in the 221-U Building canyon. The scope of work is encompassed in five steps: (1) obtaining access to the pipeline in order to perform an in-line camera survey of the line to the greatest extent possible, (2) evaluating the need for further investigation of the pipeline, (3) blanking the line, as needed, to perform a pressure test, (4) conducting the pressure test, as needed, and (5) documenting the ability of the line to maintain pressure.

  6. Numerical solutions of Einstein's equations for cosmological spacetimes with spatial topology S3 and symmetry group U(1)

    NASA Astrophysics Data System (ADS)

    Beyer, F.; Escobar, L.; Frauendiener, J.

    2016-02-01

    In this paper we consider the single patch pseudospectral scheme for tensorial and spinorial evolution problems on the 2-sphere presented by Beyer et al. [Classical Quantum Gravity 32, 175013 (2015); Classical Quantum Gravity31, 075019 (2014)], which is based on the spin-weighted spherical harmonics transform. We apply and extend this method to Einstein's equations and certain classes of spherical cosmological spacetimes. More specifically, we use the hyperbolic reductions of Einstein's equations obtained in the generalized wave map gauge formalism combined with Geroch's symmetry reduction, and focus on cosmological spacetimes with spatial S3 -topologies and symmetry groups U(1) or U (1U (1 ) . We discuss analytical and numerical issues related to our implementation. We test our code by reproducing the exact inhomogeneous cosmological solutions of the vacuum Einstein field equations obtained by Beyer and Hennig [Classical Quantum Gravity 31, 095010 (2014)].

  7. Mass-deformed ABJ and ABJM theory, Meixner-Pollaczek polynomials, and s u (1 ,1 ) oscillators

    NASA Astrophysics Data System (ADS)

    Tierz, Miguel

    2016-06-01

    We give explicit analytical expressions for the partition function of U (N )k×U (N +M )-k ABJ theory at weak coupling (k →∞ ) for finite and arbitrary values of N and M (including the ABJM case and its mass-deformed generalization). We obtain the expressions by identifying the one-matrix model formulation with a Meixner-Pollaczek ensemble and using the corresponding orthogonal polynomials, which are also eigenfunctions of a s u (1 ,1 ) quantum oscillator. Wilson loops in mass-deformed ABJM are also studied in the same limit and interpreted in terms of s u (1 ,1 ) coherent states.

  8. U(1) decoupling, Kleiss-Kuijf and Bern-Carrasco-Johansson relations in N=4 super Yang-Mills

    SciTech Connect

    Jia Yin; Huang Rijun; Liu Changyong

    2010-09-15

    By using the Britto-Cachazo-Feng-Witten recursion relation of N=4 super Yang-Mills theory, we proved the color reflection, U(1) decoupling, Kleiss-Kuijf and Bern-Carrasco-Johansson relations for color-ordered amplitudes of N=4 super Yang-Mills theory. This proof verified the conjectured Bern-Carrasco-Johansson relations of matter fields. The proof depended only on general properties of superamplitudes. We showed also that the color reflection relation and U(1)-decoupling relation are special cases of Kleiss-Kuijf relations.

  9. Electroweak theory based on S U (4 )L⊗U (1 )X gauge group

    NASA Astrophysics Data System (ADS)

    Long, H. N.; Hue, L. T.; Loi, D. V.

    2016-07-01

    This paper includes two main parts. In the first part, we present generalized gauge models based on the S U (3 )C⊗S U (4 )L⊗U (1 )X (3-4-1) gauge group with arbitrary electric charges of exotic leptons. The mixing matrix of neutral gauge bosons is analyzed, and the eigenmasses and eigenstates are obtained. The anomaly-free as well as matching conditions are discussed precisely. In the second part, we present a new development of the original 3-4-1 model [R. Foot, H. N. Long, and T. A. Tran, Phys. Rev. D 50, R34 (1994), F. Pisano and V. Pleitez, Phys. Rev. D 51, 3865 (1995).]. Different from previous works, in this paper the neutrinos, with the help of the scalar decuplet H , get the Dirac masses at the tree level. The vacuum expectation value (VEV) of the Higgs boson field in the decuplet H acquiring the VEV responsible for neutrino Dirac mass leads to mixing in separated pairs of singly charged gauge bosons, namely the Standard Model (SM) W boson and K , the new gauge boson acting in the right-handed lepton sector, as well as the singly charged bileptons X and Y . Due to the mixing, there occurs a right-handed current carried by the W boson. From the expression of the electromagnetic coupling constant, ones get the limit of the sine-squared of the Weinberg angle, sin2θW<0.25 , and a constraint on electric charges of extra leptons. In the limit of lepton number conservation, the Higgs sector contains all massless Goldstone bosons for massive gauge bosons and the SM-like Higgs boson. Some phenomenology is discussed.

  10. Fluctuation effects in rotating Bose-Einstein condensates with broken SU(2) and U (1U (1 ) symmetries in the presence of intercomponent density-density interactions

    NASA Astrophysics Data System (ADS)

    Galteland, Peder Notto; Babaev, Egor; Sudbø, Asle

    2015-01-01

    Thermal fluctuations and melting transitions for rotating single-component superfluids have been intensively studied and are well understood. In contrast, the thermal effects on vortex states for two-component superfluids with density-density interaction, which have a much richer variety of vortex ground states, have been much less studied. Here, we investigate the thermal effects on vortex matter in superfluids with U (1U (1 ) broken symmetries and intercomponent density-density interactions, as well as the case with a larger SU (2 ) broken symmetry obtainable from the [U (1U (1 )] -symmetric case by tuning scattering lengths. In the former case we find that, in addition to first-order melting transitions, the system exhibits thermally driven phase transitions between square and hexagonal lattices. Our main result, however, concerns the case where the condensate exhibits SU (2 ) symmetry, and where vortices are not topological. At finite temperature, the system exhibits effects which do not have a counterpart in single-component systems. Namely, it has a state where thermally averaged quantities show no regular vortex lattice, yet the system retains superfluid coherence along the axis of rotation. In such a state, the thermal fluctuations result in transitions between different (nearly) degenerate vortex states without undergoing a melting transition. Our results apply to multicomponent Bose-Einstein condensates, and we suggest how to detect some of these unusual effects experimentally in such systems.

  11. Chromosomal Mapping of Repetitive DNA Sequences in Five Species of Astyanax (Characiformes, Characidae) Reveals Independent Location of U1 and U2 snRNA Sites and Association of U1 snRNA and 5S rDNA.

    PubMed

    Silva, Duilio M Z A; Utsunomia, Ricardo; Pansonato-Alves, José C; Oliveira, Cláudio; Foresti, Fausto

    2015-01-01

    Astyanax is a genus of Characidae fishes currently composed of 155 valid species. Previous cytogenetic studies revealed high chromosomal diversification among them, and several studies have been performed using traditional cytogenetic techniques to investigate karyotypes and chromosomal locations of 18S and 5S rDNA genes. However, only a few studies are currently available about other repetitive sequences. Here, the chromosomal location of small nuclear RNA genes, identified as U1 and U2 snRNA clusters, was established and compared to the distribution of 5S rDNA and histone clusters in 5 Astyanax species (A. paranae, A. fasciatus, A. bockmanni, A. altiparanae, and A. jordani) using FISH. The cytogenetic mapping of U1 and U2 snRNA demonstrated a conserved pattern in the number of sites per genome independent of the location in Astyanax species. The location of the U1 snRNA gene was frequently associated with 5S rDNA sequences, indicating a possible interaction between the distinct repetitive DNA families. Finally, comparisons involving the location of U1 and U2 snRNA clusters in the chromosomes of Astyanax species revealed a very diverse pattern, suggesting that many rearrangements have occurred during the diversification process of this group. PMID:26329975

  12. Chromosomal Mapping of Repetitive DNA Sequences in Five Species of Astyanax (Characiformes, Characidae) Reveals Independent Location of U1 and U2 snRNA Sites and Association of U1 snRNA and 5S rDNA.

    PubMed

    Silva, Duilio M Z A; Utsunomia, Ricardo; Pansonato-Alves, José C; Oliveira, Cláudio; Foresti, Fausto

    2015-01-01

    Astyanax is a genus of Characidae fishes currently composed of 155 valid species. Previous cytogenetic studies revealed high chromosomal diversification among them, and several studies have been performed using traditional cytogenetic techniques to investigate karyotypes and chromosomal locations of 18S and 5S rDNA genes. However, only a few studies are currently available about other repetitive sequences. Here, the chromosomal location of small nuclear RNA genes, identified as U1 and U2 snRNA clusters, was established and compared to the distribution of 5S rDNA and histone clusters in 5 Astyanax species (A. paranae, A. fasciatus, A. bockmanni, A. altiparanae, and A. jordani) using FISH. The cytogenetic mapping of U1 and U2 snRNA demonstrated a conserved pattern in the number of sites per genome independent of the location in Astyanax species. The location of the U1 snRNA gene was frequently associated with 5S rDNA sequences, indicating a possible interaction between the distinct repetitive DNA families. Finally, comparisons involving the location of U1 and U2 snRNA clusters in the chromosomes of Astyanax species revealed a very diverse pattern, suggesting that many rearrangements have occurred during the diversification process of this group.

  13. Diphoton excess at 750 GeV in leptophobic U(1)' model inspired by E 6 GUT

    NASA Astrophysics Data System (ADS)

    Ko, P.; Omura, Yuji; Yu, Chaehyun

    2016-04-01

    We discuss the 750 GeV diphoton excess at the LHC@13TeV in the framework of leptophobic U(1)' model inspired by E 6 grand unified theory (GUT). In this model, the Standard Model (SM) chiral fermions carry charges under extra U(1)' gauge symmetry which is spontaneously broken by a U(1)'-charged singlet scalar (Φ). In addition, extra quarks and leptons are introduced to achieve the anomaly-free conditions, which is a natural consequence of the assumed E 6 GUT. These new fermions are vectorlike under the SM gauge group but chiral under new U(1)', and their masses come entirely from the nonzero vacuum expectation value of Φ through the Yukawa interactions. Then, the CP-even scalar h Φ from Φ can be produced at the LHC by the gluon fusion and decay to the diphoton via the one-loop diagram involving the extra quarks and leptons, and can be identified as the origin of diphoton excess at 750 GeV. In this model, h Φ can decay into a pair of dark matter particles as well as a pair of scalar bosons, thereby a few tens of the decay width may be possible.

  14. 17 CFR 259.101 - Form U-1, application or declaration under the Public Utility Holding Company Act of 1935.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... prescribed. Editorial Note: For Federal Register citations affecting Form U-1, see the List of CFR Sections... declaration under the Public Utility Holding Company Act of 1935. 259.101 Section 259.101 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) FORMS PRESCRIBED UNDER THE PUBLIC...

  15. Physical Properties of Main-Belt Comet P/2005 U1 (Read)

    NASA Astrophysics Data System (ADS)

    Hsieh, Henry H.; Jewitt, David; Ishiguro, Masateru

    2009-01-01

    The main-belt comets occupy dynamically asteroidal orbits in the main asteroid belt. Here we present physical observations of the second-known member of this population, P/2005 U1 (Read), which showed vigorous cometary activity from 2005 October 24 to 2005 December 27. Monte Carlo numerical simulations of P/Read's dust emission indicate that the coma and tail are optically dominated by dust particles larger than 10 μm in size with terminal ejection velocities of 0.2-3 m s-1. We estimate P/Read's mass-loss rate during this period to be approximately 0.2 kg s-1, roughly an order of magnitude larger than that calculated for 133P/Elst-Pizarro. We also find that emission likely began at least 2 months prior to P/Read's discovery, though we note this is a lower limit and that earlier start times are possible. Optical colors measured for P/Read while it was active are approximately solar (B - V = 0.63 ± 0.05, V - R = 0.37 ± 0.04, R - I = 0.39 ± 0.04) but are likely to be dominated by coma particles. Observations of P/Read in 2007 when it appears largely inactive show an extremely small nucleus with an absolute magnitude of HR ~ 20.1 ± 0.4, corresponding to an effective radius of re ~ 0.3 km. P/Read's activity is consistent with sublimation-driven dust emission and inconsistent with dust emission due to an impact, though the unusual strength of the 2005 outburst suggests the possibility that it could have been due to the sublimation of a freshly exposed reservoir of volatile material. Some of the 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. Additionally, some data were obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in

  16. The C-terminal RG dipeptide repeats of the spliceosomal Sm proteins D1 and D3 contain symmetrical dimethylarginines, which form a major B-cell epitope for anti-Sm autoantibodies.

    PubMed

    Brahms, H; Raymackers, J; Union, A; de Keyser, F; Meheus, L; Lührmann, R

    2000-06-01

    The Sm proteins B/B', D1, D2, D3, E, F, and G are components of the small nuclear ribonucleoproteins U1, U2, U4/U6, and U5 that are essential for the splicing of pre-mRNAs in eukaryotes. D1 and D3 are among the most common antigens recognized by anti-Sm autoantibodies, an autoantibody population found exclusively in patients afflicted with systemic lupus erythematosus. Here we demonstrate by protein sequencing and mass spectrometry that all arginines in the C-terminal arginine-glycine (RG) dipeptide repeats of the human Sm proteins D1 and D3, isolated from HeLa small nuclear ribonucleoproteins, contain symmetrical dimethylarginines (sDMAs), a posttranslational modification thus far only identified in the myelin basic protein. The further finding that human D1 individually overexpressed in baculovirus-infected insect cells contains asymmetrical dimethylarginines suggests that the symmetrical dimethylation of the RG repeats in D1 and D3 is dependent on the assembly status of D1 and D3. In antibody binding studies, 10 of 11 anti-Sm patient sera tested, as well as the monoclonal antibody Y12, reacted with a chemically synthesized C-terminal peptide of D1 containing sDMA, but not with peptides containing asymmetrically modified or nonmodified arginines. These results thus demonstrate that the sDMA-modified C terminus of D1 forms a major linear epitope for anti-Sm autoantibodies and Y12 and further suggest that posttranslational modifications of Sm proteins play a role in the etiology of systemic lupus erythematosus.

  17. Diphoton decay for a 750 GeV scalar boson in a SU(6)⊗U(1)X model

    NASA Astrophysics Data System (ADS)

    Mantilla, S. F.; Martinez, R.; Ochoa, F.; Sierra, C. F.

    2016-10-01

    We propose a new SU (6) ⊗ U(1)X GUT model free from anomalies, with a 750 GeV scalar candidate which can decay into two photons, compatible with the recent diphoton signal reported by ATLAS and CMS collaborations. This model gives masses to all fermions and may explain the 750 GeV signal through one loop decays to γγ with charged vector and charged Higgs bosons, as well as up- and electron-like exotic particles that arise naturally from the condition of cancellation of anomalies of the SU (6) ⊗ U(1)X group. We obtain, for different width approximations, allowed mass regions from 900 GeV to 3 TeV for the exotic up-like quark, in agreement with ATLAS and CMS collaborations data.

  18. LHC diphoton resonance at 750 {GeV} as an indication of SU(3)_L× U(1)_X electroweak symmetry

    NASA Astrophysics Data System (ADS)

    Hernández, A. E. Cárcamo; Nišandžić, Ivan

    2016-07-01

    The LHC collaborations ATLAS and CMS recently reported on the excess of the events in the diphoton final states at the invariant mass of about 750 {GeV}. In this article we speculate on the possibility that the excess arises from the neutral CP-even component φ of the scalar triplet Φ of the SU(3)c× SU(3)L× U(1)X (3{-}3{-} 1) model that has a U(1)X charge equal to X=-1/3 and acquires a vacuum expectation value larger than the electroweak symmetry breaking scale. The interactions of the scalar field φ with the photon and gluon pairs are mediated by the virtual vector-like fermions which appear as components of the anomaly-free chiral fermion representations of the 3{ -}3{-}1 gauge group.

  19. Non-commutative U(1) gauge theory on \\mth{\\mathbb{R}^4_{\\Theta}} with oscillator term and BRST symmetry

    NASA Astrophysics Data System (ADS)

    Blaschke, D. N.; Grosse, H.; Schweda, M.

    2007-09-01

    Inspired by the renormalizability of the non-commutative Φ4 model with added oscillator term, we formulate a non-commutative gauge theory, where the oscillator enters as a gauge fixing term in a BRST invariant manner. All propagators turn out to be essentially given by the Mehler kernel and the bilinear part of the action is invariant under the Langmann-Szabo duality. The model is a promising candidate for a renormalizable non-commutative U(1) gauge theory.

  20. [Autoantibodies against U1-n-RNP (ENA)--detection using a recombinant 70-kDa protein].

    PubMed

    Seelig, H P; Wieland, C; Heim, C; Renz, M

    1990-02-01

    An ELISA for the demonstration of antibodies to RNP antigens (ENA) in sera of patients with systemic rheumatic diseases was developed using the recombinant 70-kDa protein, a marker antigen of U1-n-RNP. The specificity and sensitivity of the method was evaluated with 3588 patients' sera. The results were compared with those obtained by natural antigens isolated from calf thymus and Western blot analysis using HeLa-cell nuclear extracts. The test was found to be specific and sensitive and to be superior in routine laboratory screening than the other tests commonly used.

  1. Analysis of Site Response at U1A Hole at the Nevada Test Site From Weak Motion Readings

    SciTech Connect

    Hutchings, L; Furrey, L

    2002-05-21

    We utilize weak motion recordings to evaluate the site response at the U1A hole, Nevada Test site to determine the effect on potential ground motion at the drift of the U1A hole 962 ft deep. We estimated the site response amplification of ground motion at the surface relative to the drift with the spectral ratio method. We utilized Fourier amplitude and absolute acceleration response spectra, and confined our study to frequencies of 0.5 to 25.0 Hz (.04 to 2.0 s periods). We identified 8 earthquakes in the area that were recorded at the bottom and top of the hole that were used for spectral ratios. We calculated the average and one standard deviation of ratios from all the events. Examining the data, we found that: (1) Fourier amplitude spectral ratios provided more detailed information on the site response than the absolute acceleration response that can be directly related to the effect of large earthquakes. (2) plots of the Fourier amplitude spectra for most of the recorded earthquakes show evidence for a spectral hole in the downhole recordings. This is due to downward reflected energy from the surface. This is not evident in absolute acceleration response records. (3) Fourier amplitude spectral ratios show a relative amplification at the surface of about a factor of eight for frequencies between about 9 to 15 Hz (.07 to .ll s periods) due to the spectral hole. (4) The free surface results in an amplification of about a factor of 2 for frequencies of about 13.0 to 25.0 Hz (.04 to .08 s periods). (5) The geology results in an amplification of about a factor 2 of the surface relative to the bottom for frequencies 1.0 to 25.0 Hz (0.04 to 1.0 s period). (6) A full site response function is provided as a function of frequency from the Fourier amplitude spectral ratios. This includes the effect of the spectral hole, free surface effect, and geologic amplification. It shows that strong ground motion would be diminished at the bottom of the U1A hole by a factor of .5 to

  2. Sterile neutrino dark matter with gauged U(1){sub B-L} and a low reheating temperature

    SciTech Connect

    Khalil, Shaaban; Seto, Osamu

    2009-04-17

    Sterile right-handed neutrinos can be naturally embedded in a low scale gauged U(1){sub B-L} extension of the standard model. We show that, within a low reheating scenario, such a neutrino can be produced via a novel manner, namely scattering through Z' gauge boson, and becomes an interesting dark matter candidate. In addition, we show that if the neutrino mass is of the order of MeV, then it accounts for the measured dark matter relic density and also accommodates the observed flux of 511 keV photons from the galactic bulge.

  3. Neutrino masses in the SU(4)L ⊗ U(1)X electroweak extension of the Standard Model

    NASA Astrophysics Data System (ADS)

    Palacio, Guillermo

    2016-09-01

    We study the neutrino mass generation in the SU(4)L ⊗ U(1)X electroweak extension of the Standard Model by considering nonrenormalizable dimension 5 effective operators. It is shown that there exist two topologies for the realizations of such an operator at the tree-level and for one of the three-family models the neutrino phenomenology is explored after extending its particle content with an SU(4)L fermion singlet and a scalar decuplet. Constraints in the available parameters space of the model are partially discussed.

  4. Hexagonal phase stabilization and magnetic orders of multiferroic L u1 -xS cxFe O3

    NASA Astrophysics Data System (ADS)

    Lin, L.; Zhang, H. M.; Liu, M. F.; Shen, Shoudong; Zhou, S.; Li, D.; Wang, X.; Yan, Z. B.; Zhang, Z. D.; Zhao, Jun; Dong, Shuai; Liu, J.-M.

    2016-02-01

    Hexagonal LuFe O3 has drawn a lot of research attention due to its contentious room-temperature multiferroicity. Due to the instability of hexagonal phase in the bulk form, most experimental studies focused on LuFe O3 thin films which can be stabilized by strain using proper substrates. Here we report on the hexagonal phase stabilization, magnetism, and magnetoelectric coupling of bulk LuFe O3 by partial Sc substitution of Lu. First, our first-principles calculations show that the hexagonal structure can be stabilized by partial Sc substitution, while the multiferroic properties, including the noncollinear magnetic order and geometric ferroelectricity, remain robustly unaffected. Therefore, L u1 -xS cxFe O3 can act as a platform to check the multiferroicity of LuFe O3 and related materials in the bulk form. Second, the magnetic characterizations on bulk L u1 -xS cxFe O3 demonstrate a magnetic anomaly (probable antiferromagnetic ordering) above room temperature, ˜425-445 K, followed by magnetic transitions in low temperatures (˜167-172 K). In addition, a magnetoelectric response is observed in the low-temperature region. Our study provides useful information on the multiferroic physics of hexagonal R Fe O3 and related systems.

  5. Mapping of epitopes on U1 snRNP polypeptide A with synthetic peptides and autoimmune sera.

    PubMed Central

    Barakat, S; Briand, J P; Abuaf, N; van Regenmortel, M H; Muller, S

    1991-01-01

    The ability of synthetic peptides encompassing almost the entire sequence of snRNP U1A polypeptide to be recognized in ELISA by sera of autoimmune patients was investigated. Sera from 18 patients with mixed connective tissue disease (MCTD), 145 with systemic lupus erythematosus (SLE) and 120 with other rheumatic autoimmune diseases were tested with 13 overlapping peptides. Among them, peptide 257-282 and, to a lower extent, peptide 1-11 were recognized by MCTD, SLE and Sjögren's syndrome sera. In contrast, peptide 35-58 was recognized by 94% of MCTD and only 19% of SLE sera. It did not react with any of the other patient sera. The ELISA results were compared with the pattern of reactivity observed in immunoblotting. The results indicate that peptide 35-58 probably contains a major epitope recognized by MCTD autoantibodies. It is noteworthy that in snRNP particles, this region of U1A interacts with RNA and presents only limited homology with the corresponding sequence 32-50 of U2B''. Images Fig. 3 PMID:1717192

  6. CYP2U1 mutations in two Iranian patients with activity induced dystonia, motor regression and spastic paraplegia

    PubMed Central

    Kariminejad, A.; Schöls, L.; Schüle, R.; Tonekaboni, S.H.; Abolhassani, A.; Fadaee, M.; Rosti, R.O.; Gleeson, J.G.

    2016-01-01

    Hereditary spastic paraplegia (HSP) is a heterogeneous condition characterized by progressive spasticity and weakness in the lower limbs. It is divided into two major groups, complicated and uncomplicated, based on the presence of additional features such as intellectual disability, ataxia, seizures, peripheral neuropathy and visual problems. SPG56 is an autosomal recessive form of HSP with complicated and uncomplicated manifestations, complicated being more common. CYP2U1 gene mutations have been identified as responsible for SPG56. Intellectual disability, dystonia, subclinical sensory motor neuropathy, pigmentary degenerative maculopathy, thin corpus callosum and periventricular white-matter hyperintensities were additional features noted in previous cases of SPG56. Here we identified two novel mutations in CYP2U1 in two unrelated patients by whole exome sequencing. Both patients had complicated HSP with activity-induced dystonia, suggesting dystonia as an additional finding in SPG56. Two out of 14 previously reported patients had dystonia, and the addition of our patients suggests dystonia in a quarter of SPG56 patients. Developmental regression has not been reported in SPG56 patients so far but both of our patients developed motor regression in infancy. PMID:27292318

  7. Explaining the CMS excesses, baryogenesis, and neutrino masses in a E6 motivated U (1 )N model

    NASA Astrophysics Data System (ADS)

    Dhuria, Mansi; Hati, Chandan; Sarkar, Utpal

    2016-01-01

    We study the superstring inspired E6 model motivated U (1 )N extension of the supersymmetric standard model to explore the possibility of explaining the recent excess CMS events and the baryon asymmetry of the Universe in eight possible variants of the model. In light of the hints from short-baseline neutrino experiments at the existence of one or more light sterile neutrinos, we also study the neutrino mass matrices dictated by the field assignments and the discrete symmetries in these variants. We find that all the variants can explain the excess CMS events via the exotic slepton decay, while for a standard choice of the discrete symmetry four of the variants have the feature of allowing high scale baryogenesis (leptogenesis). For one other variant three body decay induced soft baryogenesis mechanism is possible which can induce baryon number violating neutron-antineutron oscillation. We also point out a new discrete symmetry which has the feature of ensuring proton stability and forbidding tree level flavor changing neutral current processes while allowing for the possibility of high scale leptogenesis for two of the variants. On the other hand, neutrino mass matrix of the U (1 )N model variants naturally accommodates three active and two sterile neutrinos which acquire masses through their mixing with extra neutral fermions giving rise to interesting textures for neutrino masses.

  8. Role of IgE immune complexes in the regulation of HIV-1 replication and increased cell death of infected U1 monocytes: involvement of CD23/Fc epsilon RII-mediated nitric oxide and cyclic AMP pathways.

    PubMed Central

    Ouaaz, F.; Ruscetti, F. W.; Dugas, B.; Mikovits, J.; Agut, H.; Debré, P.; Mossalayi, M. D.

    1996-01-01

    BACKGROUND: IgE/anti-IgE immune complexes (IgE-IC) induce the release of multiple mediators from monocytes/macrophages and the monocytic cell line U937 following the ligation of the low-affinity Fc epsilon receptors (Fc epsilon RII/CD23). These effects are mediated through an accumulation of cAMP and the generation of L-arginine-dependent nitric oxide (NO). Since high IgE levels predict more rapid progression to acquired immunodeficiency syndrome, we attempted to define the effects of IgE-IC on human immunodeficiency virus (HIV) production in monocytes. MATERIALS AND METHODS: Two variants of HIV-1 chronically infected monocytic U1 cells were stimulated with IgE-IC and virus replication was quantified. NO and cAMP involvement was tested through the use of agonistic and antagonistic chemicals of these two pathways. RESULTS: IgE-IC induced p24 production by U1 cells with low-level constitutive expression of HIV-1 mRNAs and extracellular HIV capsid protein p24 levels (U1low), upon their pretreatment with interleukin 4 (IL-4) or IL-13. This effect was due to the crosslinking of CD23, as it was reversed by blocking the IgE binding site on CD23. The IgE-IC effect could also be mimicked by crosslinking of CD23 by a specific monoclonal antibody. p24 induction by IgE-IC was then shown to be due to CD23-mediated stimulation of cAMP, NO, and tumor necrosis factor alpha (TNF alpha) generation. In another variant of U1 cells with > 1 log higher constitutive production of p24 levels (U1high), IgE-IC addition dramatically decreased all cell functions tested and accelerated cell death. This phenomenon was reversed by blocking the nitric oxide generation. CONCLUSIONS: These data point out a regulatory role of IgE-IC on HIV-1 production in monocytic cells, through CD23-mediated stimulation of cAMP and NO pathways. IgE-IC can also stimulate increased cell death in high HIV producing cells through the NO pathway. Images FIG. 1 FIG. 2 FIG. 5 PMID:8900533

  9. Accurate and efficient N-6-adenosine methylation in spliceosomal U6 small nuclear RNA by HeLa cell extract in vitro.

    PubMed

    Shimba, S; Bokar, J A; Rottman, F; Reddy, R

    1995-07-11

    Human U6 small nuclear RNA (U6 snRNA), an abundant snRNA required for splicing of pre-mRNAs, contains several post-transcriptional modifications including a single m6A (N-6-methyladenosine) at position 43. This A-43 residue is critical for the function of U6 snRNA in splicing of pre-mRNAs. Yeast and plant U6 snRNAs also contain m6A in the corresponding position showing that this modification is evolutionarily conserved. In this study, we show that upon incubation of an unmodified U6 RNA with HeLa cell extract, A-43 residue in human U6 snRNA was rapidly converted to m6A-43. This conversion was detectable as early as 3 min after incubation and was nearly complete in 60 min; no other A residue in U6 snRNA was converted to m6A. Deletion studies showed that the stem-loop structure near the 5' end of U6 snRNA is dispensable for m6A formation; however, the integrity of the 3' stem-loop was necessary for efficient m6A formation. These data show that a short stretch of primary sequence flanking the methylation site is not sufficient for U6 m6A methyltransferase recognition and the enzyme probably recognizes secondary and/or tertiary structural features in U6 snRNA. The enzyme that catalyzes m6A formation in U6 snRNA appears to be distinct from the prolactin mRNA methyltransferase which is also present in HeLa nuclear extracts. PMID:7630720

  10. String completion of an SU(3)c ⊗ SU(3)L ⊗ U(1)X electroweak model

    NASA Astrophysics Data System (ADS)

    Addazi, Andrea; Valle, J. W. F.; Vaquera-Araujo, C. A.

    2016-08-01

    The extended electroweak SU(3)c ⊗ SU(3)L ⊗ U(1)X symmetry framework "explaining" the number of fermion families is revisited. While 331-based schemes can not easily be unified within the conventional field theory sense, we show how to do it within an approach based on D-branes and (un)oriented open strings, on Calabi-Yau singularities. We show how the theory can be UV-completed in a quiver setup, free of gauge and string anomalies. Lepton and baryon numbers are perturbatively conserved, so neutrinos are Dirac-type, and their lightness results from a novel TeV scale seesaw mechanism. Dynamical violation of baryon number by exotic instantons could induce neutron-antineutron oscillations, with proton decay and other dangerous R-parity violating processes strictly forbidden.

  11. Proof of the local mass-angular momenta inequality for U{(1)}^{2} invariant black holes

    NASA Astrophysics Data System (ADS)

    Alaee, Aghil; Kunduri, Hari K.

    2015-08-01

    We consider initial data for extreme vacuum asymptotically flat black holes with {{R}}× U{(1)}2 symmetry. Such geometries are critical points of a mass functional defined for a wide class of asymptotically flat, ‘(t-{φ }i)’ symmetric maximal initial data for the vacuum Einstein equations. We prove that the above extreme geometries are local minima of mass among nearby initial data (with the same interval structure) with fixed angular momenta. Thus the ADM mass of nearby data m≥slant f({J}1,{J}2) for some function f depending on the interval structure. The proof requires that the initial data of the critical points satisfy certain conditions that are satisfied by the extreme Myers-Perry and extreme black ring data.

  12. Explicit one-loop corrections to the strong CP-violating phase in SU(2)/sub L/ x U(1)

    SciTech Connect

    Goffin, V.; Segre, G.; Weldon, H.A.

    1980-03-01

    In a CP-invariant Lagrangian the spontaneous symmetry breaking that generates the quark mass matrix m will induce CP violations into the strong interactions with strength theta/sub QFD/=arg Detm, where QFD refers to quantum flavor dynamics. Even if Detm is real in tree approximation, it will generally not be in higher order. We show that in any SU(2)/sub L/ x U(1) model the only one-loop corrections to theta/sub QFD/ come from Higgs particles. These are explicitly calculated in a six-quark model with permutation symmetry. We find theta/sub QFD/ approx. = 10/sup -10/(m/sub s//m/sub b/)(m/sub t//m/sub b/)/sup 2/ in one case and theta/sub QFD/ approx. = 10/sup -8/(m/sub c//m/sub t/) in a second case. Cabibbo angles and CP violation in the kaon system are also examined.

  13. Models of fermion mass matrices based on a flavor- and generation-dependent U (1) gauge symmetry

    NASA Astrophysics Data System (ADS)

    Jain, Vidyut; Shrock, Robert

    1995-02-01

    We study models of fermion mass matrices based on a flavor- and generation-dependent string-motivated U(1) A gauge symmetry and report two new classes of solutions to the requisite consistency conditions. In particular, we explore the idea that the fundamental reason underlying the striking feature mb, mr ≪ mt is that all of the elements of the down-quark and charged lepton effective Yukawa matrices actually arise from higher-dimension operators, suppressed by inverse powers of the Planck mass. We construct an explicit model embodying this idea, in which only the jk = 33 element of the Q = {2}/{3} effective Yukawa matrix Yjku arises from dimension-4 operators.

  14. Neutrino masses in supersymmetric SU(3){sub c} x SU(3){sub L} x U(1){sub X} models

    SciTech Connect

    Rodriguez, J-Alexis; Duarte, J.

    2008-11-23

    The mass spectra and the superpotential of two different supersymetric models based on the gauge symmetry SU(3){sub C} x SU(3){sub L} x U(1){sub X}(331) without any exotic charges assigned to the fermionic spectra are studied. These two models have three families in different representations of the gauge group. In these kind of models, the diagonalization of the neutralino mass matrix allows that three light neutrinos get different mass values. Possible values for the neutrino masses are calculated covering the parameter space of the models. These values have to agree with the available data coming from the neutrino oscillations experiments. Therefore, a reduced space of parameters for the superpotential and the vacuum expectation values allowed in the framework of the 331 supersymetric models can be obtained.

  15. Scalar quasinormal modes of anti-de Sitter static spacetime in Horava-Lifshitz gravity with U (1 ) symmetry

    NASA Astrophysics Data System (ADS)

    Lin, Kai; Qian, Wei-Liang; Pavan, A. B.

    2016-09-01

    In this paper, we investigate the scalar quasinormal modes of Hořava-Lifshitz theory with U (1 ) symmetry in static anti-de Sitter spacetime. The static planar and spherical black hole solutions in lower energy limit are derived in nonprojectable Hořava-Lifshitz gravity. The equation of motion of a scalar field is obtained, and is utilized to study the quasinormal modes of massless scalar particles. We find that the effect of Hořava-Lifshitz correction is to increase the quasinormal period as well as to slow down the decay of the oscillation magnitude. Besides, the scalar field could be unstable when the correction becomes too large.

  16. Global analysis of general SU(2)xSU(2)xU(1) models with precision data

    SciTech Connect

    Hsieh, Ken; Yu, Jiang-Hao; Yuan, C.-P.; Schmitz, Kai

    2010-08-01

    We present the results of a global analysis of a class of models with an extended electroweak gauge group of the form SU(2)xSU(2)xU(1), often denoted as G(221) models, which include as examples the left-right, the leptophobic, the hadrophobic, the fermiophobic, the un-unified, and the nonuniversal models. Using an effective Lagrangian approach, we compute the shifts to the coefficients in the electroweak Lagrangian due to the new heavy gauge bosons, and obtain the lower bounds on the masses of the Z{sup '} and W{sup '} bosons. The analysis of the electroweak parameter bounds reveals a consistent pattern of several key observables that are especially sensitive to the effects of new physics and thus dominate the overall shape of the respective parameter contours.

  17. Resonant x-ray magnetic scattering from U1-xNpxRu2Si2 alloys

    NASA Astrophysics Data System (ADS)

    Lidström, E.; Mannix, D.; Hiess, A.; Rebizant, J.; Wastin, F.; Lander, G. H.; Marri, I.; Carra, P.; Vettier, C.; Longfield, M. J.

    2000-01-01

    We have studied U1-xNpxRu2Si2 alloys with x=0.1, 0.5, and 1.0 using resonant x-ray magnetic scattering. For the x=1 neptunium compound we have confirmed previous neutron scattering results, but with much higher count rates and improved q resolution. Using the element specificity of the method, we have found that the temperature dependence of the uranium and the neptunium moments differ in the mixed U1-xNpxRu2Si2 solid solutions and we present some tentative explanations for this behavior. In principle, by measuring the responses at the individual M edges we are able to determine the ratio of the magnetic moments on the two magnetic species in the random alloys. The observed variation of intensity versus energy is compared to a calculation of a x=0.50 alloy using a localized model and a coherent superposition of U4+ and Np3+ ions. The agreement between theory and experiment is reasonable, suggesting a ratio μU/μNp~0.25 in this alloy. Since μNp is known to be 1.5μB for 0.10<=x<=1, the uranium moment is ~0.4μB. This is much larger than 0.02μB known to exist in URu2Si2 (x=0). The increase is a consequence of the molecular field of the ordered Np3+ moments and is consistent with the crystal-field model proposed for the U4+ ground state.

  18. Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein.

    PubMed Central

    Brahms, H; Meheus, L; de Brabandere, V; Fischer, U; Lührmann, R

    2001-01-01

    Arginine residues in RG-rich proteins are frequently dimethylated posttranslationally by protein arginine methyltransferases (PRMTs). The most common methylation pattern is asymmetrical dimethylation, a modification important for protein shuttling and signal transduction. Symmetrically dimethylated arginines (sDMA) have until now been confined to the myelin basic protein MBP and the Sm proteins D1 and D3. We show here by mass spectrometry and protein sequencing that also the human Sm protein B/B' and, for the first time, one of the Sm-like proteins, LSm4, contain sDMA in vivo. The symmetrical dimethylation of B/B', LSm4, D1, and D3 decisively influences their binding to the Tudor domain of the "survival of motor neurons" protein (SMN): inhibition of dimethylation by S-adenosylhomocysteine (SAH) abolished the binding of D1, D3, B/B', and LSm4 to this domain. A synthetic peptide containing nine sDMA-glycine dipeptides, but not asymmetrically modified or nonmodified peptides, specifically inhibited the interaction of D1, D3, B/B', LSm4, and UsnRNPs with SMN-Tudor. Recombinant D1 and a synthetic peptide could be methylated in vitro by both HeLa cytosolic S100 extract and nuclear extract; however, only the cytosolic extract produced symmetrical dimethylarginines. Thus, the Sm-modifying PRMT is cytoplasmic, and symmetrical dimethylation of B/B', D1, and D3 is a prerequisite for the SMN-dependent cytoplasmic core-UsnRNP assembly. Our demonstration of sDMAs in LSm4 suggests additional functions of sDMAs in tri-UsnRNP biogenesis and mRNA decay. Our findings also have interesting implications for the understanding of the aetiology of spinal muscular atrophy (SMA). PMID:11720283

  19. Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein.

    PubMed

    Brahms, H; Meheus, L; de Brabandere, V; Fischer, U; Lührmann, R

    2001-11-01

    Arginine residues in RG-rich proteins are frequently dimethylated posttranslationally by protein arginine methyltransferases (PRMTs). The most common methylation pattern is asymmetrical dimethylation, a modification important for protein shuttling and signal transduction. Symmetrically dimethylated arginines (sDMA) have until now been confined to the myelin basic protein MBP and the Sm proteins D1 and D3. We show here by mass spectrometry and protein sequencing that also the human Sm protein B/B' and, for the first time, one of the Sm-like proteins, LSm4, contain sDMA in vivo. The symmetrical dimethylation of B/B', LSm4, D1, and D3 decisively influences their binding to the Tudor domain of the "survival of motor neurons" protein (SMN): inhibition of dimethylation by S-adenosylhomocysteine (SAH) abolished the binding of D1, D3, B/B', and LSm4 to this domain. A synthetic peptide containing nine sDMA-glycine dipeptides, but not asymmetrically modified or nonmodified peptides, specifically inhibited the interaction of D1, D3, B/B', LSm4, and UsnRNPs with SMN-Tudor. Recombinant D1 and a synthetic peptide could be methylated in vitro by both HeLa cytosolic S100 extract and nuclear extract; however, only the cytosolic extract produced symmetrical dimethylarginines. Thus, the Sm-modifying PRMT is cytoplasmic, and symmetrical dimethylation of B/B', D1, and D3 is a prerequisite for the SMN-dependent cytoplasmic core-UsnRNP assembly. Our demonstration of sDMAs in LSm4 suggests additional functions of sDMAs in tri-UsnRNP biogenesis and mRNA decay. Our findings also have interesting implications for the understanding of the aetiology of spinal muscular atrophy (SMA).

  20. 3.5 keV X-ray line signal from dark matter decay in local U(1) B- L extension of Zee-Babu model

    NASA Astrophysics Data System (ADS)

    Baek, Seungwon

    2015-08-01

    We consider a local U(1) B- L extension of Zee-Babu model to explain the recently observed 3.5 keV X-ray line signal. The model has three Standard model (SM)-singlet Dirac fermions with different U(1) B- L charges. A complex scalar field charged under U(1) B- L is introduced to break the U(1) B- L symmetry. After U(1) B- L symmetry breaking a remnant discrete symmetry stabilizes the lightest state of the Dirac fermions, which can be a stable dark matter (DM). The second lightest state, if mass splitting with the stable DM is about 3.5 keV, decays dominantly to the stable DM and 3.5 keV photon through two-loop diagrams, explaining the X-ray line signal. Two-loop suppression of the decay amplitude makes its lifetime much longer than the age of the universe and it can be a decaying DM candidate in large parameter region. We also introduce a real scalar field which is singlet under both the SM and U(1) B- L and can explain the current relic abundance of the Dirac fermionic DMs. If the mixing with the SM Higgs boson is small, it does not contribute to DM direct detection. The main contribution to the scattering of DM off atomic nuclei comes from the exchange of U(1) B- L gauge boson, Z ', and is suppressed below current experimental bound when Z' mass is heavy (≳10 TeV). If the singlet scalar mass is about 0.1-10 MeV, DM self-interaction can be large enough to solve small scale structure problems in simulations with the cold DM, such as, the core-vs-cusp problem and too-big-to-fail problem.

  1. Phenomenological implications of an S U (5 )×S4×U (1 ) SUSY GUT of flavor

    NASA Astrophysics Data System (ADS)

    Dimou, Maria; King, Stephen F.; Luhn, Christoph

    2016-04-01

    We discuss the characteristic low energy phenomenological implications of an S U (5 ) supersymmetric (SUSY) grand unified theory whose flavor structure is controlled by the family symmetry S4×U (1 ), which provides a good description of all quark and lepton masses, mixings as well as charge parity violation. Although the model closely mimics minimal flavor violation (MFV) as shown in M. Dimou, S. F. King, and C. Luhn, J. High Energy Phys. 02 (2016) 118., here we focus on the differences. We first present numerical estimates of the low energy mass insertion parameters, including canonical normalization and renormalization group running, for well-defined ranges of SUSY parameters and compare the naive model expectations to the numerical scans and the experimental bounds. Our results are then used to estimate the model-specific predictions for electric dipole moments (EDMs), lepton flavor violation (LFV), B and K meson mixing as well as rare B decays. The largest observable deviations from MFV come from the LFV process μ →e γ and the electron EDM.

  2. Computational study of the energetics of charge and cation mixing in U1-xCexO₂

    DOE PAGES

    Hanken, B. E.; Stanek, C. R.; Grønbech-Jensen, N.; Asta, M.

    2011-08-26

    The formalism of electronic density-functional theory (DFT), with Hubbard-U corrections (DFT+U), is employed in a computational study of the energetics of fluorite-structured U1-xCexO₂ mixtures. The computational approach makes use of a procedure which facilitates convergence of the calculations to multiple self-consistent DFT+U solutions for a given cation arrangement, corresponding to different charge states for the U and Ce ions in several prototypical cation arrangements. Results indicate a significant dependence of the structural and energetic properties on the nature of both charge and cation ordering. With the effective Hubbard-U parameters that reproduce well the measured oxidation-reduction energies for urania and ceria,more » we find that charge transfer between U⁴⁺ and Ce⁴⁺ ions, leading to the formation of U⁵⁺ and Ce³⁺, gives rise to an increase in the mixing energy in the range of 4–14 kJ/mol of the formula unit, depending on the nature of the cation ordering. The results suggest that although charge transfer between uranium and cerium ions is disfavored energetically, it is likely to be entropically stabilized at the high temperatures relevant to the processing and service of urania-based solid solutions.« less

  3. Low-energy effective theory of Fermi surface coupled with U(1) gauge field in 2+1 dimensions

    NASA Astrophysics Data System (ADS)

    Lee, Sung-Sik

    2009-10-01

    We study the low-energy effective theory for a non-Fermi-liquid state in 2+1 dimensions, where a transverse U(1) gauge field is coupled with a patch of Fermi surface with N flavors of fermion in the large N limit. In the low-energy limit, quantum corrections are classified according to the genus of the two-dimensional surface on which Feynman diagrams can be drawn without a crossing in a double line representation and all planar diagrams are important in the leading order. The emerging theory has the similar structure to the four-dimensional SU(N) gauge theory in the large N limit. Because of strong quantum fluctuations caused by the abundant low-energy excitations near the Fermi surface, low-energy fermions remain strongly coupled even in the large N limit. As a result, there are infinitely many quantum corrections that contribute to the leading frequency dependence of the Green’s function of fermion on the Fermi surface. On the contrary, the boson self-energy is not modified beyond the one-loop level and the theory is stable in the large N limit. The nonperturbative nature of the theory also shows up in correlation functions of gauge-invariant operators.

  4. Probing U(1) extensions of the MSSM at the LHC Run I and in dark matter searches

    NASA Astrophysics Data System (ADS)

    Bélanger, G.; Da Silva, J.; Laa, U.; Pukhov, A.

    2015-09-01

    The U(1) extended supersymmetric standard model (UMSSM) can accommodate a Higgs boson at 125 GeV without relying on large corrections from the top/stop sector. After imposing LHC results on the Higgs sector, on B-physics and on new particle searches as well as dark matter constraints, we show that this model offers two viable dark matter candidates, the right-handed (RH) sneutrino or the neutralino. Limits on super-symmetric partners from LHC simplified model searches are imposed using SM odelS and allow for light squarks and gluinos. Moreover the upper limit on the relic abundance often favours scenarios with long-lived particles. Searches for a Z ' at the LHC remain the most unambiguous probes of this model. Interestingly, the D-term contributions to the sfermion masses allow to explain the anomalous magnetic moment of the muon in specific corners of the parameter space with light smuons or left-handed (LH) sneutrinos. We finally emphasize the interplay between direct searches for dark matter and LHC simplified model searches.

  5. Global U (1 )L symmetry breaking in a neutrinophilic 2HDM: From LHC signatures to x-ray lines

    NASA Astrophysics Data System (ADS)

    Wang, Weijian; Han, Zhi-Long

    2016-09-01

    Lepton number violation plays an essential role in many scenarios of neutrino mass generation and also provides new clues to search new physics beyond the standard model. We consider the neutrinophilic two-Higgs-doublet model (ν -2 HDM ) where additional right-handed neutral fermions NR i and a complex singlet scalar σ are also involved. In the scalar sector, the global U (1 )L symmetry is spontaneously broken, leading to Nambu-Goldstone boson, the Majoron J , accompanied by the Majorana neutrino mass generation. We find that the massless Majoron will induce large invisible Higgs decay, and current experiments have already set constraints on relevant parameters. For the first time, we point out that the ν -2 HDM with NR i can be distinguished from other seesaw by the same sign trilepton signature 3 ℓ±4 j + ET. More interesting, for the O (keV ) scale Majoron, it is a good candidate of decaying dark matter to interpret the 3.5 and 511 keV line excesses by two different parameter spaces.

  6. Boson stars in a theory of complex scalar fields coupled to the U(1) gauge field and gravity

    NASA Astrophysics Data System (ADS)

    Kumar, Sanjeev; Kulshreshtha, Usha; Shankar Kulshreshtha, Daya

    2014-08-01

    We study boson shells and boson stars in a theory of a complex scalar field coupled to the U(1) gauge field {{A}_{\\mu }} and Einstein gravity with the potential V(|\\Phi |)\\;:=\\frac{1}{2}{{m}^{2}}{{\\left( |\\Phi |+a \\right)}^{2}}. This could be considered either as a theory of a massive complex scalar field coupled to an electromagnetic field and gravity in a conical potential, or as a theory in the presence of a potential that is an overlap of a parabolic and conical potential. Our theory has a positive cosmological constant (\\Lambda :=4\\pi G{{m}^{2}}{{a}^{2}}). Boson stars are found to come in two types, having either ball-like or shell-like charge density. We studied the properties of these solutions and also determined their domains of existence for some specific values of the parameters of the theory. Similar solutions have also been obtained by Kleihaus, Kunz, Laemmerzahl and List, in a V-shaped scalar potential.

  7. U(1) slave-particle study of the finite-temperature doped Hubbard model in one and two dimensions

    SciTech Connect

    Ribeiro, P.; Sacramento, P.D.; Araujo, M.A.N.

    2011-05-15

    Research Highlights: > Mean-field U(1) slave-particle description of Hubbard model. > Fractionalized phases at finite-temperature in Hubbard model. > Spectral function of 1d and 2d Hubbard model. - Abstract: One-dimensional systems have unusual properties such as fractionalization of degrees of freedom. The occurrence of similar phenomena in higher dimensional systems has been considered in the literature for the description of quantum spin liquids and some non-fermi liquid phases. In this work we construct a mean field (MF) theory of the Hubbard model which is based on a representation of the electronic fields that explicitly introduces a separation of the charge and spin degrees of freedom (the so-called Zou-Anderson transformation) and study the finite-temperature phase diagram for the Hubbard chain and square lattice. The mean field variables are defined along the links of the underlying lattice. We obtain the spectral function and identify the regions of higher spectral weight with the fractionalized fermionic (spin) and bosonic (charge) excitations.

  8. Origins and evolution of spliceosomal introns.

    PubMed

    Rodríguez-Trelles, Francisco; Tarrío, Rosa; Ayala, Francisco J

    2006-01-01

    Research into the origins of introns is at a critical juncture in the resolution of theories on the evolution of early life (which came first, RNA or DNA?), the identity of LUCA (the last universal common ancestor, was it prokaryotic- or eukaryotic-like?), and the significance of noncoding nucleotide variation. One early notion was that introns would have evolved as a component of an efficient mechanism for the origin of genes. But alternative theories emerged as well. From the debate between the "introns-early" and "introns-late" theories came the proposal that introns arose before the origin of genetically encoded proteins and DNA, and the more recent "introns-first" theory, which postulates the presence of introns at that early evolutionary stage from a reconstruction of the "RNA world." Here we review seminal and recent ideas about intron origins. Recent discoveries about the patterns and causes of intron evolution make this one of the most hotly debated and exciting topics in molecular evolutionary biology today. PMID:17094737

  9. Realistic SU (3 )c⊗SU (3 )L⊗U (1 )X model with a type II Dirac neutrino seesaw mechanism

    NASA Astrophysics Data System (ADS)

    Reig, Mario; Valle, José W. F.; Vaquera-Araujo, C. A.

    2016-08-01

    Here we propose a realistic SU (3 )c⊗SU (3 )L⊗U (1 )X electroweak gauge model with enlarged Higgs sector. The scheme allows for the natural implementation of a type II seesaw mechanism for Dirac neutrinos, while charged lepton and quark masses are reproduced in a natural way thanks to the presence of new scalars. The new SU (3 )c⊗SU (3 )L⊗U (1 )X energy scale characterizing neutrino mass generation could be accessible to the current LHC experiments.

  10. A New Fate of a Warped 5D FLRW Model with a U(1) Scalar Gauge Field

    NASA Astrophysics Data System (ADS)

    Slagter, Reinoud Jan; Pan, Supriya

    2016-09-01

    If we live on the weak brane with zero effective cosmological constant in a warped 5D bulk spacetime, gravitational waves and brane fluctuations can be generated by a part of the 5D Weyl tensor and carries information of the gravitational field outside the brane. We consider on a cylindrical symmetric warped FLRW background a U(1) self-gravitating scalar field coupled to a gauge field without bulk matter. It turns out that brane fluctuations can be formed dynamically, due to the modified energy-momentum tensor components of the scalar-gauge field ("cosmic string"). As a result, we find that the late-time behavior could significantly deviate from the standard evolution of the universe. The effect is triggered by the time-dependent warpfactor with two branches of the form ± 1/√{τ r}√{(c_1e^{√{2τ } t}+c_2e^{-√{2τ } t})(c_3e^{√{2τ } r}+c_4e^{-√{2τ } r})} ( with τ , c_i constants) and the modified brane equations comparable with a dark energy effect. This is a brane-world mechanism, not present in standard 4D FLRW, where the large disturbances are rapidly damped as the expansion proceed. Because gravity can propagate in the bulk, the cosmic string can build up a huge angle deficit (or mass per unit length) by the warpfactor and can induce massive KK-modes felt on the brane. Disturbances in the spatial components of the stress-energy tensor cause cylindrical symmetric waves, amplified due to the presence of the bulk space and warpfactor. They could survive the natural damping due to the expansion of the universe. It turns out that one of the metric components becomes singular at the moment the warp factor develops an extremum. This behavior could have influence on the possibility of a transition from acceleration to deceleration or vice versa.

  11. A New Fate of a Warped 5D FLRW Model with a U(1) Scalar Gauge Field

    NASA Astrophysics Data System (ADS)

    Slagter, Reinoud Jan; Pan, Supriya

    2016-03-01

    If we live on the weak brane with zero effective cosmological constant in a warped 5D bulk spacetime, gravitational waves and brane fluctuations can be generated by a part of the 5D Weyl tensor and carries information of the gravitational field outside the brane. We consider on a cylindrical symmetric warped FLRW background a U(1) self-gravitating scalar field coupled to a gauge field without bulk matter. It turns out that brane fluctuations can be formed dynamically, due to the modified energy-momentum tensor components of the scalar-gauge field ("cosmic string"). As a result, we find that the late-time behavior could significantly deviate from the standard evolution of the universe. The effect is triggered by the time-dependent warpfactor with two branches of the form ± 1/√{τ r}√{(c_1e^{√{2τ } t}+c_2e^{-√{2τ } t})(c_3e^{√{2τ } r}+c_4e^{-√{2τ } r})} ( with τ c_i constants) and the modified brane equations comparable with a dark energy effect. This is a brane-world mechanism, not present in standard 4D FLRW, where the large disturbances are rapidly damped as the expansion proceed. Because gravity can propagate in the bulk, the cosmic string can build up a huge angle deficit (or mass per unit length) by the warpfactor and can induce massive KK-modes felt on the brane. Disturbances in the spatial components of the stress-energy tensor cause cylindrical symmetric waves, amplified due to the presence of the bulk space and warpfactor. They could survive the natural damping due to the expansion of the universe. It turns out that one of the metric components becomes singular at the moment the warp factor develops an extremum. This behavior could have influence on the possibility of a transition from acceleration to deceleration or vice versa.

  12. Interplay of topology and interactions in quantum Hall topological insulators: U(1) symmetry, tunable Luttinger liquid, and interaction-induced phase transitions

    NASA Astrophysics Data System (ADS)

    Kharitonov, Maxim; Juergens, Stefan; Trauzettel, Björn

    2016-07-01

    We consider a class of quantum Hall topological insulators: topologically nontrivial states with zero Chern number at finite magnetic field, in which the counterpropagating edge states are protected by a symmetry (spatial or spin) other than time-reversal. HgTe-type heterostructures and graphene are among the relevant systems. We study the effect of electron interactions on the topological properties of the system. We particularly focus on the vicinity of the topological phase transition, marked by the crossing of two Landau levels, where the system is a strongly interacting quantum Hall ferromagnet. We analyze the edge properties using the formalism of the nonlinear σ -model. We establish the symmetry requirement for the topological protection in this interacting system: effective continuous U(1) symmetry with respect to uniaxial isospin rotations must be preserved. If U(1) symmetry is preserved, the topologically nontrivial phase persists; its edge is a helical Luttinger liquid with highly tunable effective interactions. We obtain explicit analytical expressions for the parameters of the Luttinger liquid in the quantum-Hall-ferromagnet regime. However, U(1) symmetry may be broken, either spontaneously or by U(1)-asymmetric interactions. In either case, interaction-induced transitions occur to the respective topologically trivial phases with gapped edge charge excitations.

  13. Light top squarks in a U (1 )R lepton number model with a right handed neutrino and the LHC

    NASA Astrophysics Data System (ADS)

    Chakraborty, Sabyasachi; Datta, AseshKrishna; Huitu, Katri; Roy, Sourov; Waltari, Harri

    2016-04-01

    We investigate the phenomenology of top squarks at the Large Hadron Collider (LHC) in a supersymmetric model where lepton number is identified with an approximate U (1 )R symmetry in such a way that one of the left-chiral sneutrinos can acquire a large vacuum expectation value and can play the role of the down-type Higgs. This R symmetry allows a subset of trilinear R -parity violating interactions, which determine the collider phenomenology of this model in a significant way. The gauginos are Dirac particles and gluinos are relatively heavy in this class of models. The model contains a right handed neutrino superfield, which gives a tree level mass to one of the active neutrinos. An order one neutrino Yukawa coupling also helps enhance the Higgs boson mass at the tree level and results in a very light bino-like neutralino (χ˜2 0 ) with mass around a few hundred MeV, which is a carrier of missing (transverse) energy (ET ). The model can accommodate two rather light top squarks, compatible with the observed mass of the Higgs boson. The lighter top squark (t˜1) can decay into t χ˜20, and thus the signal would be similar to the signal of top quark pair production at the LHC. In addition, fully visible decays such as t˜2→b e+ can give rise to interesting final states. Such signals at the LHC combined with other features like a heavy gluino could provide strong evidence for this kind of a model. Our analysis shows that mt˜1≲575 (750 ) GeV and mt˜2≲1.2 (1.4 ) TeV can be probed with 5 σ statistical significance at the 13 TeV LHC with 300 (3000 ) fb-1 of integrated luminosity. Finally, we observe that in the presence of superlight carriers of ET, the so-called "stealth" top squark scenario may naturally appear in our model.

  14. The linked units of 5S rDNA and U1 snDNA of razor shells (Mollusca: Bivalvia: Pharidae)

    PubMed Central

    Vierna, J; Jensen, K T; Martínez-Lage, A; González-Tizón, A M

    2011-01-01

    The linkage between 5S ribosomal DNA and other multigene families has been detected in many eukaryote lineages, but whether it provides any selective advantage remains unclear. In this work, we report the occurrence of linked units of 5S ribosomal DNA (5S rDNA) and U1 small nuclear DNA (U1 snDNA) in 10 razor shell species (Mollusca: Bivalvia: Pharidae) from four different genera. We obtained several clones containing partial or complete repeats of both multigene families in which both types of genes displayed the same orientation. We provide a comprehensive collection of razor shell 5S rDNA clones, both with linked and nonlinked organisation, and the first bivalve U1 snDNA sequences. We predicted the secondary structures and characterised the upstream and downstream conserved elements, including a region at −25 nucleotides from both 5S rDNA and U1 snDNA transcription start sites. The analysis of 5S rDNA showed that some nontranscribed spacers (NTSs) are more closely related to NTSs from other species (and genera) than to NTSs from the species they were retrieved from, suggesting birth-and-death evolution and ancestral polymorphism. Nucleotide conservation within the functional regions suggests the involvement of purifying selection, unequal crossing-overs and gene conversions. Taking into account this and other studies, we discuss the possible mechanisms by which both multigene families could have become linked in the Pharidae lineage. The reason why 5S rDNA is often found linked to other multigene families seems to be the result of stochastic processes within genomes in which its high copy number is determinant. PMID:21364693

  15. Constraints on general SU(2)/sub L/ x SU(2)/sub R/ x U(1) electroweak models from nuclear beta decay

    SciTech Connect

    Herczeg, P.

    1986-01-01

    The implications of beta-decay experiments for more general versions of SU(2)/sub L/ x SU(2)/sub R/ x U(1) models are analyzed, including the most general one which allows for CP-violation, unequal left- and right-handed quark mixing angles, and mixing in the leptonic sector. For each scenario, the constraints on the pertinent parameters from beta-decay measurements are compared with the constraints provided on them by other data.

  16. The linked units of 5S rDNA and U1 snDNA of razor shells (Mollusca: Bivalvia: Pharidae).

    PubMed

    Vierna, J; Jensen, K T; Martínez-Lage, A; González-Tizón, A M

    2011-08-01

    The linkage between 5S ribosomal DNA and other multigene families has been detected in many eukaryote lineages, but whether it provides any selective advantage remains unclear. In this work, we report the occurrence of linked units of 5S ribosomal DNA (5S rDNA) and U1 small nuclear DNA (U1 snDNA) in 10 razor shell species (Mollusca: Bivalvia: Pharidae) from four different genera. We obtained several clones containing partial or complete repeats of both multigene families in which both types of genes displayed the same orientation. We provide a comprehensive collection of razor shell 5S rDNA clones, both with linked and nonlinked organisation, and the first bivalve U1 snDNA sequences. We predicted the secondary structures and characterised the upstream and downstream conserved elements, including a region at -25 nucleotides from both 5S rDNA and U1 snDNA transcription start sites. The analysis of 5S rDNA showed that some nontranscribed spacers (NTSs) are more closely related to NTSs from other species (and genera) than to NTSs from the species they were retrieved from, suggesting birth-and-death evolution and ancestral polymorphism. Nucleotide conservation within the functional regions suggests the involvement of purifying selection, unequal crossing-overs and gene conversions. Taking into account this and other studies, we discuss the possible mechanisms by which both multigene families could have become linked in the Pharidae lineage. The reason why 5S rDNA is often found linked to other multigene families seems to be the result of stochastic processes within genomes in which its high copy number is determinant.

  17. The linked units of 5S rDNA and U1 snDNA of razor shells (Mollusca: Bivalvia: Pharidae).

    PubMed

    Vierna, J; Jensen, K T; Martínez-Lage, A; González-Tizón, A M

    2011-08-01

    The linkage between 5S ribosomal DNA and other multigene families has been detected in many eukaryote lineages, but whether it provides any selective advantage remains unclear. In this work, we report the occurrence of linked units of 5S ribosomal DNA (5S rDNA) and U1 small nuclear DNA (U1 snDNA) in 10 razor shell species (Mollusca: Bivalvia: Pharidae) from four different genera. We obtained several clones containing partial or complete repeats of both multigene families in which both types of genes displayed the same orientation. We provide a comprehensive collection of razor shell 5S rDNA clones, both with linked and nonlinked organisation, and the first bivalve U1 snDNA sequences. We predicted the secondary structures and characterised the upstream and downstream conserved elements, including a region at -25 nucleotides from both 5S rDNA and U1 snDNA transcription start sites. The analysis of 5S rDNA showed that some nontranscribed spacers (NTSs) are more closely related to NTSs from other species (and genera) than to NTSs from the species they were retrieved from, suggesting birth-and-death evolution and ancestral polymorphism. Nucleotide conservation within the functional regions suggests the involvement of purifying selection, unequal crossing-overs and gene conversions. Taking into account this and other studies, we discuss the possible mechanisms by which both multigene families could have become linked in the Pharidae lineage. The reason why 5S rDNA is often found linked to other multigene families seems to be the result of stochastic processes within genomes in which its high copy number is determinant. PMID:21364693

  18. U1 snRNA as an effective vector for stable expression of antisense molecules and for the inhibition of the splicing reaction.

    PubMed

    Martone, Julie; De Angelis, Fernanda Gabriella; Bozzoni, Irene

    2012-01-01

    We report the use of the U1 snRNA as a vector for the stable expression of antisense molecules against the splice junctions of specific dystrophin exons. The single-stranded 5' terminus of U1 can be replaced by unrelated sequences as long as 50 nucleotides without affecting both the stability and the ability to assemble into snRNP particles. Effective exon skipping has been obtained for different dystrophin exons by antisense sequences against 5' and 3' splice sites alone or in combination with ESE sequences. The efficacy of these molecules has been studied both in in vitro systems and in animals. In both cases the chimeric molecules, delivered as part of lentiviral or AAV vectors (De Angelis et al. Proc Natl Acad Sci USA 99:9456-9461, 2002; Denti et al. Proc Natl Acad Sci USA 103: 3758-3763, 2006; Denti et al. Hum Gene Ther 17: 565-743, 2006; Denti et al. Hum Gene Ther 19: 601-608, 2008; Incitti et al. Mol Ther 18: 1675-1682, 2010), provided high skipping activity and efficient rescue of dystrophin synthesis. Moreover, the U1-antisense molecules, delivered to mice via systemic injection of recombinant AAV viruses, displayed body wide transduction, long-term expression, dystrophin rescue as well as morphological and functional benefit (Denti et al. Hum Gene Ther 19: 601-608, 2008). In this Chapter we report methods for producing U1-antisense expression cassettes in the backbone of lentiviral constructs and for testing their activity both in patients' derived myoblasts as well as in fibroblasts reprogrammed to muscle differentiation.

  19. Sign of the neutron-proton mass difference in an SU(2)×U(1) supersymmetric toy model: A possible scenario for solving the old puzzle

    NASA Astrophysics Data System (ADS)

    Desai, Bipin R.; Xu, Guang-Hua

    1990-04-01

    Based on the idea that electromagnetism is responsible for mass differences within isotopic multiplets (e.g., pointlike neutron and proton or u and d quarks), we generalize an SU(2)×U(1) model in a toy field theory of vectors to a supersymmetric model and investigate the finite mass difference within the isotopic doublet. It is found that under soft-supersymmetry breaking, a positive n-p mass difference can be obtained under reasonable assumptions for the parameters involved.

  20. Conservation of functional domains involved in RNA binding and protein-protein interactions in human and Saccharomyces cerevisiae pre-mRNA splicing factor SF1.

    PubMed

    Rain, J C; Rafi, Z; Rhani, Z; Legrain, P; Krämer, A

    1998-05-01

    The modular structure of splicing factor SF1 is conserved from yeast to man and SF1 acts at early stages of spliceosome assembly in both organisms. The hnRNP K homology (KH) domain of human (h) SF1 is the major determinant for RNA binding and is essential for the activity of hSF1 in spliceosome assembly, supporting the view that binding of SF1 to RNA is essential for its function. Sequences N-terminal to the KH domain mediate the interaction between hSF1 and U2AF65, which binds to the polypyrimidine tract upstream of the 3' splice site. Moreover, yeast (y) SF1 interacts with Mud2p, the presumptive U2AF65 homologue in yeast, and the interaction domain is conserved in ySF1. The C-terminal degenerate RRMs in U2AF65 and Mud2p mediate the association with hSF1 and ySF1, respectively. Analysis of chimeric constructs of hSF1 and ySF indicates that the KH domain may serve a similar function in both systems, whereas sequences C-terminal to the KH domain are not exchangeable. Thus, these results argue for hSF1 and ySF1, as well as U2AF65 and Mud2p, being functional homologues.

  1. POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism.

    PubMed

    Shaheen, Ranad; Faqeih, Eissa; Shamseldin, Hanan E; Noche, Ramil R; Sunker, Asma; Alshammari, Muneera J; Al-Sheddi, Tarfa; Adly, Nouran; Al-Dosari, Mohammed S; Megason, Sean G; Al-Husain, Muneera; Al-Mohanna, Futwan; Alkuraya, Fowzan S

    2012-08-10

    Primordial dwarfism (PD) is a phenotype characterized by profound growth retardation that is prenatal in onset. Significant strides have been made in the last few years toward improved understanding of the molecular underpinning of the limited growth that characterizes the embryonic and postnatal development of PD individuals. These include impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA-damage response, defective spliceosomal machinery, and abnormal replication licensing. In three families affected by a distinct form of PD, we identified a founder truncating mutation in POC1A. This gene is one of two vertebrate paralogs of POC1, which encodes one of the most abundant proteins in the Chlamydomonas centriole proteome. Cells derived from the index individual have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis. siRNA knockdown of POC1A in fibroblast cells recapitulates this ciliogenesis defect. Our findings highlight a human ciliopathy syndrome caused by deficiency of a major centriolar protein.

  2. The (IR-)relevance of the Gribov ambiguity in SU(2)×U(1) gauge theories with fundamental Higgs matter

    SciTech Connect

    Capri, M.A.L.; Dudal, D.; Guimaraes, M.S.; Justo, I.F.; Sorella, S.P.; and others

    2014-04-15

    It is well accepted that dealing with the Gribov ambiguity has a major impact on correlation functions in gauge-fixed Yang–Mills theories, in particular in the low momentum regime where standard perturbation theory based on the Faddeev–Popov approach fails. Recent results, derived from functional tools (Dyson–Schwinger equations or exact RG) or the effective Gribov–Zwanziger action method, pointed towards e.g. gauge boson correlation functions that are not compatible with the properties of observable degrees of freedom. Although such an observation is a welcome feature for gauge theories exhibiting confinement, it would be a discomfort for gauge theories supplemented with Higgs fields, cf. the experimental success of the electroweak model based on a SU(2)×U(1) gauge group. The purpose of this short note is to assure that the effective action resolution to the Gribov ambiguity reduces to the standard Faddeev–Popov method in the perturbative regime of sufficiently small coupling/large Higgs condensate, thereby not compromising the physical particle spectrum of massive gauge bosons and a massless photon for the SU(2)×U(1) gauge–Higgs model. The closer the theory gets to the limit of vanishing Higgs condensate, the more the Gribov problem resurfaces with all its consequences. We give some speculations w.r.t. the Fradkin–Shenker insights about the phase diagram. -- Highlights: •Gribov horizon influences gauge propagators in a strong-coupling regime. •No influence of Gribov horizon in weak-coupling. •Inclusion of U(1) factor leads to very rich behavior of propagators.

  3. Muon Spin Relaxation Evidence for the U(1) Quantum Spin-Liquid Ground State in the Triangular Antiferromagnet YbMgGaO4

    NASA Astrophysics Data System (ADS)

    Li, Yuesheng; Adroja, Devashibhai; Biswas, Pabitra K.; Baker, Peter J.; Zhang, Qian; Liu, Juanjuan; Tsirlin, Alexander A.; Gegenwart, Philipp; Zhang, Qingming

    2016-08-01

    Muon spin relaxation (μ SR ) experiments on single crystals of the structurally perfect triangular antiferromagnet YbMgGaO4 indicate the absence of both static long-range magnetic order and spin freezing down to 0.048 K in a zero field. Below 0.4 K, the μ+ spin relaxation rates, which are proportional to the dynamic correlation function of the Yb3 + spins, exhibit temperature-independent plateaus. All these μ SR results unequivocally support the formation of a gapless U(1) quantum spin liquid ground state in the triangular antiferromagnet YbMgGaO4 .

  4. Muon Spin Relaxation Evidence for the U(1) Quantum Spin-Liquid Ground State in the Triangular Antiferromagnet YbMgGaO_{4}.

    PubMed

    Li, Yuesheng; Adroja, Devashibhai; Biswas, Pabitra K; Baker, Peter J; Zhang, Qian; Liu, Juanjuan; Tsirlin, Alexander A; Gegenwart, Philipp; Zhang, Qingming

    2016-08-26

    Muon spin relaxation (μSR) experiments on single crystals of the structurally perfect triangular antiferromagnet YbMgGaO_{4} indicate the absence of both static long-range magnetic order and spin freezing down to 0.048 K in a zero field. Below 0.4 K, the μ^{+} spin relaxation rates, which are proportional to the dynamic correlation function of the Yb^{3+} spins, exhibit temperature-independent plateaus. All these μSR results unequivocally support the formation of a gapless U(1) quantum spin liquid ground state in the triangular antiferromagnet YbMgGaO_{4}. PMID:27610879

  5. Experimental oxygen potentials of U1-yPryO2± x and thermodynamic assessment of the U-Pr-O system

    DOE PAGES

    McMurray, Jake W.; Silva, Chinthaka M.

    2015-12-09

    Thermogravimetric analysis (TGA) was used to determine the oxygen potentials of fluorite urania-praseodymia (U1-yPryO2± x) solid solutions for y = 0.10 and 0.20 between 1000 and 1500 °C. A thermodynamic assessment of U-Pr-O system was performed using the CALPHAD (CALculation of PHAse Diagrams) method. Furthermore, the models well reproduce the TGA measurements and the computed phase relations are in good agreement with those proposed from an X-ray diffraction investigation.

  6. Muon Spin Relaxation Evidence for the U(1) Quantum Spin-Liquid Ground State in the Triangular Antiferromagnet YbMgGaO_{4}.

    PubMed

    Li, Yuesheng; Adroja, Devashibhai; Biswas, Pabitra K; Baker, Peter J; Zhang, Qian; Liu, Juanjuan; Tsirlin, Alexander A; Gegenwart, Philipp; Zhang, Qingming

    2016-08-26

    Muon spin relaxation (μSR) experiments on single crystals of the structurally perfect triangular antiferromagnet YbMgGaO_{4} indicate the absence of both static long-range magnetic order and spin freezing down to 0.048 K in a zero field. Below 0.4 K, the μ^{+} spin relaxation rates, which are proportional to the dynamic correlation function of the Yb^{3+} spins, exhibit temperature-independent plateaus. All these μSR results unequivocally support the formation of a gapless U(1) quantum spin liquid ground state in the triangular antiferromagnet YbMgGaO_{4}.

  7. Free-Spinning-Tunnel Investigation of a 1/25-Scale Model of the Chance Vought F8U-1P Airplane

    NASA Technical Reports Server (NTRS)

    Browman, James S., Jr.; Healy, Frederick M.

    1959-01-01

    An investigation has been made in the Langley 20-foot free-spinning tunnel on a 1/25-scale dynamic model to determine the spin and recovery characteristics of the Chance Vought F8U-1P airplane. Results indicated that the F8U-IP airplane would have spin-recovery characteristics similar to the XF8U-1 design, a model of which was tested and the results of the tests reported in NACA Research Memorandum SL56L31b. The results indicate that some modification in the design, or some special technique for recovery, is required in order to insure satisfactory recovery from fully developed erect spins. The recommended recovery technique for the F8U-lP will be full rudder reversal and movement of ailerons full with the spin (stick right in a right spin) with full deflection of the wing leading- edge flap. Inverted spins will be difficult to obtain and any inverted spin obtained should be readily terminated by full rudder reversal to oppose the yawing rotation and neutralization of the longitudinal and lateral controls. In an emergency, the same size parachute recommended for the XFBU-1 airplane will be adequate for termination of the spin: a stable parachute 17.7 feet in diameter (projected) with a drag coefficient of 1.14 (based on projected diameter) and a towline length of 36.5 feet.

  8. An intermediate scale induced by F-typeK SUSY breaking in {SU(n, 1) }/{SU(n) × U(1) } SUGRA

    NASA Astrophysics Data System (ADS)

    Murayama, Akihiro

    1994-04-01

    In the framework of {SU(n,1) }/{SU(n) × U(1) } supergravity theory, the F-type SUSY breaking mass splitting for a gauge non-singlet chiral scalar superfield is shown to radiatively induce both the intermediate symmetry breaking and electroweak symmetry breaking with the breaking scales MINT(≈10 11-12 GeV) and < h>≈O(10 2 GeV) being heirarchically separated. this hierarchy is due to a mechanism that there exists a non-renormalizable superpotential term which gives rise to a (Higgs field) 6 term in the scalar potential for the intermediate symmetry breaking Higgses but there appears no such term for the electroweak symmetry breaking Higgs. In case of the SU(4)×SU(2) L × SU(2) R string model, this mechanism explains the reason why SU(2)R breaks down earlier (i.e., at a bigger scale) than SU(2)L.

  9. Complementary test of the dark matter self-interaction in dark U(1) model by direct and indirect dark matter detection

    SciTech Connect

    Chen, Chian-Shu; Lin, Guey-Lin; Lin, Yen-Hsun E-mail: glin@cc.nctu.edu.tw

    2016-01-01

    The halo dark matter (DM) can be captured by the Sun if its final velocity after the collision with a nucleus in the Sun is less than the escape velocity. We consider a selfinteracting dark matter (SIDM) model where U(1) gauge symmetry is introduced to account for the DM self-interaction. Such a model naturally leads to isospin violating DM-nucleon interaction, although isospin symmetric interaction is still allowed as a special case. We present the IceCube-PINGU 2σ sensitivity to the parameter range of the above model with 5 years of search for neutrino signature from DM annihilation in the Sun. This indirect detection complements the direct detection by probing those SIDM parameter ranges which are either the region for very small m{sub χ} or the region opened up due to isospin violations.

  10. Specific heat and materials analysis on U_1-xTh_xPt3 for 0 ≤ x ≤ 0.05

    NASA Astrophysics Data System (ADS)

    Hettinger, J. D.; Cooley, J. C.; Smith, J. L.; Peterson, E. J.; Hackenberg, R. E.; Kelly, A. M.; Papin, P. A.; de Visser, A.; Graf, M. J.

    2004-03-01

    UPt3 exhibits anomalous, possibly time-fluctuating antiferromagnetic (AFM) order below 6K that is only detectable via neutron and x-ray scattering. Th substitution induces conventional AFM order with the same magnetic structure and an ordering temperature TN ≤ 6 K. Recent μSR studies on U_1-xTh_xPt3 for 0 ≤ x ≤ 0.05 showed that the transition from the anomalous into conventional antiferromagnetic state was very broad (Graf et al., Phys. Rev. B 68,in press), indicative of a crossover behavior. X-ray diffraction and high-resolution transmission electron microscopy show no evidence for chemical or material inhomogeneity. Nonetheless, specific heat measurements corroborate the μSR measurements and show signs of an increase near 6K for x ≥ 0.01. This supports the conjecture that Th impurities slow down the fluctuating AFM, rendering them observable on the timescale of thermodynamic measurements.

  11. Thermodynamic properties of Th xU 1-xO 2 (0 < x < 1) based on quantum-mechanical calculations and Monte-Carlo simulations

    NASA Astrophysics Data System (ADS)

    Shuller, Lindsay C.; Ewing, Rodney C.; Becker, Udo

    2011-05-01

    Th xU 1-xO 2+y binary compositions occur in nature, uranothorianite, and as a mixed oxide nuclear fuel. As a nuclear fuel, important properties, such as the melting point, thermal conductivity, and the thermal expansion coefficient change as a function of composition. Additionally, for direct disposal of Th xU 1-xO 2, the chemical durability changes as a function of composition, with the dissolution rate decreasing with increasing thoria content. UO 2 and ThO 2 have the same isometric structure, and the ionic radii of 8-fold coordinated U 4+ and Th 4+ are similar (1.14 nm and 1.19 nm, respectively). Thus, this binary is expected to form a complete solid solution. However, atomic-scale measurements or simulations of cation ordering and the associated thermodynamic properties of the Th xU 1-xO 2 system have yet to be determined. A combination of density-functional theory, Monte-Carlo methods, and thermodynamic integration are used to calculate thermodynamic properties of the Th xU 1-xO 2 binary (Δ H mix, Δ G mix, Δ S mix, phase diagram). The Gibbs free energy of mixing (Δ G mix) shows a miscibility gap at equilibration temperatures below 1000 K (e.g., E exsoln = 0.13 kJ/(mol cations) at 750 K). Such a miscibility gap may indicate possible exsolution (i.e., phase separation upon cooling). A unique approach to evaluate the likelihood and kinetics of forming interfaces between U-rich and Th-rich has been chosen that compares the energy gain of forming separate phases with estimated energy losses of forming necessary interfaces. The result of such an approach is that the thermodynamic gain of phase separation does not overcome the increase in interface energy between exsolution lamellae for thin exsolution lamellae (10 Å). Lamella formation becomes energetically favorable with a reduction of the interface area and, thus, an increase in lamella thickness to >45 Å. However, this increase in lamellae thickness may be diffusion limited. Monte-Carlo simulations converge

  12. Spontaneous CP violation in E{sub 6} supersymmetric grand unified theory with SU(2) flavor and anomalous U(1) symmetries

    SciTech Connect

    Ishiduki, M.; Maekawa, N.; Kim, S.-G.; Sakurai, K.

    2009-12-01

    We construct a model of spontaneous CP violation in E{sub 6} supersymmetric grand unified theory. In the model, we employ an SU(2){sub F} flavor symmetry and an anomalous U(1){sub A} symmetry. The SU(2){sub F} flavor symmetry is introduced to provide the origin of hierarchical structures of Yukawa coupling and to ensure the universality of sfermion soft masses. The anomalous U(1){sub A} symmetry is introduced to realize the doublet-triplet mass splitting, to provide the origin of hierarchical structures of Yukawa couplings, and to solve the {mu} problem. In the model, CP is spontaneously broken by the SU(2){sub F} breaking in order to provide a Kobayashi-Maskawa phase and to evade the supersymmetric CP problem. However, a naive construction of the model generally leads to an unwanted outcome, arg[{mu}b*]=O(1), when CP violating effects in the flavor sector are taken into account. We cure this difficulty by imposing a discrete symmetry and find that this prescription can play additional roles. It ensures that the realistic up-quark mass and Cabibbo angle are simultaneously realized without cancellation between O(1) coefficients. Also, severe constraints from the chromo-electric dipole moment of the quark can be satisfied without destabilizing the weak scale. The discrete symmetry reduces the number of free parameters, but the model is capable of reproducing quark and lepton mass spectra, mixing angles, and a Jarlskog invariant. We obtain characteristic predictions V{sub ub}{approx}O({lambda}{sup 4}) ({lambda}=0.22) and |V{sub cb}Y{sub b}|=|Y{sub c}| at the grand unified theory scale.

  13. Characteristics of miniature electronic brachytherapy x-ray sources based on TG-43U1 formalism using Monte Carlo simulation techniques

    SciTech Connect

    Safigholi, Habib; Faghihi, Reza; Jashni, Somaye Karimi; Meigooni, Ali S.

    2012-04-15

    Purpose: The goal of this study is to determine a method for Monte Carlo (MC) characterization of the miniature electronic brachytherapy x-ray sources (MEBXS) and to set dosimetric parameters according to TG-43U1 formalism. TG-43U1 parameters were used to get optimal designs of MEBXS. Parameters that affect the dose distribution such as anode shapes, target thickness, target angles, and electron beam source characteristics were evaluated. Optimized MEBXS designs were obtained and used to determine radial dose functions and 2D anisotropy functions in the electron energy range of 25-80 keV. Methods: Tungsten anode material was considered in two different geometries, hemispherical and conical-hemisphere. These configurations were analyzed by the 4C MC code with several different optimization techniques. The first optimization compared target thickness layers versus electron energy. These optimized thicknesses were compared with published results by Ihsan et al.[Nucl. Instrum. Methods Phys. Res. B 264, 371-377 (2007)]. The second optimization evaluated electron source characteristics by changing the cathode shapes and electron energies. Electron sources studied included; (1) point sources, (2) uniform cylinders, and (3) nonuniform cylindrical shell geometries. The third optimization was used to assess the apex angle of the conical-hemisphere target. The goal of these optimizations was to produce 2D-dose anisotropy functions closer to unity. An overall optimized MEBXS was developed from this analysis. The results obtained from this model were compared to known characteristics of HDR {sup 125}I, LDR {sup 103}Pd, and Xoft Axxent electronic brachytherapy source (XAEBS) [Med. Phys. 33, 4020-4032 (2006)]. Results: The optimized anode thicknesses as a function of electron energy is fitted by the linear equation Y ({mu}m) = 0.0459X (keV)-0.7342. The optimized electron source geometry is obtained for a disk-shaped parallel beam (uniform cylinder) with 0.9 mm radius. The TG-43

  14. Monte Carlo calculations and experimental measurements of the TG-43U1-recommended dosimetric parameters of 125I (Model IR-Seed2) brachytherapy source.

    PubMed

    Sheikholeslami, Sahar; Nedaie, Hasan Ali; Sadeghi, Mahdi; Pourbeigi, Hossein; Shahzadi, Sohrab; Zehtabian, Mehdi; Hasani, Mohsen; Meigooni, Ali S

    2016-01-01

    A new design of 125I (Model IR-Seed2) brachytherapy source has been manufactured recently at the Applied Radiation Research School, Nuclear Science and Technology Research Institute in Iran. The source consists of six resin beads (0.5 mm diameter) that are sealed in a cylindrical titanium capsule of 0.7 mm internal and 0.8 mm external diameters. This work aims to evaluate the dosimetric parameters of the newly designed 125I source using experimental measurements and Monte Carlo (MC) simulations. Dosimetric characteristics (dose rate constant, radial dose function, and 2D and 1D anisotropy functions) of the IR-Seed2 were determined using experimental measurements and MC simulations following the recommendations by the Task Group 43 (TG-43U1) report of the American Association of Physicists in Medicine (AAPM). MC simulations were performed using the MCNP5 code in water and Plexiglas, and experimental measurements were carried out using thermoluminescent dosimeters (TLD-GR207A) in Plexiglas phantoms. The measured dose to water in Plexiglas data were used for verification of the accuracy of the source and phantom geometry in the Monte Carlo simulations. The final MC simulated data to water in water were recommended for clinical applications. The MC calculated dose rate constant (Λ) of the IR-Seed2 125I seed in water was found to be 0.992 ± 0.025 cGy h-1U-1. Additionally, its radial dose function by line and point source approximations, gL(r) and gp(r), calculated for distances from 0.1 cm to 7 cm. The values of gL(r) at radial distances from 0.5 cm to 5 cm were measured in a Plexiglas phantom to be between 1.212 and 0.413. The calculated and measured of values for 2D anisotropy function, F(r, θ), were obtained for the radial distances ranging from 1.5 cm to 5 cm and angular range of 0°-90° in a Plexiglas phantom. Also, the 2D anisotropy function was calculated in water for the clinical application. The results of these investigations show that the uncertainty of

  15. P-23 Highlights 6/10/12: Cygnus Dual Beam Radiographic Facility Refurbishment completed at U1A tunnel in Nevada NNSS meeting Level 2 milestone

    SciTech Connect

    Deyoung, Anemarie; Smith, John R.

    2012-05-03

    A moratorium was placed on U.S. underground nuclear testing in 1992. In response, the Stockpile Stewardship Program was created to maintain readiness of the existing nuclear inventory through several efforts such as computer modeling, material analysis, and subcritical nuclear experiments (SCEs). As in the underground test era, the Nevada National Security Site (NNSS), formerly the Nevada Test Site, provides a safe and secure environment for SCEs by the nature of its isolated and secure facilities. A major tool for SCE diagnosis installed in the 05 drift laboratory is a high energy x-ray source used for time resolved imaging. This tool consists of two identical sources (Cygnus 1 and Cygnus 2) and is called the Cygnus Dual Beam Radiographic Facility (Figs. 2-6). Each Cygnus machine has 5 major elements: Marx Generator, Pulse Forming Line (PFL), Coaxial Transmission Line (CTL), 3-cell Inductive Voltage Adder (IVA), and Rod Pinch Diode. Each machine is independently triggered and may be fired in separate tests (staggered mode), or in a single test where there is submicrosecond separation between the pulses (dual mode). Cygnus must operate as a single shot machine since on each pulse the diode electrodes are destroyed. The diode is vented to atmosphere, cleaned, and new electrodes are inserted for each shot. There is normally two shots per day on each machine. Since its installation in 2003, Cygnus has participated in: 4 Subcritical Experiments (Armando, Bacchus, Barolo A, and Barolo B), a 12 shot plutonium physics series (Thermos), and 2 plutonium step wedge calibration series (2005, 2011), resulting in well over 1000 shots. Currently the Facility is in preparation for 2 SCEs scheduled for this calendar year - Castor and Pollux. Cygnus has performed well during 8 years of operations at NNSS. Many improvements in operations and performance have been implemented during this time. Throughout its service at U1a, major maintenance and replacement of many hardware items

  16. Neonatal lupus erythematosus: discordant disease expression of U1RNP-positive antibodies in fraternal twins--is this a subset of neonatal lupus erythematosus or a new distinct syndrome?

    PubMed

    Solomon, B A; Laude, T A; Shalita, A R

    1995-05-01

    Neonatal lupus erythematosus (NLE) is an uncommon disease that is manifested by cutaneous lesions, cardiac conduction defects, or both, that appear in utero or shortly after birth. In approximately 95% of patients, anti-Ro antibody (Ro[SS-A]) has been identified and has become the serologic marker for NLE. Since 1987 there have been four reported cases of Ro- and anti-La antibody (La[SS-B])-negative, U1RNP antibody-positive, NLE. Our affected twin, as well as all other infants with U1RNP-positive NLE, had cutaneous lesions similar to those in Ro-positive NLE, although they lacked systemic abnormalities, including cardiac conduction defects. HLA typing of mothers with infants with U1RNP-positive NLE revealed the presence of HLA-DR4, DQw1, or DQw3 phenotypes. Our typing confirms these findings. As with Ro-positive NLE, no distinct HLA associations were demonstrated in the infants. Unlike Ro-positive mothers, all mothers with a U1RNP-positive infant with NLE had connective tissue disease at the time of the diagnosis and had a different spectrum of disease. We describe the clinical, serologic, and immunogenetic findings in the first reported case of U1RNP-positive NLE in dizygotic twins in whom the NLE disease expression was discordant. PMID:7722044

  17. Longitudinal Trim and Tumble Characteristics of a 0.057-Scale Model of the Chance Vought XF7U-1 Airplane, TED NO. NACA DE311

    NASA Technical Reports Server (NTRS)

    Bryant, Robert L.

    1948-01-01

    Based on results of longitudinal trim and tumble tests of a 0.057-scale model of the Chance Vought XF7U-1 airplane, the following conclusions regarding the trim and tumble characteristics of the airplane have been drawn: 1. The airplane will not trim at any unusual or uncontrolled angles of attack. 2. The airplane will not tumble with the center of gravity located forward of 24 percent of the mean aerodynamic chord. When the center of gravity is located at 24 percent of the mean aerodynamic chord and slats are extended and elevators are deflected full up, the airplane may tumble if given an external positive pitching moment. 3. The tumbling motion obtained will be readily terminated by deflecting the elevators full down so as to oppose the rotation. 4. The accelerations encountered during an established tumble may be dangerous to the pilot and, therefore, action should be taken to terminate a tumble immediately upon its inception. 5. Simultaneous opening of two wing-tip parachutes having diameters of 4 feet or larger and having drag coefficients of approximately 0.7 will effectively terminate the tumble. 6. Model results indicate that the pilot will not be struck by the airplane if it becomes necessary to leave the airplane during a tumble. The pilot may require aid from an ejection-seat arrangement.

  18. Ditching Tests of a 1/8-Scale Model of the Chance Vought XF6U-1 Airplane, TED No. NACA DE319

    NASA Technical Reports Server (NTRS)

    Fisher, Lloyd J., Jr.; McBride, Ellis E.

    1953-01-01

    Tests were made with a 1/8-scale dynamically similar model of the Chance Vought XF6U-1 airplane to study its behavior when ditched. The model was ditched in calm water at the Langley tank no. 2 monorail. Various landing attitudes, speeds, and conditions of damage were simulated. The behavior of the model was determined from visual observations, by recording time histories of the accelerations, and by taking motion pictures of the ditchings. From the results of the tests it was concluded that the airplane should be ditched at the near-stall, tail-down attitude (12 deg). The flaps should be fully extended to obtain the lowest possible landing speed. The wing-tip tanks should be jettisoned. The underside of the fuselage will be critically damaged in a ditching and the airplane will dive violently after a run of about three fuselage lengths. Maximum longitudinal decelerations up to about 7g and maximum vertical accelerations up to about 5g will be encountered.

  19. Application of the UMACS process to highly dense U1-xAmxO2±δ MABB fuel fabrication for the DIAMINO irradiation

    NASA Astrophysics Data System (ADS)

    Delahaye, Thibaud; Lebreton, Florent; Horlait, Denis; Herlet, Nathalie; Dehaudt, Philippe

    2013-01-01

    The DIAMINO irradiation program aims to assess the influence of Am content and microstructure on He release and fuel swelling for different irradiation temperatures during heterogeneous transmutation in the OSIRIS reactor. Such irradiation programs call for ceramic fuels compliant with strict specifications. In the case of the DIAMINO experiment, Am-bearing blanket fuels with two compositions (U1-xAmxO2±δ (x = 0.075, 0.15)) and two microstructures (dense and porous) were selected, corresponding with four sample sets. Porous samples (<85%TD) were fabricated using a process previously developed for a similar irradiation program while a new dedicated process, UMACS, was developed and applied to produce dense samples. Despite americium presence, this process, based on conventional sintering, produces samples with high density (˜96%TD) close to that usually obtained for UO2. In the case of Minor Actinide Bearing Blankets (MABB), such a result has never been obtained reproducibly even with reactive sintering or impregnation methods.

  20. Parity oscillations and photon correlation functions in the Z2-U (1 ) Dicke model at a finite number of atoms or qubits

    NASA Astrophysics Data System (ADS)

    Yi-Xiang, Yu; Ye, Jinwu; Zhang, CunLin

    2016-08-01

    Four standard quantum optics models, that is, the Rabi, Dicke, Jaynes-Cummings, and Tavis-Cummings models, were proposed by physicists many decades ago. Despite their relative simple forms and many previous theoretical works, their physics at a finite N , especially inside the superradiant regime, remain unknown. In this work, by using the strong-coupling expansion and exact diagonalization (ED), we study the Z2-U(1 ) Dicke model with independent rotating-wave coupling g and counterrotating-wave coupling g' at a finite N . This model includes the four standard quantum optics models as its various special limits. We show that in the superradiant phase, the system's energy levels are grouped into doublets with even and odd parity. Any anisotropy β =g'/g ≠1 leads to the oscillation of parities in both the ground and excited doublets as the atom-photon coupling strength increases. The oscillations will be pushed to the infinite coupling strength in the isotropic Z2 limit β =1 . We find nearly perfect agreement between the strong-coupling expansion and the ED in the superradiant regime when β is not too small. We also compute the photon correlation functions, squeezing spectrum, and number correlation functions that can be measured by various standard optical techniques.

  1. Fabrication and characterization of U1-xAmxO2±δ compounds with high americium contents (x = 0.3, 0.4 and 0.5)

    NASA Astrophysics Data System (ADS)

    Lebreton, Florent; Horlait, Denis; Delahaye, Thibaud; Blanchart, Philippe

    2013-08-01

    Mixed uranium-americium oxides are considered promising compounds for americium transmutation in fast neutron reactors. A better understanding of these materials and of the U-Am-O phase diagram is, however, needed. Though many results in the literature describe U1-xAmxO2±δ (x ⩽ 0.2) compounds, very few studies concern higher Am contents. In this context, this article reports the fabrication method of U1-xAmxO2±δ (0.3 ⩽ x ⩽ 0.5) and their preliminary characterization, notably by X-ray diffraction.

  2. Belt-hierarchic structure of th ring, satellite and planet systems: prediction S/2001 U1 and others objects in Solar system

    NASA Astrophysics Data System (ADS)

    Barkin, Yu. V.

    2003-04-01

    BELT-HIERARCHIC STRUCTURE OF THE RING, SATELLITE AND PLANET SYSTEMS: PREDICTION S/2001 U1 AND OTHERS OBJECTS IN SOLAR SYSTEM Yu.V.Barkin Sternberg Astronomical Institute, Moscow, Russia, barkin@sai.msu.ru Structure regularities of the planet and satellite systems have been studied. Statistic analysis of the distribution of the major semi-axes of the orbits of the planets, comets and centaurs of the Solar system, satellite and ring systems of Jupiter, Saturn, Neptune and Uran, exoplanet systems of the pulsars PSR 1257+12, PSR 1828-11 and of the main consequence star Ups And was fulfilled. The following empirical regularities were described [1]: 1) the bodies of systems are combined into hierarchic groups and main from them combine 5 companions; 2) differences of the major semi-axes of the neighboring orbits for bodies of every group are constant; 4) for main neighboring hierarchic group these distances are distinguished in 6 times increasing to external grope; 5) the filling of the gropes and some present changes in their structure are caused by the past catastrophes in corresponding systems. The special method of reconstruction of the catastrophes which had place in the life of the Solar system (SS) was developed. Suggested method has let us to explain uniformly observed values of the major semi-axes and average values of eccentricities of the planets. In particular the Pancul’s hypothesis about Jupiter formation from two giant protoplanets (Jupiter I and Jupiter II) was confirmed. The new empirical law of the filling of the orbits of the regular groups of the planets or satellites (or rings structures) of the hierarchic ordered systems of celestial bodies was established. It was shown that sum number of bodies is proportional to the value of catastrophic value of the eccentricities which are same for first, second ,.... and fifth orbits of all gropes. The theoretical numbers of bodies for pointed orbits practically coincide with their observed numbers in main

  3. Composite bound states and broken U(1) symmetry in the chemical-master-equation derivation of the Gray-Scott model.

    PubMed

    Cooper, Fred; Ghoshal, Gourab; Pérez-Mercader, Juan

    2013-10-01

    We give a first principles derivation of the stochastic partial differential equations that describe the chemical reactions of the Gray-Scott model (GS): U+2V →[λ]3V and V → [μ]P, U → [ν]Q, with a constant feed rate for U. We find that the conservation of probability ensured by the chemical master equation leads to a modification of the usual differential equations for the GS model, which now involves two composite fields and also intrinsic noise terms. One of the composites is ψ(1) = φ(v)(2), where {φ(v)}(η) =v is the concentration of the species V and the averaging is over the internal noise η(u,v,ψ(1)). The second composite field is the product of three fields χ = λφ(u)φ(v)(2) and requires a noise source to ensure probability conservation. A third composite ψ(2) = φ(u)φ(v) can also be identified from the noise-induced reactions. The Hamiltonian that governs the time evolution of the many-body wave function, associated with the master equation, has a broken U(1) symmetry related to particle number conservation. By expanding around the (broken symmetry) zero-energy solution of the Hamiltonian (by performing a Doi shift) one obtains from our path integral formulation the usual reaction diffusion equation, at the classical level. The Langevin equations that are derived from the chemical master equation have multiplicative noise sources for the density fields φ(u), φ(v),χ that induce higher-order processes such as n → n scattering for n>3. The amplitude of the noise acting on φ(v) is itself stochastic in nature.

  4. Molecular Cytogenetic Analysis of the European Hake Merluccius merluccius (Merlucciidae, Gadiformes): U1 and U2 snRNA Gene Clusters Map to the Same Location.

    PubMed

    García-Souto, Daniel; Troncoso, Tomás; Pérez, Montse; Pasantes, Juan José

    2015-01-01

    The European hake (Merluccius merluccius) is a highly valuable and intensely fished species in which a long-term alive stock has been established in captivity for aquaculture purposes. Due to their huge economic importance, genetic studies on hakes were mostly focused on phylogenetic and phylogeographic aspects; however chromosome numbers are still not described for any of the fifteen species in the genus Merluccius. In this work we report a chromosome number of 2n = 42 and a karyotype composed of three meta/submetacentric and 18 subtelo/telocentric chromosome pairs. Telomeric sequences appear exclusively at both ends of every single chromosome. Concerning rRNA genes, this species show a single 45S rDNA cluster at an intercalary location on the long arm of subtelocentric chromosome pair 12; the single 5S rDNA cluster is also intercalary to the long arm of chromosome pair 4. While U2 snRNA gene clusters map to a single subcentromeric position on chromosome pair 13, U1 snRNA gene clusters seem to appear on almost all chromosome pairs, but showing bigger clusters on pairs 5, 13, 16, 17 and 19. The brightest signals on pair 13 are coincident with the single U2 snRNA gene cluster signals. Therefore, the use of these probes allows the unequivocal identification of at least 7 of the chromosome pairs that compose the karyotype of Merluccius merluccius thus opening the way to integrate molecular genetics and cytological data on the study of the genome of this important species. PMID:26716701

  5. Molecular Cytogenetic Analysis of the European Hake Merluccius merluccius (Merlucciidae, Gadiformes): U1 and U2 snRNA Gene Clusters Map to the Same Location

    PubMed Central

    García-Souto, Daniel; Troncoso, Tomás; Pérez, Montse; Pasantes, Juan José

    2015-01-01

    The European hake (Merluccius merluccius) is a highly valuable and intensely fished species in which a long-term alive stock has been established in captivity for aquaculture purposes. Due to their huge economic importance, genetic studies on hakes were mostly focused on phylogenetic and phylogeographic aspects; however chromosome numbers are still not described for any of the fifteen species in the genus Merluccius. In this work we report a chromosome number of 2n = 42 and a karyotype composed of three meta/submetacentric and 18 subtelo/telocentric chromosome pairs. Telomeric sequences appear exclusively at both ends of every single chromosome. Concerning rRNA genes, this species show a single 45S rDNA cluster at an intercalary location on the long arm of subtelocentric chromosome pair 12; the single 5S rDNA cluster is also intercalary to the long arm of chromosome pair 4. While U2 snRNA gene clusters map to a single subcentromeric position on chromosome pair 13, U1 snRNA gene clusters seem to appear on almost all chromosome pairs, but showing bigger clusters on pairs 5, 13, 16, 17 and 19. The brightest signals on pair 13 are coincident with the single U2 snRNA gene cluster signals. Therefore, the use of these probes allows the unequivocal identification of at least 7 of the chromosome pairs that compose the karyotype of Merluccius merluccius thus opening the way to integrate molecular genetics and cytological data on the study of the genome of this important species. PMID:26716701

  6. Fully Coupled Modeling of Burnup-Dependent (U1- y , Pu y )O2- x Mixed Oxide Fast Reactor Fuel Performance

    NASA Astrophysics Data System (ADS)

    Liu, Rong; Zhou, Wenzhong; Zhou, Wei

    2016-03-01

    During the fast reactor nuclear fuel fission reaction, fission gases accumulate and form pores with the increase of fuel burnup, which decreases the fuel thermal conductivity, leading to overheating of the fuel element. The diffusion of plutonium and oxygen with high temperature gradient is also one of the important fuel performance concerns as it will affect the fuel material properties, power distribution, and overall performance of the fuel pin. In order to investigate these important issues, the (U1- y Pu y )O2- x fuel pellet is studied by fully coupling thermal transport, deformation, oxygen diffusion, fission gas release and swelling, and plutonium redistribution to evaluate the effects on each other with burnup-dependent models, accounting for the evolution of fuel porosity. The approach was developed using self-defined multiphysics models based on the framework of COMSOL Multiphysics to manage the nonlinearities associated with fast reactor mixed oxide fuel performance analysis. The modeling results showed a consistent fuel performance comparable with the previous results. Burnup degrades the fuel thermal conductivity, resulting in a significant fuel temperature increase. The fission gas release increased rapidly first and then steadily with the burnup increase. The fuel porosity increased dramatically at the beginning of the burnup and then kept constant as the fission gas released to the fuel free volume, causing the fuel temperature to increase. Another important finding is that the deviation from stoichiometry of oxygen affects greatly not only the fuel properties, for example, thermal conductivity, but also the fuel performance, for example, temperature distribution, porosity evolution, grain size growth, fission gas release, deformation, and plutonium redistribution. Special attention needs to be paid to the deviation from stoichiometry of oxygen in fuel fabrication. Plutonium content will also affect the fuel material properties and performance

  7. Monte Carlo simulations of the relative biological effectiveness for DNA double strand breaks from 300 MeV u-1 carbon-ion beams

    NASA Astrophysics Data System (ADS)

    Huang, Y. W.; Pan, C. Y.; Hsiao, Y. Y.; Chao, T. C.; Lee, C. C.; Tung, C. J.

    2015-08-01

    Monte Carlo simulations are used to calculate the relative biological effectiveness (RBE) of 300 MeV u-1 carbon-ion beams at different depths in a cylindrical water phantom of 10 cm radius and 30 cm long. RBE values for the induction of DNA double strand breaks (DSB), a biological endpoint closely related to cell inactivation, are estimated for monoenergetic and energy-modulated carbon ion beams. Individual contributions to the RBE from primary ions and secondary nuclear fragments are simulated separately. These simulations are based on a multi-scale modelling approach by first applying the FLUKA (version 2011.2.17) transport code to estimate the absorbed doses and fluence energy spectra, then using the MCDS (version 3.10A) damage code for DSB yields. The approach is efficient since it separates the non-stochastic dosimetry problem from the stochastic DNA damage problem. The MCDS code predicts the major trends of the DSB yields from detailed track structure simulations. It is found that, as depth is increasing, RBE values increase slowly from the entrance depth to the plateau region and change substantially in the Bragg peak region. RBE values reach their maxima at the distal edge of the Bragg peak. Beyond this edge, contributions to RBE are entirely from nuclear fragments. Maximum RBE values at the distal edges of the Bragg peak and the spread-out Bragg peak are, respectively, 3.0 and 2.8. The present approach has the flexibility to weight RBE contributions from different DSB classes, i.e. DSB0, DSB+ and DSB++.

  8. Identification of 13 novel human modification guide RNAs

    PubMed Central

    Vitali, Patrice; Royo, Hélène; Seitz, Hervé; Bachellerie, Jean-Pierre; Hüttenhofer, Alexander; Cavaillé, Jérôme

    2003-01-01

    Members of the two expanding RNA subclasses termed C/D and H/ACA RNAs guide the 2′-O-methylations and pseudouridylations, respectively, of rRNA and spliceosomal RNAs (snRNAs). Here, we report on the identification of 13 novel human intron-encoded small RNAs (U94–U106) belonging to the two subclasses of modification guides. Seven of them are predicted to direct 2′-O-methylations in rRNA or snRNAs, while the remainder represent novel orphan RNA modification guides. From these, U100, which is exclusively detected in Cajal bodies (CBs), is predicted to direct modification of a U6 snRNA uridine, U9, which to date has not been found to be pseudouridylated. Hence, within CBs, U100 might function in the folding pathway or other aspects of U6 snRNA metabolism rather than acting as a pseudouridylation guide. U106 C/D snoRNA might also possess an RNA chaperone activity only since its two conserved antisense elements match two rRNA sequences devoid of methylated nucleotides and located remarkably close to each other within the 18S rRNA secondary structure. Finally, we have identified a retrogene for U99 snoRNA located within an intron of the Siat5 gene, supporting the notion that retro-transposition events might have played a substantial role in the mobility and diversification of snoRNA genes during evolution. PMID:14602913

  9. Identification of 13 novel human modification guide RNAs.

    PubMed

    Vitali, Patrice; Royo, Hélène; Seitz, Hervé; Bachellerie, Jean-Pierre; Hüttenhofer, Alexander; Cavaillé, Jérôme

    2003-11-15

    Members of the two expanding RNA subclasses termed C/D and H/ACA RNAs guide the 2'-O-methylations and pseudouridylations, respectively, of rRNA and spliceosomal RNAs (snRNAs). Here, we report on the identification of 13 novel human intron-encoded small RNAs (U94-U106) belonging to the two subclasses of modification guides. Seven of them are predicted to direct 2'-O-methylations in rRNA or snRNAs, while the remainder represent novel orphan RNA modification guides. From these, U100, which is exclusively detected in Cajal bodies (CBs), is predicted to direct modification of a U6 snRNA uridine, U(9), which to date has not been found to be pseudouridylated. Hence, within CBs, U100 might function in the folding pathway or other aspects of U6 snRNA metabolism rather than acting as a pseudouridylation guide. U106 C/D snoRNA might also possess an RNA chaperone activity only since its two conserved antisense elements match two rRNA sequences devoid of methylated nucleotides and located remarkably close to each other within the 18S rRNA secondary structure. Finally, we have identified a retrogene for U99 snoRNA located within an intron of the Siat5 gene, supporting the notion that retro-transposition events might have played a substantial role in the mobility and diversification of snoRNA genes during evolution.

  10. Mechanisms and Regulation of Alternative Pre-mRNA Splicing

    PubMed Central

    Lee, Yeon

    2015-01-01

    Precursor messenger RNA (pre-mRNA) splicing is a critical step in the posttranscriptional regulation of gene expression, providing significant expansion of the functional proteome of eukaryotic organisms with limited gene numbers. Split eukaryotic genes contain intervening sequences or introns disrupting protein-coding exons, and intron removal occurs by repeated assembly of a large and highly dynamic ribonucleoprotein complex termed the spliceosome, which is composed of five small nuclear ribonucleoprotein particles, U1, U2, U4/U6, and U5. Biochemical studies over the past 10 years have allowed the isolation as well as compositional, functional, and structural analysis of splicing complexes at distinct stages along the spliceosome cycle. The average human gene contains eight exons and seven introns, producing an average of three or more alternatively spliced mRNA isoforms. Recent high-throughput sequencing studies indicate that 100% of human genes produce at least two alternative mRNA isoforms. Mechanisms of alternative splicing include RNA–protein interactions of splicing factors with regulatory sites termed silencers or enhancers, RNA–RNA base-pairing interactions, or chromatin-based effects that can change or determine splicing patterns. Disease-causing mutations can often occur in splice sites near intron borders or in exonic or intronic RNA regulatory silencer or enhancer elements, as well as in genes that encode splicing factors. Together, these studies provide mechanistic insights into how spliceosome assembly, dynamics, and catalysis occur; how alternative splicing is regulated and evolves; and how splicing can be disrupted by cis- and trans-acting mutations leading to disease states. These findings make the spliceosome an attractive new target for small-molecule, antisense, and genome-editing therapeutic interventions. PMID:25784052

  11. Dynamics of the Q2Π1u(1 ) state studied from the isotope effect on the cross sections for the formation of the 2 p atom pair in the photoexcitation of H2 and D2

    NASA Astrophysics Data System (ADS)

    Hosaka, Kouichi; Shiino, Kennichi; Nakanishi, Yuko; Odagiri, Takeshi; Kitajima, Masashi; Kouchi, Noriyuki

    2016-06-01

    The absolute values of the cross section for formation of a 2 p atom pair in the photoexcitation of H2 and D2 are measured against the incident photon energy in the range of doubly excited states by means of the coincidence detection of two Lyman-α photons. The cross-section curves are explained only by the contribution of the doubly excited Q2Π1u(1 ) state. The isotope effect on the oscillator strengths of 2 p +2 p pair formation for H2 and D2 from the Q2Π1u(1 ) state is almost the same as that on the oscillator strengths of 2 s +2 p pair formation from the Q2Π1u(1 ) state obtained by our group [T. Odagiri et al., Phys. Rev. A 84, 053401 (2011), 10.1103/PhysRevA.84.053401]. This channel independence indicates that both isotope effects are dominated by the early dynamics of the Q2Π1u(1 ) state, before reaching the branching point into 2 p +2 p pair formation and 2 s +2 p pair formation.

  12. Aggregates of Small Nuclear Ribonucleic Acids (snRNAs) in Alzheimer’s Disease’

    PubMed Central

    Hales, Chadwick M.; Dammer, Eric B.; Diner, Ian; Yi, Hong; Seyfried, Nicholas T.; Gearing, Marla; Glass, Jonathan D.; Montine, Thomas J.; Levey, Allan I.; Lah, James J.

    2014-01-01

    We recently discovered that protein components of the ribonucleic acid (RNA) spliceosome form cytoplasmic aggregates in Alzheimer’s disease (AD) brain, resulting in widespread changes in RNA splicing. However, the involvement of small nuclear RNAs (snRNAs), also key components of the spliceosome complex, in the pathology of AD remains unknown. Using immunohistochemical staining of post-mortem human brain and spinal cord, we identified cytoplasmic tangle-shaped aggregates of snRNA in both sporadic and familial AD cases but not in aged controls or other neurodegenerative disorders. Immunofluorescence using antibodies reactive with the 2,2,7-trimethylguanosine cap of snRNAs and transmission electron microscopy demonstrated snRNA localization with tau and paired helical filaments, the main component of neurofibrillary tangles. Quantitative real-time polymerase chain reaction (PCR) showed U1 snRNA accumulation in the insoluble fraction of AD brains whereas other U snRNAs were not enriched. In combination with our previous results, these findings demonstrate that aggregates of U1 snRNA and U1 small nuclear ribonucleoproteins represent a new pathological hallmark of AD. PMID:24571648

  13. Functional stabilization of an RNA recognition motif by a noncanonical N-terminal expansion.

    PubMed

    Netter, Catharina; Weber, Gert; Benecke, Heike; Wahl, Markus C

    2009-07-01

    RNA recognition motifs (RRMs) constitute versatile macromolecular interaction platforms. They are found in many components of spliceosomes, in which they mediate RNA and protein interactions by diverse molecular strategies. The human U11/U12-65K protein of the minor spliceosome employs a C-terminal RRM to bind hairpin III of the U12 small nuclear RNA (snRNA). This interaction comprises one side of a molecular bridge between the U11 and U12 small nuclear ribonucleoprotein particles (snRNPs) and is reminiscent of the binding of the N-terminal RRMs in the major spliceosomal U1A and U2B'' proteins to hairpins in their cognate snRNAs. Here we show by mutagenesis and electrophoretic mobility shift assays that the beta-sheet surface and a neighboring loop of 65K C-terminal RRM are involved in RNA binding, as previously seen in canonical RRMs like the N-terminal RRMs of the U1A and U2B'' proteins. However, unlike U1A and U2B'', some 30 residues N-terminal of the 65K C-terminal RRM core are additionally required for stable U12 snRNA binding. The crystal structure of the expanded 65K C-terminal RRM revealed that the N-terminal tail adopts an alpha-helical conformation and wraps around the protein toward the face opposite the RNA-binding platform. Point mutations in this part of the protein had only minor effects on RNA affinity. Removal of the N-terminal extension significantly decreased the thermal stability of the 65K C-terminal RRM. These results demonstrate that the 65K C-terminal RRM is augmented by an N-terminal element that confers stability to the domain, and thereby facilitates stable RNA binding.

  14. Human UBL5 protein interacts with coilin and meets the Cajal bodies

    SciTech Connect

    Švéda, Martin; Častorálová, Markéta; Lipov, Jan; Ruml, Tomáš; Knejzlík, Zdeněk

    2013-06-28

    Highlights: •Localization of the UBL5 protein in Hela cells was determined by fluorescence microscopy and biochemical fractionation. •Colocalization of UBL5 with Cajal bodies was observed. •Interaction of UBL5 with coilin was proven by pull-down. -- Abstract: UBL5 protein, a structural homologue of ubiquitin, was shown to be involved in pre-mRNA splicing and transcription regulation in yeast and Caenorhabditis elegans, respectively. However, role of the UBL5 human orthologue is still elusive. In our study, we observed that endogenous human UBL5 that was localized in the nucleus, partially associates with Cajal bodies (CBs), nuclear domains where spliceosomal components are assembled. Simultaneous expression of exogenous UBL5 and coilin resulted in their nuclear colocalization in HeLa cells. The ability of UBL5 to interact with coilin was proved by GST pull-down assay using coilin that was either in vitro translated or extracted from HEK293T cells. Further, our results showed that the UBL5–coilin interaction was not influenced by coilin phosphorylation. These results suggest that UBL5 could be targeted to CBs via its interaction with coilin. Relation between human UBL5 protein and CBs is in the agreement with current observations about yeast orthologue Hub1 playing important role in alternative splicing.

  15. Directed evolution of human scFvs in DT40 cells

    PubMed Central

    Lim, Alfred W.Y.; Williams, Gareth T.; Rada, Cristina; Sale, Julian E.

    2016-01-01

    Cells that constitutively diversify their immunoglobulin genes can be used for selection of novel antibodies and for refining existing affinities and specificities. Here, we report an adaptation of the chicken DT40 system wherein its capacity for somatic hypermutation is harnessed to evolve human antibodies expressed as single-chain variable fragments (scFvs). Expression of membrane-anchored scFvs from within the rearranged Igλ locus created self-diversifying scFv libraries from which we could both select scFvs of a desired specificity and evolve both the specificity and affinity of existing scFvs by iterative expansion and selection. From these scFvs, we were able to create fully human IgG antibodies with nanomolar affinities. We further enhanced the functionality of the system by creating a pool of DT40 scFv lines with high levels of mutation driven by the overexpression of a hyperactive variant of activation-induced deaminase. From this library, we successfully isolated scFvs that bound the spliceosome factor CWC15 and the cytokine human IFNγ. Our results demonstrate the flexibility and utility of DT40 for rapid generation of scFv repertoires and efficient selection, evolution and affinity maturation of scFv specificities. PMID:26519451

  16. Directed evolution of human scFvs in DT40 cells.

    PubMed

    Lim, Alfred W Y; Williams, Gareth T; Rada, Cristina; Sale, Julian E

    2016-02-01

    Cells that constitutively diversify their immunoglobulin genes can be used for selection of novel antibodies and for refining existing affinities and specificities. Here, we report an adaptation of the chicken DT40 system wherein its capacity for somatic hypermutation is harnessed to evolve human antibodies expressed as single-chain variable fragments (scFvs). Expression of membrane-anchored scFvs from within the rearranged Igλ locus created self-diversifying scFv libraries from which we could both select scFvs of a desired specificity and evolve both the specificity and affinity of existing scFvs by iterative expansion and selection. From these scFvs, we were able to create fully human IgG antibodies with nanomolar affinities. We further enhanced the functionality of the system by creating a pool of DT40 scFv lines with high levels of mutation driven by the overexpression of a hyperactive variant of activation-induced deaminase. From this library, we successfully isolated scFvs that bound the spliceosome factor CWC15 and the cytokine human IFNγ. Our results demonstrate the flexibility and utility of DT40 for rapid generation of scFv repertoires and efficient selection, evolution and affinity maturation of scFv specificities.

  17. A new Drosophila spliceosomal intron position is common in plants.

    PubMed

    Tarrio, Rosa; Rodríguez-Trelles, Francisco; Ayala, Francisco J

    2003-05-27

    The 25-year-old debate about the origin of introns between proponents of "introns early" and "introns late" has yielded significant advances, yet important questions remain to be ascertained. One question concerns the density of introns in the last common ancestor of the three multicellular kingdoms. Approaches to this issue thus far have relied on counts of the numbers of identical intron positions across present-day taxa on the assumption that the introns at those sites are orthologous. However, dismissing parallel intron gain for those sites may be unwarranted, because various factors can potentially constrain the site of intron insertion. Demonstrating parallel intron gain is severely handicapped, because intron sequences often evolve exceedingly fast and intron phylogenetic distributions are usually ambiguous, such that alternative loss and gain scenarios cannot be clearly distinguished. We have identified an intron position that was gained independently in animals and plants in the xanthine dehydrogenase gene. The extremely disjointed phylogenetic distribution of the intron argues strongly for separate gain rather than recurrent loss. If the observed phylogenetic pattern had resulted from recurrent loss, all observational support previously gathered for the introns-late theory of intron origins based on the phylogenetic distribution of introns would be invalidated.

  18. Quantitative proteomic analysis of human breast epithelial cells with differential telomere length

    SciTech Connect

    Yu, Li-Rong . E-mail: lyu@ncifcrf.gov; Chan, King C.; Tahara, Hidetoshi; Lucas, David A.; Chatterjee, Koushik; Issaq, Haleem J.; Veenstra, Timothy D. . E-mail: veenstra@ncifcrf.gov

    2007-05-18

    Telomeres play important functional roles in cell proliferation, cell cycle regulation, and genetic stability, in which telomere length is critical. In this study, quantitative proteome comparisons for the human breast epithelial cells with short and long telomeres (184-hTERT{sub L} vs. 184-hTERT{sub S} and 90P-hTERT{sub L} vs. 90P-hTERT{sub S}), resulting from transfection of the human telomerase reverse transcriptase (hTERT) gene, were performed using cleavable isotope-coded affinity tags. More than 2000 proteins were quantified in each comparative experiment, with approximately 77% of the proteins identified in both analyses. In the cells with long telomeres, significant and consistent alterations were observed in metabolism (amino acid, nucleotide, and lipid metabolism), genetic information transmission (transcription and translation regulation, spliceosome and ribosome complexes), and cell signaling. Interestingly, the DNA excision repair pathway is enhanced, while integrin and its ligands are downregulated in the cells with long telomeres. These results may provide valuable information related to telomere functions.

  19. A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor

    PubMed Central

    Colombo, Elisa A.; Carra, Silvia; Fontana, Laura; Bresciani, Erica; Cotelli, Franco; Larizza, Lidia

    2015-01-01

    Poikiloderma with Neutropenia (PN) is an autosomal recessive genodermatosis characterized by early-onset poikiloderma, pachyonychia, hyperkeratosis, bone anomalies and neutropenia, predisposing to myelodysplasia. The causative C16orf57/USB1 gene encodes a conserved phosphodiesterase that regulates the stability of spliceosomal U6-RNA. The involvement of USB1 in splicing has not yet allowed to unveil the pathogenesis of PN and how the gene defects impact on skin and bone tissues besides than on the haematological compartment. We established a zebrafish model of PN using a morpholino-knockdown approach with two different splicing morpholinos. Both usb1-depleted embryos displayed developmental abnormalities recapitulating the signs of the human syndrome. Besides the pigmentation and osteochondral defects, usb1-knockdown caused defects in circulation, manifested by a reduced number of circulating cells. The overall morphant phenotype was also obtained by co-injecting sub-phenotypic dosages of the two morpholinos and could be rescued by human USB1 RNA. Integrated in situ and real-time expression analyses of stage-specific markers highlighted defects of primitive haematopoiesis and traced back the dramatic reduction in neutrophil myeloperoxidase to the myeloid progenitors showing down-regulated pu.1 expression. Our vertebrate model of PN demonstrates the intrinsic requirement of usb1 in haematopoiesis and highlights PN as a disorder of myeloid progenitors associated with bone marrow dysfunction. PMID:26522474

  20. Identification and functional analysis of hPRP17, the human homologue of the PRP17/CDC40 yeast gene involved in splicing and cell cycle control.

    PubMed Central

    Ben Yehuda, S; Dix, I; Russell, C S; Levy, S; Beggs, J D; Kupiec, M

    1998-01-01

    The PRP17 gene of the yeast Saccharomyces cerevisiae encodes a protein that participates in the second step of the splicing reaction. It was found recently that the yeast PRP17 gene is identical to the cell division cycle CDC40 gene. The PRP17/CDC40 gene codes for a protein with several copies of the WD repeat, a motif found in a large family of proteins that play important roles in signal transduction, cell cycle progression, splicing, transcription, and development. In this report, we describe the identification of human, nematode, and fission yeast homologues of the PRP17/CDC40 gene of S. cerevisiae. The newly identified proteins share homology with the budding yeast protein throughout their entire sequence, with the similarity being greatest in the C-terminal two thirds that includes the conserved WD repeats. We show that a yeast-human chimera, carrying the C-terminal two thirds of the hPRP17 protein, is able to complement the cell cycle and splicing defects of a yeast prp17 mutant. Moreover, the yeast and yeast-human chimeric proteins co-precipitate the intron-exon 2 lariat intermediate and the intron lariat product, providing evidence that these proteins are spliceosome-associated. These results show the functional conservation of the Prp17 proteins in evolution and suggest that the second step of splicing takes place by a similar mechanism throughout eukaryotes. PMID:9769104

  1. Investigation of the Spin and Recovery Characteristics of a 0.057-Scale Model of the Modified Chance Vought XF7U-1 Airplane. TED No. NACA DE 311

    NASA Technical Reports Server (NTRS)

    Berman, Theodore; Pumphrey, Norman E.

    1950-01-01

    An investigation has been conducted in the Langley 20-foot free-spinning tunnel to determine the spin and recovery characteristics of a 0.057-scale model of the modified Chance Vought XF7U-1 airplane. The primary change in the design from that previously tested was a revision of the twin vertical tails. Tests were also made to determine the effect of installation of external wing tanks. The results indicated that the revision in the vertical tails did not greatly alter the spin and recovery characteristics of the model and recovery by normal use of controls (fill rapid rudder reversal followed approximately one-half turn later by movement of the stick forward of neutral) was satisfactory. Adding the external wing tanks to cause the recovery characteristics to become critical and border on an unsatisfactory condition; however, it was shown that satisfactory recovery could be obtained by jettisoning the tanks, followed by normal recovery technique.

  2. Investigation of the Stability and Control Characteristics of a 1/10-Scale Model of the Chance Vought XF7U-1 Airplane in the Langley Free-Flight Tunnel, TED No. NACA DE306

    NASA Technical Reports Server (NTRS)

    Draper, John W.; Hewes, Donald E.

    1948-01-01

    At the request of the Bureau of Aeronautics, Navy Department, a stability and control investigation of a 1/10-scale model of the Chance Vought XF7U-1 airplane has been conducted in the Langley free-flight tunnel. Results of force end flight tests to determine the power-off stability and control characteristics of the model with slats retracted and extended are presented herein. The longitudinal and lateral stability characteristics were satisfactory for both the slats retracted and extended conditions over the lift range up to the stall. With the slats retracted, the stall was fairly gentle but the model rolled off out of control. With the slats extended, control could be maintained at the stall so that the wings could be kept level even as the model dropped.

  3. Downregulation of Type II Diabetes Mellitus and Maturity Onset Diabetes of Young Pathways in Human Pancreatic Islets from Hyperglycemic Donors

    PubMed Central

    Groop, Leif

    2014-01-01

    Although several molecular pathways have been linked to type 2 diabetes (T2D) pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia (n = 20) and normoglycemia (n = 58) were subjected to Gene Set Enrichment Analysis (GSEA). About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM) and maturity onset diabetes of the young (MODY) pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis. PMID:25379510

  4. Anomalous U(1), Dark Matter and Asymmetry

    NASA Astrophysics Data System (ADS)

    Moynihan, Michael W.

    This dissertation uses ordinary least squares regression analysis to measure the impact of gasoline price changes on sprawl defined as land density of population, employment and light visible from space over multiple decades. Using census data compiled and normalized to 2000 boundaries in the Geolytics Neighborhood Change Database (NCDB) for the decennial census years 1970 through 2000 and energy price data published by the Energy Information Agency (EIA), it tests the effect of gasoline prices on eight population density-derived measures of sprawl for 72 Primary Metropolitan Statistical Areas and 48 states. Using data contained in the Zipcode Business Patterns (ZPB) database maintained by the Census Bureau, it tests the impact of gasoline prices published by ACCRA on a variety of employment dispersion measures of sprawl for Metropolitan Statistical Areas (MSAs). And using a dataset created by Burchfield et al of light visible from space, it tests the effect of gasoline prices published by ACCRA on the Burchfield et al sprawl index for 275 MSAs. The regressions control for a variety of socioeconomic, demographic, legal and physical variables and use instrumental variables and other techniques to test for causal relationships. The dissertation finds robust evidence that gasoline price changes did influence sprawl at the 95% confidence level over the periods studied with higher prices leading to less marginal sprawl and lower prices leading to more marginal sprawl. In turn, it discusses ways that policymakers might intervene using this pathway to influence sprawl, notably through the imposition of gasoline taxes.

  5. The diagnostic performance of classical molecular tests used for detecting human papillomavirus.

    PubMed

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C; Rojas-Villarraga, Adriana; Sanchez, Ricardo; Jaimes, Camilo; Perez-Prados, Antonio; Patarroyo, Manuel E; Patarroyo, Manuel A

    2012-10-01

    Cervical samples were evaluated for human papillomavirus (HPV) presence using the hybrid capture-2 (HC2) assay and the polymerase chain reaction (PCR) with three different primer sets (GP5+/6+, MY09/11 and pU1M/2R). PCR results were compared to HC2 and results of all assays were compared to cytological and colposcopy findings. Post-test probability was assessed in individual assays and test combinations. HPV-DNA prevalence was 36.5% with HC2 and 55.2% with PCR. MY09/11 detected HPV-DNA in 38% of samples, GP5+/6+ in 19.1% and pU1M/2R in 16.4%. pU1M/2R and HC2 had the highest concordance (75.31%, k=0.39 in the whole population; 74.1%, k=0.5 in women with abnormal cytology). pU1M/2R had the best diagnostic performance, including optimal post-test probabilities and cervical abnormality detection (individually or in a panel of tests). Women positive for pU1M/2R may be at higher risk of disease progression; the assay performance when combined with a Pap smear in cervical cancer screening programs should be evaluated.

  6. Human See, Human Do.

    ERIC Educational Resources Information Center

    Tomasello, Michael

    1997-01-01

    A human demonstrator showed human children and captive chimpanzees how to drag food or toys closer using a rakelike tool. One side of the rake was less efficient than the other for dragging. Chimps tried to reproduce results rather than methods while children imitated and used the more efficient rake side. Concludes that imitation leads to…

  7. Syntenic conservation between humans and cattle. I. Human chromosome 9.

    PubMed

    Threadgill, D W; Womack, J E

    1990-09-01

    Bovine X hamster hybrid somatic cells have been used to investigate the syntenic relationship of nine loci in the bovine that have homologous loci on human chromosome 9. Six loci, ALDH1, ALDOB, C5, GGTB2, GSN, and ITIL, were assigned to the previously identified bovine syntenic group U18 represented by ACO1, whereas the other three loci, ABL, ASS, and GRP78, mapped to a new, previously unidentified autosomal syntenic group. Additionally, a secondary locus, ABLL, which cross-hybridized with the ABL probe, was mapped to bovine syntenic group U1 with the HSA 1 loci PGD and ENO1. The results predict that ACO1 will map proximal to ALDH1; GRP78 distal to ITIL and C5; GSN proximal to AK1, ABL, and ASS on HSA 9; GRP78 to MMU 2; and ITIL and GSN to MMU 4. PMID:2081596

  8. Splicing-coupled 3' end formation requires a terminal splice acceptor site, but not intron excision.

    PubMed

    Davidson, Lee; West, Steven

    2013-08-01

    Splicing of human pre-mRNA is reciprocally coupled to 3' end formation by terminal exon definition, which occurs co-transcriptionally. It is required for the final maturation of most human pre-mRNAs and is therefore important to understand. We have used several strategies to block splicing at specific stages in vivo and studied their effect on 3' end formation. We demonstrate that a terminal splice acceptor site is essential to establish coupling with the poly(A) signal in a chromosomally integrated β-globin gene. This is in part to alleviate the suppression of 3' end formation by U1 small nuclear RNA, which is known to bind pre-mRNA at the earliest stage of spliceosome assembly. Interestingly, blocks to splicing that are subsequent to terminal splice acceptor site function, but before catalysis, have little observable effect on 3' end formation. These data suggest that early stages of spliceosome assembly are sufficient to functionally couple splicing and 3' end formation, but that on-going intron removal is less critical. PMID:23716637

  9. Evolution of magnetism in single-crystal C a2R u1 -xI rxO4(0 ≤x ≤0.65 )

    NASA Astrophysics Data System (ADS)

    Yuan, S. J.; Terzic, J.; Wang, J. C.; Li, L.; Aswartham, S.; Song, W. H.; Ye, F.; Cao, G.

    2015-07-01

    We report structural, magnetic, transport, and thermal properties of single-crystal C a2R u1 -xI rxO4(0 ≤x ≤0.65 ) . C a2Ru O4 is a structurally driven Mott insulator with a metal-insulator transition at TMI=357 K , which is well separated from antiferromagnetic order at TN=110 K . Substitution of a 5 d element, Ir, for Ru enhances spin-orbit coupling and locking between the structural distortions and magnetic moment canting. Ir doping intensifies the distortion or rotation of Ru /Ir O6 octahedra and induces weak ferromagnetic behavior along the c axis. In particular, Ir doping suppresses TN but concurrently causes an additional magnetic ordering TN 2 at a higher temperature up to 210 K for x =0.65 . The effect of Ir doping sharply contrasts with that of 3 d -element doping such as Cr, Mn, and Fe, which suppresses TN and induces unusual negative volume thermal expansion. The stark difference between 3 d - and 5 d -element doping underlines a strong magnetoelastic coupling inherent in the Ir-rich oxides.

  10. Cosmological Bounds of Sterile Neutrinos in a S U(3) C ⊗ S U(3) L ⊗ S U(3) R ⊗ U(1) N Model as Dark Matter Candidates

    NASA Astrophysics Data System (ADS)

    Ferreira, C. P.; Guzzo, M. M.; de Holanda, P. C.

    2016-08-01

    We study sterile neutrinos in an extension of the standard model, based on the gauge group S U(3) C ⊗ S U(3) L ⊗ S U(3) R ⊗ U(1) N , and use this model to illustrate how to apply cosmological limits to thermalized particles that decouple while relativistic. These neutrinos, N a L , can be dark matter candidates, with a kiloelectron volt mass range arising rather naturally in this model. We analyse the cosmological limits imposed by N e f f and dark matter abundance on these neutrinos. Assuming that these neutrinos have roughly equal masses and are not CDM, we conclude that the N e f f experimental value can be satisfied in some cases and the abundance constraint implies that these neutrinos are hot dark matter. With this information, we give upper bounds on the Yukawa coupling between the sterile neutrinos and a scalar field, the possible values of the VEV of this scalar field and lower bounds to the mass of one gauge boson of the model.

  11. Molecular characterization and chromosomal mapping of the 5S rRNA gene in Solea senegalensis: a new linkage to the U1, U2, and U5 small nuclear RNA genes.

    PubMed

    Manchado, Manuel; Zuasti, Eugenia; Cross, Ismael; Merlo, Alejandro; Infante, Carlos; Rebordinos, Laureana

    2006-01-01

    Some units of the 5S rDNA of Solea senegalensis were amplified by PCR and sequenced. Three main PCR products (227, 441, and 2166 bp) were identified. The 227- and 441-bp fragments were characterized by highly divergent nontranscribed spacer sequences (referred to as NTS-I and NTS-II) that were 109 and 324 bp long, respectively, yet their coding sequences were nearly identical. The 2166-bp 5S rDNA unit was composed of two 5S rRNA genes separated by NTS-I and followed by a 1721-bp spacer containing the U2, U5, and U1 small nuclear RNA genes (snRNAs). They were inverted and arranged in the transcriptional direction opposite that of the 5S rRNA gene. This simultaneous linkage of 3 different snRNAs had never been observed before. The PCR products were used as probes in fluorescence in situ hybridization experiments to locate the corresponding loci on the chromosomes of S. senegalensis. A major 5S rDNA chromosomal site was located along most of the short arm of a submetacentric pair, while a minor site was detected near the centromeric region of an acrocentric pair.

  12. Retrohoming of a Mobile Group II Intron in Human Cells Suggests How Eukaryotes Limit Group II Intron Proliferation.

    PubMed

    Truong, David M; Hewitt, F Curtis; Hanson, Joseph H; Cui, Xiaoxia; Lambowitz, Alan M

    2015-08-01

    Mobile bacterial group II introns are evolutionary ancestors of spliceosomal introns and retroelements in eukaryotes. They consist of an autocatalytic intron RNA (a "ribozyme") and an intron-encoded reverse transcriptase, which function together to promote intron integration into new DNA sites by a mechanism termed "retrohoming". Although mobile group II introns splice and retrohome efficiently in bacteria, all examined thus far function inefficiently in eukaryotes, where their ribozyme activity is limited by low Mg2+ concentrations, and intron-containing transcripts are subject to nonsense-mediated decay (NMD) and translational repression. Here, by using RNA polymerase II to express a humanized group II intron reverse transcriptase and T7 RNA polymerase to express intron transcripts resistant to NMD, we find that simply supplementing culture medium with Mg2+ induces the Lactococcus lactis Ll.LtrB intron to retrohome into plasmid and chromosomal sites, the latter at frequencies up to ~0.1%, in viable HEK-293 cells. Surprisingly, under these conditions, the Ll.LtrB intron reverse transcriptase is required for retrohoming but not for RNA splicing as in bacteria. By using a genetic assay for in vivo selections combined with deep sequencing, we identified intron RNA mutations that enhance retrohoming in human cells, but <4-fold and not without added Mg2+. Further, the selected mutations lie outside the ribozyme catalytic core, which appears not readily modified to function efficiently at low Mg2+ concentrations. Our results reveal differences between group II intron retrohoming in human cells and bacteria and suggest constraints on critical nucleotide residues of the ribozyme core that limit how much group II intron retrohoming in eukaryotes can be enhanced. These findings have implications for group II intron use for gene targeting in eukaryotes and suggest how differences in intracellular Mg2+ concentrations between bacteria and eukarya may have impacted the

  13. Retrohoming of a Mobile Group II Intron in Human Cells Suggests How Eukaryotes Limit Group II Intron Proliferation

    PubMed Central

    Truong, David M.; Hewitt, F. Curtis; Hanson, Joseph H.; Cui, Xiaoxia; Lambowitz, Alan M.

    2015-01-01

    Mobile bacterial group II introns are evolutionary ancestors of spliceosomal introns and retroelements in eukaryotes. They consist of an autocatalytic intron RNA (a “ribozyme”) and an intron-encoded reverse transcriptase, which function together to promote intron integration into new DNA sites by a mechanism termed “retrohoming”. Although mobile group II introns splice and retrohome efficiently in bacteria, all examined thus far function inefficiently in eukaryotes, where their ribozyme activity is limited by low Mg2+ concentrations, and intron-containing transcripts are subject to nonsense-mediated decay (NMD) and translational repression. Here, by using RNA polymerase II to express a humanized group II intron reverse transcriptase and T7 RNA polymerase to express intron transcripts resistant to NMD, we find that simply supplementing culture medium with Mg2+ induces the Lactococcus lactis Ll.LtrB intron to retrohome into plasmid and chromosomal sites, the latter at frequencies up to ~0.1%, in viable HEK-293 cells. Surprisingly, under these conditions, the Ll.LtrB intron reverse transcriptase is required for retrohoming but not for RNA splicing as in bacteria. By using a genetic assay for in vivo selections combined with deep sequencing, we identified intron RNA mutations that enhance retrohoming in human cells, but <4-fold and not without added Mg2+. Further, the selected mutations lie outside the ribozyme catalytic core, which appears not readily modified to function efficiently at low Mg2+ concentrations. Our results reveal differences between group II intron retrohoming in human cells and bacteria and suggest constraints on critical nucleotide residues of the ribozyme core that limit how much group II intron retrohoming in eukaryotes can be enhanced. These findings have implications for group II intron use for gene targeting in eukaryotes and suggest how differences in intracellular Mg2+ concentrations between bacteria and eukarya may have impacted the

  14. The intronic splicing code: multiple factors involved in ATM pseudoexon definition.

    PubMed

    Dhir, Ashish; Buratti, Emanuele; van Santen, Maria A; Lührmann, Reinhard; Baralle, Francisco E

    2010-02-17

    Abundance of pseudo splice sites in introns can potentially give rise to innumerable pseudoexons, outnumbering the real ones. Nonetheless, these are efficiently ignored by the splicing machinery, a process yet to be understood completely. Although numerous 5' splice site-like sequences functioning as splicing silencers have been found to be enriched in predicted human pseudoexons, the lack of active pseudoexons pose a fundamental challenge to how these U1snRNP-binding sites function in splicing inhibition. Here, we address this issue by focusing on a previously described pathological ATM pseudoexon whose inhibition is mediated by U1snRNP binding at intronic splicing processing element (ISPE), composed of a consensus donor splice site. Spliceosomal complex assembly demonstrates inefficient A complex formation when ISPE is intact, implying U1snRNP-mediated unproductive U2snRNP recruitment. Furthermore, interaction of SF2/ASF with its motif seems to be dependent on RNA structure and U1snRNP interaction. Our results suggest a complex combinatorial interplay of RNA structure and trans-acting factors in determining the splicing outcome and contribute to understanding the intronic splicing code for the ATM pseudoexon.

  15. Longitudinal Stability and Control Characteristics of a Semispan Wind-Tunnel Model of the XF7U-1 Airplane and a Comparison with Complete-Model Wind-Tunnel Tests and Semispan-Model Wing-Flow Tests

    NASA Technical Reports Server (NTRS)

    Goodson, Kenneth W.; King, Thomas J., Jr.

    1949-01-01

    An investigation was conducted on an 0.08-scale semispan model of the Chance Vought XF7U-1 airplane in the Langley high-speed 7- by 10-foot tunnel in the Mach number range from 0.40 to 0.97. The results are compared with those obtained with an 0.08-scale sting-mounted complete model tested in the same tunnel and with an 0.026-scale semispan model tested by the wing-flow method. The lift-curve slopes obtained for the 0.08-scale semispan model and the 0.026-scale wing-flow model were in good agreement but both were generally lower than the values obtained for the sting model. The results of an unpublished investigation have shown that tunnel-wall boundary-layer and strut-leakage effects can came the difference noted between the lift-curve slopes of the sting and the semispan data. Fair agreement was obtained among the data of the three models as regard the variation of pitching-moment coefficients with lift coefficient. The agreement between the complete and the semispan models was more favorable with the vertical fine on, because the wall-boundary-layer and strut leakage effects were less severe. In the Mach number range between 0.94 and 0.97, ailavator-control reversal was indicated in the wing-flow data near zero lift; Whereas, these same trends were indicated in the larger scale semispan data at somewhat higher lift coefficients.

  16. Human Development, Human Evolution.

    ERIC Educational Resources Information Center

    Smillie, David

    One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a wholly new…

  17. Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells.

    PubMed

    Butler, John T; Hall, Lisa L; Smith, Kelly P; Lawrence, Jeanne B

    2009-07-01

    The complex nuclear structure of somatic cells is important to epigenomic regulation, yet little is known about nuclear organization of human embryonic stem cells (hESC). Here we surveyed several nuclear structures in pluripotent and transitioning hESC. Observations of centromeres, telomeres, SC35 speckles, Cajal Bodies, lamin A/C and emerin, nuclear shape and size demonstrate a very different "nuclear landscape" in hESC. This landscape is remodeled during a brief transitional window, concomitant with or just prior to differentiation onset. Notably, hESC initially contain abundant signal for spliceosome assembly factor, SC35, but lack discrete SC35 domains; these form as cells begin to specialize, likely reflecting cell-type specific genomic organization. Concomitantly, nuclear size increases and shape changes as lamin A/C and emerin incorporate into the lamina. During this brief window, hESC exhibit dramatically different PML-defined structures, which in somatic cells are linked to gene regulation and cancer. Unlike the numerous, spherical somatic PML bodies, hES cells often display approximately 1-3 large PML structures of two morphological types: long linear "rods" or elaborate "rosettes", which lack substantial SUMO-1, Daxx, and Sp100. These occur primarily between Day 0-2 of differentiation and become rare thereafter. PML rods may be "taut" between other structures, such as centromeres, but clearly show some relationship with the lamina, where PML often abuts or fills a "gap" in early lamin A/C staining. Findings demonstrate that pluripotent hES cells have a markedly different overall nuclear architecture, remodeling of which is linked to early epigenomic programming and involves formation of unique PML-defined structures.

  18. Human Health

    MedlinePlus

    ... effects of climate change Video not supported Human Health Climate change threatens human health and well-being ... Copy link to clipboard Key Message: Wide-ranging Health Impacts Climate change threatens human health and well- ...

  19. Human Trafficking

    MedlinePlus

    ... TRAFFICKING (English) Listen < Back to Search FACT SHEET: HUMAN TRAFFICKING (English) Published: August 2, 2012 Topics: Public Awareness , ... organizations that protect and serve trafficking victims. National Human Trafficking Resource Center at 1.888.373.7888 Last ...

  20. EFTUD2 deficiency in vertebrates: identification of a novel human mutation and generation of a zebrafish model

    PubMed Central

    Deml, Brett; Reis, Linda M.; Muheisen, Sanaa; Bick, David; Semina, Elena V.

    2015-01-01

    Background Congenital microphthalmia and coloboma are severe developmental defects that are frequently associated with additional systemic anomalies and display a high level of genetic heterogeneity. Methods To identify the pathogenic variant in a patient with microphthalmia, coloboma, retinal dystrophy, microcephaly and other features, whole exome sequencing (WES) analysis of the patient and parental samples was undertaken. To further explore the identified variant/gene, expression and functional studies in zebrafish were performed. Results WES revealed a de novo variant, c.473_474delGA, p.(Arg158Lysfs*4), in EFTUD2 which encodes a component of the spliceosome complex. Dominant mutations in EFTUD2 cause Mandibulofacial Dysostosis, Guion-Almeida type (MFDGA) which does not involve microphthalmia, coloboma or retinal dystrophy; analysis of genes known to cause these ocular phenotypes identified several variants of unknown significance but no causal alleles in the affected patient. Zebrafish eftud2 demonstrated high sequence conservation with the human gene and broad embryonic expression. TALEN-mediated disruption was employed to generate a c.378_385 del, p.(Ser127Aspfs*23) truncation mutation in eftud2. Homozygous mutants displayed a reduced head size, small eye, curved body, and early embryonic lethality. Apoptosis assays demonstrated a striking increase in TUNEL-positive cells in the developing brain, eye, spinal cord and other tissues starting at 30 hours post fertilization. Conclusion This study reports a novel mutation in EFTUD2 in an MFDGA patient with unusual ocular features and the generation of a first animal model of eftud2 deficiency. The severe embryonic phenotype observed in eftud2 mutants indicates an important conserved role during development of diverse tissues in vertebrates. PMID:26118977

  1. An Investigation of the Aerodynamic Characteristics of an 0.08-Scale Model of the Chance Vought XF7U-1 Airplane in the Langley High-Speed 7- by 10-Foot Tunnel. Part I - Basic Longitudinal Stability Characteristics, TED No. NACA DE308. Part 1; Basic Longitudinal Stability Characteristics, TED No. NACA DE308

    NASA Technical Reports Server (NTRS)

    Kemp, William B., Jr.; Kuhn, Richard E.; Goodson, Kenneth W.

    1947-01-01

    The stability and control characteristics of an 0.08-scale model of the Chance Vought XF7U-1 airplane have been investigated over a Mach number range from 0.40 to 0.91. Results of the basic longitudinal tests of the complete model with undeflected control surfaces are given in the present report with a very limited analysis of the results.

  2. An Investigation of the Aerodynamic Characteristics of an 0.08-Scale Model of the Chance Vought XF7U-1 Airplane in the Langley High-Speed 7- by 10-Foot Tunnel. Part IV - Aileron Characteristics TED No. NACA DE308. Part 4; Aileron Characteristics, TED No. NACA DE308

    NASA Technical Reports Server (NTRS)

    Goodson, Kenneth W.; Myers, Boyd C., II

    1947-01-01

    Tests have been conducted in the Langley high-speed 7- by 10-foot tunnel over a Mach number range from 0.40 to 0.91 to determine the stability and control characteristics of an 0.08-scale model of the Chance Vought XF7U-1 airplane. The aileron characteristics of the complete model are presented in the present report with a very limited analysis of the results.

  3. Human Rights/Human Needs.

    ERIC Educational Resources Information Center

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  4. Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo.

    PubMed

    Martinez, E; Palhan, V B; Tjernberg, A; Lymar, E S; Gamper, A M; Kundu, T K; Chait, B T; Roeder, R G

    2001-10-01

    GCN5 is a histone acetyltransferase (HAT) originally identified in Saccharomyces cerevisiae and required for transcription of specific genes within chromatin as part of the SAGA (SPT-ADA-GCN5 acetylase) coactivator complex. Mammalian cells have two distinct GCN5 homologs (PCAF and GCN5L) that have been found in three different SAGA-like complexes (PCAF complex, TFTC [TATA-binding-protein-free TAF(II)-containing complex], and STAGA [SPT3-TAF(II)31-GCN5L acetylase]). The composition and roles of these mammalian HAT complexes are still poorly characterized. Here, we present the purification and characterization of the human STAGA complex. We show that STAGA contains homologs of most yeast SAGA components, including two novel human proteins with histone-like folds and sequence relationships to yeast SPT7 and ADA1. Furthermore, we demonstrate that STAGA has acetyl coenzyme A-dependent transcriptional coactivator functions from a chromatin-assembled template in vitro and associates in HeLa cells with spliceosome-associated protein 130 (SAP130) and DDB1, two structurally related proteins. SAP130 is a component of the splicing factor SF3b that associates with U2 snRNP and is recruited to prespliceosomal complexes. DDB1 (p127) is a UV-damaged-DNA-binding protein that is involved, as part of a complex with DDB2 (p48), in nucleotide excision repair and the hereditary disease xeroderma pigmentosum. Our results thus suggest cellular roles of STAGA in chromatin modification, transcription, and transcription-coupled processes through direct physical interactions with sequence-specific transcription activators and with components of the splicing and DNA repair machineries. PMID:11564863

  5. Spinal muscular atrophy phenotype is ameliorated in human motor neurons by SMN increase via different novel RNA therapeutic approaches.

    PubMed

    Nizzardo, Monica; Simone, Chiara; Dametti, Sara; Salani, Sabrina; Ulzi, Gianna; Pagliarani, Serena; Rizzo, Federica; Frattini, Emanuele; Pagani, Franco; Bresolin, Nereo; Comi, Giacomo; Corti, Stefania

    2015-01-01

    Spinal muscular atrophy (SMA) is a primary genetic cause of infant mortality due to mutations in the Survival Motor Neuron (SMN) 1 gene. No cure is available. Antisense oligonucleotides (ASOs) aimed at increasing SMN levels from the paralogous SMN2 gene represent a possible therapeutic strategy. Here, we tested in SMA human induced pluripotent stem cells (iPSCs) and iPSC-differentiated motor neurons, three different RNA approaches based on morpholino antisense targeting of the ISSN-1, exon-specific U1 small nuclear RNA (ExSpeU1), and Transcription Activator-Like Effector-Transcription Factor (TALE-TF). All strategies act modulating SMN2 RNA: ASO affects exon 7 splicing, TALE-TF increase SMN2 RNA acting on the promoter, while ExSpeU1 improves pre-mRNA processing. These approaches induced up-regulation of full-length SMN mRNA and differentially affected the Delta-7 isoform: ASO reduced this isoform, while ExSpeU1 and TALE-TF increased it. All approaches upregulate the SMN protein and significantly improve the in vitro SMA motor neurons survival. Thus, these findings demonstrate that therapeutic tools that act on SMN2 RNA are able to rescue the SMA disease phenotype. Our data confirm the feasibility of SMA iPSCs as in vitro disease models and we propose novel RNA approaches as potential therapeutic strategies for treating SMA and other genetic neurological disorders. PMID:26123042

  6. Teaching humanism.

    PubMed

    Stern, David T; Cohen, Jordan J; Bruder, Ann; Packer, Barbara; Sole, Allison

    2008-01-01

    As the "passion that animates authentic professionalism," humanism must be infused into medical education and clinical care as a central feature of medicine's professionalism movement. In this article, we discuss a current definition of humanism in medicine. We will also provide detailed descriptions of educational programs intended to promote humanism at a number of medical schools in the United States (and beyond) and identify the key factors that make these programs effective. Common elements of programs that effectively teach humanism include: (1) opportunities for students to gain perspective in the lives of patients; (2) structured time for reflection on those experiences; and (3) focused mentoring to ensure that these events convert to positive, formative learning experiences. By describing educational experiences that both promote and sustain humanism in doctors, we hope to stimulate the thinking of other medical educators and to disseminate the impact of these innovative educational programs to help the profession meet its obligation to provide the public with humanistic physicians.

  7. Human Issues in Human Rights

    ERIC Educational Resources Information Center

    Kates, Robert W.

    1978-01-01

    Presents the report of the National Academy of Sciences' Committee in Human Rights which seeks to ease the plight of individual scientists, engineers, and medical personnel suffering severe repression. Case studies of instances of negligence of human rights are provided. (CP)

  8. Human rights

    PubMed Central

    Powell, J Enoch

    1977-01-01

    What are human rights? In this article Enoch Powell, MP (a former Conservative Minister of Health), approaches this question through a critical discussion of Article 25 (I) of the United Nations Universal Declaration of Human Rights. Professor R S Downie in his accompanying commentary analyses Mr Powell's statements and takes up in particular Mr Powell's argument that claiming rights for one person entails compulsion on another person. In Professor Downie's view there is nothing in Article 25 (I) that cannot embody acceptable moral rights, the commonly accepted interpretation of that Article of the UN Universal Declaration of Human Rights which many people think is wholly acceptable. PMID:604483

  9. RNA splicing and genes

    SciTech Connect

    Sharp, P.A.

    1988-11-25

    The splicing of long transcripts RNA (copied from DNA in the cell nucleus) into smaller specific mRNA is an important event in the regulation of gene expression in eukaryotic cells. The splicing reaction occurs as a late step in the nuclear pathway for synthesis of mRNAs. This pathway commences with initiation of transcription by RNA polymerase II and probably involves an integrated series of steps each dependent on previous events. Splicing of precursors to mRNAs involves the formation of a spliceosome complex containing 5' and 3' splice sites. This complex contains the evolutionary highly conserved small nuclear RNAs (snRNAs) Us, U4, U5, and U6. The most abundant snRNA, U1, is required to form the spliceosome and may be a part of the spliceosome. Analogues of these snRNAs have been identified in yeast. Assembly of the spliceosome probably involves the binding of a multi-snRNA complex containing U4, U5, and U6 snRNAs. Several observations suggest that the association of snRNAs in such complexes is quite dynamic. It is argued that the snRANs in the spliceosome form a catalytic RNA structure that is responsible for the cleavage and ligation steps during splicing.

  10. Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3

    PubMed Central

    Park, Joon Kyu; Das, Tanuza; Song, Eun Joo; Kim, Eunice EunKyeong

    2016-01-01

    Squamous cell carcinoma antigen recognized by T-cells 3 (SART3) is a U4/U6 recycling factor as well as a targeting factor of USP4 and USP15. However, the details of how SART3 recognizes these deubiquitinases and how they get subsequently translocated into the nucleus are not known. Here, we present the crystal structures of the SART3 half-a-tetratricopeptide (HAT) repeat domain alone and in complex with the domain present in ubiquitin-specific protease (DUSP)-ubiquitin-like (UBL) domains of ubiquitin specific protease 4 (USP4). The 12 HAT repeats of SART3 are in two sub-domains (HAT-N and HAT-C) forming a dimer through HAT-C. USP4 binds SART3 at the opposite surface of the HAT-C dimer interface utilizing the β-structured linker between the DUSP and the UBL domains. The binding affinities of USP4 and USP15 to SART3 are 0.9 μM and 0.2 μM, respectively. The complex structure of SART3 nuclear localization signal (NLS) and importin-α reveals bipartite binding, and removal of SART3 NLS prevents the entry of USP4 (and USP15) into the nucleus and abrogates the subsequent deubiquitinase activity of USP4. PMID:27060135

  11. A Bidirectional SF2/ASF- and SRp40-Dependent Splicing Enhancer Regulates Human Immunodeficiency Virus Type 1 rev, env, vpu, and nef Gene Expression

    PubMed Central

    Caputi, Massimo; Freund, Marcel; Kammler, Susanne; Asang, Corinna; Schaal, Heiner

    2004-01-01

    The integrated human immunodeficiency virus type 1 (HIV-1) genome is transcribed in a single pre-mRNA that is alternatively spliced into more than 40 mRNAs. We characterized a novel bidirectional exonic splicing enhancer (ESE) that regulates the expression of the HIV-1 env, vpu, rev, and nef mRNAs. The ESE is localized downstream of the vpu-, env-, and nef-specific 3′ splice site no. 5. SF2/ASF and SRp40 activate the ESE and are required for efficient 3′ splice site usage and binding of the U1 snRNP to the downstream 5′ splice site no. 4. U1 snRNP binding to the 5′ splice site no. 4 is required for splicing of the rev and nef mRNAs and to increase expression of the partially spliced env mRNA. Finally, our results indicate that this ESE is necessary for the recruitment of the U1 snRNP to the 5′ splice site no. 4, even when the 5′ splice site and the U1 snRNA have been mutated to obtain a perfect complementary match. The ESE characterized here is highly conserved in most viral subtypes. PMID:15163745

  12. Human immunodeficiency virus type 1 stimulatory activity by Gardnerella vaginalis: relationship to biotypes and other pathogenic characteristics.

    PubMed

    Simoes, J A; Hashemi, F B; Aroutcheva, A A; Heimler, I; Spear, G T; Shott, S; Faro, S

    2001-07-01

    Stimulation of human immunodeficiency virus (HIV) type 1 expression by Gardnerella vaginalis is one possible cause for an increase in the amount of virus in the genital tract. The ability of G. vaginalis to induce HIV expression in chronically infected U1 cells was investigated, along with its possible relationship to biotype, genotype, and resistance to metronidazole and bacteriocin. Significant HIV stimulatory activity was found in 5 (50%) lysates of G. vaginalis. The ability to induce HIV expression in U1 cells was statistically associated with G. vaginalis biotype (P=.048) but not with genotype or resistance to metronidazole and bacteriocin. Further studies to explore the in vivo relevance of HIV activation by G. vaginalis in the female genital tract are warranted, since prevention strategies of bacterial vaginosis and colonization by certain biotypes of G. vaginalis may be valuable in reducing the risk of sexual transmission of HIV.

  13. [Human monkeypox].

    PubMed

    Chastel, C

    2009-03-01

    Unlike other recent viral emergences, which were in majority caused by RNA viruses, the monkeypox results from infection by a DNA virus, an orthopoxvirus closely related to both vaccine and smallpox viruses and whose two genomic variants are known. Unexpectedly isolated from captive Asiatic monkeys and first considered as an laboratory curiosity, this virus was recognised in 1970 as an human pathogen in tropical Africa. Here it was responsible for sporadic cases following intrusions (for hunting) into tropical rain forests or rare outbreak with human-to-human transmission as observed in 1996 in Democratic Republic of Congo. As monkeypox in humans is not distinguishable from smallpox (a disease globally eradicated in 1977) it was only subjected to vigilant epidemiological surveillance and not considered as a potential threat outside Africa. This point of view radically changed in 2003 when monkeypox was introduced in the USA by African wild rodents and spread to 11 different states of this country. Responsible for 82 infections in American children and adults, this outbreak led to realize the sanitary hazards resulting from international trade of exotic animals and scientific investigations increasing extensively our knowledge of this zoonosis. PMID:18394820

  14. Humanizing Calculus

    ERIC Educational Resources Information Center

    Cirillo, Michelle

    2007-01-01

    In this article, the author explores the history and the mathematics used by Newton and Leibniz in their invention of calculus. The exploration of this topic is intended to show students that mathematics is a human invention. Suggestions are made to help teachers incorporate the mathematics and the history into their own lessons. (Contains 3…

  15. Human Trafficking

    ERIC Educational Resources Information Center

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  16. Nothing Human

    ERIC Educational Resources Information Center

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  17. Modeling structural and functional deficiencies of RBM20 familial dilated cardiomyopathy using human induced pluripotent stem cells.

    PubMed

    Wyles, Saranya P; Li, Xing; Hrstka, Sybil C; Reyes, Santiago; Oommen, Saji; Beraldi, Rosanna; Edwards, Jessica; Terzic, Andre; Olson, Timothy M; Nelson, Timothy J

    2016-01-15

    Dilated cardiomyopathy (DCM) is a leading cause of heart failure. In families with autosomal-dominant DCM, heterozygous missense mutations were identified in RNA-binding motif protein 20 (RBM20), a spliceosome protein induced during early cardiogenesis. Dermal fibroblasts from two unrelated patients harboring an RBM20 R636S missense mutation were reprogrammed to human induced pluripotent stem cells (hiPSCs) and differentiated to beating cardiomyocytes (CMs). Stage-specific transcriptome profiling identified differentially expressed genes ranging from angiogenesis regulator to embryonic heart transcription factor as initial molecular aberrations. Furthermore, gene expression analysis for RBM20-dependent splice variants affected sarcomeric (TTN and LDB3) and calcium (Ca(2+)) handling (CAMK2D and CACNA1C) genes. Indeed, RBM20 hiPSC-CMs exhibited increased sarcomeric length (RBM20: 1.747 ± 0.238 µm versus control: 1.404 ± 0.194 µm; P < 0.0001) and decreased sarcomeric width (RBM20: 0.791 ± 0.609 µm versus control: 0.943 ± 0.166 µm; P < 0.0001). Additionally, CMs showed defective Ca(2+) handling machinery with prolonged Ca(2+) levels in the cytoplasm as measured by greater area under the curve (RBM20: 814.718 ± 94.343 AU versus control: 206.941 ± 22.417 AU; P < 0.05) and higher Ca(2+) spike amplitude (RBM20: 35.281 ± 4.060 AU versus control:18.484 ± 1.518 AU; P < 0.05). β-adrenergic stress induced with 10 µm norepinephrine demonstrated increased susceptibility to sarcomeric disorganization (RBM20: 86 ± 10.5% versus control: 40 ± 7%; P < 0.001). This study features the first hiPSC model of RBM20 familial DCM. By monitoring human cardiac disease according to stage-specific cardiogenesis, this study demonstrates RBM20 familial DCM is a developmental disorder initiated by molecular defects that pattern maladaptive cellular mechanisms of pathological cardiac remodeling. Indeed, hiPSC-CMs recapitulate RBM20 familial DCM phenotype in a dish and establish a tool

  18. Human Rights in the Humanities

    ERIC Educational Resources Information Center

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  19. The Supraspliceosome — A Multi-Task Machine for Regulated Pre-mRNA Processing in the Cell Nucleus

    PubMed Central

    Shefer, Kinneret; Sperling, Joseph; Sperling, Ruth

    2014-01-01

    Pre-mRNA splicing of Pol II transcripts is executed in the mammalian cell nucleus within a huge (21 MDa) and highly dynamic RNP machine — the supraspliceosome. It is composed of four splicing active native spliceosomes, each resembling an in vitro assembled spliceosome, which are connected by the pre-mRNA. Supraspliceosomes harbor protein splicing factors and all the five-spliceosomal U snRNPs. Recent analysis of specific supraspliceosomes at defined splicing stages revealed that they harbor all five spliceosomal U snRNAs at all splicing stages. Supraspliceosomes harbor additional pre-mRNA processing components, such as the 5′-end and 3′-end processing components, and the RNA editing enzymes ADAR1 and ADAR2. The structure of the native spliceosome, at a resolution of 20 Å, was determined by cryo-EM. A unique spatial arrangement of the spliceosomal U snRNPs within the native spliceosome emerged from in-silico studies, localizing the five U snRNPs mostly within its large subunit, and sheltering the active core components deep within the spliceosomal cavity. The supraspliceosome provides a platform for coordinating the numerous processing steps that the pre-mRNA undergoes: 5′ and 3′-end processing activities, RNA editing, constitutive and alternative splicing, and processing of intronic microRNAs. It also harbors a quality control mechanism termed suppression of splicing (SOS) that, under normal growth conditions, suppresses splicing at abundant intronic latent 5′ splice sites in a reading frame-dependent fashion. Notably, changes in these regulatory processing activities are associated with human disease and cancer. These findings emphasize the supraspliceosome as a multi-task master regulator of pre-mRNA processing in the cell nucleus. PMID:25408845

  20. Human genetics

    SciTech Connect

    Carlson, E.A.

    1984-01-01

    This text provides full and balanced coverage of the concepts requisite for a thorough understanding of human genetics. Applications to both the individual and society are integrated throughout the lively and personal narrative, and the essential principles of heredity are clearly presented to prepare students for informed participation in public controversies. High-interest, controversial topics, including recombinant DNA technology, oncogenes, embryo transfer, environmental mutagens and carcinogens, IQ testing, and eugenics encourage understanding of important social issues.

  1. Human evolution.

    PubMed

    Wood, B

    1996-12-01

    The common ancestor of modern humans and the great apes is estimated to have lived between 5 and 8 Myrs ago, but the earliest evidence in the human, or hominid, fossil record is Ardipithecus ramidus, from a 4.5 Myr Ethiopian site. This genus was succeeded by Australopithecus, within which four species are presently recognised. All combine a relatively primitive postcranial skeleton, a dentition with expanded chewing teeth and a small brain. The most primitive species in our own genus, Homo habilis and Homo rudolfensis, are little advanced over the australopithecines and with hindsight their inclusion in Homo may not be appropriate. The first species to share a substantial number of features with later Homo is Homo ergaster, or 'early African Homo erectus', which appears in the fossil record around 2.0 Myr. Outside Africa, fossil hominids appear as Homo erectus-like hominids, in mainland Asia and in Indonesia close to 2 Myr ago; the earliest good evidence of 'archaic Homo' in Europe is dated at between 600-700 Kyr before the present. Anatomically modern human, or Homo sapiens, fossils are seen first in the fossil record in Africa around 150 Kyr ago. Taken together with molecular evidence on the extent of DNA variation, this suggests that the transition from 'archaic' to 'modern' Homo may have taken place in Africa. PMID:8976151

  2. Human evolution.

    PubMed

    Wood, B

    1996-12-01

    The common ancestor of modern humans and the great apes is estimated to have lived between 5 and 8 Myrs ago, but the earliest evidence in the human, or hominid, fossil record is Ardipithecus ramidus, from a 4.5 Myr Ethiopian site. This genus was succeeded by Australopithecus, within which four species are presently recognised. All combine a relatively primitive postcranial skeleton, a dentition with expanded chewing teeth and a small brain. The most primitive species in our own genus, Homo habilis and Homo rudolfensis, are little advanced over the australopithecines and with hindsight their inclusion in Homo may not be appropriate. The first species to share a substantial number of features with later Homo is Homo ergaster, or 'early African Homo erectus', which appears in the fossil record around 2.0 Myr. Outside Africa, fossil hominids appear as Homo erectus-like hominids, in mainland Asia and in Indonesia close to 2 Myr ago; the earliest good evidence of 'archaic Homo' in Europe is dated at between 600-700 Kyr before the present. Anatomically modern human, or Homo sapiens, fossils are seen first in the fossil record in Africa around 150 Kyr ago. Taken together with molecular evidence on the extent of DNA variation, this suggests that the transition from 'archaic' to 'modern' Homo may have taken place in Africa.

  3. An Investigation of the Aerodynamic Characteristics of an 0.08-Scale Model of the Chance Vought XF7U-1 Airplane in the Langley High-Speed 7-by 10-Foot Tunnel: TED No. DE308. Part 6; Estimated High-Speed Flying Qualities

    NASA Technical Reports Server (NTRS)

    Donlan, Charles J.; Kuhn, Richard E.

    1948-01-01

    An analysis of the estimated high-speed flying qualities of the Chance Vought XF7U-1 airplane in the Mach number range from 0.40 to 0.91 has been made, based on tests of an 0.08-scale model of this airplane in the Langley high-speed 7- by 10-foot wind tunnel. The analysis indicates longitudinal control-position instability at transonic speeds, but the accompanying trim changes are not large. Control-position maneuvering stability, however, is present for all speeds. Longitudinal lateral control appear adequate, but the damping of the short-period longitudinal and lateral oscillations at high altitudes is poor and may require artificial damping.

  4. Underground storage tank 253-D1U1 Closure Plan

    SciTech Connect

    Mancieri, S.; Giuntoli, N.

    1993-09-01

    This report is a closure plan for a diesel fuel tank at the Lawrence Livermore National Laboratory. Included are maps of the site, work plans, and personnel information regarding training and qualification.

  5. U1/U2 crib groundwater biological treatment demonstration project

    SciTech Connect

    Koegler, S.S.; Brouns, T.M.; Heath, W.O.

    1989-11-01

    The primary objective of the biological treatment project is to develop and demonstrate a process for Hanford groundwater remediation. Biodenitrification using facultative anaerobic microorganisms is a promising technology for the simultaneous removal of nitrates and organics from contaminated aqueous streams. During FY 1988, a consortium of Hanford groundwater microorganisms was shown to degrade both nitrates and carbon tetrachloride (CC1{sub 4}). A pilot-scale treatment system was designed and constructed based on the results of laboratory-and-bench-scale testing. This report summarizes the results of biological groundwater treatment studies performed during FY 1989 at the pilot-scale. These tests were conducted using a simulated Hanford groundwater with a continuous stirred-tank bioreactor, and a fluidized-bed bioreactor that was added to the pilot-scale treatment system in FY 1989. The pilot-scale system demonstrated continuous degradation of nitrates and CC1{sub 4} in a simulated groundwater. 4 refs., 7 figs., 1 tab.

  6. Quark masses, chiral symmetry, and the U(1) anomaly

    SciTech Connect

    Creutz, M.

    1996-09-17

    The author discusses the mass parameters appearing in the gauge theory of the strong interactions, concentrating on the two flavor case. He shows how the effect of the CP violating parameter {theta} is simply interpreted in terms of the state of the aether via an effective potential for meson fields. For degenerate flavors he shows that a first order phase transition is expected at {theta} = {pi}. The author speculates on the implications of this structure for Wilson`s lattice fermions.

  7. SUL(4) × U(1) model for electroweak unification

    NASA Astrophysics Data System (ADS)

    Fayyazuddin; Riazuddin

    2004-12-01

    After some general remarks about SUL(4) electroweak unification, the model is extended to SUL(4) × UX(1) to accomodate fractionally charged quarks. The unification scale is expected to be in TeV region. A right-handed Majorana neutrino along with known lepton are put in the fundamental representation of SUL(4) with YX = 0. The see-saw mechanism for neutrino masses and flavor mixing in neutrino sector is a natural feature of the model. The lepton number violating processes can occure through dilepton gauge bosons contained in the model.

  8. Higher U(1)-gerbe connections in geometric prequantization

    NASA Astrophysics Data System (ADS)

    Fiorenza, Domenico; Rogers, Christopher L.; Schreiber, Urs

    2016-07-01

    We promote geometric prequantization to higher geometry (higher stacks), where a prequantization is given by a higher principal connection (a higher gerbe with connection). We show fairly generally how there is canonically a tower of higher gauge groupoids and Courant groupoids assigned to a higher prequantization, and establish the corresponding Atiyah sequence as an integrated Kostant-Souriau ∞-group extension of higher Hamiltonian symplectomorphisms by higher quantomorphisms. We also exhibit the ∞-group cocycle which classifies this extension and discuss how its restrictions along Hamiltonian ∞-actions yield higher Heisenberg cocycles. In the special case of higher differential geometry over smooth manifolds, we find the L∞-algebra extension of Hamiltonian vector fields — which is the higher Poisson bracket of local observables — and show that it is equivalent to the construction proposed by the second author in n-plectic geometry. Finally, we indicate a list of examples of applications of higher prequantization in the extended geometric quantization of local quantum field theories and specifically in string geometry.

  9. Higgs bosons of a supersymmetric U(1)' model

    SciTech Connect

    Ham, Seung Woo; Oh, Sun Kun

    2008-11-23

    The lightest scalar Higgs boson is predicted to be smaller than 162 GeV in the leptophobic {eta}-model, at the one-loop level, for a reasonable region of parameter space. In the NMSSM, the sum of the square of the normalized scalar Higgs coupling coefficients to a pair of Z bosons is unity, whereas the corresponding quantity in the leptophobic {eta}-model is less than unity. Thus, by measuring the scalar Higgs coupling coefficients at the ILC, the leptophobic {eta}-model might be distinguished from the NMSSM.

  10. Human Capital, (Human) Capabilities and Higher Education

    ERIC Educational Resources Information Center

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  11. Human Heredity: Genetic Mechanisms in Humans.

    ERIC Educational Resources Information Center

    Blank, C. E.

    1988-01-01

    Discussed are some of the uncertainties in human genetic mechanisms that are often presented as dogma in Biology textbooks. Presented is a brief historical background and illustrations involving chromosome abnormality in humans and linkage studies in humans. (CW)

  12. Human Astroviruses

    PubMed Central

    Pintó, Rosa M.; Guix, Susana

    2014-01-01

    SUMMARY Human astroviruses (HAtVs) are positive-sense single-stranded RNA viruses that were discovered in 1975. Astroviruses infecting other species, particularly mammalian and avian, were identified and classified into the genera Mamastrovirus and Avastrovirus. Through next-generation sequencing, many new astroviruses infecting different species, including humans, have been described, and the Astroviridae family shows a high diversity and zoonotic potential. Three divergent groups of HAstVs are recognized: the classic (MAstV 1), HAstV-MLB (MAstV 6), and HAstV-VA/HMO (MAstV 8 and MAstV 9) groups. Classic HAstVs contain 8 serotypes and account for 2 to 9% of all acute nonbacterial gastroenteritis in children worldwide. Infections are usually self-limiting but can also spread systemically and cause severe infections in immunocompromised patients. The other groups have also been identified in children with gastroenteritis, but extraintestinal pathologies have been suggested for them as well. Classic HAstVs may be grown in cells, allowing the study of their cell cycle, which is similar to that of caliciviruses. The continuous emergence of new astroviruses with a potential zoonotic transmission highlights the need to gain insights on their biology in order to prevent future health threats. This review focuses on the basic virology, pathogenesis, host response, epidemiology, diagnostic assays, and prevention strategies for HAstVs. PMID:25278582

  13. Human schistosomiasis

    PubMed Central

    Colley, Daniel G; Bustinduy, Amaya L; Secor, W Evan; King, Charles H

    2015-01-01

    Human schistosomiasis—or bilharzia—is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination. PMID:24698483

  14. NATO Human View Architecture and Human Networks

    NASA Technical Reports Server (NTRS)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  15. The Digital Humanities as a Humanities Project

    ERIC Educational Resources Information Center

    Svensson, Patrik

    2012-01-01

    This article argues that the digital humanities can be seen as a humanities project in a time of significant change in the academy. The background is a number of scholarly, educational and technical challenges, the multiple epistemic traditions linked to the digital humanities, the potential reach of the field across and outside the humanities,…

  16. Human Rhinoviruses

    PubMed Central

    Lamson, Daryl M.; St. George, Kirsten; Walsh, Thomas J.

    2013-01-01

    Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. Advances in molecular methods have enhanced our understanding of the genomic structure of HRV and have led to the characterization of three genetically distinct HRV groups, designated groups A, B, and C, within the genus Enterovirus and the family Picornaviridae. HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis. In recent years, the increasing implementation of PCR assays for respiratory virus detection in clinical laboratories has facilitated the recognition of HRV as a lower respiratory tract pathogen, particularly in patients with asthma, infants, elderly patients, and immunocompromised hosts. Cultured isolates of HRV remain important for studies of viral characteristics and disease pathogenesis. Indeed, whether the clinical manifestations of HRV are related directly to viral pathogenicity or secondary to the host immune response is the subject of ongoing research. There are currently no approved antiviral therapies for HRVs, and treatment remains primarily supportive. This review provides a comprehensive, up-to-date assessment of the basic virology, pathogenesis, clinical epidemiology, and laboratory features of and treatment and prevention strategies for HRVs. PMID:23297263

  17. Human oestrus

    PubMed Central

    Gangestad, Steven W; Thornhill, Randy

    2008-01-01

    For several decades, scholars of human sexuality have almost uniformly assumed that women evolutionarily lost oestrus—a phase of female sexuality occurring near ovulation and distinct from other phases of the ovarian cycle in terms of female sexual motivations and attractivity. In fact, we argue, this long-standing assumption is wrong. We review evidence that women's fertile-phase sexuality differs in a variety of ways from their sexuality during infertile phases of their cycles. In particular, when fertile in their cycles, women are particularly sexually attracted to a variety of features that likely are (or, ancestrally, were) indicators of genetic quality. As women's fertile-phase sexuality shares with other vertebrate females' fertile-phase sexuality a variety of functional and physiological features, we propose that the term oestrus appropriately applies to this phase in women. We discuss the function of women's non-fertile or extended sexuality and, based on empirical findings, suggest ways that fertile-phase sexuality in women has been shaped to partly function in the context of extra-pair mating. Men are particularly attracted to some features of fertile-phase women, but probably based on by-products of physiological changes males have been selected to detect, not because women signal their cycle-based fertility status. PMID:18252670

  18. Infrared radiative decay dynamics from the γ 1u (3P2), H 1u (3P1), and 1u (1D2) ion-pair states of I2 observed by a perturbation facilitated optical-optical double resonance technique

    NASA Astrophysics Data System (ADS)

    Hoshino, Shoma; Araki, Mitsunori; Nakano, Yukio; Ishiwata, Takashi; Tsukiyama, Koichi

    2016-01-01

    We report the spectroscopic and temporal analyses on the amplified spontaneous emission (ASE) from the single rovibrational levels of the Ω = 1u ion-pair series, γ 1u (3P2), H 1u (3P1), and 1u (1D2), of I2 by using a perturbation facilitated optical-optical double resonance technique through the c 1 Π g ˜ B 3 Π ( 0u + ) hyperfine mixed valence state as the intermediate state. The ASE detected in the infrared region was assigned to the parallel transitions from the Ω = 1u ion-pair states down to the nearby Ω = 1g ion-pair states. The subsequent ultraviolet (UV) fluorescence from the Ω = 1g states was also observed and the relative vibrational populations in the Ω = 1g states were derived through the Franck-Condon simulation of the intensity pattern of the vibrational progression. In the temporal profiles of the UV fluorescence, an obvious delay in the onset of the fluorescence was recognized after the excitation laser pulse. These results revealed that ASE is a dominant energy relaxation process between the Ω = 1u and 1g ion-pair states of I2. Finally, the lifetimes of the relevant ion-pair states were evaluated by temporal analyses of the UV fluorescence. The propensity was found which was the longer lifetime in the upper level of the ASE transitions tends to give intense ASE.

  19. Human Factors in Human-Systems Integration

    NASA Technical Reports Server (NTRS)

    Fitts, David J.; Sandor, Aniko; Litaker, Harry L., Jr.; Tillman, Barry

    2008-01-01

    Any large organization whose mission is to design and develop systems for humans, and train humans needs a well-developed integration and process plan to deal with the challenges that arise from managing multiple subsystems. Human capabilities, skills, and needs must be considered early in the design and development process, and must be continuously considered throughout the development lifecycle. This integration of human needs within system design is typically formalized through a Human-Systems Integration (HSI) program. By having an HSI program, an institution or organization can reduce lifecycle costs and increase the efficiency, usability, and quality of its products because human needs have been considered from the beginning.

  20. Humane Education: An Overview.

    ERIC Educational Resources Information Center

    Whitlock, Eileen S.; Westerlund, Stuart R.

    This booklet traces the historical development of human education as it has been instilled into the young people of America from colonial times to the present and provides a future prognosis of humaneness in the schools. Humane education promotes humane behavior and is an important part of the humane movement in the United States, although until…

  1. In Human Pseudouridine Synthase 1 (hPus1), a C-terminal Helical Insert Blocks tRNA From Binding in the Same Orientation as in the Pus1 Bacterial Homologue TruA, Consistent with their Different Target Selectivities

    PubMed Central

    Czudnochowski, Nadine; Wang, Amy Liya; Finer-Moore, Janet; Stroud, Robert M.

    2013-01-01

    Human pseudouridine (Ψ) synthase Pus1 (hPus1) modifies specific uridine residues in several non-coding RNAs; tRNA, U2 spliceosomal RNA and steroid receptor activator RNA. We report three structures of the catalytic core domain of hPus1 from two crystal forms, at 1.8 Å resolution. The structures are the first of a mammalian Ψ synthase from the set of five Ψ synthase families common to all kingdoms of life. hPus1 adopts a fold similar to bacterial Ψ synthases, with a central antiparallel ß-sheet flanked by helices and loops. A flexible hinge at the base of the sheet allows the enzyme to open and close around an electropositive active site cleft. In one crystal form a molecule of MES mimics the target uridine of an RNA substrate. A positively charged electrostatic surface extends from the active site towards the N-terminus of the catalytic domain suggesting an extensive binding site specific for target RNAs. Two alpha helices C-terminal to the core domain, but unique to hPus1, extend along the back and top of the central ß-sheet and form the walls of the RNA binding surface. Docking of tRNA to hPus1 in a productive orientation requires only minor conformational changes to enzyme and tRNA. The docked tRNA is bound by the electropositive surface of the protein employing a completely different binding mode than that seen for the tRNA complex of the E. coli homolog TruA. PMID:23707380

  2. Human Research Risk Management

    NASA Video Gallery

    Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) investigates and mitigates the highest risks to human health and per...

  3. Human-machine interactions

    DOEpatents

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  4. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. . Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  5. Cwc24p Is a General Saccharomyces cerevisiae Splicing Factor Required for the Stable U2 snRNP Binding to Primary Transcripts

    PubMed Central

    Coltri, Patricia P.; Oliveira, Carla C.

    2012-01-01

    Splicing of primary transcripts is an essential process for the control of gene expression. Specific conserved sequences in premature transcripts are important to recruit the spliceosome machinery. The Saccharomyces cerevisiae catalytic spliceosome is composed of about 60 proteins and 5 snRNAs (U1, U2, U4/U6 and U5). Among these proteins, there are core components and regulatory factors, which might stabilize or facilitate splicing of specific substrates. Assembly of a catalytic complex depends on the dynamics of interactions between these proteins and RNAs. Cwc24p is an essential S. cerevisiae protein, originally identified as a component of the NTC complex, and later shown to affect splicing in vivo. In this work, we show that Cwc24p also affects splicing in vitro. We show that Cwc24p is important for the U2 snRNP binding to primary transcripts, co-migrates with spliceosomes, and that it interacts with Brr2p. Additionally, we show that Cwc24p is important for the stable binding of Prp19p to the spliceosome. We propose a model in which Cwc24p is required for stabilizing the U2 association with primary transcripts, and therefore, especially important for splicing of RNAs containing non-consensus branchpoint sequences. PMID:23029180

  6. Structural study of (N2H5,H)2.9U1.1Ce0.9(C2O4)5·10H2O from a conventional X-ray diffraction diagram obtained on a powder synthesized by a fast vortex process

    NASA Astrophysics Data System (ADS)

    Brackx, E.; Laval, J. P.; Dugne, O.; Feraud, J. P.; Arab-Chapelet, B.

    2015-01-01

    In the context of research on U/minor actinides for nuclear fuel reprocessing in the transmutation process, developments are first studied with surrogates containing uranium and lanthanides to facilitate testing. The tests consist of precipitating and calcining a hydrazinium uranium/cerium oxalate. The structure of this oxalate had not been previously determined, but was necessary to validate the physicochemical mechanisms involved. The present study, firstly demonstrates the structural similarity of the U/Ce oxalate phase (N2H5,H)2.9U1.1Ce0.9(C2O4)5·10H2O, synthesized using a vortex precipitator for continuous synthesis of actinide oxalates, with previously known oxalates, crystallizing in P63/mmc symmetry, obtained by more classical methods. This fast precipitation process induces massive nucleation of fine powders. Their structural and microstructural determination confirms that the raw and dried phases belong to the same structural family as (NH4)2U2(C2O4)5·0.7H2O whose structure was described by Chapelet-Arab in P63/mmc symmetry, using single crystal data. However, they present an extended disorder inside the tunnels of the structure, even after drying at 100 °C, between water and hydrazinium ions. This disorder is directly related to the fast vortex method. This structure determination can be used as a basis for further semi-quantitative analysis on the U/minor actinides products formed under various experimental conditions.

  7. Visualizing Humans by Computer.

    ERIC Educational Resources Information Center

    Magnenat-Thalmann, Nadia

    1992-01-01

    Presents an overview of the problems and techniques involved in visualizing humans in a three-dimensional scene. Topics discussed include human shape modeling, including shape creation and deformation; human motion control, including facial animation and interaction with synthetic actors; and human rendering and clothing, including textures and…

  8. Special Section: Human Rights

    ERIC Educational Resources Information Center

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  9. Human Research Program Opportunities

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.

    2014-01-01

    The goal of HRP is to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. The Human Research Program was designed to meet the needs of human space exploration, and understand and reduce the risk to crew health and performance in exploration missions.

  10. The Humanities: Interconnections.

    ERIC Educational Resources Information Center

    Salomone, Ronald E., Ed.

    1985-01-01

    Focusing on a wide range of interdisciplinary themes and ideas for humanities instruction, the 17 articles in this journal issue discuss the following topics: (1) literature, humanities, and the adult learner; (2) the role of the humanities in educating for a democracy; (3) humanities in the marketplace; (4) literature versus "great books" in high…

  11. Sequences more than 500 base pairs upstream of the human U3 small nuclear RNA gene stimulate the synthesis of U3 RNA in frog oocytes

    SciTech Connect

    Suh, D.; Reddy, R. ); Wright, D. )

    1991-06-04

    Small nuclear RNA (snRNA) genes contain strong promoters capable of initiating transcription once every 4 s. Studies on the human U1 snRNA gene, carried out in other laboratories, showed that sequences within 400 bp of the 5' flanking region are sufficient for maximal levels of transcription both in vivo and in frog oocytes (reviewed in Dahlberg and Lund (1988)). The authors studied the expression of a human U3 snRNA gene by injecting 5' deletion mutants into frog oocytes. The results show that sequences more than 500 bp upstream of the U3 snRNA gene have a 2-3-fold stimulatory effect on the U3 snRNA synthesis. These results indicate that the human U3 snRNA gene is different from human U1 snRNA gene in containing regulatory elements more than 500 bp upstream. The U3 snRNA gene upstream sequences contain an AluI homologous sequence in the {minus}1,200 region; these AluI sequences were transcribed in vitro and in frog oocytes but were not detectable in Hela cells.

  12. ISS Payload Human Factors

    NASA Technical Reports Server (NTRS)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  13. Human papillomavirus detection from human immunodeficiency virus-infected Colombian women's paired urine and cervical samples.

    PubMed

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C; Sanchez, Ricardo; Parra, Diana; Pineda, Andrea C; Sussmann, Otto; Perez-Prados, Antonio; Patarroyo, Manuel E; Patarroyo, Manuel A

    2013-01-01

    Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.

  14. Alterations in transcription factor binding in radioresistant human melanoma cells after ionizing radiation

    SciTech Connect

    Sahijdak, W.M.; Yang, Chin-Rang; Zuckerman, J.S.; Meyers, M.; Boothman, D.A.

    1994-04-01

    We analyzed alterations in transcription factor binding to specific, known promoter DNA consensus sequences between irradiated and unirradiated radioresistant human melanoma (U1-Mel) cells. The goal of this study was to begin to investigate which transcription factors and DNA-binding sites are responsible for the induction of specific transcripts and proteins after ionizing radiation. Transcription factor binding was observed using DNA band-shift assays and oligonucleotide competition analyses. Confluence-arrested U1-Mel cells were irradiated (4.5 Gy) and harvested at 4 h. Double-stranded oligonucleotides containing known DNA-binding consensus sites for specific transcription factors were used. Increased DNA binding activity after ionizing radiation was noted with oligonucleotides containing the CREB, NF-kB and Sp1 consensus sites. No changes in protein binding to AP-1, AP-2, AP-3, or CTF/NF1, GRE or Oct-1 consensus sequences were noted. X-ray activation of select transcription factors, which bind certain consensus sites in promoters, may cause specific induction or repression of gene transcription. 22 refs., 2 figs.

  15. Economics of human trafficking.

    PubMed

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  16. Economics of human trafficking.

    PubMed

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans. PMID:20645472

  17. Origins of De Novo Genes in Human and Chimpanzee

    PubMed Central

    Ruiz-Orera, Jorge; Hernandez-Rodriguez, Jessica; Chiva, Cristina; Sabidó, Eduard; Kondova, Ivanela; Bontrop, Ronald; Marqués-Bonet, Tomàs; Albà, M.Mar

    2015-01-01

    The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species—human, chimpanzee, macaque, and mouse—and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins. PMID:26720152

  18. Origins of De Novo Genes in Human and Chimpanzee.

    PubMed

    Ruiz-Orera, Jorge; Hernandez-Rodriguez, Jessica; Chiva, Cristina; Sabidó, Eduard; Kondova, Ivanela; Bontrop, Ronald; Marqués-Bonet, Tomàs; Albà, M Mar

    2015-12-01

    The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species--human, chimpanzee, macaque, and mouse--and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins.

  19. Mobile Bacterial Group II Introns at the Crux of Eukaryotic Evolution.

    PubMed

    Lambowitz, Alan M; Belfort, Marlene

    2015-02-01

    This review focuses on recent developments in our understanding of group II intron function, the relationships of these introns to retrotransposons and spliceosomes, and how their common features have informed thinking about bacterial group II introns as key elements in eukaryotic evolution. Reverse transcriptase-mediated and host factor-aided intron retrohoming pathways are considered along with retrotransposition mechanisms to novel sites in bacteria, where group II introns are thought to have originated. DNA target recognition and movement by target-primed reverse transcription infer an evolutionary relationship among group II introns, non-LTR retrotransposons, such as LINE elements, and telomerase. Additionally, group II introns are almost certainly the progenitors of spliceosomal introns. Their profound similarities include splicing chemistry extending to RNA catalysis, reaction stereochemistry, and the position of two divalent metals that perform catalysis at the RNA active site. There are also sequence and structural similarities between group II introns and the spliceosome's small nuclear RNAs (snRNAs) and between a highly conserved core spliceosomal protein Prp8 and a group II intron-like reverse transcriptase. It has been proposed that group II introns entered eukaryotes during bacterial endosymbiosis or bacterial-archaeal fusion, proliferated within the nuclear genome, necessitating evolution of the nuclear envelope, and fragmented giving rise to spliceosomal introns. Thus, these bacterial self-splicing mobile elements have fundamentally impacted the composition of extant eukaryotic genomes, including the human genome, most of which is derived from close relatives of mobile group II introns.

  20. Mice with human livers.

    PubMed

    Grompe, Markus; Strom, Stephen

    2013-12-01

    Animal models are used to study many aspects of human disease and to test therapeutic interventions. However, some very important features of human biology cannot be replicated in animals, even in nonhuman primates or transgenic rodents engineered with human genes. Most human microbial pathogens do not infect animals and the metabolism of many xenobiotics is different between human beings and animals. The advent of transgenic immune-deficient mice has made it possible to generate chimeric animals harboring human tissues and cells, including hepatocytes. The liver plays a central role in many human-specific biological processes and mice with humanized livers can be used to model human metabolism, liver injury, gene regulation, drug toxicity, and hepatotropic infections.

  1. Virtual Human Project

    SciTech Connect

    Ward, RD

    2001-06-12

    This paper describes the development of a comprehensive human modeling environment, the Virtual Human, which will be used initially to model the human respiratory system for purposes of predicting pulmonary disease or injury using lung sounds. The details of the computational environment, including the development of a Virtual Human Thorax, a database for storing models, model parameters, and experimental data, and a Virtual Human web interface are outlined. Preliminary progress in developing this environment will be presented. A separate paper at the conference describes the modeling of sound generation using computational fluid dynamics and the modeling of sound propagation in the human respiratory system.

  2. Classical molecular tests using urine samples as a potential screening tool for human papillomavirus detection in human immunodeficiency virus-infected women.

    PubMed

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C; Sanchez, Ricardo; Pineda-Peña, Andrea C; Perez-Prados, Antonio; Patarroyo, Manuel E; Patarroyo, Manuel A

    2013-11-01

    Human papillomavirus (HPV) is the main risk factor associated with the development of cervical cancer (CC); however, there are other factors, such as immunosuppression caused by the human immunodeficiency virus (HIV), that favor progression of the illness. This study was thus aimed at evaluating the functionality of classical PCR-based molecular tests for the generic identification of HPV DNA (GP5+/GP6+, MY09/MY11, and pU1M/2R primers, individually or in combination) using cervical and urine samples from 194 HIV-positive women. Infected samples were tested with type-specific primers for six high-risk types (HPV-16, -18, -31, -33, -45, and -58) and two low-risk types (HPV-6 and -11). HPV infection prevalence rates were 70.1% for the cervical samples and 63.9% for the urine samples. HPV-16 was the most prevalent viral type in the cervical and urine samples, with higher rates of multiple infections than single infections detected in such samples. HPV DNA detection by PCR (mainly with the pU1M/2R primer set) in urine samples was positively associated with abnormal cytological findings (atypical squamous cells of undetermined significance/squamous intraepithelial lesions [ASCUS/SIL]). It was determined that the operative characteristics for detection of cytological abnormalities were similar for cervical and urine samples. This suggested using PCR for the detection of HPV DNA in urine samples as a potential screening strategy for CC prevention in future prevention and control programs along with currently implemented strategies for reducing the impact of the disease, i.e., urine samples are economical, are easy to collect, have wide acceptability among women, and have operative characteristics similar to those of cervical samples.

  3. Mining human antibody repertoires

    PubMed Central

    2010-01-01

    Human monoclonal antibodies (mAbs) have become drugs of choice for the management of an increasing number of human diseases. Human antibody repertoires provide a rich source for human mAbs. Here we review the characteristics of natural and non-natural human antibody repertoires and their mining with non-combinatorial and combinatorial strategies. In particular, we discuss the selection of human mAbs from naïve, immune, transgenic and synthetic human antibody repertoires using methods based on hybridoma technology, clonal expansion of peripheral B cells, single-cell PCR, phage display, yeast display and mammalian cell display. Our reliance on different strategies is shifting as we gain experience and refine methods to the efficient generation of human mAbs with superior pharmacokinetic and pharmacodynamic properties. PMID:20505349

  4. Pathfinder: Humans in space

    NASA Technical Reports Server (NTRS)

    Anderson, John L.

    1988-01-01

    Viewgraphs are presented on the Pathfinder program. Information is given on human exploration of the solar system, technical requirements interfaces, program objectives, space suits, human performance, man-machine systems, space habitats, life support systems, and artificial gravity

  5. Human bites (image)

    MedlinePlus

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  6. Telling the Human Story.

    ERIC Educational Resources Information Center

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  7. Human assisted robotic exploration

    NASA Astrophysics Data System (ADS)

    Files, B. T.; Canady, J.; Warnell, G.; Stump, E.; Nothwang, W. D.; Marathe, A. R.

    2016-05-01

    In support of achieving better performance on autonomous mapping and exploration tasks by incorporating human input, we seek here to first characterize humans' ability to recognize locations from limited visual information. Such a characterization is critical to the design of a human-in-the-loop system faced with deciding whether and when human input is useful. In this work, we develop a novel and practical place-recognition task that presents humans with video clips captured by a navigating ground robot. Using this task, we find experimentally that human performance does not seem to depend on factors such as clip length or familiarity with the scene and also that there is significant variability across subjects. Moreover, we find that humans significantly outperform a state-of-the-art computational solution to this problem, suggesting the utility of incorporating human input in autonomous mapping and exploration techniques.

  8. Human productivity program definition

    NASA Technical Reports Server (NTRS)

    Cramer, D. B.

    1985-01-01

    The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

  9. Evolution of small nuclear RNAs in S. cerevisiae, C. albicans, and other hemiascomycetous yeasts.

    PubMed

    Mitrovich, Quinn M; Guthrie, Christine

    2007-12-01

    The spliceosome is a large, dynamic ribonuclear protein complex, required for the removal of intron sequences from newly synthesized eukaryotic RNAs. The spliceosome contains five essential small nuclear RNAs (snRNAs): U1, U2, U4, U5, and U6. Phylogenetic comparisons of snRNAs from protists to mammals have long demonstrated remarkable conservation in both primary sequence and secondary structure. In contrast, the snRNAs of the hemiascomycetous yeast Saccharomyces cerevisiae have highly unusual features that set them apart from the snRNAs of other eukaryotes. With an emphasis on the pathogenic yeast Candida albicans, we have now identified and compared snRNAs from newly sequenced yeast genomes, providing a perspective on spliceosome evolution within the hemiascomycetes. In addition to tracing the origins of previously identified snRNA variations present in Saccharomyces cerevisiae, we have found numerous unexpected changes occurring throughout the hemiascomycetous lineages. Our observations reveal interesting examples of RNA and protein coevolution, giving rise to altered interaction domains, losses of deeply conserved snRNA-binding proteins, and unique snRNA sequence changes within the catalytic center of the spliceosome. These same yeast lineages have experienced exceptionally high rates of intron loss, such that modern hemiascomycetous genomes contain introns in only approximately 5% of their genes. Also, the splice site sequences of those introns that remain adhere to an unusually strict consensus. Some of the snRNA variations we observe may thus reflect the altered intron landscape with which the hemiascomycetous spliceosome must contend.

  10. Some Criteria for Humanizing.

    ERIC Educational Resources Information Center

    Read, Charlotte S.

    Patterns for humanizing the information sciences include recognizing essential "humanness," taking a holistic approach to the subject field, and being aware of the epistemological nature of how people communicate and relate to others and themselves. The complete inclusion of the human factor in information theory researches can only amplify the…

  11. A Human Rights Glossary.

    ERIC Educational Resources Information Center

    Flowers, Nancy

    1998-01-01

    Presents a human rights glossary that includes definitions of basic terms, treaties, charters, and groups/organizations that have been featured in previous articles in this edition of "Update on Law-Related Education"; the human rights terms have been compiled as part of the celebration of the Universal Declaration of Human Rights (UDHR). (CMK)

  12. Human Resource Development.

    ERIC Educational Resources Information Center

    Mensel, R. Frank

    The contradictions of campus management are examined in this speech and applied to the problems of human resource development. The author suggests that human resource development cannot be considered fully without taking into account the state of the institution and institutional development. Since human resources represents 75 percent or more of…

  13. Demystifying the Humanities.

    ERIC Educational Resources Information Center

    Bonham, George

    1980-01-01

    The new Rockefeller Foundation's Commission on the Humanities' report is discussed. Some of the commission's recommendations include: improved quality of elementary and secondary schools, strengthening of humanities research, reaffirmation within education of the values of the humanities, and closer collaboration of educational and cultural…

  14. Visible Human Project

    MedlinePlus

    ... Mobile Gallery Site Navigation Home The Visible Human Project ® Overview The Visible Human Project ® is an outgrowth of the NLM's 1986 Long- ... The long-term goal of the Visible Human Project ® is to produce a system of knowledge structures ...

  15. Whose Human Rights?

    ERIC Educational Resources Information Center

    Rendel, Margherita

    During the last 50 years, principles, institutions, and policies of human rights have been developed worldwide. This book brings together European and international conventions on human rights, the rights of women, and the users and uses of education, and places them in their wider context. It examines issues in how human rights work, the ways in…

  16. Human nature and enhancement.

    PubMed

    Buchanan, Allen

    2009-03-01

    Appeals to the idea of human nature are frequent in the voluminous literature on the ethics of enhancing human beings through biotechnology. Two chief concerns about the impact of enhancements on human nature have been voiced. The first is that enhancement may alter or destroy human nature. The second is that if enhancement alters or destroys human nature, this will undercut our ability to ascertain the good because, for us, the good is determined by our nature. The first concern assumes that altering or destroying human nature is in itself a bad thing. The second concern assumes that human nature provides a standard without which we cannot make coherent, defensible judgments about what is good. I will argue (1) that there is nothing wrong, per se, with altering or destroying human nature, because, on a plausible understanding of what human nature is, it contains bad as well as good characteristics and there is no reason to believe that eliminating some of the bad would so imperil the good as to make the elimination of the bad impermissible, and (2) that altering or destroying human nature need not result in the loss of our ability to make judgments about the good, because we possess a conception of the good by which we can and do evaluate human nature. I will argue that appeals to human nature tend to obscure rather than illuminate the debate over the ethics of enhancement and can be eliminated in favor of more cogent considerations.

  17. Production Of Human Antibodies

    NASA Technical Reports Server (NTRS)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  18. Has Human Evolution Stopped?

    PubMed Central

    Templeton, Alan R.

    2010-01-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences. PMID:23908778

  19. Financing Human Capital.

    ERIC Educational Resources Information Center

    Juffras, Jason; Sawhill, Isabel V.

    This paper examines the government's role in financing human capital investments. It first examines why private investments in education, training, and other forms of human capital are likely to fall short of socially desirable levels. It then reviews past trends in public support for human resource investments. Finally, it discusses current…

  20. A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal.

    PubMed

    Mueller, Nancy; Das, Atze T; Berkhout, Ben

    2016-01-01

    RNA splicing is a critical step in the human immunodeficiency virus type 1 (HIV-1) replication cycle because it controls the expression of the complex viral proteome. The major 5' splice site (5'ss) that is positioned in the untranslated leader of the HIV-1 RNA transcript is of particular interest because it is used for the production of the more than 40 differentially spliced subgenomic mRNAs. HIV-1 splicing needs to be balanced tightly to ensure the proper levels of all viral proteins, including the Gag-Pol proteins that are translated from the unspliced RNA. We previously presented evidence that the major 5'ss is regulated by a repressive local RNA structure, the splice donor (SD) hairpin, that masks the 11 nucleotides (nts) of the 5'ss signal for recognition by U1 small nuclear RNA (snRNA) of the spliceosome machinery. A strikingly different multiple-hairpin RNA conformation was recently proposed for this part of the HIV-1 leader RNA. We therefore inspected the sequence of natural HIV-1 isolates in search for support, in the form of base pair (bp) co-variations, for the different RNA conformations. PMID:27455303

  1. A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal

    PubMed Central

    Mueller, Nancy; Das, Atze T.; Berkhout, Ben

    2016-01-01

    RNA splicing is a critical step in the human immunodeficiency virus type 1 (HIV-1) replication cycle because it controls the expression of the complex viral proteome. The major 5′ splice site (5′ss) that is positioned in the untranslated leader of the HIV-1 RNA transcript is of particular interest because it is used for the production of the more than 40 differentially spliced subgenomic mRNAs. HIV-1 splicing needs to be balanced tightly to ensure the proper levels of all viral proteins, including the Gag-Pol proteins that are translated from the unspliced RNA. We previously presented evidence that the major 5′ss is regulated by a repressive local RNA structure, the splice donor (SD) hairpin, that masks the 11 nucleotides (nts) of the 5′ss signal for recognition by U1 small nuclear RNA (snRNA) of the spliceosome machinery. A strikingly different multiple-hairpin RNA conformation was recently proposed for this part of the HIV-1 leader RNA. We therefore inspected the sequence of natural HIV-1 isolates in search for support, in the form of base pair (bp) co-variations, for the different RNA conformations. PMID:27455303

  2. A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal.

    PubMed

    Mueller, Nancy; Das, Atze T; Berkhout, Ben

    2016-07-21

    RNA splicing is a critical step in the human immunodeficiency virus type 1 (HIV-1) replication cycle because it controls the expression of the complex viral proteome. The major 5' splice site (5'ss) that is positioned in the untranslated leader of the HIV-1 RNA transcript is of particular interest because it is used for the production of the more than 40 differentially spliced subgenomic mRNAs. HIV-1 splicing needs to be balanced tightly to ensure the proper levels of all viral proteins, including the Gag-Pol proteins that are translated from the unspliced RNA. We previously presented evidence that the major 5'ss is regulated by a repressive local RNA structure, the splice donor (SD) hairpin, that masks the 11 nucleotides (nts) of the 5'ss signal for recognition by U1 small nuclear RNA (snRNA) of the spliceosome machinery. A strikingly different multiple-hairpin RNA conformation was recently proposed for this part of the HIV-1 leader RNA. We therefore inspected the sequence of natural HIV-1 isolates in search for support, in the form of base pair (bp) co-variations, for the different RNA conformations.

  3. Human Mitochondrial Protein Database

    National Institute of Standards and Technology Data Gateway

    SRD 131 Human Mitochondrial Protein Database (Web, free access)   The Human Mitochondrial Protein Database (HMPDb) provides comprehensive data on mitochondrial and human nuclear encoded proteins involved in mitochondrial biogenesis and function. This database consolidates information from SwissProt, LocusLink, Protein Data Bank (PDB), GenBank, Genome Database (GDB), Online Mendelian Inheritance in Man (OMIM), Human Mitochondrial Genome Database (mtDB), MITOMAP, Neuromuscular Disease Center and Human 2-D PAGE Databases. This database is intended as a tool not only to aid in studying the mitochondrion but in studying the associated diseases.

  4. Human-technology Integration

    NASA Astrophysics Data System (ADS)

    Mullen, Katharine M.

    Human-technology integration is the replacement of human parts and extension of human capabilities with engineered devices and substrates. Its result is hybrid biological-artificial systems. We discuss here four categories of products furthering human-technology integration: wearable computers, pervasive computing environments, engineered tissues and organs, and prosthetics, and introduce examples of currently realized systems in each category. We then note that realization of a completely artificial sytem via the path of human-technology integration presents the prospect of empirical confirmation of an aware artificially embodied system.

  5. Biological Races in Humans

    PubMed Central

    Templeton, Alan R.

    2013-01-01

    Races may exist in humans in a cultural sense, but biological concepts of race are needed to access their reality in a non-species-specific manner and to see if cultural categories correspond to biological categories within humans. Modern biological concepts of race can be implemented objectively with molecular genetic data through hypothesis-testing. Genetic data sets are used to see if biological races exist in humans and in our closest evolutionary relative, the chimpanzee. Using the two most commonly used biological concepts of race, chimpanzees are indeed subdivided into races but humans are not. Adaptive traits, such as skin color, have frequently been used to define races in humans, but such adaptive traits reflect the underlying environmental factor to which they are adaptive and not overall genetic differentiation, and different adaptive traits define discordant groups. There are no objective criteria for choosing one adaptive trait over another to define race. As a consequence, adaptive traits do not define races in humans. Much of the recent scientific literature on human evolution portrays human populations as separate branches on an evolutionary tree. A tree-like structure among humans has been falsified whenever tested, so this practice is scientifically indefensible. It is also socially irresponsible as these pictorial representations of human evolution have more impact on the general public than nuanced phrases in the text of a scientific paper. Humans have much genetic diversity, but the vast majority of this diversity reflects individual uniqueness and not race. PMID:23684745

  6. Mapping human genetic ancestry.

    PubMed

    Ebersberger, Ingo; Galgoczy, Petra; Taudien, Stefan; Taenzer, Simone; Platzer, Matthias; von Haeseler, Arndt

    2007-10-01

    The human genome is a mosaic with respect to its evolutionary history. Based on a phylogenetic analysis of 23,210 DNA sequence alignments from human, chimpanzee, gorilla, orangutan, and rhesus, we present a map of human genetic ancestry. For about 23% of our genome, we share no immediate genetic ancestry with our closest living relative, the chimpanzee. This encompasses genes and exons to the same extent as intergenic regions. We conclude that about 1/3 of our genes started to evolve as human-specific lineages before the differentiation of human, chimps, and gorillas took place. This explains recurrent findings of very old human-specific morphological traits in the fossils record, which predate the recent emergence of the human species about 5-6 MYA. Furthermore, the sorting of such ancestral phenotypic polymorphisms in subsequent speciation events provides a parsimonious explanation why evolutionary derived characteristics are shared among species that are not each other's closest relatives.

  7. Human rights and bioethics.

    PubMed

    Barilan, Y M; Brusa, M

    2008-05-01

    In the first part of this article we survey the concept of human rights from a philosophical perspective and especially in relation to the "right to healthcare". It is argued that regardless of meta-ethical debates on the nature of rights, the ethos and language of moral deliberation associated with human rights is indispensable to any ethics that places the victim and the sufferer in its centre. In the second part we discuss the rise of the "right to privacy", particularly in the USA, as an attempt to make the element of personal free will dominate over the element of basic human interest within the structure of rights and when different rights seem to conflict. We conclude by discussing the relationship of human rights with moral values beyond the realm of rights, mainly human dignity, free will, human rationality and response to basic human needs.

  8. Office for Human Research Protections

    MedlinePlus

    ... Office for Human Research Protections The Office for Human Research Protections (OHRP) provides leadership in the protection of the rights, welfare, and wellbeing of human subjects involved in ...

  9. Human research subjects as human research workers.

    PubMed

    Lynch, Holly Fernandez

    2014-01-01

    Biomedical research involving human subjects has traditionally been treated as a unique endeavor, presenting special risks and demanding special protections. But in several ways, the regulatory scheme governing human subjects research is counter-intuitively less protective than the labor and employment laws applicable to many workers. This Article relies on analogical and legal reasoning to demonstrate that this should not be the case; in a number of ways, human research subjects ought to be fundamentally recast as human research workers. Like other workers protected under worklaw, biomedical research subjects often have interests that diverge from those in positions of control but little bargaining power for change. Bearing these important similarities in mind, the question becomes whether there is any good reason to treat subjects and protected workers differently as a matter of law. With regard to unrestricted payment, eligibility for a minimum wage, compensation for injury, and rights to engage in concerted activity, the answer is no and human subjects regulations ought to be revised accordingly. PMID:25051653

  10. Integrated Environmental Modelling: human decisions, human challenges

    USGS Publications Warehouse

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  11. Human organ markets and inherent human dignity.

    PubMed

    MacKellar, Calum

    2014-01-01

    It has been suggested that human organs should be bought and sold on a regulated market as any other material property belongingto an individual. This would have the advantage of both addressing the grave shortage of organs available for transplantation and respecting the freedom of individuals to choose to do whatever they want with their body parts. The old arguments against such a market in human organs are, therefore, being brought back into question. The article examines the different arguments both in favour and against the sale of human organs. It concludes that the body and any of its elements is a full expression of the whole person. As such, they cannot have a price if the individual is to retain his or her full inherent dignity and if society is to retain and protect this very important concept.

  12. [The embryo, the human and the humanized].

    PubMed

    Roa, A

    1992-03-01

    Since the moment of fecundation the human embryo is endowed with the properties of unity and uniqueness and its existence is therefore inviolable. Disputing arguments against this thesis are analyzed. Recent views of some biologists negate the human character to the embryo since the essence of a human being would be its cultural nature and ability to communicate. However, the embryo contains all the genetic information that will allow him to develop the ability to communicate. Any attempt to separate the 3 moments of time, past present and future is a definitive violation of ethics. A basic foundation of ethics is that present and future are implicit in the past and vice-versa. Finally, the idea that the unwanted child is not a cultural being should be discarded.

  13. Human organ markets and inherent human dignity.

    PubMed

    MacKellar, Calum

    2014-01-01

    It has been suggested that human organs should be bought and sold on a regulated market as any other material property belongingto an individual. This would have the advantage of both addressing the grave shortage of organs available for transplantation and respecting the freedom of individuals to choose to do whatever they want with their body parts. The old arguments against such a market in human organs are, therefore, being brought back into question. The article examines the different arguments both in favour and against the sale of human organs. It concludes that the body and any of its elements is a full expression of the whole person. As such, they cannot have a price if the individual is to retain his or her full inherent dignity and if society is to retain and protect this very important concept. PMID:24979876

  14. Human Performance in Space

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  15. Chimeras and human dignity.

    PubMed

    de Melo-Martín, Inmaculada

    2008-12-01

    Discussions about whether new biomedical technologies threaten or violate human dignity are now common. Indeed, appeals to human dignity have played a central role in national and international debates about whether to allow particular kinds of biomedical investigations. The focus of this paper is on chimera research. I argue here that both those who claim that particular types of human-nonhuman chimera research threaten human dignity and those who argue that such threat does not exist fail to make their case. I first introduce some of the arguments that have been offered supporting the claim that the creation of certain sorts of chimeras threatens or violates human dignity. I next present opponents' assessments of such arguments. Finally I critically analyze both the critics' and the supporters' claims about whether chimera research threatens human dignity.

  16. [Humanization and nursing work].

    PubMed

    Collet, Neusa; Rozendo, Célia Alves

    2003-01-01

    In this work we have as our objective to reflect on the theme of the 63rd. Annual Nursing Week "Humanization and Work: reason and meaning in Nursing". We discuss the relationship between humanization/work in nursing, differentiating the aspects related to the humanization of nursing work to those of the humanized work in nursing. The challenges of the process of humanization of assistance and of work relationships imply on the overcoming of the relevance given to the technical scientific competence, routine patterns which are crystallized, conventional models of management, corporativism of the different professional categories in favor of interdependence and the complementarity in health actions; construction of an utopia of the humanization as collective process which can be reached and implemented.

  17. Human reliability analysis

    SciTech Connect

    Dougherty, E.M.; Fragola, J.R.

    1988-01-01

    The authors present a treatment of human reliability analysis incorporating an introduction to probabilistic risk assessment for nuclear power generating stations. They treat the subject according to the framework established for general systems theory. Draws upon reliability analysis, psychology, human factors engineering, and statistics, integrating elements of these fields within a systems framework. Provides a history of human reliability analysis, and includes examples of the application of the systems approach.

  18. Robotics for Human Exploration

    NASA Technical Reports Server (NTRS)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  19. Human cloning 2001.

    PubMed

    Healy, David L; Weston, Gareth; Pera, Martin F; Rombauts, Luk; Trounson, Alan O

    2002-05-01

    This review summaries human cloning from a clinical perspective. Natural human clones, that is, monozygotic twins, are increasing in the general community. Iatrogenic human clones have been produced for decades in infertile couples given fertility treatment such as ovulation induction. A clear distinction must be made between therapeutic cloning using embryonic stem cells and reproductive cloning attempts. Unlike the early clinical years of in vitro fertilization, with cloning there is no animal model that is safe and dependable. Until there is such a model, 'Dolly'-style human cloning is medically unacceptable.

  20. Artificial human vision camera

    NASA Astrophysics Data System (ADS)

    Goudou, J.-F.; Maggio, S.; Fagno, M.

    2014-10-01

    In this paper we present a real-time vision system modeling the human vision system. Our purpose is to inspire from human vision bio-mechanics to improve robotic capabilities for tasks such as objects detection and tracking. This work describes first the bio-mechanical discrepancies between human vision and classic cameras and the retinal processing stage that takes place in the eye, before the optic nerve. The second part describes our implementation of these principles on a 3-camera optical, mechanical and software model of the human eyes and associated bio-inspired attention model.