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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. Molecular characterization of the spliceosomal proteins U1A and U2B" from higher plants.

    PubMed Central

    Simpson, G G; Clark, G P; Rothnie, H M; Boelens, W; van Venrooij, W; Brown, J W

    1995-01-01

    In addition to their role in pre-mRNA splicing, the human spliceosomal proteins U1A and U2B" are important models of how RNP motif-containing proteins execute sequence-specific RNA binding. Genes encoding U1A and U2B" have been isolated from potato and thereby provide the only evolutionary comparison available for both proteins and represent the only full-length genes encoding plant spliceosomal proteins to have been cloned and characterized. In vitro RNA binding experiments revealed the ability of potato U2B" to interact with human U2A' to enhance sequence-specific binding and to distinguish cognate RNAs of either plant or animal origin. A comparison of the sequence of U1A and U2B" proteins indicated that multiple residues which could affect RNP motif conformation probably govern the specific distinction in RNA binding by these proteins. Since human U1A modulates polyadenylation in vertebrates, the possibility that plant U1A might be exploited in the characterization of this process in plants was examined. However, unlike vertebrate U1A, neither U1A from potato nor Arabidopsis bound their own mRNA and no evidence for binding to upstream efficiency elements in polyadenylation signals was obtained, suggesting that plant U1A is not involved in polyadenylation. Images PMID:7556097

  4. Structural bioinformatics of the human spliceosomal proteome

    PubMed Central

    Korneta, Iga; Magnus, Marcin; Bujnicki, Janusz M.

    2012-01-01

    In this work, we describe the results of a comprehensive structural bioinformatics analysis of the spliceosomal proteome. We used fold recognition analysis to complement prior data on the ordered domains of 252 human splicing proteins. Examples of newly identified domains include a PWI domain in the U5 snRNP protein 200K (hBrr2, residues 258–338), while examples of previously known domains with a newly determined fold include the DUF1115 domain of the U4/U6 di-snRNP protein 90K (hPrp3, residues 540–683). We also established a non-redundant set of experimental models of spliceosomal proteins, as well as constructed in silico models for regions without an experimental structure. The combined set of structural models is available for download. Altogether, over 90% of the ordered regions of the spliceosomal proteome can be represented structurally with a high degree of confidence. We analyzed the reduced spliceosomal proteome of the intron-poor organism Giardia lamblia, and as a result, we proposed a candidate set of ordered structural regions necessary for a functional spliceosome. The results of this work will aid experimental and structural analyses of the spliceosomal proteins and complexes, and can serve as a starting point for multiscale modeling of the structure of the entire spliceosome. PMID:22573172

  5. 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.

  6. Large-Scale Proteomic Analysis of the Human Spliceosome

    PubMed Central

    Rappsilber, Juri; Ryder, Ursula; Lamond, Angus I.; Mann, Matthias

    2002-01-01

    In a previous proteomic study of the human spliceosome, we identified 42 spliceosome-associated factors, including 19 novel ones. Using enhanced mass spectrometric tools and improved databases, we now report identification of 311 proteins that copurify with splicing complexes assembled on two separate pre-mRNAs. All known essential human splicing factors were found, and 96 novel proteins were identified, of which 55 contain domains directly linking them to functions in splicing/RNA processing. We also detected 20 proteins related to transcription, which indicates a direct connection between this process and splicing. This investigation provides the most detailed inventory of human spliceosome-associated factors to date, and the data indicate a number of interesting links coordinating splicing with other steps in the gene expression pathway. PMID:12176931

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

    PubMed Central

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

    2014-01-01

    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. PMID:24914973

  8. 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.

  9. 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

  10. Functional mammalian spliceosomal complex E contains SMN complex proteins in addition to U1 and U2 snRNPs

    PubMed Central

    Makarov, Evgeny M.; Owen, Nicholas; Bottrill, Andrew; Makarova, Olga V.

    2012-01-01

    Spliceosomes remove introns from primary gene transcripts. They assemble de novo on each intron through a series of steps that involve the incorporation of five snRNP particles and multiple non-snRNP proteins. In mammals, all the intermediate complexes have been characterized on one transcript (MINX), with the exception of the very first, complex E. We have purified this complex by two independent procedures using antibodies to either U1-A or PRPF40A proteins, which are known to associate at an early stage of assembly. We demonstrate that the purified complexes are functional in splicing using commitment assays. These complexes contain components expected to be in the E complex and a number of previously unrecognized factors, including survival of motor neurons (SMN) and proteins of the SMN-associated complex. Depletion of the SMN complex proteins from nuclear extracts inhibits formation of the E complex and causes non-productive complexes to accumulate. This suggests that the SMN complex stabilizes the association of U1 and U2 snRNPs with pre-mRNA. In addition, the antibody to PRPF40A precipitated U2 snRNPs from nuclear extracts, indicating that PRPF40A associates with U2 snRNPs. PMID:22110043

  11. Major spliceosome defects cause male infertility and are associated with nonobstructive azoospermia in humans.

    PubMed

    Wu, Hao; Sun, Liwei; Wen, Yang; Liu, Yujuan; Yu, Jun; Mao, Feiyu; Wang, Ya; Tong, Chao; Guo, Xuejiang; Hu, Zhibin; Sha, Jiahao; Liu, Mingxi; Xia, Laixin

    2016-04-12

    Processing of pre-mRNA into mRNA is an important regulatory mechanism in eukaryotes that is mediated by the spliceosome, a huge and dynamic ribonucleoprotein complex. Splicing defects are implicated in a spectrum of human disease, but the underlying mechanistic links remain largely unresolved. Using a genome-wide association approach, we have recently identified single nucleotide polymorphisms in humans that associate with nonobstructive azoospermia (NOA), a common cause of male infertility. Here, using genetic manipulation of corresponding candidate loci in Drosophila, we show that the spliceosome component SNRPA1/U2A is essential for male fertility. Loss of U2A in germ cells of the Drosophila testis does not affect germline stem cells, but does result in the accumulation of mitotic spermatogonia that fail to differentiate into spermatocytes and mature sperm. Lack of U2A causes insufficient splicing of mRNAs required for the transition of germ cells from proliferation to differentiation. We show that germ cell-specific disruption of other components of the major spliceosome manifests with the same phenotype, demonstrating that mRNA processing is required for the differentiation of spermatogonia. This requirement is conserved, and expression of human SNRPA1 fully restores spermatogenesis in U2A mutant flies. We further report that several missense mutations in human SNRPA1 that inhibit the assembly of the major spliceosome dominantly disrupt spermatogonial differentiation in Drosophila. Collectively, our findings uncover a conserved and specific requirement for the major spliceosome during the transition from spermatogonial proliferation to differentiation in the male testis, suggesting that spliceosome defects affecting the differentiation of human spermatogonia contribute to NOA. PMID:27035939

  12. 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

  13. Biochemical and proteomic analysis of spliceosome factors interacting with intron-1 of human papillomavirus type-16.

    PubMed

    Martínez-Salazar, Martha; López-Urrutia, Eduardo; Arechaga-Ocampo, Elena; Bonilla-Moreno, Raul; Martínez-Castillo, Macario; Díaz-Hernández, Job; Del Moral-Hernández, Oscar; Cedillo-Barrón, Leticia; Martines-Juarez, Víctor; De Nova-Ocampo, Monica; Valdes, Jesús; Berumen, Jaime; Villegas-Sepúlveda, Nicolás

    2014-12-01

    The human papillomavirus type 16 (HPV-16) E6/E7 spliced transcripts are heterogeneously expressed in cervical carcinoma. The heterogeneity of the E6/E7 splicing profile might be in part due to the intrinsic variation of splicing factors in tumor cells. However, the splicing factors that bind the E6/E7 intron 1 (In-1) have not been defined. Therefore, we aimed to identify these factors; we used HeLa nuclear extracts (NE) for in vitro spliceosome assembly. The proteins were allowed to bind to an RNA/DNA hybrid formed by the In-1 transcript and a 5'-biotinylated DNA oligonucleotide complementary to the upstream exon sequence, which prevented interference in protein binding to the intron. The hybrid probes bound with the nuclear proteins were coupled to streptavidin magnetic beads for chromatography affinity purification. Proteins were eluted and identified by mass spectrometry (MS). Approximately 170 proteins were identified by MS, 80% of which were RNA binding proteins, including canonical spliceosome core components, helicases and regulatory splicing factors. The canonical factors were identified as components of the spliceosomal B-complex. Although 35-40 of the identified factors were cognate splicing factors or helicases, they have not been previously detected in spliceosome complexes that were assembled using in vivo or in vitro models. PMID:25108200

  14. Cwc2 and its human homologue RBM22 promote an active conformation of the spliceosome catalytic centre

    PubMed Central

    Rasche, Nicolas; Dybkov, Olexandr; Schmitzová, Jana; Akyildiz, Berktan; Fabrizio, Patrizia; Lührmann, Reinhard

    2012-01-01

    RNA-structural elements play key roles in pre-mRNA splicing catalysis; yet, the formation of catalytically competent RNA structures requires the assistance of spliceosomal proteins. We show that the S. cerevisiae Cwc2 protein functions prior to step 1 of splicing, and it is not required for the Prp2-mediated spliceosome remodelling that generates the catalytically active B* complex, suggesting that Cwc2 plays a more sophisticated role in the generation of a functional catalytic centre. In active spliceosomes, Cwc2 contacts catalytically important RNA elements, including the U6 internal stem-loop (ISL), and regions of U6 and the pre-mRNA intron near the 5′ splice site, placing Cwc2 at/near the spliceosome's catalytic centre. These interactions are evolutionarily conserved, as shown by studies with Cwc2's human counterpart RBM22, indicating that Cwc2/RBM22–RNA contacts are functionally important. We propose that Cwc2 induces an active conformation of the spliceosome's catalytic RNA elements. Thus, the function of RNA–RNA tertiary interactions within group II introns, namely to induce an active conformation of domain V, may be fulfilled by proteins that contact the functionally analogous U6-ISL, within the spliceosome. PMID:22246180

  15. 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

  16. Spliceosomal intronogenesis.

    PubMed

    Lee, Sujin; Stevens, Scott W

    2016-06-01

    The presence of intervening sequences, termed introns, is a defining characteristic of eukaryotic nuclear genomes. Once transcribed into pre-mRNA, these introns must be removed within the spliceosome before export of the processed mRNA to the cytoplasm, where it is translated into protein. Although intron loss has been demonstrated experimentally, several mysteries remain regarding the origin and propagation of introns. Indeed, documented evidence of gain of an intron has only been suggested by phylogenetic analyses. We report the use of a strategy that detects selected intron gain and loss events. We have experimentally verified, to our knowledge, the first demonstrations of intron transposition in any organism. From our screen, we detected two separate intron gain events characterized by the perfect transposition of a reporter intron into the yeast genes RPL8B and ADH2, respectively. We show that the newly acquired introns are able to be removed from their respective pre-mRNAs by the spliceosome. Additionally, the novel allele, RPL8Bint, is functional when overexpressed within the genome in a strain lacking the Rpl8 paralogue RPL8A, demonstrating that the gene targeted for intronogenesis is functional. PMID:27217561

  17. A human RNA helicase-like protein, HRH1, facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome.

    PubMed

    Ohno, M; Shimura, Y

    1996-04-15

    Because the nuclear export of mRNA occurs only after the splicing reaction is completed, intron-containing pre-mRNA does not normally appear in the cytoplasm. As a mechanism to secure this, intron-containing RNA is retained in the nucleus via formation of the spliceosome. Therefore, the process of releasing spliced mRNA from the spliceosome after completion of splicing is an essential step for triggering the nuclear export of the spliced mRNA. In budding yeast, RNA helicase-like protein Prp22 is implicated in this process. Here we demonstrate the function of HRH1, a human protein homologous to Prp22, in mammalian cells using dominant-negative HRH1++ mutants (dn-HRH1). dn-HRH1 protein stalls on the spliceosome and prevents release of the spliced RNA from the spliceosome in vitro. Expression of dn-HRH1 in mammalian cells leads to inhibition of splicing and to extensive nuclear export of unspliced pre-mRNA, probably because of the incapability of recycling spliceosome components that normally retain the pre-mRNA in the nucleus. The arginine/serine-rich domain (RS domain) of HRH1, which is missing in Prp22, confers a nuclear localization signal, and appears to facilitate the interaction of HRH1 with the spliceosome. This is the first report on a bona fide mammalian homolog of yeast Prp splicing factor, and also on a mammalian RNA helicase-like splicing factor. PMID:8608946

  18. 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

  19. The N-terminus of Prp1 (Prp6/U5-102 K) is essential for spliceosome activation in vivo

    PubMed Central

    Lützelberger, Martin; Bottner, Claudia A.; Schwelnus, Wiebke; Zock-Emmenthal, Susanne; Razanau, Aleh; Käufer, Norbert F.

    2010-01-01

    The spliceosomal protein Prp1 (Prp6/U5-102 K) is necessary for the integrity of pre-catalytic spliceosomal complexes. We have identified a novel regulatory function for Prp1. Expression of mutations in the N-terminus of Prp1 leads to the accumulation of pre-catalytic spliceosomal complexes containing the five snRNAs U1, U2, U5 and U4/U6 and pre-mRNAs. The mutations in the N-terminus, which prevent splicing to occur, include in vitro and in vivo identified phosphorylation sites of Prp4 kinase. These sites are highly conserved in the human ortholog U5-102 K. The results presented here demonstrate that structural integrity of the N-terminus is required to mediate a splicing event, but is not necessary for the assembly of spliceosomes. PMID:20007600

  20. 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.

  1. 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

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

    PubMed

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

    2016-02-01

    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

  3. 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

  4. 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

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

    PubMed Central

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

    2016-01-01

    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

  6. 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

  7. U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer's disease.

    PubMed

    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

    2013-10-01

    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

  8. Crystal structure of a core spliceosomal protein interface.

    PubMed

    Schellenberg, Matthew J; Edwards, Ross A; Ritchie, Dustin B; Kent, Oliver A; Golas, Monika M; Stark, Holger; Lührmann, Reinhard; Glover, J N Mark; MacMillan, Andrew M

    2006-01-31

    The precise excision of introns from precursor mRNAs (pre-mRNAs) in eukaryotes is accomplished by the spliceosome, a complex assembly containing five small nuclear ribonucleoprotein (snRNP) particles. Human p14, a component of the spliceosomal U2 and U11/U12 snRNPs, has been shown to associate directly with the pre-mRNA branch adenosine early in spliceosome assembly and within the fully assembled spliceosome. Here we report the 2.5-A crystal structure of a complex containing p14 and a peptide derived from the p14-associated U2 snRNP component SF3b155. p14 contains an RNA recognition motif (RRM), the surface of which is largely occluded by a C-terminal alpha-helix and a portion of the SF3b155 peptide. An analysis of RNA.protein crosslinking to wild-type and mutant p14 shows that the branch adenosine directly interacts with a conserved aromatic within a pocket on the surface of the complex. This result, combined with a comparison of the structure with known RRMs and pseudoRRMs as well as model-building by using the electron cryomicroscopy structure of a spliceosomal U11/U12 di-snRNP, suggests that p14.SF3b155 presents a noncanonical surface for RNA recognition at the heart of the mammalian spliceosome. PMID:16432215

  9. Conserved structure of Snu13 from the highly reduced spliceosome of Cyanidioschyzon merolae.

    PubMed

    Black, C S; Garside, E L; MacMillan, A M; Rader, S D

    2016-04-01

    Structural and functional analysis of proteins involved in pre-mRNA splicing is challenging because of the complexity of the splicing machinery, known as the spliceosome. Bioinformatic, proteomic, and biochemical analyses have identified a minimal spliceosome in the red alga Cyanidioschyzon merolae. This spliceosome consists of only 40 core proteins, compared to ∼ 70 in S. cerevisiae (yeast) and ∼ 150 in humans. We report the X-ray crystallographic analysis of C. merolae Snu13 (CmSnu13), a key component of the assembling spliceosome, and present evidence for conservation of Snu13 function in this algal splicing pathway. The near identity of CmSnu13's three-dimensional structure to yeast and human Snu13 suggests that C. merolae should be an excellent model system for investigating the structure and function of the conserved core of the spliceosome. PMID:26833716

  10. Expression of a human U1 RNA gene introduced into mouse cells via bovine papillomavirus DNA vectors.

    PubMed Central

    Schenborn, E T; Lund, E; Mitchen, J L; Dahlberg, J E

    1985-01-01

    We introduced a gene for human U1 small nuclear RNA, HU1-1, into mouse C127 cells via bovine papillomavirus (BPV) vectors. After transfection, up to 15% of the total U1 RNA in transformed cells was encoded by the introduced human genes. High levels of expression of the human gene were observed when the recombinant viral DNAs were maintained either as plasmids or after integration into high-molecular-weight DNA. As few as 400 and 35 base pairs of 5' and 3' flanking region sequences, respectively, were sufficient for transcription of human U1 RNA, and no increase in the level of expression was observed with HU1-1 DNA containing several kilobases of flanking region sequences. Several of the transformed cell lines contained the recombinant BPV DNA apparently integrated into the host genome. Integration or rearrangement or both of the U1-BPV DNA was promoted when the HU1-1 gene was positioned at the BamHI site downstream of the BPV transforming region. At least two variants of the U1-BPV DNAs were able to cause morphological transformation of cells despite the fact that these DNAs lacked a BPV transcriptional enhancer element. Images PMID:2412107

  11. Nuclear cyclophilins affect spliceosome assembly and function in vitro

    PubMed Central

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

    2015-01-01

    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. PMID:25967372

  12. 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. PMID:25865758

  13. 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

  14. Re-refinement of the spliceosomal U4 snRNP core-domain structure

    PubMed Central

    Li, Jade; Leung, Adelaine K.; Kondo, Yasushi; Oubridge, Chris; Nagai, Kiyoshi

    2016-01-01

    The core domain of small nuclear ribonucleoprotein (snRNP), comprised of a ring of seven paralogous proteins bound around a single-stranded RNA sequence, functions as the assembly nucleus in the maturation of U1, U2, U4 and U5 spliceosomal snRNPs. The structure of the human U4 snRNP core domain was initially solved at 3.6 Å resolution by experimental phasing using data with tetartohedral twinning. Molecular replacement from this model followed by density modification using untwinned data recently led to a structure of the minimal U1 snRNP at 3.3 Å resolution. With the latter structure providing a search model for molecular replacement, the U4 core-domain structure has now been re-refined. The U4 Sm site-sequence AAUUUUU has been shown to bind to the seven Sm proteins SmF–SmE–SmG–SmD3–SmB–SmD1–SmD2 in an identical manner as the U1 Sm-site sequence AAUUUGU, except in SmD1 where the bound U replaces G. The progression from the initial to the re-refined structure exemplifies a tortuous route to accuracy: where well diffracting crystals of complex assemblies are initially unavailable, the early model errors are rectified by exploiting preliminary interpretations in further experiments involving homologous structures. New insights are obtained from the more accurate model. PMID:26894541

  15. 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

  16. Spliceosomal snRNAs in the unicellular eukaryote Trichomonas vaginalis are structurally conserved but lack a 5′-cap structure

    PubMed Central

    Simoes-Barbosa, Augusto; Meloni, Dionigia; Wohlschlegel, James A.; Konarska, Maria M.; Johnson, Patricia J.

    2008-01-01

    Few genes in the divergent eukaryote Trichomonas vaginalis have introns, despite the unusually large gene repertoire of this human-infective parasite. These introns are characterized by extended conserved regulatory motifs at the 5′ and 3′ boundaries, a feature shared with another divergent eukaryote, Giardia lamblia, but not with metazoan introns. This unusual characteristic of T. vaginalis introns led us to examine spliceosomal small nuclear RNAs (snRNAs) predicted to mediate splicing reactions via interaction with intron motifs. Here we identify T. vaginalis U1, U2, U4, U5, and U6 snRNAs, present predictions of their secondary structures, and provide evidence for interaction between the U2/U6 snRNA complex and a T. vaginalis intron. Structural models predict that T. vaginalis snRNAs contain conserved sequences and motifs similar to those found in other examined eukaryotes. These data indicate that mechanisms of intron recognition as well as coordination of the two catalytic steps of splicing have been conserved throughout eukaryotic evolution. Unexpectedly, we found that T. vaginalis spliceosomal snRNAs lack the 5′ trimethylguanosine cap typical of snRNAs and appear to possess unmodified 5′ ends. Despite the lack of a cap structure, U1, U2, U4, and U5 genes are transcribed by RNA polymerase II, whereas the U6 gene is transcribed by RNA polymerase III. PMID:18596255

  17. Defining the orientation of the human U1A RBD1 on its UTR by tethered-EDTA(Fe) cleavage.

    PubMed Central

    Beck, D L; Stump, W T; Hall, K B

    1998-01-01

    The N-terminal RNA binding domain of the human U1A protein (RBD1) specifically binds an RNA hairpin of U1 snRNA as well as two internal loops in the 3' UTR of its own mRNA. Here, a single cysteine has been introduced into Loop 1 of RBD1, which is subsequently used to attach (EDTA-2-aminoethyl) 2-pyridyl disulfide-Fe3+ (EPD-Fe). This EDTA-Fe derivative is used to generate hydroxyl radicals to cleave the proximal RNA sugar-phosphate backbone in the RNA-RBD complexes. RBD1(K20C)-EPD-Fe cleaves the 5' strand of the RNA hairpin stem, centered four base pairs away from the base of the loop, and cleaves the UTR in two places, again centered on the 5' side of the fourth base pair from each internal loop. These data, extrapolated to the position of Lys 20 in RBD1, orient the two proteins bound to the UTR, and provide direct biochemical evidence for the proposed model of the RBD1:UTR complex. PMID:9510334

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

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

    PubMed

    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. 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

  5. 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

  6. Expression of U1 small nuclear ribonucleoprotein 70K antisense transcript using APETALA3 promoter suppresses the development of sepals and petals.

    PubMed

    Golovkin, Maxim; Reddy, Anireddy S N

    2003-08-01

    U1 small nuclear ribonucleoprotein (snRNP)-70K (U1-70K), a U1 snRNP-specific protein, is involved in the early stages of spliceosome formation. In non-plant systems, it is involved in constitutive and alternative splicing. It has been shown that U1snRNP is dispensable for in vitro splicing of some animal pre-mRNAs, and inactivation of U1-70K in yeast (Saccharomyces cerevisiae) is not lethal. As in yeast and humans (Homo sapiens), plant U1-70K is coded by a single gene. In this study, we blocked the expression of Arabidopsis U1-70K in petals and stamens by expressing U1-70K antisense transcript using the AP3 (APETALA3) promoter specific to these floral organs. Flowers of transgenic Arabidopsis plants expressing U1-70K antisense transcript showed partially developed stamens and petals that are arrested at different stages of development. In some transgenic lines, flowers have rudimentary petals and stamens and are male sterile. The severity of the phenotype is correlated with the level of the antisense transcript. Molecular analysis of transgenic plants has confirmed that the observed phenotype is not due to disruption of whorl-specific homeotic genes, AP3 or PISTILLATA, responsible for petal and stamen development. The AP3 transcript was not detected in transgenic flowers with severe phenotype. Flowers of Arabidopsis plants transformed with a reporter gene driven by the same promoter showed no abnormalities. These results show that U1-70K is necessary for the development of sepals and petals and is an essential gene in plants. PMID:12913145

  7. Tumor suppressor microRNAs are downregulated in myelodysplastic syndrome with spliceosome mutations

    PubMed Central

    Aslan, Derya; Garde, Christian; Nygaard, Mette Katrine; Helbo, Alexandra Søgaard; Dimopoulos, Konstantinos; Hansen, Jakob Werner; Severinsen, Marianne Tang; Treppendahl, Marianne Bach; Sjø, Lene Dissing; Grønbæk, Kirsten; Kristensen, Lasse Sommer

    2016-01-01

    Spliceosome mutations are frequently observed in patients with myelodysplastic syndromes (MDS). However, it is largely unknown how these mutations contribute to the disease. MicroRNAs (miRNAs) are small noncoding RNAs, which have been implicated in most human cancers due to their role in post transcriptional gene regulation. The aim of this study was to analyze the impact of spliceosome mutations on the expression of miRNAs in a cohort of 34 MDS patients. In total, the expression of 76 miRNAs, including mirtrons and splice site overlapping miRNAs, was accurately quantified using reverse transcriptase quantitative PCR. The majority of the studied miRNAs have previously been implicated in MDS. Stably expressed miRNA genes for normalization of the data were identified using GeNorm and NormFinder algorithms. High-resolution melting assays covering all mutational hotspots within SF3B1, SRSF2, and U2AF1 (U2AF35) were developed, and all detected mutations were confirmed by Sanger sequencing. Overall, canonical miRNAs were downregulated in spliceosome mutated samples compared to wild-type (P = 0.002), and samples from spliceosome mutated patients clustered together in hierarchical cluster analyses. Among the most downregulated miRNAs were several tumor-suppressor miRNAs, including several let-7 family members, miR-423, and miR-103a. Finally, we observed that the predicted targets of the most downregulated miRNAs were involved in apoptosis, hematopoiesis, and acute myeloid leukemia among other cancer- and metabolic pathways. Our data indicate that spliceosome mutations may play an important role in MDS pathophysiology by affecting the expression of tumor suppressor miRNA genes involved in the development and progression of MDS. PMID:26848861

  8. Graded requirement for the spliceosome in cell cycle progression

    PubMed Central

    Karamysheva, Zemfira; Díaz-Martínez, Laura A; Warrington, Ross; Yu, Hongtao

    2015-01-01

    Genome stability is ensured by multiple surveillance mechanisms that monitor the duplication, segregation, and integrity of the genome throughout the cell cycle. Depletion of components of the spliceosome, a macromolecular machine essential for mRNA maturation and gene expression, has been associated with increased DNA damage and cell cycle defects. However, the specific role for the spliceosome in these processes has remained elusive, as different cell cycle defects have been reported depending on the specific spliceosome subunit depleted. Through a detailed cell cycle analysis after spliceosome depletion, we demonstrate that the spliceosome is required for progression through multiple phases of the cell cycle. Strikingly, the specific cell cycle phenotype observed after spliceosome depletion correlates with the extent of depletion. Partial depletion of a core spliceosome component results in defects at later stages of the cell cycle (G2 and mitosis), whereas a more complete depletion of the same component elicits an early cell cycle arrest in G1. We propose a quantitative model in which different functional dosages of the spliceosome are required for different cell cycle transitions. PMID:25892155

  9. 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

  10. SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly

    PubMed Central

    Grillari, Johannes; Ajuh, Paul; Stadler, Guido; Löscher, Marlies; Voglauer, Regina; Ernst, Wolfgang; Chusainow, Janet; Eisenhaber, Frank; Pokar, Marion; Fortschegger, Klaus; Grey, Martin; Lamond, Angus I.; Katinger, Hermann

    2005-01-01

    We have isolated the human protein SNEV as downregulated in replicatively senescent cells. Sequence homology to the yeast splicing factor Prp19 suggested that SNEV might be the orthologue of Prp19 and therefore might also be involved in pre-mRNA splicing. We have used various approaches including gene complementation studies in yeast using a temperature sensitive mutant with a pleiotropic phenotype and SNEV immunodepletion from human HeLa nuclear extracts to determine its function. A human–yeast chimera was indeed capable of restoring the wild-type phenotype of the yeast mutant strain. In addition, immunodepletion of SNEV from human nuclear extracts resulted in a decrease of in vitro pre-mRNA splicing efficiency. Furthermore, as part of our analysis of protein–protein interactions within the CDC5L complex, we found that SNEV interacts with itself. The self-interaction domain was mapped to amino acids 56–74 in the protein's sequence and synthetic peptides derived from this region inhibit in vitro splicing by surprisingly interfering with spliceosome formation and stability. These results indicate that SNEV is the human orthologue of yeast PRP19, functions in splicing and that homo-oligomerization of SNEV in HeLa nuclear extract is essential for spliceosome assembly and that it might also be important for spliceosome stability. PMID:16332694

  11. The Spliceosome: The Ultimate RNA Chaperone and Sculptor.

    PubMed

    Papasaikas, Panagiotis; Valcárcel, Juan

    2016-01-01

    The spliceosome, one of the most complex machineries of eukaryotic cells, removes intronic sequences from primary transcripts to generate functional messenger and long noncoding RNAs (lncRNA). Genetic, biochemical, and structural data reveal that the spliceosome is an RNA-based enzyme. Striking mechanistic and structural similarities strongly argue that pre-mRNA introns originated from self-catalytic group II ribozymes. However, in the spliceosome, protein components organize and activate the catalytic-site RNAs, and recognize and pair together splice sites at intron boundaries. The spliceosome is a dynamic, reversible, and flexible machine that chaperones small nuclear (sn) RNAs and a variety of pre-mRNA sequences into conformations that enable intron removal. This malleability likely contributes to the regulation of alternative splicing, a prevalent process contributing to cell differentiation, homeostasis, and disease. PMID:26682498

  12. Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial Dysostosis with Microcephaly

    PubMed Central

    Lines, Matthew A.; Huang, Lijia; Schwartzentruber, Jeremy; Douglas, Stuart L.; Lynch, Danielle C.; Beaulieu, Chandree; Guion-Almeida, Maria Leine; Zechi-Ceide, Roseli Maria; Gener, Blanca; Gillessen-Kaesbach, Gabriele; Nava, Caroline; Baujat, Geneviève; Horn, Denise; Kini, Usha; Caliebe, Almuth; Alanay, Yasemin; Utine, Gulen Eda; Lev, Dorit; Kohlhase, Jürgen; Grix, Arthur W.; Lohmann, Dietmar R.; Hehr, Ute; Böhm, Detlef; Majewski, Jacek; Bulman, Dennis E.; Wieczorek, Dagmar; Boycott, Kym M.

    2012-01-01

    Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. PMID:22305528

  13. 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.

  14. U1A Complex

    ScienceCinema

    None

    2015-01-09

    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.

  15. U1 RNA Induces Innate Immunity Signaling

    PubMed Central

    Hoffman, Robert W.; Gazitt, Tal; Foecking, Mark F.; Ortmann, Robert A.; Misfeldt, Michael; Jorgenson, Rebecca; Young, Steven L.; Greidinger, Eric L.

    2006-01-01

    Objective The U1–70-kd RNP is a prominent target of autoimmunity in connective tissue diseases. In this study, we explored whether its endogenous ligand, U1 RNA, mediates a proimmune signal and may be immunogenic. Methods We assayed the proliferation of control and MyD88-knockout splenocytes in response to in vitro–synthesized U1 RNA, and measured interleukin-6 (IL-6) and IL-8 secretion induced by U1 RNA in a human cell line competent for signaling through Toll-like receptor 3 (TLR-3) and TLR-5. Results Treatment with U1 RNA or with poly(I-C), a known agonist of TLR-3, induced approximately twice as much control splenocyte proliferation as did treatment with RNase-digested U1 RNA. Proliferation in response to either poly(I-C) or U1 RNA by MyD88-knockout splenocytes was similarly attenuated. Similar to poly(I-C), U1 RNA induced significant secretion of both IL-6 and IL-8 from a TLR-3–expressing human cell line; in contrast, the TLR-5 agonist flagellin induced predominantly IL-8 secretion. Pretreatment of U1 RNA with RNase abolished IL-6 and IL-8 secretion. Conclusion U1 RNA is capable of inducing manifestations consistent with TLR-3 activation. The ability of U1 RNA (which has a substantial double-stranded secondary structure) to activate TLR-3 may contribute to the immunogenicity of the U1–70-kd autoantigen. Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins. PMID:15457457

  16. Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition.

    PubMed

    Kondo, Yasushi; Oubridge, Chris; van Roon, Anne-Marie M; Nagai, Kiyoshi

    2015-01-01

    U1 snRNP binds to the 5' exon-intron junction of pre-mRNA and thus plays a crucial role at an early stage of pre-mRNA splicing. We present two crystal structures of engineered U1 sub-structures, which together reveal at atomic resolution an almost complete network of protein-protein and RNA-protein interactions within U1 snRNP, and show how the 5' splice site of pre-mRNA is recognised by U1 snRNP. The zinc-finger of U1-C interacts with the duplex between pre-mRNA and the 5'-end of U1 snRNA. The binding of the RNA duplex is stabilized by hydrogen bonds and electrostatic interactions between U1-C and the RNA backbone around the splice junction but U1-C makes no base-specific contacts with pre-mRNA. The structure, together with RNA binding assays, shows that the selection of 5'-splice site nucleotides by U1 snRNP is achieved predominantly through basepairing with U1 snRNA whilst U1-C fine-tunes relative affinities of mismatched 5'-splice sites. PMID:25555158

  17. Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5′ splice site recognition

    PubMed Central

    Kondo, Yasushi; Oubridge, Chris; van Roon, Anne-Marie M; Nagai, Kiyoshi

    2015-01-01

    U1 snRNP binds to the 5′ exon-intron junction of pre-mRNA and thus plays a crucial role at an early stage of pre-mRNA splicing. We present two crystal structures of engineered U1 sub-structures, which together reveal at atomic resolution an almost complete network of protein–protein and RNA-protein interactions within U1 snRNP, and show how the 5′ splice site of pre-mRNA is recognised by U1 snRNP. The zinc-finger of U1-C interacts with the duplex between pre-mRNA and the 5′-end of U1 snRNA. The binding of the RNA duplex is stabilized by hydrogen bonds and electrostatic interactions between U1-C and the RNA backbone around the splice junction but U1-C makes no base-specific contacts with pre-mRNA. The structure, together with RNA binding assays, shows that the selection of 5′-splice site nucleotides by U1 snRNP is achieved predominantly through basepairing with U1 snRNA whilst U1-C fine-tunes relative affinities of mismatched 5′-splice sites. DOI: http://dx.doi.org/10.7554/eLife.04986.001 PMID:25555158

  18. New insights into the spliceosome by single molecule fluorescence microscopy.

    PubMed

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

    2011-12-01

    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. Because of 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

  19. Analysis of spliceosomal proteins in Trypanosomatids reveals novel functions in mRNA processing.

    PubMed

    Tkacz, Itai Dov; Gupta, Sachin Kumar; Volkov, Vadim; Romano, Mali; Haham, Tomer; Tulinski, Pawel; Lebenthal, Ilana; Michaeli, Shulamit

    2010-09-01

    In trypanosomatids, all mRNAs are processed via trans-splicing, although cis-splicing also occurs. In trans-splicing, a common small exon, the spliced leader (SL), which is derived from a small SL RNA species, is added to all mRNAs. Sm and Lsm proteins are core proteins that bind to U snRNAs and are essential for both these splicing processes. In this study, SmD3- and Lsm3-associated complexes were purified to homogeneity from Leishmania tarentolae. The purified complexes were analyzed by mass spectrometry, and 54 and 39 proteins were purified from SmD3 and Lsm complexes, respectively. Interestingly, among the proteins purified from Lsm3, no mRNA degradation factors were detected, as in Lsm complexes from other eukaryotes. The U1A complex was purified and mass spectrometry analysis identified, in addition to U1 small nuclear ribonucleoprotein (snRNP) proteins, additional co-purified proteins, including the polyadenylation factor CPSF73. Defects observed in cells silenced for U1 snRNP proteins suggest that the U1 snRNP functions exclusively in cis-splicing, although U1A also participates in polyadenylation and affects trans-splicing. The study characterized several trypanosome-specific nuclear factors involved in snRNP biogenesis, whose function was elucidated in Trypanosoma brucei. Conserved factors, such as PRP19, which functions at the heart of every cis-spliceosome, also affect SL RNA modification; GEMIN2, a protein associated with SMN (survival of motor neurons) and implicated in selective association of U snRNA with core Sm proteins in trypanosomes, is a master regulator of snRNP assembly. This study demonstrates the existence of trypanosomatid-specific splicing factors but also that conserved snRNP proteins possess trypanosome-specific functions. PMID:20592024

  20. 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

  1. Use of the U1A Protein to Facilitate Crystallization and Structure Determination of Large RNAs.

    PubMed

    Ferré-D'Amaré, Adrian R

    2016-01-01

    The preparation of well-ordered crystals of RNAs with complex three-dimensional architecture can be facilitated by engineering a binding site for the spliceosomal protein U1A into a functionally and structurally dispensable stem-loop of the RNA of interest. Once suitable crystals are obtained, the U1A protein, of known structure, can be employed to facilitate preparation of heavy atom or anomalously scattering atom derivatives, or as a source of partial model phases for the molecular replacement method. Here, we describe the methods for making U1A preparations suitable for cocrystallization with RNA. As an example, the cocrystallization of the tetracycline aptamer with U1A is also described. PMID:26227038

  2. Rhodamine 123 phototoxicity in laser-irradiated MGH-U1 human carcinoma cells studied in vitro by electron microscopy and confocal laser scanning microscopy

    SciTech Connect

    Shea, C.R.; Sherwood, M.E.; Flotte, T.J.; Chen, N.; Scholz, M.; Hasan, T. )

    1990-07-01

    Rhodamine 123 (R123) is a permeant, cationic, fluorescent dye that localizes preferentially within mitochondria of living carcinoma cells. MGH-U1 human bladder carcinoma cells incubated in vitro with 10 microM R123 for 30 min and then irradiated at 514.5 nm with an argon ion laser underwent selective, phototoxic injury to mitochondria. Ultrastructurally, treatment with R123 plus irradiation with 10 J/cm2 caused selective, progressive mitochondrial alterations consisting of disruption of cristae, vacuolization, swelling, increasing numbers of ring-shaped and angulated mitochondria at 4 to 8 h after irradiation, and obliteration of many mitochondria at 24 to 48 h. Confocal laser scanning microscopy after treatment with R123 plus irradiation with 10 to 30 J/cm2 demonstrated altered uptake and localization of subsequently administered R123, accompanied by striking mitochondrial fragmentation. Irradiation caused a dose-dependent depletion of extractable R123, due to a photosensitized efflux that began immediately and progressed by 4 h after irradiation with 10 to 30 J/cm2; further uptake after reincubation in the presence of R123 was also quantitatively impaired in cells previously irradiated with 30 J/cm2.

  3. 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.

  4. Vought XF3U-1

    NASA Technical Reports Server (NTRS)

    1933-01-01

    Vought XF3U-1: The Vought XF3U-1 was tested in Langley's 30 x 60 Full Scale Tunnel in 1933. The XF3U-1 was built in response to a Navy specification for a two-seat fighter. This aircraft was later used as an engine testbed. The design was revised for a scout bomber requirement and in this form saw service as the SBU.

  5. Vought XSB3U-1

    NASA Technical Reports Server (NTRS)

    1938-01-01

    Vought XSB3U-1: This Navy biplane scout bomber was the first biplane built by Vought with retractable gear. Note that his XSB3U-1 has a test boom off the left upper wing. The bomber was at Langley for NACA's investigation of tail loads.

  6. 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

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

    PubMed

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

    2015-02-01

    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

  8. Imaging dynamic interactions between spliceosomal proteins and pre-mRNA in living cells.

    PubMed

    Rino, José; Martin, Robert M; Carvalho, Teresa; Carmo-Fonseca, Maria

    2014-02-01

    The ability to observe protein dynamics in living cells is critical for the mechanistic understanding of highly flexible biological processes such as pre-mRNA splicing by the spliceosome. Splicing relies on intricate RNA and protein networks that are repeatedly rearranged during spliceosome assembly. Here we describe a method based on fluorescence microscopy that has been used by our and other laboratories to study interaction of spliceosomal proteins with nascent pre-mRNA in living cells. The method involves co-expressing in mammalian cells the target pre-mRNA labeled with one color, and the spliceosomal protein tagged with another color. The diffusion coefficient of the protein as well as its association and dissociation rates with the pre-mRNA are estimated by fluorescence recovery after photobleaching (FRAP) or photoactivation. PMID:23969316

  9. Spliceosomal DEAH-Box ATPases Remodel Pre-mRNA to Activate Alternative Splice Sites.

    PubMed

    Semlow, Daniel R; Blanco, Mario R; Walter, Nils G; Staley, Jonathan P

    2016-02-25

    During pre-mRNA splicing, a central step in the expression and regulation of eukaryotic genes, the spliceosome selects splice sites for intron excision and exon ligation. In doing so, the spliceosome must distinguish optimal from suboptimal splice sites. At the catalytic stage of splicing, suboptimal splice sites are repressed by the DEAH-box ATPases Prp16 and Prp22. Here, using budding yeast, we show that these ATPases function further by enabling the spliceosome to search for and utilize alternative branch sites and 3' splice sites. The ATPases facilitate this search by remodeling the splicing substrate to disengage candidate splice sites. Our data support a mechanism involving 3' to 5' translocation of the ATPases along substrate RNA and toward a candidate site, but, surprisingly, not across the site. Thus, our data implicate DEAH-box ATPases in acting at a distance by pulling substrate RNA from the catalytic core of the spliceosome. PMID:26919433

  10. Functional splicing network reveals extensive regulatory potential of the core spliceosomal machinery.

    PubMed

    Papasaikas, Panagiotis; Tejedor, J Ramón; Vigevani, Luisa; Valcárcel, Juan

    2015-01-01

    Pre-mRNA splicing relies on the poorly understood dynamic interplay between >150 protein components of the spliceosome. The steps at which splicing can be regulated remain largely unknown. We systematically analyzed the effect of knocking down the components of the splicing machinery on alternative splicing events relevant for cell proliferation and apoptosis and used this information to reconstruct a network of functional interactions. The network accurately captures known physical and functional associations and identifies new ones, revealing remarkable regulatory potential of core spliceosomal components, related to the order and duration of their recruitment during spliceosome assembly. In contrast with standard models of regulation at early steps of splice site recognition, factors involved in catalytic activation of the spliceosome display regulatory properties. The network also sheds light on the antagonism between hnRNP C and U2AF, and on targets of antitumor drugs, and can be widely used to identify mechanisms of splicing regulation. PMID:25482510

  11. U1h shaft project

    SciTech Connect

    Brian Briggs; R. G. Musick

    2000-06-30

    The U1h shaft project is a design/build subcontract to construct one 20 foot (ft) finished diameter shaft to a depth of 1,045 ft at the Nevada Test Site. Atkinson Construction was subcontracted by Bechtel Nevada to construct the U1h Shaft for the Department of Energy. The project consists of furnishing and installing the sinking plant, construction of the 1,045 ft of concrete lined shaft, development of a shaft station at a depth of 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 should be of interest to those involved with the construction of relatively deep shafts and underground excavations.

  12. 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

  13. 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

  14. Structural features important for the U12 snRNA binding and minor spliceosome assembly of Arabidopsis U11/U12-small nuclear ribonucleoproteins.

    PubMed

    Park, Su Jung; Jung, Hyun Ju; Nguyen Dinh, Sy; Kang, Hunseung

    2016-07-01

    Although seven proteins unique to U12 intron-specific minor spliceosomes, denoted as U11/U12-65K, -59K, -48K, -35K, -31K, -25K, and -20K, have been identified in humans and the roles of some of them have been demonstrated, the functional role of most of these proteins in plants is not understood. A recent study demonstrated that Arabidopsis U11/U12-65K is essential for U12 intron splicing and normal plant development. However, the structural features and sequence motifs important for 65 K binding to U12 snRNA and other spliceosomal proteins remain unclear. Here, we demonstrated by domain-deletion analysis that the C-terminal region of the 65 K protein bound specifically to the stem-loop III of U12 snRNA, whereas the N-terminal region of the 65 K protein was responsible for interacting with the 59 K protein. Analysis of the interactions between each snRNP protein using yeast two-hybrid analysis and in planta bimolecular fluorescence complementation and luciferase complementation imaging assays demonstrated that the core interactions among the 65 K, 59 K, and 48 K proteins were conserved between plants and animals, and multiple interactions were observed among the U11/U12-snRNP proteins. Taken together, these results reveal that U11/U12-65K is an indispensible component of the minor spliceosome complex by binding to both U11/U12-59K and U12 snRNA, and that multiple interactions among the U11/U12-snRNP proteins are necessary for minor spliceosome assembly. PMID:27232356

  15. 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

  16. Aberrant 3' oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia.

    PubMed

    Hilcenko, Christine; Simpson, Paul J; Finch, Andrew J; Bowler, Frank R; Churcher, Mark J; Jin, Li; Packman, Len C; Shlien, Adam; Campbell, Peter; Kirwan, Michael; Dokal, Inderjeet; Warren, Alan J

    2013-02-01

    The recessive disorder poikiloderma with neutropenia (PN) is caused by mutations in the C16orf57 gene that encodes the highly conserved USB1 protein. Here, we present the 1.1 Å resolution crystal structure of human USB1, defining it as a member of the LigT-like superfamily of 2H phosphoesterases. We show that human USB1 is a distributive 3'-5' exoribonuclease that posttranscriptionally removes uridine and adenosine nucleosides from the 3' end of spliceosomal U6 small nuclear RNA (snRNA), directly catalyzing terminal 2', 3' cyclic phosphate formation. USB1 measures the appropriate length of the U6 oligo(U) tail by reading the position of a key adenine nucleotide (A102) and pausing 5 uridine residues downstream.We show that the 3' ends of U6 snRNA in PN patient lymphoblasts are elongated and unexpectedly carry nontemplated 3' oligo(A) tails that are characteristic of nuclear RNA surveillance targets. Thus, our study reveals a novel quality control pathway in which posttranscriptional 3'-end processing by USB1 protects U6 snRNA from targeting and destruction by the nuclear exosome. Our data implicate aberrant oligoadenylation of U6 snRNA in the pathogenesis of the leukemia predisposition disorder PN. PMID:23190533

  17. The Spliceosomal Phosphopeptide P140 Controls the Lupus Disease by Interacting with the HSC70 Protein and via a Mechanism Mediated by γδ T Cells

    PubMed Central

    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 γδ 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. PMID:19390596

  18. Plant Spliceosomal Introns: Not Only Cut and Paste

    PubMed Central

    Morello, L; Breviario, D

    2008-01-01

    Spliceosomal introns in higher eukaryotes are present in a high percentage of protein coding genes and represent a high proportion of transcribed nuclear DNA. In the last fifteen years, a growing mass of data concerning functional roles carried out by such intervening sequences elevated them from a selfish burden carried over by the nucleus to important active regulatory elements. Introns mediate complex gene regulation via alternative splicing; they may act in cis as expression enhancers through IME (intron-mediated enhancement of gene expression) and in trans as negative regulators through the generation of intronic microRNA. Furthermore, some introns also contain promoter sequences for alternative transcripts. Nevertheless, such regulatory roles do not require long conserved sequences, so that introns are relatively free to evolve faster than exons: this feature makes them important tools for evolutionary studies and provides the basis for the development of DNA molecular markers for polymorphisms detection. A survey of introns functions in the plant kingdom is presented. PMID:19452040

  19. Spliceosomal introns as tools for genomic and evolutionary analysis

    PubMed Central

    Irimia, Manuel; Roy, Scott William

    2008-01-01

    Over the past 5 years, the availability of dozens of whole genomic sequences from a wide variety of eukaryotic lineages has revealed a very large amount of information about the dynamics of intron loss and gain through eukaryotic history, as well as the evolution of intron sequences. Implicit in these advances is a great deal of information about the structure and evolution of surrounding sequences. Here, we review the wealth of ways in which structures of spliceosomal introns as well as their conservation and change through evolution may be harnessed for evolutionary and genomic analysis. First, we discuss uses of intron length distributions and positions in sequence assembly and annotation, and for improving alignment of homologous regions. Second, we review uses of introns in evolutionary studies, including the utility of introns as indicators of rates of sequence evolution, for inferences about molecular evolution, as signatures of orthology and paralogy, and for estimating rates of nucleotide substitution. We conclude with a discussion of phylogenetic methods utilizing intron sequences and positions. PMID:18263615

  20. A Stochastic View of Spliceosome Assembly and Recycling in the Nucleus

    PubMed Central

    Desterro, Joana M. P; Lührmann, Reinhard; Carmo-Fonseca, Maria

    2007-01-01

    How splicing factors are recruited to nascent transcripts in the nucleus in order to assemble spliceosomes on newly synthesised pre-mRNAs is unknown. To address this question, we compared the intranuclear trafficking kinetics of small nuclear ribonucleoprotein particles (snRNP) and non-snRNP proteins in the presence and absence of splicing activity. Photobleaching experiments clearly show that spliceosomal proteins move continuously throughout the entire nucleus independently of ongoing transcription or splicing. Using quantitative experimental data, a mathematical model was applied for spliceosome assembly and recycling in the nucleus. The model assumes that splicing proteins move by Brownian diffusion and interact stochastically with binding sites located at different subnuclear compartments. Inhibition of splicing, which reduces the number of pre-mRNA binding sites available for spliceosome assembly, was modeled as a decrease in the on-rate binding constant in the nucleoplasm. Simulation of microscopy experiments before and after splicing inhibition yielded results consistent with the experimental observations. Taken together, our data argue against the view that spliceosomal components are stored in nuclear speckles until a signal triggers their recruitment to nascent transcripts. Rather, the results suggest that splicing proteins are constantly diffusing throughout the entire nucleus and collide randomly and transiently with pre-mRNAs. PMID:17967051

  1. Spliceosome-mediated decay (SMD) regulates expression of nonintronic genes in budding yeast

    PubMed Central

    Volanakis, Adam; Passoni, Monica; Hector, Ralph D.; Shah, Sneha; Kilchert, Cornelia; Granneman, Sander; Vasiljeva, Lidia

    2013-01-01

    We uncovered a novel role for the spliceosome in regulating mRNA expression levels that involves splicing coupled to RNA decay, which we refer to as spliceosome-mediated decay (SMD). Our transcriptome-wide studies identified numerous transcripts that are not known to have introns but are spliced by the spliceosome at canonical splice sites in Saccharomyces cerevisiae. Products of SMD are primarily degraded by the nuclear RNA surveillance machinery. We demonstrate that SMD can significantly down-regulate mRNA levels; splicing at canonical splice sites in the bromodomain factor 2 (BDF2) transcript reduced transcript levels roughly threefold by generating unstable products that are rapidly degraded by the nuclear surveillance machinery. Regulation of BDF2 mRNA levels by SMD requires Bdf1, a functionally redundant Bdf2 paralog that plays a role in recruiting the spliceosome to the BDF2 mRNA. Interestingly, mutating BDF2 5′ splice site and branch point consensus sequences partially suppresses the bdf1Δ temperature-sensitive phenotype, suggesting that maintaining proper levels of Bdf2 via SMD is biologically important. We propose that the spliceosome can also repress protein-coding gene expression by promoting nuclear turnover of spliced RNA products and provide an insight for coordinated regulation of Bdf1 and Bdf2 levels in the cell. PMID:24065768

  2. Suppressors of a cold-sensitive mutation in yeast U4 RNA define five domains in the splicing factor Prp8 that influence spliceosome activation.

    PubMed Central

    Kuhn, A N; Brow, D A

    2000-01-01

    The highly conserved splicing factor Prp8 has been implicated in multiple stages of the splicing reaction. However, assignment of a specific function to any part of the 280-kD U5 snRNP protein has been difficult, in part because Prp8 lacks recognizable functional or structural motifs. We have used a large-scale screen for Saccharomyces cerevisiae PRP8 alleles that suppress the cold sensitivity caused by U4-cs1, a mutant U4 RNA that blocks U4/U6 unwinding, to identify with high resolution five distinct regions of PRP8 involved in the control of spliceosome activation. Genetic interactions between two of these regions reveal a potential long-range intramolecular fold. Identification of a yeast two-hybrid interaction, together with previously reported results, implicates two other regions in direct and indirect contacts to the U1 snRNP. In contrast to the suppressor mutations in PRP8, loss-of-function mutations in the genes for two other splicing factors implicated in U4/U6 unwinding, Prp44 (Brr2/Rss1/Slt22/Snu246) and Prp24, show synthetic enhancement with U4-cs1. On the basis of these results we propose a model in which allosteric changes in Prp8 initiate spliceosome activation by (1) disrupting contacts between the U1 snRNP and the U4/U6-U5 tri-snRNP and (2) orchestrating the activities of Prp44 and Prp24. PMID:10924465

  3. Use of RNA tertiary interaction modules for the crystallisation of the spliceosomal snRNP core domain.

    PubMed

    Leung, Adelaine K W; Kambach, Christian; Kondo, Yasushi; Kampmann, Martin; Jinek, Martin; Nagai, Kiyoshi

    2010-09-10

    RNA is known to perform diverse roles in the cell, often as ribonucleoprotein (RNP) particles. While the crystal structure of these RNP particles could provide crucial insights into their functions, crystallographic work on RNP complexes is often hampered by difficulties in obtaining well-diffracting crystals. The small nuclear ribonucleoprotein (snRNP) core domain, acting as an assembly nucleus for the maturation of snRNPs, plays a crucial role in the biogenesis of four of the spliceosomal snRNPs. We have succeeded in crystallising the human U4 snRNP core domain containing seven Sm proteins and a truncated U4 snRNA variant. The most critical factor in our success in the crystallisation was the introduction of various tertiary interaction modules into the RNA that could promote crystal packing without altering the core structure. Here, we describe various strategies employed in our crystallisation effort that could be applied to crystallisation of other RNP particles. PMID:20643141

  4. Mutations in U4atac snRNA, a Component of the Minor Spliceosome, in the Developmental Disorder MOPD I

    PubMed Central

    He, Huiling; Liyanarachchi, Sandya; Akagi, Keiko; Nagy, Rebecca; Li, Jingfeng; Dietrich, Rosemary C; Li, Wei; Sebastian, Nikhil; Wen, Bernard; Xin, Baozhong; Singh, Jarnail; Yan, Pearlly; Alder, Hansjuerg; Haan, Eric; Wieczorek, Dagmar; Albrecht, Beate; Puffenberger, Erik; Wang, Heng; Westman, Judith A.; Padgett, Richard A; Symer, David E; de la Chapelle, Albert

    2012-01-01

    Small nuclear RNAs (snRNAs) are essential factors in mRNA splicing. By homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities. Functional assays show that mutations (30G>A, 51G>A, 55G>A, and 111G>A) associated with MOPD I cause defective U12-dependent splicing. Endogenous U12-dependent but not U2-dependent introns are poorly spliced in MOPD I patient fibroblast cells while introduction of wild type U4atac snRNA into MOPD I cells enhances U12-dependent splicing. These results illustrate the critical role of minor intron splicing in human development. PMID:21474760

  5. 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

  6. Spliceosome discards intermediates via the DEAH box ATPase Prp43p

    PubMed Central

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

    2010-01-01

    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. PMID:20463285

  7. 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. PMID:20463285

  8. Structure of a yeast spliceosome at 3.6-angstrom resolution.

    PubMed

    Yan, Chuangye; Hang, Jing; Wan, Ruixue; Huang, Min; Wong, Catherine C L; Shi, Yigong

    2015-09-11

    Splicing of precursor messenger RNA (pre-mRNA) in yeast is executed by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs), NTC (nineteen complex), NTC-related proteins (NTR), and a number of associated enzymes and cofactors. Here, we report the three-dimensional structure of a Schizosaccharomyces pombe spliceosome at 3.6-angstrom resolution, revealed by means of single-particle cryogenic electron microscopy. This spliceosome contains U2 and U5 snRNPs, NTC, NTR, U6 small nuclear RNA, and an RNA intron lariat. The atomic model includes 10,574 amino acids from 37 proteins and four RNA molecules, with a combined molecular mass of approximately 1.3 megadaltons. Spp42 (Prp8 in Saccharomyces cerevisiae), the key protein component of the U5 snRNP, forms a central scaffold and anchors the catalytic center. Both the morphology and the placement of protein components appear to have evolved to facilitate the dynamic process of pre-mRNA splicing. Our near-atomic-resolution structure of a central spliceosome provides a molecular framework for mechanistic understanding of pre-mRNA splicing. PMID:26292707

  9. A protein map of the yeast activated spliceosome as obtained by electron microscopy.

    PubMed

    Sun, Chengfu; Rigo, Norbert; Fabrizio, Patrizia; Kastner, Berthold; Lührmann, Reinhard

    2016-09-01

    We have elucidated the spatial arrangement of proteins and snRNP subunits within the purified spliceosomal B(act) complex from Saccharomyces cerevisiae, using negative-stain immunoelectron microscopy. The B(act) spliceosome exhibits a mushroom-like shape with a main body connected to a foot and a steep and a shallow slope. The U5 core components, including proteins Snu114 and Prp8, are located in the main body and foot, while Brr2 is on the shallow slope. U2 snRNP components and the RNA helicase Prp2 were predominantly located in the upper regions of both slopes. While several proteins of the "nineteen complex" are located on the steep slope, Prp19, Cef1, and the U6 snRNA-binding protein Cwc2 are on the main body. Our results also indicate that the catalytic core RNP of the spliceosome resides in its main body. We thus assign distinct domains of the B(act) complex to its snRNP and protein components, and we provide first structural insights into the remodeling events at the spliceosome during its transformation from the B to the B(act) complex. PMID:27368340

  10. 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

  11. 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

  12. 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

  13. 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

  14. Vought O2U-1 Corsair

    NASA Technical Reports Server (NTRS)

    1930-01-01

    Vought O2U-1 Corsair: The Vought O2U-1 was the first Vought airplane to carry the name Corsair. The O2U was built as an observation aircraft for the Navy, and the example flown by the NACA for evaluation and cowling tests was one of the last O2U-1s built. This Corsair came from the Naval Reserve squadron at Naval Air Station Anacostia, Washington, D. C.

  15. U1 small nuclear RNA variants differentially form ribonucleoprotein particles in vitro.

    PubMed

    Somarelli, Jason A; Mesa, Annia; Rodriguez, Carol E; Sharma, Shalini; Herrera, Rene J

    2014-04-25

    The U1 small nuclear (sn)RNA participates in splicing of pre-mRNAs by recognizing and binding to 5' splice sites at exon/intron boundaries. U1 snRNAs associate with 5' splice sites in the form of ribonucleoprotein particles (snRNPs) that are comprised of the U1 snRNA and 10 core components, including U1A, U1-70K, U1C and the 'Smith antigen', or Sm, heptamer. The U1 snRNA is highly conserved across a wide range of taxa; however, a number of reports have identified the presence of expressed U1-like snRNAs in multiple species, including humans. While numerous U1-like molecules have been shown to be expressed, it is unclear whether these variant snRNAs have the capacity to form snRNPs and participate in splicing. The purpose of the present study was to further characterize biochemically the ability of previously identified human U1-like variants to form snRNPs and bind to U1 snRNP proteins. A bioinformatics analysis provided support for the existence of multiple expressed variants. In vitro gel shift assays, competition assays, and immunoprecipitations (IPs) revealed that the variants formed high molecular weight assemblies to varying degrees and associated with core U1 snRNP proteins to a lesser extent than the canonical U1 snRNA. Together, these data suggest that the human U1 snRNA variants analyzed here are unable to efficiently bind U1 snRNP proteins. The current work provides additional biochemical insights into the ability of the variants to assemble into snRNPs. PMID:24583175

  16. Vought F4U-1 Corsair

    NASA Technical Reports Server (NTRS)

    1943-01-01

    Vought F4U-1 Corsair: This is a 'Birdcage' Corsair, so called for the canopy framing around the cockpit. Several F4Us were flown by the NACA , but this F4U-1 only flew at Langley for two months in 1943 before going to the U. S. Navy at Norfolk Naval Air Station.

  17. Vought O2U-1 Corsair

    NASA Technical Reports Server (NTRS)

    1928-01-01

    Vought O2U-1 Corsair: Suspended from the roof of the NACA's hangar at Langley Field, this Vought O2U-1 Corsair retains its float undercarriage, a contrast to other O2Us flown by the NACA which were operated on wheeled landing gear.

  18. Vought F4U-1 Corsair

    NASA Technical Reports Server (NTRS)

    1942-01-01

    Vought F4U-1 Corsair: Even though the prototype Corsair had previously been tested, this production F4U-1 also underwent trials in Langley's 30 x 60 Full Scale Tunnel. In this manner, engineers could learn what recommendations bore drag reduction 'fruit.'

  19. Vought F4U-1D Corsair

    NASA Technical Reports Server (NTRS)

    1945-01-01

    Vought F4U-1D Corsair: In February and March of 1945 this Corsair was examined in the NACA's 30 x 60 Full Scale Tunnel at Langley Field. The F4U-1D has rockets mounted on its wings for this test. After installation and during testing, the wings would be lowered to their flight position.

  20. Vought SB2U-1 Vindicator

    NASA Technical Reports Server (NTRS)

    1937-01-01

    Vought SB2U-1 Vindicator: The graceful lines of an airplane were aided by a concerted effort in drag reduction. Here a Vought SB2U-1 Vindicator is studied in Langley's 30 x 60 Full Scale Tunnel. This evaluation took place in September 1937.

  1. Lights, camera, action! Capturing the spliceosome and pre-mRNA splicing with single-molecule fluorescence microscopy.

    PubMed

    DeHaven, Alexander C; Norden, Ian S; Hoskins, Aaron A

    2016-09-01

    The process of removing intronic sequences from a precursor to messenger RNA (pre-mRNA) to yield a mature mRNA transcript via splicing is an integral step in eukaryotic gene expression. Splicing is carried out by a cellular nanomachine called the spliceosome that is composed of RNA components and dozens of proteins. Despite decades of study, many fundamentals of spliceosome function have remained elusive. Recent developments in single-molecule fluorescence microscopy have afforded new tools to better probe the spliceosome and the complex, dynamic process of splicing by direct observation of single molecules. These cutting-edge technologies enable investigators to monitor the dynamics of specific splicing components, whole spliceosomes, and even cotranscriptional splicing within living cells. WIREs RNA 2016, 7:683-701. doi: 10.1002/wrna.1358 For further resources related to this article, please visit the WIREs website. PMID:27198613

  2. 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.

  3. The SNW Domain of SKIP Is Required for Its Integration into the Spliceosome and Its Interaction with the Paf1 Complex in Arabidopsis.

    PubMed

    Li, Yan; Xia, Congcong; Feng, Jinlin; Yang, Dong; Wu, Fangming; Cao, Ying; Li, Legong; Ma, Ligeng

    2016-07-01

    SKIP is a conserved protein from yeasts to plants and humans. In plant cells, SKIP is a bifunctional regulator that works in the nucleus as a splicing factor by integrating into the spliceosome and as a transcriptional activator by interacting with the Paf1 complex. In this study, we identified two nuclear localization signals in SKIP and confirmed that each is sufficient to target SKIP to the nucleus. The SNW domain of SKIP is required for both its function as a splicing factor by promoting integration into the spliceosome in response to stress, and its function as a transcriptional activator by controlling its interaction with the Paf1 complex to participate in flowering. Truncated proteins that included the SNW domain and the N- or C-terminus of SKIP were still able to carry out the functions of the full-length protein in gene splicing and transcriptional activation in Arabidopsis. In addition, we found that SKIP undergoes 26S proteasome-mediated degradation, and that the C-terminus of SKIP is required to maintain the stability of the protein in plant cells. Together, our findings demonstrate the structural domain organization of SKIP and reveal the core domains and motifs underlying SKIP function in plants. PMID:27130079

  4. A small nucleolar guide RNA functions both in 2′-O-ribose methylation and pseudouridylation of the U5 spliceosomal RNA

    PubMed Central

    Jády, Beáta E.; Kiss, Tamás

    2001-01-01

    In eukaryotes, two distinct classes of small nucleolar RNAs (snoRNAs), namely the fibrillarin-associated box C/D snoRNAs and the Gar1p-associated box H/ACA snoRNAs, direct the site-specific 2′-O-ribose methylation and pseudouridylation of ribosomal RNAs (rRNAs), respectively. We have identified a novel evolutionarily conserved snoRNA, called U85, which possesses the box elements of both classes of snoRNAs and associates with both fibrillarin and Gar1p. In vitro and in vivo pseudouridylation and 2′-O-methylation experiments provide evidence that the U85 snoRNA directs 2′-O-methylation of the C45 and pseudouridylation of the U46 residues in the invariant loop 1 of the human U5 spliceosomal RNA. The U85 is the first example of a snoRNA that directs modification of an RNA polymerase II-transcribed spliceosomal RNA and that functions both in RNA pseudouridylation and 2′-O-methylation. PMID:11157760

  5. Vought SB2U-1 Vindicator

    NASA Technical Reports Server (NTRS)

    1938-01-01

    Vought SB2U-1 Vindicator: This Vought SB2U-1 Vindicator was acquired for one month in late 1938 from NAS Anacostia, Washington, D. C. Anacostia was the source of many of the naval aircraft flown by the NACA, in part due to its proximity and in part became it was the Navy's flight test base. The nose slot cowling was aimed at improving engine cooling.

  6. Vought XF7U-1 Cutlass

    NASA Technical Reports Server (NTRS)

    1948-01-01

    Vought XF7U-1 Cutlass: This is the first Vought Cutlass, the XF7U-1. This tailless fighter, powered by two Westinghouse J34 turbojets, arrived at Langley in December 1948. Aircraft number NAVY 122472. Wing detail, servicing, fueling, nose detail, front view, side view, side view, side view with ladder, 3/4 rear view, rear view, interior of cockpit, nose strake, exterior of cockpit with pilot, pilot climbing out of aircraft.

  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. Network of coregulated spliceosome components revealed by zebrafish mutant in recycling factor p110

    PubMed Central

    Trede, Nikolaus S.; Medenbach, Jan; Damianov, Andrey; Hung, Lee-Hsueh; Weber, Gerhard J.; Paw, Barry H.; Zhou, Yi; Hersey, Candace; Zapata, Agustin; Keefe, Matthew; Barut, Bruce A.; Stuart, Andrew B.; Katz, Tammisty; Amemiya, Chris T.; Zon, Leonard I.; Bindereif, Albrecht

    2007-01-01

    The spliceosome cycle consists of assembly, catalysis, and recycling phases. Recycling of postspliceosomal U4 and U6 small nuclear ribonucleoproteins (snRNPs) requires p110/SART3, a general splicing factor. In this article, we report that the zebrafish earl grey (egy) mutation maps in the p110 gene and results in a phenotype characterized by thymus hypoplasia, other organ-specific defects, and death by 7 to 8 days postfertilization. U4/U6 snRNPs were disrupted in egy mutant embryos, demonstrating the importance of p110 for U4/U6 snRNP recycling in vivo. Surprisingly, expression profiling of the egy mutant revealed an extensive network of coordinately up-regulated components of the spliceosome cycle, providing a mechanism compensating for the recycling defect. Together, our data demonstrate that a mutation in a general splicing factor can lead to distinct defects in organ development and cause disease. PMID:17416673

  9. 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.

  10. The exosome controls alternative splicing by mediating the gene expression and assembly of the spliceosome complex

    PubMed Central

    Zhang, Lin; Wan, Yufeng; Huang, Guobin; Wang, Dongni; Yu, Xinyang; Huang, Guocun; Guo, Jinhu

    2015-01-01

    The exosome is a complex with exoribonuclease activity that regulates RNA surveillance and turnover. The exosome also plays a role in regulating the degradation of precursor mRNAs to maintain the expression of splicing variants. In Neurospora, the silencing of rrp44, which encodes the catalytic subunit of the exosome, changed the expression of a set of spliceosomal snRNA, snRNP genes and SR protein related genes. The knockdown of rrp44 also affected the assembly of the spliceosome. RNA-seq analysis revealed a global change in bulk splicing events. Exosome-mediated splicing may regulate alternative splicing of NCU05290, NCU07421 and the circadian clock gene frequency (frq). The knockdown of rrp44 led to an increased ratio of splicing variants without intron 6 (I-6) and shorter protein isoform small FRQ (s-FRQ) as a consequence. These findings suggest that the exosome controls splicing events by regulating the degradation of precursor mRNAs and the gene expression, assembly and function of the spliceosome. PMID:26306464

  11. Structure of a yeast catalytic step I spliceosome at 3.4 Å resolution.

    PubMed

    Wan, Ruixue; Yan, Chuangye; Bai, Rui; Huang, Gaoxingyu; Shi, Yigong

    2016-08-26

    Each cycle of pre-messenger RNA splicing, carried out by the spliceosome, comprises two sequential transesterification reactions, which result in the removal of an intron and the joining of two exons. Here we report an atomic structure of a catalytic step I spliceosome (known as the C complex) from Saccharomyces cerevisiae, as determined by cryo-electron microscopy at an average resolution of 3.4 angstroms. In the structure, the 2'-OH of the invariant adenine nucleotide in the branch point sequence (BPS) is covalently joined to the phosphate at the 5' end of the 5' splice site (5'SS), forming an intron lariat. The freed 5' exon remains anchored to loop I of U5 small nuclear RNA (snRNA), and the 5'SS and BPS of the intron form duplexes with conserved U6 and U2 snRNA sequences, respectively. Specific placement of these RNA elements at the catalytic cavity of Prp8 is stabilized by 15 protein components, including Snu114 and the splicing factors Cwc21, Cwc22, Cwc25, and Yju2. These features, representing the conformation of the spliceosome after the first-step reaction, predict structural changes that are needed for the execution of the second-step transesterification reaction. PMID:27445308

  12. The importin-β binding domain of snurportin1 is responsible for the Ran- and energy-independent nuclear import of spliceosomal U snRNPs in vitro

    PubMed Central

    Huber, Jochen; Dickmanns, Achim; Lührmann, Reinhard

    2002-01-01

    The nuclear localization signal (NLS) of spliceosomal U snRNPs is composed of the U snRNA's 2,2,7-trimethyl-guanosine (m3G)-cap and the Sm core domain. The m3G-cap is specifically bound by snurportin1, which contains an NH2-terminal importin-β binding (IBB) domain and a COOH-terminal m3G-cap–binding region that bears no structural similarity to known import adaptors like importin-α (impα). Here, we show that recombinant snurportin1 and importin-β (impβ) are not only necessary, but also sufficient for U1 snRNP transport to the nuclei of digitonin-permeabilized HeLa cells. In contrast to impα–dependent import, single rounds of U1 snRNP import, mediated by the nuclear import receptor complex snurportin1–impβ, did not require Ran and energy. The same Ran- and energy-independent import was even observed for U5 snRNP, which has a molecular weight of more than one million. Interestingly, in the presence of impβ and a snurportin1 mutant containing an impα IBB domain (IBBimpα), nuclear U1 snRNP import was Ran dependent. Furthermore, β-galactosidase (βGal) containing a snurportin1 IBB domain, but not IBBimpα-βGal, was imported into the nucleus in a Ran-independent manner. Our results suggest that the nature of the IBB domain modulates the strength and/or site of interaction of impβ with nucleoporins of the nuclear pore complex, and thus whether or not Ran is required to dissociate these interactions. PMID:11815630

  13. Multiple components of the spliceosome regulate Mcl1 activity in neuroblastoma

    PubMed Central

    Laetsch, T W; Liu, X; Vu, A; Sliozberg, M; Vido, M; Elci, O U; Goldsmith, K C; Hogarty, M D

    2014-01-01

    Cancer treatments induce cell stress to trigger apoptosis in tumor cells. Many cancers repress these apoptotic signals through alterations in the Bcl2 proteins that regulate this process. Therapeutics that target these specific survival biases are in development, and drugs that inhibit Bcl2 activities have shown clinical activity for some cancers. Mcl1 is a survival factor for which no effective antagonists have been developed, so it remains a principal mediator of therapy resistance, including to Bcl2 inhibitors. We used a synthetic-lethal screening strategy to identify genes that regulate Mcl1 survival activity using the pediatric tumor neuroblastoma (NB) as a model, as a large subset are functionally verified to be Mcl1 dependent and Bcl2 inhibitor resistant. A targeted siRNA screen identified genes whose knockdown restores sensitivity of Mcl1-dependent NBs to ABT-737, a small molecule inhibitor of Bcl2, BclXL and BclW. Three target genes that shifted the ABT-737 IC50 >1 log were identified and validated: PSMD14, UBL5 and PRPF8. The latter two are members of a recently characterized subcomplex of the spliceosome that along with SART1 is responsible for non-canonical 5′-splice sequence recognition in yeast. We showed that SART1 knockdown similarly sensitized Mcl1-dependent NB to ABT-737 and that triple knockdown of UBL5/PRPF8/SART1 phenocopied direct MCL1 knockdown, whereas having no effect on Bcl2-dependent NBs. Both genetic spliceosome knockdown or treatment with SF3b-interacting spliceosome inhibitors like spliceostatin A led to preferential pro-apoptotic Mcl1-S splicing and reduced translation and abundance of Mcl1 protein. In contrast, BN82865, which inhibits the second transesterification step in terminal spliceosome processing, did not have this effect. These findings demonstrate a prominent role for the spliceosome in mediating Mcl1 activity and suggest that drugs that target either the specific UBL5/PRPF8/SART1 subcomplex or SF3b functions may have a

  14. Chemical modifications of ribonuclease U1.

    PubMed

    Hashimoto, J; Takahashi, K

    1977-04-01

    In order to obtain information on the nature of the amino acid residues involved in the activity of ribonuclease U1 [EC 3.1.4.8], various chemical modifications of the enzyme were carried out. RNase U1 was inactivated by reaction with iodoacetate at pH 5.5 with concomitant incorporation of 1 carboxymethyl group per molecule of the enzyme. The residue specifically modified by iodoacetate was identified as one of the glutamic acid residues, as in the case of RNase T1. The enzyme was also inactivated extensively by reaction with iodoacetamide at pH 8.0 with the loss of about one residue each of histidine and lysine. When RNase U1 was treated with a large excess of phenylglyoxal, the enzymatic activity and binding ability toward 3'-GMP were lost, with simultaneous modification of about 1 residue of arginine. The reaction of citraconic anhydride with RNase U1 led to the loss of enzymatic activity and modification of about 1 residue of lysine. The inactivated enzyme, however, retained binding ability toward 3'-GMP. These results indicate that there are marked similarities in the active sites of RNases T1 and U1. PMID:18450

  15. Vought O3U-1 Corsair

    NASA Technical Reports Server (NTRS)

    1931-01-01

    Vought O3U-1 Corsair: This aircraft, the Vought O3U-1 Corsair, was the first aircraft tested in the Full Scale Tunnel. It is shown here during preliminary tests in the FST before the balance was enclosed. NACA engineers checked the lift and drag characteristics of several aircraft with the results of earlier flight tests. Smith DeFrance concluded NACA TR No. 459, 'The agreement that has been obtained between the flight and full-scale tunnel results, together with the consistent manner in which measurements can be repeated when check tests are made, has demonstrated the accuracy and value of the equipment for aeronautical research.' (p. 298)

  16. The spliceosome assembly factor GEMIN2 attenuates the effects of temperature on alternative splicing and circadian rhythms

    PubMed Central

    Schlaen, Rubén Gustavo; Mancini, Estefanía; Sanchez, Sabrina Elena; Perez-Santángelo, Soledad; Rugnone, Matías L.; Simpson, Craig G.; Brown, John W. S.; Zhang, Xu; Chernomoretz, Ariel; Yanovsky, Marcelo J.

    2015-01-01

    The mechanisms by which poikilothermic organisms ensure that biological processes are robust to temperature changes are largely unknown. Temperature compensation, the ability of circadian rhythms to maintain a relatively constant period over the broad range of temperatures resulting from seasonal fluctuations in environmental conditions, is a defining property of circadian networks. Temperature affects the alternative splicing (AS) of several clock genes in fungi, plants, and flies, but the splicing factors that modulate these effects to ensure clock accuracy throughout the year remain to be identified. Here we show that GEMIN2, a spliceosomal small nuclear ribonucleoprotein assembly factor conserved from yeast to humans, modulates low temperature effects on a large subset of pre-mRNA splicing events. In particular, GEMIN2 controls the AS of several clock genes and attenuates the effects of temperature on the circadian period in Arabidopsis thaliana. We conclude that GEMIN2 is a key component of a posttranscriptional regulatory mechanism that ensures the appropriate acclimation of plants to daily and seasonal changes in temperature conditions. PMID:26170331

  17. 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. PMID:25731616

  18. Supergravity solutions without triholomorphic U(1) isometries

    SciTech Connect

    Ghezelbash, A. M.

    2008-12-15

    We investigate the construction of five-dimensional supergravity solutions that do not have any triholomorphic U(1) isometries. We construct a class of solutions that in various limits of parameters reduces to many of previously constructed five-dimensional supergravity solutions based on both hyper-Kaehler base spaces that can be put into a Gibbons-Hawking form and hyper-Kaehler base spaces that cannot be put into a Gibbons-Hawking form. We find a new solution which is over triaxial Bianchi type IX Einstein-hyper-Kaehler base space with no triholomorphic U(1) symmetry. One special case of this solution corresponds to a five-dimensional solution based on Eguchi-Hanson type II geometry.

  19. More modular invariant anomalous U(1) breaking

    SciTech Connect

    Gaillard, Mary K.; Giedt, Joel

    2002-06-27

    We consider the case of several scalar fields, charged under a number of U(1) factors, acquiring vacuum expectation values due to anomalous U(1). We demonstrate how to make redefinitions at the superfield level in order to account for tree-level exchange of vector supermultiplets in the effective supergravity theory of the light fields in the supersymmetric vacuum phase. Our approach builds up on previous results that we obtained in a more elementary case. We find that the modular weights of light fields are typically shifted from their original values, allowing an interpretation in terms of the preservation of modular invariance in the effective theory. We address various subtleties in defining unitary gauge that are associated with the noncanonical Kahler potential of modular invariant supergravity, the vacuum degeneracy, and the role of the dilaton field. We discuss the effective superpotential for the light fields and note how proton decay operators may be obtained when the heavy fields are integrated out of the theory at the tree-level. We also address how our formalism may be extended to describe the generalized Green-Schwarz mechanism for multiple anomalous U(1)'s that occur in four-dimensional Type I and Type IIB string constructions.

  20. Retrofitted natural supersymmetry from a U(1)

    NASA Astrophysics Data System (ADS)

    Hardy, Edward; March-Russell, John

    2013-05-01

    We propose that a single, spontaneously broken, U(1) gauge symmetry may be responsible for suppressing both the first two generation Yukawa couplings, and also, in a correlated manner, parameters in the dynamical supersymmetry (SUSY) breaking sector by the mechanism of retrofitting. In the dynamical SUSY breaking sector, these small parameters are typically required in order to introduce R-symmetry breaking in a controlled manner and obtain phenomenologically viable meta-stable vacua. The heavy U(1) multiplet mediates a dominant contribution to the first two generation MSSM sfermion soft masses, while gauge mediation provides a parametrically suppressed soft term contribution to the stop and most other states, so realising a natural SUSY spectrum in a fashion consistent with SUSY unification. In explicit models the spectra obtained can be such that current LHC limits are evaded, and predictions of flavour changing processes are consistent with observation. We examine both implementations with low scale mediation, and string-motivated examples where the U(1) is anomalous before the inclusion of a generalised Green-Schwarz mechanism.

  1. Tetramers reveal IL-17-secreting CD4+ T cells that are specific for U1-70 in lupus and mixed connective tissue disease.

    PubMed

    Kattah, Nicole H; Newell, Evan W; Jarrell, Justin Ansel; Chu, Alvina D; Xie, Jianming; Kattah, Michael G; Goldberger, Ofir; Ye, Jessica; Chakravarty, Eliza F; Davis, Mark M; Utz, Paul J

    2015-03-10

    Antigen-specific CD4(+) T cells are implicated in the autoimmune disease systemic lupus erythematosus (SLE), but little is known about the peptide antigens that they recognize and their precise function in disease. We generated a series of MHC class II tetramers of I-E(k)-containing peptides from the spliceosomal protein U1-70 that specifically stain distinct CD4(+) T-cell populations in MRL/lpr mice. The T-cell populations recognize an epitope differing only by the presence or absence of a single phosphate residue at position serine(140). The frequency of CD4(+) T cells specific for U1-70(131-150):I-E(k) (without phosphorylation) correlates with disease severity and anti-U1-70 autoantibody production. These T cells also express RORγt and produce IL-17A. Furthermore, the U1-70-specific CD4(+) T cells that produce IL-17A are detected in a subset of patients with SLE and are significantly increased in patients with mixed connective tissue disease. These studies provide tools for studying antigen-specific CD4(+) T cells in lupus, and demonstrate an antigen-specific source of IL-17A in autoimmune disease. PMID:25713364

  2. 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.

  3. 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

  4. 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

  5. Crystal structures of a group II intron maturase reveal a missing link in spliceosome evolution.

    PubMed

    Zhao, Chen; Pyle, Anna Marie

    2016-06-01

    Group II introns are self-splicing ribozymes that are essential in many organisms, and they have been hypothesized to share a common evolutionary ancestor with the spliceosome. Although structural similarity of RNA components supports this connection, it is of interest to determine whether associated protein factors also share an evolutionary heritage. Here we present the crystal structures of reverse transcriptase (RT) domains from two group II intron-encoded proteins (maturases) from Roseburia intestinalis and Eubacterium rectale, obtained at 1.2-Å and 2.1-Å resolution, respectively. These domains are more similar in architecture to the spliceosomal Prp8 RT-like domain than to any other RTs, and they share substantial similarity with flaviviral RNA polymerases. The RT domain itself is sufficient for binding intron RNA with high affinity and specificity, and it is contained within an active RT enzyme. These studies provide a foundation for understanding structure-function relationships within group II intron-maturase complexes. PMID:27136328

  6. 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

  7. Structure of a yeast activated spliceosome at 3.5 Å resolution.

    PubMed

    Yan, Chuangye; Wan, Ruixue; Bai, Rui; Huang, Gaoxingyu; Shi, Yigong

    2016-08-26

    Pre-messenger RNA (pre-mRNA) splicing is carried out by the spliceosome, which undergoes an intricate assembly and activation process. Here, we report an atomic structure of an activated spliceosome (known as the B(act) complex) from Saccharomyces cerevisiae, determined by cryo-electron microscopy at an average resolution of 3.52 angstroms. The final refined model contains U2 and U5 small nuclear ribonucleoprotein particles (snRNPs), U6 small nuclear RNA (snRNA), nineteen complex (NTC), NTC-related (NTR) protein, and a 71-nucleotide pre-mRNA molecule, which amount to 13,505 amino acids from 38 proteins and a combined molecular mass of about 1.6 megadaltons. The 5' exon is anchored by loop I of U5 snRNA, whereas the 5' splice site (5'SS) and the branch-point sequence (BPS) of the intron are specifically recognized by U6 and U2 snRNA, respectively. Except for coordination of the catalytic metal ions, the RNA elements at the catalytic cavity of Prp8 are mostly primed for catalysis. The catalytic latency is maintained by the SF3b complex, which encircles the BPS, and the splicing factors Cwc24 and Prp11, which shield the 5' exon-5'SS junction. This structure, together with those determined earlier, outlines a molecular framework for the pre-mRNA splicing reaction. PMID:27445306

  8. 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

  9. 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

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

    PubMed

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

    2016-07-01

    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

  11. 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. PMID:26443080

  12. 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

  13. 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.

  14. Vought O3U-1 'Corsair'

    NASA Technical Reports Server (NTRS)

    1931-01-01

    Vought O3U-1 'Corsair' in Full-Scale Tunnel (FST). This photograph was taken in September 1931 after the balance had been enclosed. This aircraft was also used earlier during the summer for preliminary tests in the FST and as the subject of some of the first publicity photographs taken of FST operations. NACA engineers checked the lift and drag characteristics of several aircraft with the results of earlier flight tests. Smith DeFrance concluded NACA TR No. 459, 'The agreement that has been obtained between the flight and full-scale tunnel results, together with the consistent manner in which measurements can be repeated when check tests are made, has demonstrated the accuracy and value of the equipment for aeronautical research.' (p. 298)

  15. U(1) problem at finite temperature

    SciTech Connect

    Janik, Romuald A.; Nowak, Maciej A.; Papp, Gabor; Zahed, Ismail

    1999-11-22

    We model the effects of a large number of zero and near-zero modes in the QCD partition function by using sparse chiral matrix models with an emphasis on the quenched topological susceptibility in the choice of the measure. At finite temperature, the zero modes are not affected by temperature but are allowed to pair into topologically neutral near-zero modes which are gapped at high temperature. In equilibrium, chiral and U(1) symmetry are simultaneously restored for total pairing, evading mean-field arguments. We analyze a number of susceptibilities versus the light quark masses. At the transition point the topological susceptibility vanishes, and the dependence on the vacuum angle {theta} drops out. Our results are briefly contrasted with recent lattice simulations.

  16. Anomalies, U(1)' and the MSSM

    NASA Astrophysics Data System (ADS)

    Racioppi, Antonio

    2009-07-01

    This Thesis reviews an extension of the MSSM by the addition of an anomalous abelian vector multiplet and contains some original results concerning the phenomenology of an anomalous Z'. The review part covers an introduction of the MSSM focusing on its main features, a discussion on the chiral anomalies and how to cancel them in the Standard Model and by the Green-Schwarz mechanism. Then, the original results are presented. We build the Lagrangian for the Minimal Anomalous U(1)' Extension of the MSSM where the anomalies are cancelled by the Green-Schwarz mechanism and the addition of Chern-Simons terms, stressing the main differences between our model and the MSSM. 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 towards 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'to Z_0 g and Z'to Z_0 Z_0. We find that the largest values of the decay rate are sim 10^{-4} GeV, while the expected number of events per year at LHC is at most of the order of 10. Then we compute the relic density predicted by our model with a new dark matter candidate, the axino, which is the LSP of the theory. We find agreement with experimental data admitting a bino-higgsino NLSP or a wino-like NLSP, almost degenerate in mass to the axino.

  17. 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.

  18. 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

  19. Substrate-assisted mechanism of RNP disruption by the spliceosomal Brr2 RNA helicase.

    PubMed

    Theuser, Matthias; Höbartner, Claudia; Wahl, Markus C; Santos, Karine F

    2016-07-12

    The Brr2 RNA helicase disrupts the U4/U6 di-small nuclear RNA-protein complex (di-snRNP) during spliceosome activation via ATP-driven translocation on the U4 snRNA strand. However, it is unclear how bound proteins influence U4/U6 unwinding, which regions of the U4/U6 duplex the helicase actively unwinds, and whether U4/U6 components are released as individual molecules or as subcomplexes. Here, we set up a recombinant Brr2-mediated U4/U6 di-snRNP disruption system, showing that sequential addition of the U4/U6 proteins small nuclear ribonucleoprotein-associated protein 1 (Snu13), pre-mRNA processing factor 31 (Prp31), and Prp3 to U4/U6 di-snRNA leads to a stepwise decrease of Brr2-mediated U4/U6 unwinding, but that unwinding is largely restored by a Brr2 cofactor, the C-terminal Jab1/MPN domain of the Prp8 protein. Brr2-mediated U4/U6 unwinding was strongly inhibited by mutations in U4/U6 di-snRNAs that diminish the ability of U6 snRNA to adopt an alternative conformation but leave the number and kind of U4/U6 base pairs unchanged. Irrespective of the presence of the cofactor, the helicase segregated a Prp3-Prp31-Snu13-U4/U6 RNP into an intact Prp31-Snu13-U4 snRNA particle, free Prp3, and free U6 snRNA. Together, these observations suggest that Brr2 translocates only a limited distance on the U4 snRNA strand and does not actively release RNA-bound proteins. Unwinding is then completed by the partially displaced U6 snRNA adopting an alternative conformation, which leads to dismantling of the Prp3-binding site on U4/U6 di-snRNA but leaves the Prp31- and Snu13-binding sites on U4 snRNA unaffected. In this fashion, Brr2 can activate the spliceosome by stripping U6 snRNA of all precatalytic binding partners, while minimizing logistic requirements for U4/U6 di-snRNP reassembly after splicing. PMID:27354531

  20. Evidence for a group II intron-like catalytic triplex in the spliceosome

    PubMed Central

    Piccirilli, Joseph A.; Staley, Jonathan P.

    2014-01-01

    To catalyze pre-mRNA splicing, U6 snRNA positions two metals that interact directly with the scissile phosphates. The U6 metal ligands correspond stereospecifically to metal ligands within the catalytic domain V of a group II self-splicing intron. In domain V, the ligands are organized by base-triple interactions, which also juxtapose the 3′ splice site with the catalytic metals. However, in the spliceosome, the mechanism for organizing catalytic metals and recruiting the substrate has remained unclear. Here we show by genetics, crosslinking, and biochemistry in yeast that analogous triples form in U6 and promote catalytic metal binding and both chemical steps of splicing. Because the triples include an element that defines the 5′ splice site, the triples also provide a mechanism for juxtaposing the pre-mRNA substrate with the catalytic metals. Our data indicate that U6 adopts a group II intron-like tertiary conformation to catalyze splicing. PMID:24747940

  1. 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

  2. Impact of allogeneic hematopoietic cell transplant in patients with myeloid neoplasms carrying spliceosomal mutations.

    PubMed

    Hamilton, Betty Ky; Visconte, Valeria; Jia, Xuefei; Tabarroki, Ali; Makishima, Hideki; Hasrouni, Edy; Abounader, Donna; Kalaycio, Matt; Sekeres, Mikkael A; Sobecks, Ronald; Duong Liu, Hien; Bolwell, Brian; Maciejewski, Jaroslaw P; Copelan, Edward; Tiu, Ramon V

    2016-06-01

    Molecular predictors of outcome are increasingly important in determining optimal therapy for myeloid neoplasms. Mutations in the spliceosomal genes (U2AF1 and SRSF2) predict for poor outcomes in myelodysplastic syndromes (MDS) and related diseases. We investigated the effect of hematopoietic cell transplant (HCT) on the negative prognostic impact of U2AF1 and SRSF2 mutations. In total, 122 patients with MDS (30%), acute myeloid leukemia (51%), myeloproliferative neoplasms (MPN) (11%), and MDS/MPN (8%) receiving a HCT from 2003 to 2012 were evaluated for mutations in U2AF1 and SRSF2 by direct sequencing. Median time of follow up was 24 months (range 0.46-110). SRSF2 mutations were detected in 11 (10%) patients and U2AF1 in 3 (3%) patients. There were no significant differences in baseline characteristics between mutated and wild-type (WT) patients. Patients carrying SRSF2 and U2AF1 mutations had similar overall survival (P = 0.84), relapse mortality (P = 0.50), and non-relapse mortality (P = 0.72) compared to WT patients. However, taking into account disease status and cytogenetics in a subset of AML patients, SRSF2 and U2AF1 mutations were associated with worse survival (HR 3.71, P = 0.035). Am. J. Hematol. 91:406-409, 2016. © 2016 Wiley Periodicals, Inc. PMID:26799334

  3. 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. PMID:25619725

  4. 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

  5. Repair of Rhodopsin mRNA by Spliceosome-Mediated RNA Trans-Splicing: A New Approach for Autosomal Dominant Retinitis Pigmentosa

    PubMed Central

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

    2015-01-01

    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. PMID:25619725

  6. 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

  7. Mapping epitopes of U1-70K autoantibodies at single-amino acid resolution.

    PubMed

    Haddon, David James; Jarrell, Justin Ansel; Diep, Vivian K; Wand, Hannah E; Price, Jordan V; Tangsombatvisit, Stephanie; Credo, Grace M; Mackey, Sally; Dekker, Cornelia L; Baechler, Emily C; Liu, Chih Long; Varma, Madoo; Utz, Paul J

    2015-01-01

    The mechanisms underlying development of ribonucleoprotein (RNP) autoantibodies are unclear. The U1-70K protein is the predominant target of RNP autoantibodies, and the RNA binding domain has been shown to be the immunodominant autoantigenic region of U1-70K, although the specific epitopes are not known. To precisely map U1-70K epitopes, we developed silicon-based peptide microarrays with >5700 features, corresponding to 843 unique peptides derived from the U1-70K protein. The microarrays feature overlapping peptides, with single-amino acid resolution in length and location, spanning amino acids 110-170 within the U1-70K RNA binding domain. We evaluated the serum IgG of a cohort of patients with systemic lupus erythematosus (SLE; n = 26) using the microarrays, and identified multiple reactive epitopes, including peptides 116-121 and 143-148. Indirect peptide ELISA analysis of the sera of patients with SLE (n = 88) revealed that ∼14% of patients had serum IgG reactivity to 116-121, while reactivity to 143-148 appeared to be limited to a single patient. SLE patients with serum reactivity to 116-121 had significantly lower SLE Disease Activity Index (SLEDAI) scores at the time of sampling, compared to non-reactive patients. Minimal reactivity to the peptides was observed in the sera of healthy controls (n = 92). Competitive ELISA showed antibodies to 116-121 bind a common epitope in U1-70K (68-72) and the matrix protein M1 of human influenza B viruses. Institutional Review Boards approved this study. Knowledge of the precise epitopes of U1-70K autoantibodies may provide insight into the mechanisms of development of anti-RNP, identify potential clinical biomarkers and inform ongoing clinical trails of peptide-based therapeutics. PMID:26333287

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

    PubMed

    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

    2015-12-15

    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

  9. 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

  10. The MUC1 Extracellular Domain Subunit Is Found in Nuclear Speckles and Associates with Spliceosomes

    PubMed Central

    Kumar, Priyadarsina; Ji, Jennifer W.; Martsching, Lindsay; Douglas, Gordon C.

    2012-01-01

    MUC1 is a large transmembrane glycoprotein and oncogene expressed by epithelial cells and overexpressed and underglycosylated in cancer cells. The MUC1 cytoplasmic subunit (MUC1-C) can translocate to the nucleus and regulate gene expression. It is frequently assumed that the MUC1 extracellular subunit (MUC1-N) does not enter the nucleus. Based on an unexpected observation that MUC1 extracellular domain antibody produced an apparently nucleus-associated staining pattern in trophoblasts, we have tested the hypothesis that MUC1-N is expressed inside the nucleus. Three different antibodies were used to identify MUC1-N in normal epithelial cells and tissues as well as in several cancer cell lines. The results of immunofluorescence and confocal microscopy analyses as well as subcellular fractionation, Western blotting, and siRNA/shRNA studies, confirm that MUC1-N is found within nuclei of all cell types examined. More detailed examination of its intranuclear distribution using a proximity ligation assay, subcellular fractionation, and immunoprecipitation suggests that MUC1-N is located in nuclear speckles (interchromatin granule clusters) and closely associates with the spliceosome protein U2AF65. Nuclear localization of MUC1-N was abolished when cells were treated with RNase A and nuclear localization was altered when cells were incubated with the transcription inhibitor 5,6-dichloro-1-b-d-ribofuranosylbenzimidazole (DRB). While MUC1-N predominantly associated with speckles, MUC1-C was present in the nuclear matrix, nucleoli, and the nuclear periphery. In some nuclei, confocal microscopic analysis suggest that MUC1-C staining is located close to, but only partially overlaps, MUC1-N in speckles. However, only MUC1-N was found in isolated speckles by Western blotting. Also, MUC1-C and MUC1-N distributed differently during mitosis. These results suggest that MUC1-N translocates to the nucleus where it is expressed in nuclear speckles and that MUC1-N and MUC1-C have

  11. 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

  12. 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).

  13. 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.

  14. 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.

  15. 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.

  16. Structural Basis of the Recruitment of Ubiquitin-specific Protease USP15 by Spliceosome Recycling Factor SART3.

    PubMed

    Zhang, Qi; Harding, Rachel; Hou, Feng; Dong, Aiping; Walker, John R; Bteich, Joseph; Tong, Yufeng

    2016-08-12

    Ubiquitin-specific proteases (USPs) USP15 and USP4 belong to a subset of USPs featuring an N-terminal tandem domain in USP (DUSP) and ubiquitin-like (UBL) domain. Squamous cell carcinoma antigen recognized by T-cell 3 (SART3), a spliceosome recycling factor, binds to the DUSP-UBL domain of USP15 and USP4, recruiting them to the nucleus from the cytosol to control deubiquitination of histone H2B and spliceosomal proteins, respectively. To provide structural insight, we solved crystal structures of SART3 in the apo-form and in complex with the DUSP-UBL domain of USP15 at 2.0 and 3.0 Å, respectively. Structural analysis reveals SART3 contains 12 half-a-tetratricopeptide (HAT) repeats, organized into two subdomains, HAT-N and HAT-C. SART3 dimerizes through the concave surface of HAT-C, whereas the HAT-C convex surface binds USP15 in a novel bipartite mode. Isothermal titration calorimetry measurements and mutagenesis analysis confirmed key residues of USP15 involved in the interaction and indicated USP15 binds 20-fold stronger than USP4. PMID:27255711

  17. 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

  18. Dysferlin rescue by spliceosome-mediated pre-mRNA trans-splicing targeting introns harbouring weakly defined 3' splice sites.

    PubMed

    Philippi, Susanne; Lorain, Stéphanie; Beley, Cyriaque; Peccate, Cécile; Précigout, Guillaume; Spuler, Simone; Garcia, Luis

    2015-07-15

    The modification of the pre-mRNA cis-splicing process employing a pre-mRNA trans-splicing molecule (PTM) is an attractive strategy for the in situ correction of genes whose careful transcription regulation and full-length expression is determinative for protein function, as it is the case for the dysferlin (DYSF, Dysf) gene. Loss-of-function mutations of DYSF result in different types of muscular dystrophy mainly manifesting as limb girdle muscular dystrophy 2B (LGMD2B) and Miyoshi muscular dystrophy 1 (MMD1). We established a 3' replacement strategy for mutated DYSF pre-mRNAs induced by spliceosome-mediated pre-mRNA trans-splicing (SmaRT) by the use of a PTM. In contrast to previously established SmaRT strategies, we particularly focused on the identification of a suitable pre-mRNA target intron other than the optimization of the PTM design. By targeting DYSF pre-mRNA introns harbouring differentially defined 3' splice sites (3' SS), we found that target introns encoding weakly defined 3' SSs were trans-spliced successfully in vitro in human LGMD2B myoblasts as well as in vivo in skeletal muscle of wild-type and Dysf(-/-) mice. For the first time, we demonstrate rescue of Dysf protein by SmaRT in vivo. Moreover, we identified concordant qualities among the successfully targeted Dysf introns and targeted endogenous introns in previously reported SmaRT approaches that might facilitate a selective choice of target introns in future SmaRT strategies. PMID:25904108

  19. In vitro synthesis of vertebrate U1 snRNA.

    PubMed Central

    Lund, E; Dahlberg, J E

    1989-01-01

    We have developed a DNA-dependent in vitro transcription system for vertebrate snRNA genes. By isolating the nuclei (germinal vesicles, GVs) of Xenopus laevis oocytes under oil to maintain the in vivo composition of their internal milieu, we are able to prepare nuclei that retain their ability to synthesize snRNAs efficiently. Homogenates of these GVs synthesize correctly initiated and terminated U1 snRNA using exogenous X.laevis U1 genes as templates. The templates may be either injected into the nucleus prior to its isolation or added to the nuclear homogenate. Images PMID:2714253

  20. On the Partical Conservation of the U(1) Current

    NASA Astrophysics Data System (ADS)

    Kawarabayashi, K.; Ohta, N.

    1981-11-01

    Recently proposed partial conservation of the U(1) current(PCU1C) is applied to estimate the decay rates of various OZIforbidden processes. The results obtained are in good agreement withexperiments and thus indicate the important role played by the U(1)axial-vector anomaly in these decay processes. Octet Jp = (1/2)+ baryons are next introduced into this scheme and low energy theorems related to the θ dependence of the matrix elements are investigated. Physical consequences of non-zero θ (strong CP-violation) are also discussed with the help of the PCU1C. The results are used to give the bound on θ.

  1. 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.

  2. Meta-Analysis and Gene Set Analysis of Archived Microarrays Suggest Implication of the Spliceosome in Metastatic and Hypoxic Phenotypes

    PubMed Central

    Bareke, Eric; Depiereux, Sophie; Michiels, Carine; Depiereux, Eric

    2014-01-01

    We propose to make use of the wealth of underused DNA chip data available in public repositories to study the molecular mechanisms behind the adaptation of cancer cells to hypoxic conditions leading to the metastatic phenotype. We have developed new bioinformatics tools and adapted others to identify with maximum sensitivity those genes which are expressed differentially across several experiments. The comparison of two analytical approaches, based on either Over Representation Analysis or Functional Class Scoring, by a meta-analysis-based approach, led to the retrieval of known information about the biological situation – thus validating the model – but also more importantly to the discovery of the previously unknown implication of the spliceosome, the cellular machinery responsible for mRNA splicing, in the development of metastasis. PMID:24497970

  3. The evolution of single-copy Drosophila nuclear 4f-rnp genes: spliceosomal intron losses create polymorphic alleles.

    PubMed

    Feiber, Amy L; Rangarajan, Janaki; Vaughn, Jack C

    2002-10-01

    This study provides the first report in which spliceosomal intron losses within a single-copy gene create functional polymorphic alleles in a population. 4f-rnp has previously been shown to be a nuclear gene that is localized on the X chromosome in D. melanogaster and to have eight short spliceosomal introns. An insect species survey was done via polymerase chain reaction (PCR) amplification and sequencing of a 1028-bp gene fragment spanning introns 4-8, which are located in the 3' half of the gene. The results show that 4f-rnp and (thus far) introns 7 and 8 are at least as old as order Odonata (dragonflies), an early-diverging insect line. Unexpectedly, several species within the dipteran family Drosophilidae were found to contain two differently sized 4f-rnp gene sequence variants, owing to precise in-frame intron losses. Results of single-male D. melanogaster PCR analyses show that the two gene size variants are allelic and that the intron loss mechanism appears to be biased toward the 3' end of the gene. A stable potential stem-loop has been identified in D. melanogaster, predicted to fold the 4f-rnp mRNA 3' terminus into a natural primer for subsequent reverse transcription into cDNA. When results are displayed in a phylogenetic context, multiple independent intron loss events are identified. These observations support a model in which frequently occurring cDNAs have led to numerous independent intron losses via homologous recombination/gene conversion during 4f-rnp gene evolution. The results provide insights into the evolution of intron loss and may lead to improved understanding of the dynamics of this process in natural populations. PMID:12355261

  4. 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.

  5. 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.

  6. U(1) gauge symmetry breaking in a charged closed universe

    SciTech Connect

    Kim, J.E. ); Lee, T. )

    1990-10-30

    In this paper, the authors obtain the consistency condition on a U(1) gauge boson mass in a charged closed universe, m{sup 2} = 8{pi}GJ{sup 0}J{sub 0}/(R {minus} 2{Lambda}), where J{sup 0} is the charge density.

  7. 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.

  8. H2B Ubiquitylation Modulates Spliceosome Assembly and Function in Budding Yeast

    PubMed Central

    Hérissant, Lucas; Moehle, Erica A.; Bertaccini, Diego; Van Dorsselaer, Alain; Schaeffer-Reiss, Christine; Guthrie, Christine; Dargemont, Catherine

    2014-01-01

    Background information Commitment to splicing occurs co-transcriptionally, but a major unanswered question is the extent to which various modifications of chromatin, the template for transcription in vivo, contribute to the regulation of splicing. Results Here we perform genome-wide analyses showing that inhibition of specific marks – H2B ubiquitylation, H3K4 methylation, and H3K36 methylation – perturbs splicing in budding yeast, with each modification exerting gene-specific effects. Furthermore, semi-quantitative mass spectrometry on purified nuclear mRNPs and chromatin immunoprecipitation analysis on intron-containing genes indicated that H2B ubiquitylation, but not Set1-, Set2- or Dot1-dependent H3 methylation, stimulates recruitment of the early splicing factors, namely U1 and U2 snRNPs, onto nascent RNAs. Conclusions These results suggest that histone modifications impact splicing of distinct subsets of genes using distinct pathways. PMID:24476359

  9. Compendium of models from a gauge U(1) framework

    NASA Astrophysics Data System (ADS)

    Ma, Ernest

    2016-06-01

    A gauge U(1) framework was established in 2002 to extend the supersymmetric Standard Model. It has many possible realizations. Whereas all have the necessary and sufficient ingredients to explain the possible 750 GeV diphoton excess, observed recently by the ATLAS and CMS Collaborations at the large hadron collider (LHC), they differ in other essential aspects. A compendium of such models is discussed.

  10. 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.

  11. The 3.8 Å structure of the U4/U6.U5 tri-snRNP: Insights into spliceosome assembly and catalysis.

    PubMed

    Wan, Ruixue; Yan, Chuangye; Bai, Rui; Wang, Lin; Huang, Min; Wong, Catherine C L; Shi, Yigong

    2016-01-29

    Splicing of precursor messenger RNA is accomplished by a dynamic megacomplex known as the spliceosome. Assembly of a functional spliceosome requires a preassembled U4/U6.U5 tri-snRNP complex, which comprises the U5 small nuclear ribonucleoprotein (snRNP), the U4 and U6 small nuclear RNA (snRNA) duplex, and a number of protein factors. Here we report the three-dimensional structure of a Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at an overall resolution of 3.8 angstroms by single-particle electron cryomicroscopy. The local resolution for the core regions of the tri-snRNP reaches 3.0 to 3.5 angstroms, allowing construction of a refined atomic model. Our structure contains U5 snRNA, the extensively base-paired U4/U6 snRNA, and 30 proteins including Prp8 and Snu114, which amount to 8495 amino acids and 263 nucleotides with a combined molecular mass of ~1 megadalton. The catalytic nucleotide U80 from U6 snRNA exists in an inactive conformation, stabilized by its base-pairing interactions with U4 snRNA and protected by Prp3. Pre-messenger RNA is bound in the tri-snRNP through base-pairing interactions with U6 snRNA and loop I of U5 snRNA. This structure, together with that of the spliceosome, reveals the molecular choreography of the snRNAs in the activation process of the spliceosomal ribozyme. PMID:26743623

  12. Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia

    PubMed Central

    Kar, Sarah Abu; Jankowska, Anna; Makishima, Hideki; Visconte, Valeria; Jerez, Andres; Sugimoto, Yuka; Muramatsu, Hideki; Traina, Fabiola; Afable, Manuel; Guinta, Kathryn; Tiu, Ramon V.; Przychodzen, Bartlomiej; Sakaguchi, Hirotoshi; Kojima, Seiji; Sekeres, Mikkael A.; List, Alan F.; McDevitt, Michael A.; Maciejewski, Jaroslaw P.

    2013-01-01

    Chronic myelomonocytic leukemia is a heterogeneous disease with multifactorial molecular pathogenesis. Various recurrent somatic mutations have been detected alone or in combination in chronic myelomonocytic leukemia. Recently, recurrent mutations in spliceosomal genes have been discovered. We investigated the contribution of U2AF1, SRSF2 and SF3B1 mutations in the pathogenesis of chronic myelomonocytic leukemia and closely related diseases. We genotyped a cohort of patients with chronic myelomonocytic leukemia, secondary acute myeloid leukemia derived from chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia for somatic mutations in U2AF1, SRSF2, SF3B1 and in the other 12 most frequently affected genes in these conditions. Chromosomal abnormalities were assessed by nucleotide polymorphism array-based karyotyping. The presence of molecular lesions was correlated with clinical endpoints. Mutations in SRSF2, U2AF1 and SF3B1 were found in 32%, 13% and 6% of cases of chronic myelomonocytic leukemia, secondary acute myeloid leukemia derived from chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia, respectively. Spliceosomal genes were affected in various combinations with other mutations, including TET2, ASXL1, CBL, EZH2, RAS, IDH1/2, DNMT3A, TP53, UTX and RUNX1. Worse overall survival was associated with mutations in U2AF1 (P=0.047) and DNMT3A (P=0.015). RAS mutations had an impact on overall survival in secondary acute myeloid leukemia (P=0.0456). By comparison, our screening of juvenile myelomonocytic leukemia cases showed mutations in ASXL1 (4%), CBL (10%), and RAS (6%) but not in IDH1/2, TET2, EZH2, DNMT3A or the three spliceosomal genes. SRSF2 and U2AF1 along with TET2 (48%) and ASXL1 (38%) are frequently affected by somatic mutations in chronic myelomonocytic leukemia, quite distinctly from the profile seen in juvenile myelomonocytic leukemia. Our data also suggest that spliceosomal mutations are of ancestral origin. PMID:22773603

  13. 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

  14. 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.

  15. Lepton-Flavor Violating Signatures in Supersymmetric U(1)' Seesaw

    NASA Astrophysics Data System (ADS)

    Chun, Eung Jin

    In a supersymmetric U(1)' seesaw model, a right-handed sneutrino can be a good thermal dark matter candidate if the extra gaugino tilde{Z}^{prime} is light enough to provide an appropriate annihilation cross-section through a t-channel diagram. We first discuss how right thermal relic density of the right-handed sneutrino dark matter can arise and then explore lepton number and flavor violating signatures followed by cascade production of tilde{Z}^{prime} from the third generation squarks at the LHC.

  16. U1 adaptors result in reduction of multiple pre-mRNA species principally by sequestering U1snRNP.

    PubMed

    Vickers, Timothy A; Sabripour, Mahyar; Crooke, Stanley T

    2011-05-01

    U1 Adaptors are a recently reported novel approach for targeted reduction of mRNA transcripts. A U1 adaptor oligonucleotide comprising of a target-complimentary hybridization domain and a U1 recruitment domain, directs the U1 snRNP complex to the terminal exon of a targeted gene, subsequently inhibiting poly(A) tail addition and leading to degradation of that RNA species within the nucleus. Here, we present data demonstrating U1 adapter-mediated gene silencing can result in significant 'off-target' silencing effects as demonstrated by the reduction of multiple mRNA species that were not intended to be targeted. Our data suggest that a substantial portion of this U1 adaptor-mediated off-target mRNA reduction is the result of sequestration U1 snRNP at levels sufficient to affect splicing and processing of non-target transcripts. PMID:21415007

  17. 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.

  18. 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

  19. 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

  20. Regularized path integrals and anomalies: U(1) chiral gauge theory

    NASA Astrophysics Data System (ADS)

    Kopper, Christoph; Lévêque, Benjamin

    2012-02-01

    We analyze the origin of the Adler-Bell-Jackiw anomaly of chiral U(1) gauge theory within the framework of regularized path integrals. Momentum or position space regulators allow for mathematically well-defined path integrals but violate local gauge symmetry. It is known how (nonanomalous) gauge symmetry can be recovered in the renormalized theory in this case [Kopper, C. and Müller, V. F., "Renormalization of spontaneously broken SU(2) Yang-Mills theory with flow equations," Rev. Math. Phys. 21, 781 (2009)], 10.1142/S0129055X0900375X. Here we analyze U(1) chiral gauge theory to show how the appearance of anomalies manifests itself in such a context. We show that the three-photon amplitude leads to a violation of the Slavnov-Taylor identities which cannot be restored on taking the UV limit in the renormalized theory. We point out that this fact is related to the nonanalyticity of this amplitude in the infrared region.

  1. 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.

  2. A quantum defect analysis of heavy Rydberg behaviour in the B(u+1Σ) and B″ B ‾ (u+1Σ) states of H2 and the B(u+1Σ) state of D2

    NASA Astrophysics Data System (ADS)

    Lawley, Kenneth P.; Donovan, Robert J.

    2016-08-01

    Heavy Rydberg behaviour in the B(u+1Σ) and B″ B ‾ (u+1Σ) ion-pair states of H2 and the B(u+1Σ) state of D2, is analysed in terms of the absolute quantum defects of the vibronic levels. The influence of the inner repulsive wall of ion-pair potentials on heavy Rydberg behaviour is considered and shown to determine the size of both absolute quantum defects and their energy dependence.

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

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

    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 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 equals 10 at their CM frame, the objections against the origin of these events in cosmic ray interactions are overcome. A relationship then between their lifetime, tau, and the threshold energy for bubble formation, E sub th, appears to be insensitive to the value of tau and always close to E sub th approximately 10 to 15th power eV. Finally it is speculated that these bubbles might be manifestations of the SU(2) x U(1) false vacuum excited in these collisions. The absence of in the Centauro events is then explained by the decay modes of these excitations.

  4. 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.

  5. 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

  6. Multivalent binding of formin-binding protein 21 (FBP21)-tandem-WW domains fosters protein recognition in the pre-spliceosome.

    PubMed

    Klippel, Stefan; Wieczorek, Marek; Schümann, Michael; Krause, Eberhard; Marg, Berenice; Seidel, Thorsten; Meyer, Tim; Knapp, Ernst-Walter; Freund, Christian

    2011-11-01

    The high abundance of repetitive but nonidentical proline-rich sequences in spliceosomal proteins raises the question of how these known interaction motifs recruit their interacting protein domains. Whereas complex formation of these adaptors with individual motifs has been studied in great detail, little is known about the binding mode of domains arranged in tandem repeats and long proline-rich sequences including multiple motifs. Here we studied the interaction of the two adjacent WW domains of spliceosomal protein FBP21 with several ligands of different lengths and composition to elucidate the hallmarks of multivalent binding for this class of recognition domains. First, we show that many of the proteins that define the cellular proteome interacting with FBP21-WW1-WW2 contain multiple proline-rich motifs. Among these is the newly identified binding partner SF3B4. Fluorescence resonance energy transfer (FRET) analysis reveals the tandem-WW domains of FBP21 to interact with splicing factor 3B4 (SF3B4) in nuclear speckles where splicing takes place. Isothermal titration calorimetry and NMR shows that the tandem arrangement of WW domains and the multivalency of the proline-rich ligands both contribute to affinity enhancement. However, ligand exchange remains fast compared with the NMR time scale. Surprisingly, a N-terminal spin label attached to a bivalent ligand induces NMR line broadening of signals corresponding to both WW domains of the FBP21-WW1-WW2 protein. This suggests that distinct orientations of the ligand contribute to a delocalized and semispecific binding mode that should facilitate search processes within the spliceosome. PMID:21917930

  7. U(1) × SU(2) from the tangent bundle

    NASA Astrophysics Data System (ADS)

    Vargas, Jose G.

    2013-11-01

    Élie Cartan developed modern differential geometry as theory of moving frames. Particles do not enter the equations of structure and thus play a less fundamental role. A Kaluza-Klein (KK) space without compactification brings particles into the core of geometry by making propertime (τ) the fifth dimension. (xi, τ) emerges as the subspace for the quantum sector. This KK space does not make sense in SR, by virtue of non-orthogonality of τ to 3-space (actually), which brings a preferred frame to the fore. In contrast, propertime is perpendicular to 3-space in the "para-Lorentzian structure" with absolute time dilation (PL). Its (xi,τ) subspace looks very much like (t,xi) in SR. And its (t,xi) sector is not made of orthogonal frames but does not cause contradictions with SR, which supporters of the thesis of conventionality of synchronizations have been claiming for many decades. In PL, the conjunction of the Clifford algebras of differential forms (Kaehler's) and of their valuedness gives rise to a commutative algebra of primitive idempotents that embodies the U(1) × SU(2) symmetry. SU(3) also emerges in the process, but we do not deal with this issue beyond proposing the geometric palet of quarks.

  8. Maneuverability Investigation of an O3U-1 Observation Airplane

    NASA Technical Reports Server (NTRS)

    Thompson, F L; Kirschbaum, H W

    1934-01-01

    This report presents the results of maneuverability tests of an O3U-1 observation airplane. This investigation is the third in a series of similar investigations requested by the Bureau of Aeronautics (Navy) for the purpose of comparing the maneuverability of different airplane types and to provide quantitative data for use in establishing a criterion or method for rating the maneuverability of an airplane. The two former investigations were conducted with the fighter types designated F6C-3 and F6C-4 and have been reported previously. Measurement of the air speed, the angular velocity, the linear acceleration, and positions of the controls were made during abrupt single-control maneuvers with three stop positions for each control, during steady horizontal turns for the determination of minimum radius, and during 180 degree turns by various methods. Flight-path coordinates in two dimensions were determined for the 180 degree turns by means of a special camera obscura designed for the previous investigation of the F6C-4 airplane. All maneuvers were performed at an altitude of approximately 3,000 feet.

  9. 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

  10. 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.

  11. 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.

  12. Molecular architecture of the human U4/U6.U5 tri-snRNP.

    PubMed

    Agafonov, Dmitry E; Kastner, Berthold; Dybkov, Olexandr; Hofele, Romina V; Liu, Wen-Ti; Urlaub, Henning; Lührmann, Reinhard; Stark, Holger

    2016-03-25

    The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution of 7 angstroms using single-particle cryo-electron microscopy (cryo-EM). We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein cross-linking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the ubiquitin C-terminal hydrolase-like protein Sad1 likely tethers the helicase Brr2 to its preactivation position. Comparison of our model with cryo-EM three-dimensional structures of the Saccharomyces cerevisiae tri-snRNP and Schizosaccharomyces pombe spliceosome indicates that Brr2 undergoes a marked conformational change during spliceosome activation, and that the scaffolding protein Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network. PMID:26912367

  13. Human GC-AG alternative intron isoforms with weak donor sites show enhanced consensus at acceptor exon positions

    PubMed Central

    Thanaraj, T. A.; Clark, Francis

    2001-01-01

    It has been previously observed that the intrinsically weak variant GC donor sites, in order to be recognized by the U2-type spliceosome, possess strong consensus sequences maximized for base pair formation with U1 and U5/U6 snRNAs. However, variability in signal strength is a fundamental mechanism for splice site selection in alternative splicing. Here we report human alternative GC-AG introns (for the first time from any species), and show that while constitutive GC-AG introns do possess strong signals at their donor sites, a large subset of alternative GC-AG introns possess weak consensus sequences at their donor sites. Surprisingly, this subset of alternative isoforms shows strong consensus at acceptor exon positions 1 and 2. The improved consensus at the acceptor exon can facilitate a strong interaction with U5 snRNA, which tethers the two exons for ligation during the second step of splicing. Further, these isoforms nearly always possess alternative acceptor sites and exhibit particularly weak polypyrimidine tracts characteristic of AG-dependent introns. The acceptor exon nucleotides are part of the consensus required for the U2AF35-mediated recognition of AG in such introns. Such improved consensus at acceptor exons is not found in either normal or alternative GT-AG introns having weak donor sites or weak polypyrimidine tracts. The changes probably reflect mechanisms that allow GC-AG alternative intron isoforms to cope with two conflicting requirements, namely an apparent need for differential splice strength to direct the choice of alternative sites and a need for improved donor signals to compensate for the central mismatch base pair (C-A) in the RNA duplex of U1 snRNA and the pre-mRNA. The other important findings include (i) one in every twenty alternative introns is a GC-AG intron, and (ii) three of every five observed GC-AG introns are alternative isoforms. PMID:11410667

  14. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27058959

  16. 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. PMID:27058959

  17. Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry

    PubMed Central

    Ajuh, Paul; Kuster, Bernhard; Panov, Kostya; Zomerdijk, Joost C.B.M.; Mann, Matthias; Lamond, Angus I.

    2000-01-01

    Recently, we identified proteins that co-purify with the human spliceosome using mass spectrometry. One of the identified proteins, CDC5L, corresponds to the human homologue of the Schizosaccharomyces pombe CDC5+ gene product. Here we show that CDC5L is part of a larger multiprotein complex in HeLa nuclear extract that incorporates into the spliceosome in an ATP-dependent step. We also show that this complex is required for the second catalytic step of pre-mRNA splicing. Immunodepletion of the CDC5L complex from HeLa nuclear extract inhibits the formation of pre-mRNA splicing products in vitro but does not prevent spliceosome assembly. The first catalytic step of pre-mRNA splicing is less affected by immunodepleting the complex. The purified CDC5L complex in HeLa nuclear extract restores pre-mRNA splicing activity when added to extracts that have been immunodepleted using anti-CDC5L antibodies. Using mass spectrometry and database searches, the major protein components of the CDC5L complex have been identified. This work reports a first purification and characterization of a functional, human non-snRNA spliceosome subunit containing CDC5L and at least five additional protein factors. PMID:11101529

  18. A 62,000 molecular weight spliceosome protein crosslinks to the intron polypyrimidine tract.

    PubMed

    Wang, J; Pederson, T

    1990-10-25

    Incubation in HeLa nuclear extract of a 32P-labeled 61 nucleotide-long RNA corresponding to the lariat branch site/polypyrimidine tract/3' splice site of the first intron of human beta-globin pre-mRNA led to the crosslinking of a single protein of approximately 62,000 mol. wt. (p62). p62 corresponds to a polypyrimidine tract-binding protein recently described by Garcia-Blanco et al. (Genes & Dev. 3: 1874-1886, 1989). Crosslinking of p62 to the 61 nt RNA was highly sequence specific. No p62 crosslinking was observed with a 60 nt pGEM vector RNA, a 63 nt RNA antisense to the 61-mer or a 72 nt U2 RNA sequence. p62 crosslinking to the 61 nt RNA was competed by unlabeled 61 nt RNA, by beta-globin pre-mRNA containing intron 1, and by poly(U) and poly(C), but was competed to a lesser extent or not at all by pGEM RNA, a beta-globin RNA lacking intron 1, or poly(A). Experiments with mutated RNAs revealed that neither the lariat branch site adenosine nor the 3' splice site were required for p62 crosslinking to polypyrimidine tract-containing RNA. Elimination of the polypyrimidine tract reduced p62 crosslinking, as did mutation of a polypyrimidine tract UU dinucleotide to GA. However, replacement of a pyrimidine-rich tract immediately adjacent (3') to the lariat branch site with a 57% A + G pGEM vector RNA sequence also significantly reduced p62 crosslinking, indicating the involvement of both this pyrimidine-rich region and the classical polypyrimidine tract adjacent to the 3' splice site. The sites of protein interaction were further defined by RNase H protection experiments, the results of which confirmed the patterns of p62 crosslinking to mutant RNAs. p62 crosslinking was efficiently competed by a DNA oligonucleotide having the same sequence as the 61 nt RNA, showing that p62 requires neither ribose 2' OH groups nor uracil bases for its interaction with the polypyrimidine tract. p62 was not crosslinked to double-stranded 61 nt RNA. Q-Sepharose chromatography of He

  19. Climbing the vertebrate branch of U1A/U2B″ protein evolution

    PubMed Central

    Delaney, Kimberly J.; Williams, Sandra G.; Lawler, Mariah; Hall, Kathleen B.

    2014-01-01

    In the vertebrate lineage of the U1A/U2B″/SNF protein family, the U1A and U2B″ proteins bind to RNA stem–loops in the U1 or U2 snRNPs, respectively. However, their specialization is fairly recent, as they evolved from a single ancestral protein. The progress of their specialization (subfunctionalization) can be monitored by the amino acid sequence changes that give rise to their modern RNA-binding specificity. Using ancestral sequence reconstruction to predict the intermediates on the evolutionary branch, a probable path of sequential changes is defined for U1A and U2B″. The RNA-binding affinity for U1A/U2B″ protein ancestors was measured using modern U1 and U2 snRNA stem–loops and RNA stem–loop variants to understand how the proteins’ RNA specificities evolved. PMID:24840944

  20. 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.

  1. Spin Tests of 1/20-Scale Models of the Chance Vought Revised XF6U-1 and F6U-1 Airplanes, TED No. NACA 2390

    NASA Technical Reports Server (NTRS)

    Klinar, Walter J.; Berman, Theodore

    1948-01-01

    An investigation has been conducted in the Langley 20-foot free-spinning tunnel on the 1/20-scale model of the Chance Vought XF6U-1 airplane altered to represent the XF6U-1 airplane as it will be spin-tested in flight, and also altered to represent the F6U-1 airplane as it will be produced for service use. Spin tests were made to determine the effects of control settings and movements at the normal loading. The results show that the spins obtained on the revised XF6U-1 airplane will be oscillatory in roll and yaw and that recoveries by rudder reversal will be rapid. Model test results indicate that the F6U-1 airplane will probably not spin. Inasmuch as the results of this investigation show that the new designs are as good as or better than the original XF6U-1 design in regard to spin recovery, it is felt that the conclusions and recommendations reached for the original design can be applied to the new designs for all loading conditions.

  2. 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.

  3. 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

  4. 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

  5. 46 CFR 54.01-10 - Steam-generating pressure vessels (modifies U-1(g)).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Steam-generating pressure vessels (modifies U-1(g)). 54... ENGINEERING PRESSURE VESSELS General Requirements § 54.01-10 Steam-generating pressure vessels (modifies U-1(g)). (a) Pressure vessels in which steam is generated are classed as “Unfired Steam Boilers” except...

  6. 46 CFR 54.01-10 - Steam-generating pressure vessels (modifies U-1(g)).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Steam-generating pressure vessels (modifies U-1(g)). 54... ENGINEERING PRESSURE VESSELS General Requirements § 54.01-10 Steam-generating pressure vessels (modifies U-1(g)). (a) Pressure vessels in which steam is generated are classed as “Unfired Steam Boilers” except...

  7. 46 CFR 54.01-10 - Steam-generating pressure vessels (modifies U-1(g)).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Steam-generating pressure vessels (modifies U-1(g)). 54... ENGINEERING PRESSURE VESSELS General Requirements § 54.01-10 Steam-generating pressure vessels (modifies U-1(g)). (a) Pressure vessels in which steam is generated are classed as “Unfired Steam Boilers” except...

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. New U(1) gauge model of radiative lepton masses with sterile neutrino and dark matter

    NASA Astrophysics Data System (ADS)

    Adhikari, Rathin; Borah, Debasish; Ma, Ernest

    2016-04-01

    An anomaly-free U(1) gauge extension of the standard model (SM) is presented. Only one Higgs doublet with a nonzero vacuum expectation is required as in the SM. New fermions and scalars as well as all SM particles transform nontrivially under this U(1), resulting in a model of three active neutrinos and one sterile neutrino, all acquiring radiative masses. Charged-lepton masses are also radiative as well as the mixing between active and sterile neutrinos. At the same time, a residual Z2 symmetry of the U(1) gauge symmetry remains exact, allowing for the existence of dark matter.

  13. 10. DETAILED INTERIOR VIEW OF WEB AT U1L1, SHOWING VERTICAL, ...

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

    10. DETAILED INTERIOR VIEW OF WEB AT U1L1, SHOWING VERTICAL, ARCH RIB WELDED/BOLTED GUSSET PLATE AND GUARDRAIL, LOOKING SOUTH - Cottonville Bridge, County Road D-61 at Farmer's Creek, Maquoketa, Jackson County, IA

  14. Constraints on the U(1)L gauge boson in a wide mass range

    NASA Astrophysics Data System (ADS)

    Jeong, Yu Seon; Kim, C. S.; Lee, Hye-Sung

    2016-04-01

    There is a growing interest for the search of new light gauge bosons. The small mass of a new boson can turn various kinds of low-energy experiments to a new discovery machine, depending on their couplings to the Standard Model particles. It is important to understand the properties of each type of gauge boson and their current constraints for a given mass. While the dark photon (which couples to the electric charges) and the U(1)B‑L gauge boson have been well studied in an extensive mass range, the U(1)L gauge boson has not been fully investigated yet. We consider the gauge boson of the U(1)L in a wide mass range mZ‧≈ 0-1012eV and investigate the constraints on its coupling from various experiments, discussing the similarities and differences from the dark photon and the U(1)B‑L gauge boson.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 46 CFR 54.01-5 - Scope (modifies U-1 and U-2).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Scope (modifies U-1 and U-2). 54.01-5 Section 54.01-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-5 Scope (modifies U-1 and U-2). (a) This part contains requirements for pressure vessels. table 54.01-5(a) gives...

  1. F-theory and all things rational: surveying U(1) symmetries with rational sections

    NASA Astrophysics Data System (ADS)

    Lawrie, Craig; Schäfer-Nameki, Sakura; Wong, Jin-Mann

    2015-09-01

    We study elliptic fibrations for F-theory compactifications realizing 4d and 6d supersymmetric gauge theories with abelian gauge factors. In the fibration these U(1) symmetries are realized in terms of additional rational section. We obtain a universal characterization of all the possible U(1) charges of matter fields by determining the corresponding codimension two fibers with rational sections. In view of modelling supersymmetric Grand Unified Theories, one of the main examples that we analyze are U(1) symmetries for SU(5) gauge theories with overline{5} and 10 matter. We use a combination of constraints on the normal bundle of rational curves in Calabi-Yau three- and four-folds, as well as the splitting of rational curves in the fibers in codimension two, to determine the possible configurations of smooth rational sections. This analysis straightforwardly generalizes to multiple U(1)s. We study the flops of such fibers, as well as some of the Yukawa couplings in codimension three. Furthermore, we carry out a universal study of the U(1)-charged GUT singlets, including their KK-charges, and determine all realizations of singlet fibers. By giving vacuum expectation values to these singlets, we propose a systematic way to analyze the Higgsing of U(1)s to discrete gauge symmetries in F-theory.

  2. 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.

  3. 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.

  4. Defective control of pre–messenger RNA splicing in human disease

    PubMed Central

    Shkreta, Lulzim

    2016-01-01

    Examples of associations between human disease and defects in pre–messenger RNA splicing/alternative splicing are accumulating. Although many alterations are caused by mutations in splicing signals or regulatory sequence elements, recent studies have noted the disruptive impact of mutated generic spliceosome components and splicing regulatory proteins. This review highlights recent progress in our understanding of how the altered splicing function of RNA-binding proteins contributes to myelodysplastic syndromes, cancer, and neuropathologies. PMID:26728853

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  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. Investigation of gauge-fixed pure U(1) theory at strong coupling

    NASA Astrophysics Data System (ADS)

    Basak, S.; De, Asit K.

    2002-03-01

    We numerically investigate the phase diagram of pure U(1) gauge theory with gauge fixing at strong gauge coupling. The FM-FMD phase transition, which proved useful in defining Abelian lattice chiral gauge theory, persists also at strong gauge coupling. However, there the transition seems no longer to be continuous. At large gauge couplings we find evidences for confinement.

  18. Low scale nonuniversal, nonanomalous U(1)F' in a minimal supersymmetric standard model

    NASA Astrophysics Data System (ADS)

    Chen, Mu-Chun; Huang, Jinrui

    2010-10-01

    We propose a nonuniversal U(1)F' 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)F' charges, upon the breaking of the U(1)F' 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)F' charges of the chiral superfields also naturally suppress the μ-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 D0-D¯0 turns out to be much more stringent than the constraints from the precision electroweak data.

  19. 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 Carbonates U Table U-1 to Subpart U of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Miscellaneous Uses of Carbonate...

  20. 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 Carbonates U Table U-1 to Subpart U of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Miscellaneous Uses of Carbonate...

  1. 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.

  2. 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.

  3. 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.

  4. Instantons and the 5D U(1) gauge theory with extra adjoint

    NASA Astrophysics Data System (ADS)

    Poghossian, Rubik; Samsonyan, Marine

    2009-07-01

    In this paper, we compute the partition function of 5D supersymmetric U(1) gauge theory with extra adjoint matter in general Ω background. It is well known that such partition functions encode very rich topological information. We show in particular that unlike the case with no extra matter, the partition function with extra adjoint at some special values of the parameters directly reproduces the generating function for the Poincare polynomial of the moduli space of instantons. We compare our results with those recently obtained by Iqbal et al (Refined topological vertex, cylindric partitions and the U(1) adjoint theory, arXiv:0803.2260), who used the so-called refined topological vertex method.

  5. Program package for multicanonical simulations of U(1) lattice gauge theory-Second version

    NASA Astrophysics Data System (ADS)

    Bazavov, Alexei; Berg, Bernd A.

    2013-03-01

    A new version STMCMUCA_V1_1 of our program package is available. It eliminates compatibility problems of our Fortran 77 code, originally developed for the g77 compiler, with Fortran 90 and 95 compilers. New version program summaryProgram title: STMC_U1MUCA_v1_1 Catalogue identifier: AEET_v1_1 Licensing provisions: Standard CPC license, http://cpc.cs.qub.ac.uk/licence/licence.html Programming language: Fortran 77 compatible with Fortran 90 and 95 Computers: Any capable of compiling and executing Fortran code Operating systems: Any capable of compiling and executing Fortran code RAM: 10 MB and up depending on lattice size used No. of lines in distributed program, including test data, etc.: 15059 No. of bytes in distributed program, including test data, etc.: 215733 Keywords: Markov chain Monte Carlo, multicanonical, Wang-Landau recursion, Fortran, lattice gauge theory, U(1) gauge group, phase transitions of continuous systems Classification: 11.5 Catalogue identifier of previous version: AEET_v1_0 Journal Reference of previous version: Computer Physics Communications 180 (2009) 2339-2347 Does the new version supersede the previous version?: Yes Nature of problem: Efficient Markov chain Monte Carlo simulation of U(1) lattice gauge theory (or other continuous systems) 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 factors. Reweighting to physical values using logarithmic coding and calculating jackknife error bars. Reasons for the new version: The previous version was developed for the g77 compiler Fortran 77 version. Compiler errors were encountered with Fortran 90 and Fortran 95 compilers (specified below). Summary of revisions: epsilon=one/10**10 is replaced by epsilon/10.0D10 in the parameter statements of the subroutines u1_bmha.f, u1_mucabmha.f, u1wl

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. First-order phase transition and tricritical point in multiband U (1 ) London superconductors

    NASA Astrophysics Data System (ADS)

    Sellin, Karl A. H.; Babaev, Egor

    2016-02-01

    The order of the superconducting phase transition is a classical problem. Single-component type-2 superconductors exhibit a continuous "inverted-X Y " phase transition, as was first demonstrated for U (1 ) lattice London superconductors by a celebrated duality mapping with subsequent backing by numerical simulations. Here we study this problem in multiband U (1 ) London superconductors and find evidence that by contrast the model has a tricritical point. The superconducting phase transition becomes first order when the Josephson length is sufficiently large compared to the magnetic field penetration length. We present evidence that the fluctuation-induced dipolar interaction between vortex loops makes the phase transition discontinuous. We discuss that this mechanism is also relevant for the phase transitions in multicomponent gauge theories with higher broken symmetry.

  12. 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.

  13. 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

  14. U1 snRNA mis-binding: a new cause of CMT1B.

    PubMed

    Crehalet, Hervé; Latour, Philippe; Bonnet, Véronique; Attarian, Shahram; Labauge, Pierre; Bonello, Nathalie; Bernard, Rafaelle; Millat, Gilles; Rousson, Robert; Bozon, Dominique

    2010-02-01

    We report the molecular characterization of two splice mutations in two different French families affected with a late onset form of Charcot-Marie-Tooth disease type 1B (CMT1B), an autosomal dominant inherited disorder caused by mutations in the myelin protein zero gene. The first substitution, c.306G>A, located in exon 3, does not change the codon p.Val102Val but is co-transmitted with the disease in the first family. The second substitution, c.675+3dup, is an insertion of a T at position +3 of intron 5. To identify the functional impact of these nucleotide changes on splicing and because no RNA sample was available, we used in silico prediction and in vitro splicing assay. Mutation c.306G>A increases the strength of a preexisting cryptic donor site at position c.304 which becomes stronger than the normal donor site of intron 3. This variation creates a sequence that better matches the U1 small nuclear RNA (snRNA) binding consensus, and HeLa cells, transfected with the mutant minigene, produce a truncated exon 3 messenger RNA (mRNA). Mutation c.675+3dup was predicted to abolish the donor site of intron 5, and, indeed, HeLa cells transfected with the mutant minigene completely skip exon 5 from the transcript. The mutated sequence abolishes U1 snRNA binding and co-transfection of a mutated complementary U1 snRNA restored exon 5 inclusion in the mRNA. This work provides valuable information regarding the molecular basis of two forms of late onset of CMT1B, U1 snRNA mis-binding, and provides more evidence that a "silent" polymorphism may be a disease causing mutation. PMID:19475438

  15. Drag force of Anisotropic plasma at finite U(1) chemical potential

    NASA Astrophysics Data System (ADS)

    Cheng, Long; Ge, Xian-Hui; Wu, Shang-Yu

    2016-05-01

    We perform the calculation of the drag force acting on a massive quark moving through an anisotropic N=4 SU(N) Super Yang-Mills plasma in the presence of a U(1) chemical potential. We present the numerical results for any value of the anisotropy and arbitrary direction of the quark velocity with respect to the direction of the anisotropy. We find the effect of the chemical potential or charge density will enhance the drag force for our charged solution.

  16. 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.

  17. 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

  18. Chiral four-dimensional F-theory compactifications with SU(5) and multiple U(1)-factors

    NASA Astrophysics Data System (ADS)

    Cvetič, Mirjam; Grassi, Antonella; Klevers, Denis; Piragua, Hernan

    2014-04-01

    We develop geometric techniques to determine the spectrum and the chiral indices of matter multiplets for four-dimensional F-theory compactifications on elliptic Calabi-Yau fourfolds with rank two Mordell-Weil group. The general elliptic fiber is the Calabi-Yau onefold in dP 2. We classify its resolved elliptic fibrations over a general base B. The study of singularities of these fibrations leads to explicit matter representations, that we determine both for U(1) × U(1) and SU(5) × U(1) × U(1) constructions. We determine for the first time certain matter curves and surfaces using techniques involving prime ideals. The vertical cohomology ring of these fourfolds is calculated for both cases and general formulas for the Euler numbers are derived. Explicit calculations are presented for a specific base B = ℙ3. We determine the general G 4-flux that belongs to of the resolved Calabi-Yau fourfolds. As a by-product, we derive for the first time all conditions on G 4-flux in general F-theory compactifications with a non-holomorphic zero section. These conditions have to be formulated after a circle reduction in terms of Chern-Simons terms on the 3D Coulomb branch and invoke M-theory/F-theory duality. New Chern-Simons terms are generated by Kaluza-Klein states of the circle compactification. We explicitly perform the relevant field theory computations, that yield non-vanishing results precisely for fourfolds with a non-holomorphic zero section. Taking into account the new Chern-Simons terms, all 4D matter chiralities are determined via 3D M-theory/F-theory duality. We independently check these chiralities using the subset of matter surfaces we determined. The presented techniques are general and do not rely on toric data.

  19. 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.

  20. 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.

  1. U(1) Invariant F(tilde{R}) Hořava-Lifshitz gravity

    NASA Astrophysics Data System (ADS)

    Klusoň, J.; Nojiri, S.; Odintsov, S. D.; Sáez-Gómez, D.

    2011-07-01

    This paper is devoted to the study of various aspects of projectable F( R) Hořava-Lifshitz (HL) gravity. We show that some versions of F( R) HL gravity may have stable de Sitter solution and unstable flat-space solution. In this case, the problem of scalar graviton does not appear because flat space is not vacuum state. Generalizing the U(1) HL theory proposed in arXiv:1007.2410 , we formulate U(1) extension of scalar theory and of F( R) Hořava-Lifshitz gravity. The Hamiltonian approach for such the theory is developed in full detail. It is demonstrated that its Hamiltonian structure is the same as for the non-relativistic covariant HL gravity. The spectrum analysis performed around the flat background indicates the consistency of the theory because it contains a graviton with only transverse polarization. Finally, we analyze the spatially flat FRW equations for U(1) invariant F( R) Hořava-Lifshitz gravity.

  2. 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. PMID:27114556

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

    DOE PAGESBeta

    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

  4. Dark matter and muon (g - 2) in local U(1) Lμ -Lτ-extended Ma model

    NASA Astrophysics Data System (ADS)

    Baek, Seungwon

    2016-05-01

    We consider right-handed neutrino dark matter N1 in local U(1) Lμ -Lτ-extended Ma model. With the light U(1) μ - τ gauge boson (mZ‧ ∼ O (100) MeV) and small U(1) μ - τ gauge coupling (gZ‧ ∼10-4-10-3) which can accommodate the muon (g - 2) anomaly and is still allowed by other experimental constraints, we show that we can get correct relic density of dark matter for wide range of dark matter mass (M1 ∼ 10- 200 GeV), although the gauge coupling constant gZ‧ is small. This is due to the fact that the annihilation cross section of dark matter pair is enhanced by M14/ mZ‧4 in the processes N1N1 →Z‧Z‧ or N1N1 →Z‧H2. We also consider the constraints from direct detection, collider searches.

  5. U1-RNP and TLR receptors in the pathogenesis of mixed connective tissue diseasePart I. The U1-RNP complex and its biological significance in the pathogenesis of mixed connective tissue disease

    PubMed Central

    2015-01-01

    Mixed connective tissue disease (MCTD) is a rare autoimmune syndrome, signified by complex interactions between disease-related phenomena, including inflammation, proliferative vascular arteriopathy, thrombotic events and humoral autoimmune processes. It is still controversial whether MCTD is a distinct clinical entity among systemic connective tissue diseases, although several authors consider that it is distinct and underline characteristic, distinct clinical, serological and immunogenetic features. The putative target of autoimmunity in MCTD is U1-RNP, which is a complex of U1-RNA and small nuclear RNP. Both the U1-RNA component and the specific proteins, particularly U1-70K, engage immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. U1-RNA is capable of inducing manifestations consistent with TLR activation. Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins.

  6. 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

    ... thereto pursuant to sections 6(b), 7, 9(c)(3), 10, 12(b), (c), (d), or (f) of the Public Utility Holding... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form U-1, application or... prescribed. Editorial Note: For Federal Register citations affecting Form U-1, see the List of CFR...

  7. 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...

  8. Light stops in a minimal U (1 )x extension of the MSSM

    NASA Astrophysics Data System (ADS)

    Capdevilla, R. M.; Delgado, A.; Martin, A.

    2015-12-01

    In order to reproduce the measured mass of the Higgs boson mh=125 GeV in the minimal supersymmetric standard model, one usually has to rely on heavy stops. By introducing a new gauge sector, the Higgs mass gets a tree-level contribution via a nondecoupling D -term, and mh=125 GeV can be obtained with lighter stops. In this paper, we study the values of the stops masses needed to achieve the correct Higgs mass in a setup where the gauge group is extended by a single U (1 )x interaction. We derive the experimental limits on the mass of the Z' gauge boson in this setup, then discuss how the stops masses vary as a function of the free parameters introduced by the new sector. We find that the correct Higgs mass can be reproduced with stops in a region between 700-800 GeV and a Z' resonance close to the 2.5 TeV bound from the run I of the LHC, or in a higher region 800-900 GeV if the Z' resonance is heavier (3.1 TeV). This region of parameter space will be quickly accessible at run II of the LHC, and we discuss the impact of the projected run-II bounds on the U (1 )x parameter space. We also discuss the phenomenology of the Higgs-like particles introduced to break U (1 )x and conclude their effects are too small to be detected at current colliders.

  9. 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.

  10. SU(4){sub L}xU(1){sub X} models with little Higgs mechanism

    SciTech Connect

    Nam, Soo-hyeon; Lee, Kang Young; Keum, Yong-Yeon

    2010-11-15

    We study the aspects of the fermion and gauge boson sectors in SU(4){sub L}xU(1){sub X} models with a little Higgs mechanism. We introduce a new setup of fermions, which ensures the cancellation of gauge anomaly and the cancellation of one-loop quadratic divergence to the Higgs mass for all fermion multiplets and gauge bosons. We explicitly present the interactions between the standard model fermions and the heavy gauge bosons to discuss the phenomenological implications of extra Z{sup '} and Z{sup ''} gauge bosons based on recent experimental data.

  11. 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.

  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. U(1) current from the AdS/CFT: diffusion, conductivity and causality

    NASA Astrophysics Data System (ADS)

    Bu, Yanyan; Lublinsky, Michael; Sharon, Amir

    2016-04-01

    For a holographically defined finite temperature theory, we derive an off-shell constitutive relation for a global U(1) current driven by a weak external non-dynamical electromagnetic field. The constitutive relation involves an all order gradient expansion resummed into three momenta-dependent transport coefficient functions: diffusion, electric conductivity, and "magnetic" conductivity. These transport functions are first computed analytically in the hydrodynamic limit, up to third order in the derivative expansion, and then numerically for generic values of momenta. We also compute a diffusion memory function, which, as a result of all order gradient resummation, is found to be causal.

  14. 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

  15. 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.

  16. Neutrino masses in SU(4){sub L}⊗U(1){sub X} gauge models

    SciTech Connect

    Palcu, Adrian

    2013-11-13

    Neutrino masses are obtained within SU(4){sub L}⊗U(1){sub X} electroweak gauge models with spontaneous symmetry breaking by simply exploiting the tree level realization of certain dimension-five effective operators. The scalar sector needs not to be enlarged, since these operators are constructed as direct products among scalar multiplets already existing in the model. There is a unique generic matrix for Yukawa couplings in the neutrino sector, while the charged leptons are already in their diagonal basis. The experimentally observed phenomenology in the neutrino sector is obtained as a natural consequence of this particular approach.

  17. X-ray line in radiative neutrino model with global U (1 ) symmetry

    NASA Astrophysics Data System (ADS)

    Okada, Hiroshi; Orikasa, Yuta

    2014-10-01

    We study a three-loop-induced radiative neutrino model with global U (1 ) symmetry at the TeV scale, in which we consider two-component dark matter particles. We explain the x-ray line signal at about 3.55 keV recently reported by the XMM-Newton X-ray Observatory using the data of various galaxy clusters and the Andromeda Galaxy. Subsequently, we also discuss and show that a sizable muon anomalous magnetic moment, a discrepancy of the effective number of neutrino species Δ Neff≈0.39 , and a scattering cross section detected by direct detection searches can be derived.

  18. 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.

  19. Quantum decoherence of photons in the presence of hidden U(1)s

    SciTech Connect

    Ahlers, M.; Anchordoqui, L. A.; Gonzalez-Garcia, M. C.

    2010-04-15

    Many extensions of the standard model predict the existence of hidden sectors that may contain unbroken Abelian gauge groups. We argue that in the presence of quantum decoherence photons may convert into hidden photons on sufficiently long time scales and show that this effect is strongly constrained by CMB and supernova data. In particular, Planck-scale suppressed decoherence scales D{proportional_to}{omega}{sup 2}/M{sub Pl} (characteristic for noncritical string theories) are incompatible with the presence of even a single hidden U(1). The absence of photon decoherence in this simple standard model extension complements other strong bounds derived from solar, reactor, and atmospheric neutrinos.

  20. 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.

  1. Quantum decoherence of photons in the presence of hidden U(1)s

    NASA Astrophysics Data System (ADS)

    Ahlers, M.; Anchordoqui, L. A.; Gonzalez-Garcia, M. C.

    2010-04-01

    Many extensions of the standard model predict the existence of hidden sectors that may contain unbroken Abelian gauge groups. We argue that in the presence of quantum decoherence photons may convert into hidden photons on sufficiently long time scales and show that this effect is strongly constrained by CMB and supernova data. In particular, Planck-scale suppressed decoherence scales D∝ω2/MPl (characteristic for noncritical string theories) are incompatible with the presence of even a single hidden U(1). The absence of photon decoherence in this simple standard model extension complements other strong bounds derived from solar, reactor, and atmospheric neutrinos.

  2. 750 GeV diphoton excess in a U (1 ) hidden symmetry model

    NASA Astrophysics Data System (ADS)

    Das, Kasinath; Rai, Santosh Kumar

    2016-05-01

    Recent results from the experimental collaborations at LHC give hints of a resonance in the diphoton channel at an invariant mass of 750 GeV. We show that such a scalar resonance would be possible in an U (1 ) extension of the standard model where the extended symmetry is hidden and yet to be discovered. We explore the possibilities of accommodating this excess by introducing a minimal extension to the matter content and highlight the parameter space that can accommodate the observed diphoton resonance in the model. The model also predicts new interesting signals that may be observed at the current LHC run.

  3. Identification of a novel transcript of human MD2 gene.

    PubMed

    Shen, Chen; Shen, A-Dong

    2016-09-15

    Myeloid differentiation protein 2 (MD2) regulates bacterial lipopolysaccharide (LPS) triggered anti-bacterial immune response as a broker between LPS and Toll-like receptor 4 (TLR4). In this study, we identified a novel naturally occurring spliceosome of human MD2, termed as MD2-T3. This transcript lacked two exons of MD2 gene. By protein structure analysis and literature review, we predicted that MD2-T3 isoform might execute regulatory biological effects such as limiting LPS-triggered TLR4 signaling. PMID:27317890

  4. U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7.

    PubMed

    Savarese, Emina; Chae, Ohk-wha; Trowitzsch, Simon; Weber, Gert; Kastner, Berthold; Akira, Shizuo; Wagner, Hermann; Schmid, Roland M; Bauer, Stefan; Krug, Anne

    2006-04-15

    Plasmacytoid dendritic cells (PDCs), which produce IFN-alpha in response to autoimmune complexes containing nuclear antigens, are thought to be critically involved in the pathogenesis of systemic lupus erythematosus (SLE). One of the immunostimulatory components of SLE immune complexes (SLE-ICs) is self DNA, which is recognized through Tlr9 in PDCs and B cells. Small nuclear ribonucleoproteins (snRNPs) are another major component of SLE-ICs in 30% to 40% of patients. In this study, we show that murine PDCs are activated by purified U1snRNP/anti-Sm ICs to produce IFN-alpha and proinflammatory cytokines and to up-regulate costimulatory molecules. The induction of IFN-alpha and IL-6 by U1snRNPs in murine bone marrow-derived PDCs required the presence of intact U1RNA and was largely dependent on Tlr7 but independent of Tlr3. Intracellularly delivered isolated U1snRNA and oligoribonucleotides derived from the stem loop regions and the Sm-binding site of U1snRNA efficiently induced IFN-alpha and IL-6 in Flt3L-cultured DCs in a Tlr7-dependent manner. The U1snRNA component of U1snRNP immune complexes, found in patients with SLE, acts as an endogenous "self" ligand for Tlr7 and triggers IFN-alpha and IL-6 production in PDCs. PMID:16368889

  5. 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.

  6. 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.

  7. 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.

  8. Tricritical points in a compact U (1 ) lattice gauge theory at strong coupling

    NASA Astrophysics Data System (ADS)

    De, Asit K.; Sarkar, Mugdha

    2016-06-01

    Pure compact U (1 ) lattice gauge theory exhibits a phase transition at gauge coupling g ˜O (1 ) separating a familiar weak coupling Coulomb phase, having free massless photons, from a strong coupling phase. However, the phase transition was found to be of first order, ruling out any nontrivial theory resulting from a continuum limit from the strong coupling side. In this work, a compact U (1 ) lattice gauge theory is studied with addition of a dimension-two mass counterterm and a higher derivative (HD) term that ensures a unique vacuum and produces a covariant gauge-fixing term in the naive continuum limit. For a reasonably large coefficient of the HD term, now there exists a continuous transition from a regular ordered phase to a spatially modulated ordered phase. For weak gauge couplings, a continuum limit from the regular ordered phase results in a familiar theory consisting of free massless photons. For strong gauge couplings with g ≥O (1 ), this transition changes from first order to continuous as the coefficient of the HD term is increased, resulting in tricritical points which appear to be a candidate in this theory for a possible nontrivial continuum limit.

  9. TG-43 U1 based dosimetric characterization of model 67-6520 Cs-137 brachytherapy source

    SciTech Connect

    Meigooni, Ali S.; Wright, Clarissa; Koona, Rafiq A.; Awan, Shahid B.; Granero, Domingo; Perez-Calatayud, Jose; Ballester, Facundo

    2009-10-15

    Purpose: Brachytherapy treatment has been a cornerstone for management of various cancer sites, particularly for the treatment of gynecological malignancies. In low dose rate brachytherapy treatments, {sup 137}Cs sources have been used for several decades. A new {sup 137}Cs source design has been introduced (model 67-6520, source B3-561) by Isotope Products Laboratories (IPL) for clinical application. The goal of the present work is to implement the TG-43 U1 protocol in the characterization of the aforementioned {sup 137}Cs source. Methods: The dosimetric characteristics of the IPL {sup 137}Cs source are measured using LiF thermoluminescent dosimeters in a Solid Water phantom material and calculated using Monte Carlo simulations with the GEANT4 code in Solid Water and liquid water. The dose rate constant, radial dose function, and two-dimensional anisotropy function of this source model were obtained following the TG-43 U1 recommendations. In addition, the primary and scatter dose separation (PSS) formalism that could be used in convolution/superposition methods to calculate dose distributions around brachytherapy sources in heterogeneous media was studied. Results: The measured and calculated dose rate constants of the IPL {sup 137}Cs source in Solid Water were found to be 0.930({+-}7.3%) and 0.928({+-}2.6%) cGy h{sup -1} U{sup -1}, respectively. The agreement between these two methods was within our experimental uncertainties. The Monte Carlo calculated value in liquid water of the dose rate constant was {Lambda}=0.948({+-}2.6%) cGy h{sup -1} U{sup -1}. Similarly, the agreement between measured and calculated radial dose functions and the anisotropy functions was found to be within {+-}5%. In addition, the tabulated data that are required to characterize the source using the PSS formalism were derived. Conclusions: In this article the complete dosimetry of the newly designed {sup 137}Cs IPL source following the AAPM TG-43 U1 dosimetric protocol and the PSS

  10. 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.

  11. 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.

  12. 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.

  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. A numerical solution to the local cohomology problem in U(1) chiral gauge theories

    NASA Astrophysics Data System (ADS)

    Kadoh, Daisuke; Kikukawa, Yoshio

    2005-01-01

    We consider a numerical method to solve the local cohomology problem related to the gauge anomaly cancellation in U(1) chiral gauge theories. In the cohomological analysis of the chiral anomaly, it is required to carry out the differentiation and the integration of the anomaly with respect to the continuous parameter for the interpolation of the admissible gauge fields. In our numerical approach, the differentiation is evaluated explicitly through the rational approximation of the overlap Dirac operator with Zolotarev optimization. The integration is performed with a Gaussian Quadrature formula, which turns out to show rather good convergence. The Poincaré lemma is reformulated for the finite lattice and is implemented numerically. We compute the current associated with the cohomologically trivial part of the chiral anomaly in two-dimensions and check its locality properties.

  15. 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.

  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. Warped Self-Gravitating U(1) Gauge Cosmic Strings in 5D

    NASA Astrophysics Data System (ADS)

    Slagter, Reinoud J.

    2015-01-01

    We present a U(1) gauge cosmic string solution on a warped 5-dimensional space time, where we solved the effective 4-dimensional equations modified by the projection of the Weyl tensor on the brane together with the junction and boundary conditions. Where the mass per unit length of the string in the bulk can be of order of the Planck scale, in the brane it will be warped down to unobservable GUT scale. It turns out that the induced 4-dimensional space time does not show asymptotic conical behavior as in the 4D counterpart model. So there is no angle deficit and the space time seems to be unphysical at finite distance from the core of the string. This could explain the absence of observational evidence of the lensing effect cosmic strings would produce and could have consequences for the (2+1)-dimensional related models.

  18. 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.

  19. 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.

  20. 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

  1. FUS functions in coupling transcription to splicing by mediating an interaction between RNAP II and U1 snRNP

    PubMed Central

    Yu, Yong; Reed, Robin

    2015-01-01

    Pre-mRNA splicing is coupled to transcription by RNA polymerase II (RNAP II). We previously showed that U1 small nuclear ribonucleoprotein (snRNP) associates with RNAP II, and both RNAP II and U1 snRNP are also the most abundant factors associated with the protein fused-in-sarcoma (FUS), which is mutated to cause the neurodegenerative disease amyotrophic lateral sclerosis. Here, we show that an antisense morpholino that base-pairs to the 5′ end of U1 snRNA blocks splicing in the coupled system and completely disrupts the association between U1 snRNP and both FUS and RNAP II, but has no effect on the association between FUS and RNAP II. Conversely, we found that U1 snRNP does not interact with RNAP II in FUS knockdown extracts. Moreover, using these extracts, we found that FUS must be present during the transcription reaction in order for splicing to occur. Together, our data lead to a model that FUS functions in coupling transcription to splicing via mediating an interaction between RNAP II and U1 snRNP. PMID:26124092

  2. Multiple cis-acting signals for export of pre-U1 snRNA from the nucleus.

    PubMed

    Terns, M P; Dahlberg, J E; Lund, E

    1993-10-01

    We have identified cis-acting sequences that promote nuclear export of pre-U1 RNA injected into Xenopus oocyte nuclei. At least three elements, the 5' m7G cap, the 3'-terminal stem-loop structure, and sequences in the 5'-terminal 124 nucleotides, contribute to efficient export of this RNA. Both the 5' and 3' export signals can function separately and do so independently of the cap structure. Experiments using hybrid RNAs indicate that the 5' and 3' export sequences of U1 RNA are sufficient to direct export of the heterologous, otherwise nonexportable, U6 RNA. The absence of comparable export signals in U6 RNA appears to be responsible for its retention in the nucleus. Stability of the pre-snRNAs in the nucleus depends on the presence of both a 5' cap structure and a 3' base-paired stem. The 5' m7G cap is neither sufficient nor necessary for nuclear export. The m7G cap by itself did not promote export of U6 RNA or nonspecific small RNAs. Moreover, substitution of this cap with either an AppG cap or gamma-mppG cap did not eliminate export of either full-length or a "minimal" U1 RNA (lacking most of the internal U1 RNA sequences), but it reduced the rate of export by about two to threefold. However, in the absence of the 3' stem-loop, substitution of the m7G cap led to a greater decrease in export rate, underscoring the cooperative action of the three different export elements of pre-U1 RNA. The m7G cap analog, m7GpppG, selectively destabilized pre-U1 RNA within the nucleus. Thus, nuclear components that recognize the 5' m7G cap may be important for both the stability and the export of pre-U1 RNA. PMID:8405997

  3. Improvement of SMN2 Pre-mRNA Processing Mediated by Exon-Specific U1 Small Nuclear RNA

    PubMed Central

    Dal Mas, Andrea; Rogalska, Malgorzata Ewa; Bussani, Erica; Pagani, Franco

    2015-01-01

    Exon-specific U1 snRNAs (ExSpe U1s) are modified U1 snRNAs that interact with intronic sequences downstream of the 5′ splice site (ss) by complementarity. This process restores exon skipping caused by different types of mutation. We have investigated the molecular mechanism and activity of these molecules in spinal muscular atrophy (SMA), a genetic neuromuscular disease where a silent exonic transition on the survival motor neuron 2 (SMN2) leads to exon 7 (E7) skipping. By using different cellular models, we show that a single chromosome-integrated copy of ExSpe U1 induced a significant correction of endogenous SMN2 E7 splicing and resulted in the restoration of the corresponding SMN protein levels. Interestingly, the analysis of pre-mRNA transcript abundance and decay showed that ExSpe U1s promote E7 inclusion and stabilizes the SMN pre-mRNA intermediate. This selective effect on pre-mRNA stability resulted in higher levels of SMN mRNAs in comparison with those after treatment with an antisense oligonucleotide (AON) that targets corresponding intronic sequences. In mice harboring the SMN2 transgene, AAV-mediated delivery of ExSpe U1 increased E7 inclusion in brain, heart, liver, kidney, and skeletal muscle. The positive effect of ExSpe U1s on SMN pre-mRNA processing highlights their therapeutic potential in SMA and in other pathologies caused by exon-skipping mutations. PMID:25557785

  4. 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. PMID:24988355

  5. 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.

  6. Intronic cleavage and polyadenylation regulates gene expression during DNA damage response through U1 snRNA

    PubMed Central

    Devany, Emral; Park, Ji Yeon; Murphy, Michael R; Zakusilo, George; Baquero, Jorge; Zhang, Xiaokan; Hoque, Mainul; Tian, Bin; Kleiman, Frida E

    2016-01-01

    The DNA damage response involves coordinated control of gene expression and DNA repair. Using deep sequencing, we found widespread changes of alternative cleavage and polyadenylation site usage on ultraviolet-treatment in mammalian cells. Alternative cleavage and polyadenylation regulation in the 3ʹ untranslated region is substantial, leading to both shortening and lengthening of 3ʹ untranslated regions of genes. Interestingly, a strong activation of intronic alternative cleavage and polyadenylation sites is detected, resulting in widespread expression of truncated transcripts. Intronic alternative cleavage and polyadenylation events are biased to the 5ʹ end of genes and affect gene groups with important functions in DNA damage response and cancer. Moreover, intronic alternative cleavage and polyadenylation site activation during DNA damage response correlates with a decrease in U1 snRNA levels, and is reversible by U1 snRNA overexpression. Importantly, U1 snRNA overexpression mitigates ultraviolet-induced apoptosis. Together, these data reveal a significant gene regulatory scheme in DNA damage response where U1 snRNA impacts gene expression via the U1-alternative cleavage and polyadenylation axis. PMID:27462460

  7. Electromagnons, magnons, and phonons in E u1 -xH oxMn O3

    NASA Astrophysics Data System (ADS)

    Chen, Zhenyu; Schmidt, M.; Wang, Zhe; Mayr, F.; Deisenhofer, J.; Mukhin, A. A.; Balbashov, A. M.; Loidl, A.

    2016-04-01

    Here we present a detailed study of the terahertz and far-infrared response of the mixed perovskite manganite system E u1 -xH oxMn O3 for holmium concentrations x =0.1 and 0.3. We compare the magnetic excitations of the four different magnetically ordered phases (A -type antiferromagnetic, sinusoidally modulated collinear, helical phases with spin planes perpendicular to the crystallographic a and c axes). The transition between the two latter phases goes hand in hand with a switching of the ferroelectric polarization from P ∥a to P ∥c . Special emphasis is paid to the temperature dependence of the excitations at this transition. We find a significant change of intensity indicating that the exchange-striction mechanism may not be the only mechanism to induce dipolar weight to spin-wave excitations. We also focus on excitations within the incommensurate collinear antiferromagnetic phase and find an excitation close to 40 c m-1 . A detailed analysis of optical weight gives a further unexpected result: In the multiferroic phase with P ∥c all the spectral weight of the electromagnons comes from the lowest-phonon mode. However, for the phase with the polarization P ∥a additional spectral weight must be transferred from higher frequencies.

  8. Boundary conditions, gauge fixing ambiguities and exact expectation values in U(1) lattice gauge theory

    NASA Astrophysics Data System (ADS)

    Pinto, Carlos

    2016-03-01

    We analyze the interplay between gauge fixing and boundary conditions in two-dimensional U(1) lattice gauge theory. We show on the basis of a general argument that periodic boundary conditions result in an ill-defined weak coupling approximation but that the approximation can be made well-defined if the boundaries are fixed to zero. We confirm this result in the particular case of the Feynman gauge. We show that the zero momentum mode divergence in the propagator that appears in the Feynman gauge vanishes when the weak coupling approximation is well-defined. In addition we obtain exact results (for arbitrary coupling), including finite size corrections, for the partition function and for general one-point and two-point functions in the axial gauge under both periodic and zero boundary conditions and confirm these results numerically. The dependence of these objects on both lattice size and coupling constant is investigated using specific examples. These exact results may provide insight into similar gauge fixing issues in more complex models.

  9. 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.

  10. Real-Time Dynamics in U(1) Lattice Gauge Theories with Tensor Networks

    NASA Astrophysics Data System (ADS)

    Pichler, T.; Dalmonte, M.; Rico, E.; Zoller, P.; Montangero, S.

    2016-01-01

    Tensor network algorithms provide a suitable route for tackling real-time-dependent problems in lattice gauge theories, enabling the investigation of out-of-equilibrium dynamics. We analyze a U(1) lattice gauge theory in (1 +1 ) dimensions in the presence of dynamical matter for different mass and electric-field couplings, a theory akin to quantum electrodynamics in one dimension, which displays string breaking: The confining string between charges can spontaneously break during quench experiments, giving rise to charge-anticharge pairs according to the Schwinger mechanism. We study the real-time spreading of excitations in the system by means of electric-field and particle fluctuations. We determine a dynamical state diagram for string breaking and quantitatively evaluate the time scales for mass production. We also show that the time evolution of the quantum correlations can be detected via bipartite von Neumann entropies, thus demonstrating that the Schwinger mechanism is tightly linked to entanglement spreading. To present a variety of possible applications of this simulation platform, we show how one could follow the real-time scattering processes between mesons and the creation of entanglement during scattering processes. Finally, we test the quality of quantum simulations of these dynamics, quantifying the role of possible imperfections in cold atoms, trapped ions, and superconducting circuit systems. Our results demonstrate how entanglement properties can be used to deepen our understanding of basic phenomena in the real-time dynamics of gauge theories such as string breaking and collisions.

  11. Crystallographic peculiarities of the eutectoid and martensite structures in the U-1.5 % Mo alloy

    NASA Astrophysics Data System (ADS)

    Kabanova, I. G.; Klyukina, M. F.; Sagaradze, V. V.; Pecherkina, N. L.; Zuev, Yu. N.

    2016-06-01

    Using electron microscopy, samples of U-1.5 wt % Mo alloy with a partial structure of eutectoid, which consists of alternating plates of α phase depleted of molybdenum (α-U) and ordered γ' phase (U2Mo), have been studied. The structures of a eutectoid and martensite have been obtained by the quenching of samples characterized by delayed cooling from 1000°C. It has been shown that, in the eutectoid, the constant orientation relationships (ORs) are observed between the α-U and U2Mo phases, namely, {[ {100} ]_α }{| {[ {331} ]} ._{γ '}},{( {010} )_α }{| {( {11bar 6} )} ._{γ '}},{( {010} )_α }{| {( {bar 110} )} ._{γ '}} These relationships are similar to the ORs observed in the martensite between an orthorhombic α' martensite and initial bcc γ phase that have been found in low alloys of U-Nb, U-Zr, U-Mo and experimentally confirmed in this work. It has been established that, in the γ' phase, principal axes a, b, c remain parallel to the principal axes of the matrix γ phase. However, its axis of tetragonality c has the only nonequivalent crystallographic direction at which the plates in the eutectoid colonies that are parallel to the planes of atomic ordering of the γ' phase have interphase boundaries of (001)_{γ '} ||(130)_α.

  12. Implications of SU(2)_L x U(1) Symmetry for SIM(2) Invariant Neutrino Masses

    SciTech Connect

    Alan Dunn; Thomas Mehen

    2006-10-16

    We consider SU(2){sub L} x U(1) gauge invariant generalizations of a nonlocal, Lorentz violating mass term for neutrinos that preserves a SIM(2) subgroup. This induces Lorentz violating effects in QED as well as tree-level lepton family number violating interactions. Measurements of g{sub e} - 2 with trapped electrons severely constrain possible SIM(2) mass terms for electrons which violate C invariance. We study Lorentz violating effects in a C invariant and SIM(2) invariant extension of QED. We examine the Lorentz violating interactions of nonrelativistic electrons with electromagnetic fields to determine their impact on the spectroscopy of hydrogen-like atoms and g{sub e} - 2 measurements with trapped electrons. Generically, Lorentz violating corrections are suppressed by m{sub v}{sup 2}/m{sub e}{sup 2} and are within experimental limits. We study one-loop corrections to electron and photon self-energies and point out the need for a prescription to handle IR divergences induced by the nonlocality of the theory. We also calculate the tree level contribution to {mu} {yields} e + {gamma} from SIM(2) invariant mass terms.

  13. All supersymmetric solutions of 3D U(1)3 gauged supergravity.

    NASA Astrophysics Data System (ADS)

    Colgáin, Eoin Ó.

    2015-11-01

    D3-branes wrapping constant curvature Riemann surfaces give rise to 2D N=(0,2) SCFTs, where the superconformal fixed-points are mapped to vacua of 3D N=2 U(1)3 gauged supergravity. In this work we determine the fermionic supersymmetry variations of the theory and present all supersymmetric solutions. For spacetimes with a timelike Killing vector, we identify new timelike warped AdS3 (Gödel) and timelike warped dS3 fixed-points. We outline the construction of numerical solutions interpolating between fixed-points, demonstrate that these flows are driven by an irrelevant scalar operator in the SCFT and identify the inverse of the superpotential as a candidate c-function. We further classify all spacetimes with a null Killing vector, in the process producing loci in parameter space where null-warped AdS3 vacua with Schrödinger z = 2 symmetry exist. We construct non-supersymmetric spacelike warped AdS3 geometries based on D3-branes.

  14. Constraining minimal U(1)B-L model from dark matter observations

    NASA Astrophysics Data System (ADS)

    Basak, Tanushree; Mondal, Tanmoy

    2014-03-01

    We study the B-L gauge extension of the Standard Model which contains a singlet scalar and three right-handed neutrinos. The vacuum expectation value of the singlet scalar breaks the U(1)B-L symmetry. Here the third-generation right-handed neutrino is qualified as the dark matter candidate, as an artifact of Z2-charge assignment. Relic abundance of the dark matter is consistent with WMAP9 and PLANCK data, only near scalar resonances where dark matter mass is almost half of the scalar boson masses. Requiring correct relic abundance, we restrict the parameter space of the scalar mixing angle and mass of the heavy scalar boson of this model. Besides this, the maximum value of the spin-independent scattering cross section off nucleon is well below the Xenon100 and recent LUX exclusion limits and can be probed by future Xenon1T experiments. In addition, we compute the annihilation of the dark matter into a two-photon final state in detail and compare with the Fermi-LAT upper bound on ⟨σv⟩γγ for the NFW and Einasto profile.

  15. Chiral U(1) flavor models and flavored Higgs doublets: the top FB asymmetry and the W jj

    SciTech Connect

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

    2012-01-01

    We present U(1) flavor models for leptophobic Z' with flavor dependent couplings to the right-handed up-type quarks in the Standard Model (SM), which can accommodate the recent data on the top forward-backward (FB) asymmetry and the dijet resonance associated with a W boson reported by CDF Collaboration. Such flavor-dependent leptophobic charge assignments generally require extra chiral fermions for anomaly cancellation. Also the chiral nature of U(1)' flavor symmetry calls for new U(1)'-charged Higgs doublets in order for the SM fermions to have realistic renormalizable Yukawa couplings. The stringent constraints from the top FB asymmetry at the Tevatron and the same sign top pair production at the LHC can be evaded due to contributions of the extra Higgs doublets. We also show that the extension could realize cold dark matter candidates.

  16. 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)].

  17. 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.

  18. Global SO(3) x SO(3) x U(1) symmetry of the Hubbard model on bipartite lattices

    SciTech Connect

    Carmelo, J.M.P.; Ostlund, Stellan; Sampaio, M.J.

    2010-08-15

    In this paper the global symmetry of the Hubbard model on a bipartite lattice is found to be larger than SO(4). The model is one of the most studied many-particle quantum problems, yet except in one dimension it has no exact solution, so that there remain many open questions about its properties. Symmetry plays an important role in physics and often can be used to extract useful information on unsolved non-perturbative quantum problems. Specifically, here it is found that for on-site interaction U {ne} 0 the local SU(2) x SU(2) x U(1) gauge symmetry of the Hubbard model on a bipartite lattice with N{sub a}{sup D} sites and vanishing transfer integral t = 0 can be lifted to a global [SU(2) x SU(2) x U(1)]/Z{sub 2}{sup 2} = SO(3) x SO(3) x U(1) symmetry in the presence of the kinetic-energy hopping term of the Hamiltonian with t > 0. (Examples of a bipartite lattice are the D-dimensional cubic lattices of lattice constant a and edge length L = N{sub a}a for which D = 1, 2, 3,... in the number N{sub a}{sup D} of sites.) The generator of the new found hidden independent charge global U(1) symmetry, which is not related to the ordinary U(1) gauge subgroup of electromagnetism, is one half the rotated-electron number of singly occupied sites operator. Although addition of chemical-potential and magnetic-field operator terms to the model Hamiltonian lowers its symmetry, such terms commute with it. Therefore, its 4{sup N}{sub a}{sup D} energy eigenstates refer to representations of the new found global [SU(2) x SU(2) x U(1)]/Z{sub 2}{sup 2} = SO(3) x SO(3) x U(1) symmetry. Consistently, we find that for the Hubbard model on a bipartite lattice the number of independent representations of the group SO(3) x SO(3) x U(1) equals the Hilbert-space dimension 4{sup N}{sub a}{sup D}. It is confirmed elsewhere that the new found symmetry has important physical consequences.

  19. 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

  20. 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.

  1. 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.

  2. Multi-Higgs doublet models with local U(1){sub H} gauge symmetry and neutrino physics therein

    SciTech Connect

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

    2014-01-01

    Multi-Higgs doublet models appear in many interesting extensions of the standard model (SM). But they suffer from Higgs-mediated flavor changing neutral current (FCNC) problem which is very generic. In this talk, I describe that this problem can be resolved or mitigated if we introduce local U(1){sub H} Higgs flavor gauge symmetry. As examples, I describe chiral U(1){sub H} models where the right-handed up-type quarks also carry U(1){sub H} charges and discuss the top forward-backward asymmetry (FBA) and B → D{sup (*)}τν puzzle. Next I describe the two-Higgs doublet models where the usual Z₂ symmetry is implemented to U(1){sub H} and show how the Type-I and Type-II models are extended. One possible extension of Type-II has the same fermion contents with the leptophobic E₆Z´ model by Rosner, and I discuss the neutrino sector in this model briefly.

  3. RBFOX2 Promotes Protein 4.1R Exon 16 Selection via U1 snRNP Recruitment

    PubMed Central

    Ou, Alexander C.; Park, Jennie; Yu, Faye; Yu, Brian; Lee, Angela; Yang, Guang; Zhou, Anyu; Benz, Edward J.

    2012-01-01

    The erythroid differentiation-specific splicing switch of protein 4.1R exon 16, which encodes a spectrin/actin-binding peptide critical for erythrocyte membrane stability, is modulated by the differentiation-induced splicing factor RBFOX2. We have now characterized the mechanism by which RBFOX2 regulates exon 16 splicing through the downstream intronic element UGCAUG. Exon 16 possesses a weak 5′ splice site (GAG/GTTTGT), which when strengthened to a consensus sequence (GAG/GTAAGT) leads to near-total exon 16 inclusion. Impaired RBFOX2 binding reduces exon 16 inclusion in the context of the native weak 5′ splice site, but not the engineered strong 5′ splice site, implying that RBFOX2 achieves its effect by promoting utilization of the weak 5′ splice site. We further demonstrate that RBFOX2 increases U1 snRNP recruitment to the weak 5′ splice site through direct interaction between its C-terminal domain (CTD) and the zinc finger region of U1C and that the CTD is required for the effect of RBFOX2 on exon 16 splicing. Our data suggest a novel mechanism for exon 16 5′ splice site activation in which the binding of RBFOX2 to downstream intronic splicing enhancers stabilizes the pre-mRNA–U1 snRNP complex through interactions with U1C. PMID:22083953

  4. Froggatt-Nielsen meets Mordell-Weil: a phenomenological survey of global F-theory GUTs with U(1)s

    NASA Astrophysics Data System (ADS)

    Krippendorf, Sven; Schäfer-Nameki, Sakura; Wong, Jin-Mann

    2015-11-01

    In F-theory, U(1) gauge symmetries are encoded in rational sections, which generate the Mordell-Weil group of the elliptic fibration of the compactification space. Recently the possible U(1) charges for global SU(5) F-theory GUTs with smooth rational sections were classified [1]. In this paper we utilize this classification to probe global F-theory models for their phenomenological viability. After imposing an exotic-free MSSM spectrum, anomaly cancellation (related to hypercharge flux GUT breaking in the presence of U(1) gauge symmetries), absence of dimension four and five proton decay operators and other R-parity violating couplings, and the presence of at least the third generation top Yukawa coupling, we generate the remaining quark and lepton Yukawa textures by a Froggatt-Nielsen mechanism. In this process we require that the dangerous couplings are forbidden at leading order, and when re-generated by singlet vevs, lie within the experimental bounds. We scan over all possible configurations, and show that only a small class of U(1) charge assignments and matter distributions satisfy all the requirements. The solutions give rise to the exact MSSM spectrum with realistic quark and lepton Yukawa textures, which are consistent with the CKM and PMNS mixing matrices. We also discuss the geometric realization of these models, and provide pointers to the class of elliptic fibrations with good phenomenological properties.

  5. 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

  6. U1 snRNP is mislocalized in ALS patient fibroblasts bearing NLS mutations in FUS and is required for motor neuron outgrowth in zebrafish.

    PubMed

    Yu, Yong; Chi, Binkai; Xia, Wei; Gangopadhyay, Jaya; Yamazaki, Tomohiro; Winkelbauer-Hurt, Marlene E; Yin, Shanye; Eliasse, Yoan; Adams, Edward; Shaw, Christopher E; Reed, Robin

    2015-03-31

    Mutations in FUS cause amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to neurodegeneration remain obscure. We previously found that U1 snRNP is the most abundant FUS interactor. Here, we report that components of the U1 snRNP core particle (Sm proteins and U1 snRNA), but not the mature U1 snRNP-specific proteins (U1-70K, U1A and U1C), co-mislocalize with FUS to the cytoplasm in ALS patient fibroblasts harboring mutations in the FUS nuclear localization signal (NLS). Similar results were obtained in HeLa cells expressing the ALS-causing FUS R495X NLS mutation, and mislocalization of Sm proteins is RRM-dependent. Moreover, as observed with FUS, knockdown of any of the U1 snRNP-specific proteins results in a dramatic loss of SMN-containing Gems. Significantly, knockdown of U1 snRNP in zebrafish results in motor axon truncations, a phenotype also observed with FUS, SMN and TDP-43 knockdowns. Our observations linking U1 snRNP to ALS patient cells with FUS mutations, SMN-containing Gems, and motor neurons indicate that U1 snRNP is a component of a molecular pathway associated with motor neuron disease. Linking an essential canonical splicing factor (U1 snRNP) to this pathway provides strong new evidence that splicing defects may be involved in pathogenesis and that this pathway is a potential therapeutic target. PMID:25735748

  7. U1 snRNP is mislocalized in ALS patient fibroblasts bearing NLS mutations in FUS and is required for motor neuron outgrowth in zebrafish

    PubMed Central

    Yu, Yong; Chi, Binkai; Xia, Wei; Gangopadhyay, Jaya; Yamazaki, Tomohiro; Winkelbauer-Hurt, Marlene E.; Yin, Shanye; Eliasse, Yoan; Adams, Edward; Shaw, Christopher E.; Reed, Robin

    2015-01-01

    Mutations in FUS cause amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to neurodegeneration remain obscure. We previously found that U1 snRNP is the most abundant FUS interactor. Here, we report that components of the U1 snRNP core particle (Sm proteins and U1 snRNA), but not the mature U1 snRNP-specific proteins (U1-70K, U1A and U1C), co-mislocalize with FUS to the cytoplasm in ALS patient fibroblasts harboring mutations in the FUS nuclear localization signal (NLS). Similar results were obtained in HeLa cells expressing the ALS-causing FUS R495X NLS mutation, and mislocalization of Sm proteins is RRM-dependent. Moreover, as observed with FUS, knockdown of any of the U1 snRNP-specific proteins results in a dramatic loss of SMN-containing Gems. Significantly, knockdown of U1 snRNP in zebrafish results in motor axon truncations, a phenotype also observed with FUS, SMN and TDP-43 knockdowns. Our observations linking U1 snRNP to ALS patient cells with FUS mutations, SMN-containing Gems, and motor neurons indicate that U1 snRNP is a component of a molecular pathway associated with motor neuron disease. Linking an essential canonical splicing factor (U1 snRNP) to this pathway provides strong new evidence that splicing defects may be involved in pathogenesis and that this pathway is a potential therapeutic target. PMID:25735748

  8. About a peculiar extra U(1): Z{sup '} discovery limit, muon anomalous magnetic moment, and electron electric dipole moment

    SciTech Connect

    Heo, Jae Ho

    2009-08-01

    The model (Lagrangian) with a peculiar extra U(1)[S. M. Barr and I. Dorsner, Phys. Rev. D 72, 015011 (2005); S. M. Barr and A. Khan, Phys. Rev. D 74, 085023 (2006)] is clearly presented. The assigned extra U(1) gauge charges give a strong constraint to build Lagrangians. The Z{sup '} discovery limits are estimated and predicted at the Tevatron and the LHC. The new contributions of the muon anomalous magnetic moment are investigated at one and two loops, and we predict that the deviation from the standard model may be explained. The electron electric dipole moment could also be generated because of the explicit CP-violation effect in the Higgs sector, and a sizable contribution is expected for a moderately sized CP phase [argument of the CP-odd Higgs], 0.1{<=}sin{delta}{<=}1[6 deg. {<=}arg(A){<=}90 deg.].

  9. 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.

  10. Fermions and gauge bosons in SU(4){sub L}xU(1){sub X} models with little Higgs

    SciTech Connect

    Nam, Soo-hyeon

    2008-11-23

    We discuss the aspects of the little Higgs model with the SU(4){sub L}xU(1){sub X} electroweak gauge group as an alternative solution to the naturalness and fine-tuning issues. We introduce anomaly-free fermion spectra, and present their interactions with the physical gauge bosons. We also discuss some phenomenological implications of these fermions and the extra gauge bosons based on recent experimental results.

  11. S{sub 4}xZ{sub 2} flavor symmetry in supersymmetric extra U(1) model

    SciTech Connect

    Daikoku, Y.; Okada, H.

    2010-08-01

    We propose a E{sub 6} inspired supersymmetric model with a non-Abelian discrete flavor symmetry (S{sub 4} group); that is, SU(3){sub c}xSU(2){sub W}xU(1){sub Y}xU(1){sub X}xS{sub 4}xZ{sub 2}. In our scenario, the additional Abelian gauge symmetry, U(1){sub X}, not only solves the {mu} problem in the minimal supersymmetric standard model but also requires new exotic fields which play an important role in solving flavor puzzles. If our exotic quarks can be embedded into a S{sub 4} triplet, which corresponds to the number of the generation, one finds that dangerous proton decay can be well suppressed. Hence, it might be expected that the generation structure for lepton and quark in the standard model can be understood as a new system in order to stabilize the proton in a supersymmetric standard model. Moreover, because of the nature of the discrete non-Abelian symmetry itself, Yukawa coupling constants of our model are drastically reduced. In our paper, we show two predictive examples of the models for quark sector and lepton sector, respectively.

  12. The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms

    PubMed Central

    Emmert, Steffen; Schneider, Thomas D.; Khan, Sikandar G.; Kraemer, Kenneth H.

    2001-01-01

    Defects in the XPG DNA repair endonuclease gene can result in the cancer-prone disorders xeroderma pigmentosum (XP) or the XP–Cockayne syndrome complex. While the XPG cDNA sequence was known, determination of the genomic sequence was required to understand its different functions. In cells from normal donors, we found that the genomic sequence of the human XPG gene spans 30 kb, contains 15 exons that range from 61 to 1074 bp and 14 introns that range from 250 to 5763 bp. Analysis of the splice donor and acceptor sites using an information theory-based approach revealed three splice sites with low information content, which are components of the minor (U12) spliceosome. We identified six alternatively spliced XPG mRNA isoforms in cells from normal donors and from XPG patients: partial deletion of exon 8, partial retention of intron 8, two with alternative exons (in introns 1 and 6) and two that retained complete introns (introns 3 and 9). The amount of alternatively spliced XPG mRNA isoforms varied in different tissues. Most alternative splice donor and acceptor sites had a relatively high information content, but one has the U12 spliceosome sequence. A single nucleotide polymorphism has allele frequencies of 0.74 for 3507G and 0.26 for 3507C in 91 donors. The human XPG gene contains multiple splice sites with low information content in association with multiple alternatively spliced isoforms of XPG mRNA. PMID:11266544

  13. Characterization of the Dynamics of an Essential Helix in the U1A Protein by Time-Resolved Fluorescence Measurements†

    PubMed Central

    Anunciado, Divina; Agumeh, Michael; Kormos, Bethany L.; Beveridge, David L.; Knee, Joseph L.; Baranger, Anne M.

    2008-01-01

    The RNA recognition motif (RRM), one of the most common RNA-binding domains, recognizes single-stranded RNA. A C-terminal helix that undergoes conformational changes upon binding is often an important contributor to RNA recognition. The N-terminal RRM of the U1A protein contains a C-terminal helix (helix C) that interacts with the RNA-binding surface of a β-sheet in the free protein (closed conformation), but is directed away from this β-sheet in the complex with RNA (open conformation). The dynamics of helix C in the free protein have been proposed to contribute to binding affinity and specificity. We report here a direct investigation of the dynamics of helix C in the free U1A protein on the nanosecond time scale using time-resolved fluorescence anisotropy. The results indicate that helix C is dynamic on a 2–3 ns time scale within a 20° range of motion. Steady-state fluorescence experiments and molecular dynamics simulations suggest that the dynamical motion of helix C occurs within the closed conformation. Mutation of a residue on the β-sheet that contacts helix C in the closed conformation dramatically destabilizes the complex (Phe56Ala) and alters the steady-state fluorescence, but not the time-resolved fluorescence anisotropy, of a Trp in helix C. Mutation of Asp90 in the hinge region between helix C and the remainder of the protein to Ala or Gly subtly alters the dynamics of the U1A protein and destabilizes the complex. Together these results show that helix C maintains a dynamic closed conformation that is stable to these targeted protein modifications and does not equilibrate with the open conformation on the nanosecond time scale. PMID:18293956

  14. SU(3){sub c} x SU(3){sub L} x U(1){sub X} models with four families

    SciTech Connect

    Benavides, Richard H.; Ponce, William A.; Giraldo, Yithsbey

    2010-07-01

    In the context of the local gauge group SU(3){sub c} x SU(3){sub L} x U(1){sub X}, we look for possible four family models, where all the particles carry ordinary electric charges. Thirteen different anomaly-free fermion structures emerge, out of which only two are realistic. For the simplest physical structure, we calculate the charged and neutral weak currents and the tree-level Fermion masses. We also look for new sources of flavor changing neutral currents in the quark sector in connection with the upcoming experimental results at the Large Hadron Collider.

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

    SciTech Connect

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

    2007-08-07

    We devise minimalistic gauged U(1)_X Froggatt-Nielsen models which at low-energy give rise to the recently suggested discrete gauge Z_6 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_string, g_X and G_SM's Kac-Moody levels. The only mass scale apart from M_grav is m_soft.

  16. 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.

  17. 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

  18. PHYSICS OF ELEMENTARY PARTICLES AND FIELDS: Effective Action for Noncommutative U(1) Gauge Theory with Higher Dimensional Terms

    NASA Astrophysics Data System (ADS)

    Mirza, Behrouz; Zarei, Moslem

    2010-08-01

    In this paper we apply the assumption of our recent work in noncommutative scalar models to the noncommutative U(1) gauge theories. This assumption is that the noncommutative effects start to be visible continuously from a scale ΛNC and that below this scale the theory is a commutative one. Based on this assumption and using background field method and loop calculations, an effective action is derived for noncommutative U(1) gauge theory. It will be shown that the corresponding low energy effective theory is asymptotically free and that under this condition the noncommutative quadratic IR divergences will not appear. The effective theory contains higher dimensional terms, which become more important at high energies. These terms predict an elastic photon-photon scattering due to the noncommutativity of space. The coefficients of these higher dimensional terms also satisfy a positivity constraint indicating that in this theory the related diseases of superluminal signal propagating and bad analytic properties of S-matrix do not exist. In the last section, we will apply our method to the noncommutative extra dimension theories.

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

    PubMed

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

    2016-09-01

    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

  20. 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.

  1. First-principles molecular dynamics study of water dissociation on the γ-U(1 0 0) surface.

    PubMed

    Yang, Yu; Zhang, Ping

    2015-05-01

    Based on first-principles molecular dynamics simulations at finite temperatures, we systematically study the adsorption and dissociation of water molecules on the γ-U(1 0 0) surface. We predict that water molecules spontaneously dissociate upon approaching the native γ-U(1 0 0) surface. The dissociation results from electronic interactions between surface uranium 6d states and 1b2, 3a1, and 1b1 molecular orbitals of water. With segregated Nb atoms existing on the surface, adsorbing water molecules also dissociate spontaneously because Nb 3d electronic states can also interact with the molecular orbitals similarly. After dissociation, the isolated hydrogen atoms are found to diffuse fast on both the γ-U surface and that with a surface substitutional Nb atom, which is very similar to the 'Hot-Atom' dissociation of oxygen molecules on the Al(1 1 1) surface. From a series of consecutive molecular dynamics simulations, we further reveal that on both the γ-U surface and that with a surface substitutional Nb atom, one surface U atom will be pulled out to form the U-O-U structure after dissociative adsorption of 0.44 ML water molecules. This result indicates that oxide nucleus can form at low coverage of water adsorption on the two surfaces. PMID:25835568

  2. First-principles molecular dynamics study of water dissociation on the γ-U(1 0 0) surface

    NASA Astrophysics Data System (ADS)

    Yang, Yu; Zhang, Ping

    2015-05-01

    Based on first-principles molecular dynamics simulations at finite temperatures, we systematically study the adsorption and dissociation of water molecules on the γ-U(1 0 0) surface. We predict that water molecules spontaneously dissociate upon approaching the native γ-U(1 0 0) surface. The dissociation results from electronic interactions between surface uranium 6d states and 1b2, 3a1, and 1b1 molecular orbitals of water. With segregated Nb atoms existing on the surface, adsorbing water molecules also dissociate spontaneously because Nb 3d electronic states can also interact with the molecular orbitals similarly. After dissociation, the isolated hydrogen atoms are found to diffuse fast on both the γ-U surface and that with a surface substitutional Nb atom, which is very similar to the ‘Hot-Atom’ dissociation of oxygen molecules on the Al(1 1 1) surface. From a series of consecutive molecular dynamics simulations, we further reveal that on both the γ-U surface and that with a surface substitutional Nb atom, one surface U atom will be pulled out to form the U-O-U structure after dissociative adsorption of 0.44 ML water molecules. This result indicates that oxide nucleus can form at low coverage of water adsorption on the two surfaces.

  3. SU(4){sub L} x U(1){sub X} three-family model for the electroweak interaction

    SciTech Connect

    Sanchez, Luis A.; Wills-Toro, Luis A.; Zuluaga, Jorge I.

    2008-02-01

    An extension of the gauge group SU(2){sub L} x U(1){sub Y} of the standard model to the symmetry group SU(4){sub L} x U(1){sub X} (3-4-1 for short) is presented. The model does not contain exotic electric charges and anomaly cancellation is achieved with a family of quarks transforming differently from the other two, thus leading to FCNC. By introducing a discrete Z{sub 2} symmetry we obtain a consistent fermion mass spectrum, and avoid unitarity violation of the Cabibbo-Kobayashi-Maskawa mixing matrix arising from the mixing of ordinary and exotic quarks. The neutral currents coupled to all neutral vector bosons are studied, and by using CERN LEP and SLAC Linear Collider data at Z-pole and atomic parity violation data, we bound parameters of the model related to tree-level Z-Z{sup '} mixing. These parameters are further constrained by using experimental input from neutral meson mixing in the analysis of sources of FCNC present in the model. Constraints coming from the contribution of exotic particles to the one-loop oblique electroweak parameters S, T and U are also briefly discussed. Finally, a comparison is done of the predictions of different classes of 3-4-1 models without exotic electric charges.

  4. 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

  5. Stable SUSY breaking model with O(10) eV gravitino from combined D-term gauge mediation and U(1)' mediation

    SciTech Connect

    Nakayama, Yu; Nakayama, Yu

    2007-12-17

    We show a calculable example of stable supersymmetry (SUSY) breaking modelswith O(10) eV gravitino mass based on the combination of D-term gauge mediationand U(1)' mediation. A potential problem of the negative mass squared for theSUSY standard model (SSM) sfermions in the D-term gauge mediation is solvedby the contribution from the U(1)' mediation. On the other hand, the splittingbetween the SSM gauginos and sfermions in the U(1)' mediation iscircumvented bythe contributions from the D-term gauge mediation. Since the U(1)' mediation doesnot introduce any new SUSY vacua, we achieve a completely stable model underthermal effects. Our model, therefore, has no cosmological difficulty.

  6. 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.

  7. 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.

  8. Determination of U (1 )A restoration from pion and a0 -meson screening masses: Toward the chiral regime

    NASA Astrophysics Data System (ADS)

    Ishii, Masahiro; Yonemura, Koji; Takahashi, Junichi; Kouno, Hiroaki; Yahiro, Masanobu

    2016-01-01

    We incorporate the effective restoration of U (1 )A symmetry in the 2 +1 -flavor entanglement Polyakov-loop extended Nambu-Jona-Lasinio (EPNJL) model by introducing a temperature-dependent strength K (T ) to the Kobayashi-Maskawa-'t Hooft determinant interaction. T dependence of K (T ) is well determined from pion and a0-meson screening masses obtained by lattice QCD (LQCD) simulations with improved p4 staggered fermions. The strength is strongly suppressed in the vicinity of the pseudocritical temperature of chiral transition. The EPNJL model with the K (T ) well reproduces meson susceptibilities calculated by LQCD with domain-wall fermions. The model shows that the chiral transition is second order at the "light-quark chiral-limit" point where the light quark mass is zero and the strange quark mass is fixed at the physical value. This indicates that there exists a tricritical point. Hence, the location is estimated.

  9. 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.

  10. Developing a Treatment Planning Software Based on TG-43U1 Formalism for Cs-137 LDR Brachytherapy

    PubMed Central

    Sina, Sedigheh; Faghihi, Reza; Soleimani Meigooni, Ali; Siavashpour, Zahra; Mosleh-Shirazi, Mohammad Amin

    2013-01-01

    Background The old Treatment Planning Systems (TPSs) used for intracavitary brachytherapy with Cs-137 Selectron source utilize traditional dose calculation methods, considering each source as a point source. Using such methods introduces significant errors in dose estimation. As of 1995, TG-43 is used as the main dose calculation formalism in treatment TPSs. Objectives The purpose of this study is to design and establish a treatment planning software for Cs-137 Solectron brachytherapy source, based on TG-43U1 formalism by applying the effects of the applicator and dummy spacers. Materials and Methods Two softwares used for treatment planning of Cs-137 sources in Iran (STPS and PLATO), are based on old formalisms. The purpose of this work is to establish and develop a TPS for Selectron source based on TG-43 formalism. In this planning system, the dosimetry parameters of each pellet in different places inside applicators were obtained by MCNP4c code. Then the dose distribution around every combination of active and inactive pellets was obtained by summing the doses. The accuracy of this algorithm was checked by comparing its results for special combination of active and inactive pellets with MC simulations. Finally, the uncertainty of old dose calculation formalism was investigated by comparing the results of STPS and PLATO softwares with those obtained by the new algorithm. Results For a typical arrangement of 10 active pellets in the applicator, the percentage difference between doses obtained by the new algorithm at 1cm distance from the tip of the applicator and those obtained by old formalisms is about 30%, while the difference between the results of MCNP and the new algorithm is less than 5%. Conclusions According to the results, the old dosimetry formalisms, overestimate the dose especially towards the applicator’s tip. While the TG-43U1 based software perform the calculations more accurately. PMID:24578840

  11. Chiral quark dynamics and topological charge: The role of the Ramond-Ramond U(1) gauge field in holographic QCD

    NASA Astrophysics Data System (ADS)

    Thacker, H. B.; Xiong, Chi; Kamat, Ajinkya S.

    2011-11-01

    The Witten-Sakai-Sugimoto construction of holographic QCD in terms of D4 color branes and D8 flavor branes in type IIA string theory is used to investigate the role of topological charge in the chiral dynamics of quarks in QCD. The QCD theta term arises from a compactified five-dimensional Chern-Simons term on the D4 branes. This term couples the QCD topological charge to the Ramond-Ramond (RR) U(1) gauge field of type IIA string theory. For large Nc the contribution of instantons (D0 branes) is suppressed, and the nonzero topological susceptibility of pure-glue QCD is attributed to the presence of D6 branes, which constitute magnetic sources of the RR gauge field. The topological charge of QCD is required, by an anomaly inflow argument, to coincide in space-time with the intersection of the D6 branes and the D4 color branes. This clarifies the relation between D6 branes and the coherent, codimension-one topological charge membranes observed in QCD Monte Carlo calculations. Using open-string/closed-string duality, we interpret a quark loop (represented by a D4-D8 open-string loop) in terms of closed-string exchange between color and flavor branes. The role of the RR gauge field in quark-antiquark annihilation processes is discussed. RR exchange in the s-channel generates a 4-quark contact term which produces an η' mass insertion and provides an explanation for the observed spin-parity structure of the Okubo-Zweig-Iizuka rule. The (log⁡DetU)2 form of the U(1) anomaly emerges naturally. RR exchange in the t-channel of the qq¯ scattering amplitude produces a Nambu-Jona-Lasinio interaction which may provide a mechanism for spontaneous breaking of SU(Nf)×SU(Nf).

  12. Inhibiting expression of specific genes in mammalian cells with 5′ end-mutated U1 small nuclear RNAs targeted to terminal exons of pre-mRNA

    PubMed Central

    Fortes, Puri; Cuevas, Yolanda; Guan, Fei; Liu, Peng; Pentlicky, Sara; Jung, Stephen P.; Martínez-Chantar, Maria L.; Prieto, Jesús; Rowe, David; Gunderson, Samuel I.

    2003-01-01

    Reducing or eliminating expression of a given gene is likely to require multiple methods to ensure coverage of all of the genes in a given mammalian cell. We and others [Furth, P. A., Choe, W. T., Rex, J. H., Byrne, J. C., and Baker, C. C. (1994) Mol. Cell. Biol. 14, 5278–5289] have previously shown that U1 small nuclear (sn) RNA, both natural or with 5′ end mutations, can specifically inhibit reporter gene expression in mammalian cells. This inhibition occurs when the U1 snRNA 5′ end base pairs near the polyadenylation signal of the reporter gene's pre-mRNA. This base pairing inhibits poly(A) tail addition, a key, nearly universal step in mRNA biosynthesis, resulting in degradation of the mRNA. Here we demonstrate that expression of endogenous mammalian genes can be efficiently inhibited by transiently or stably expressed 5′ end-mutated U1 snRNA. Also, we determine the inhibitory mechanism and establish a set of rules to use this technique and to improve the efficiency of inhibition. Two U1 snRNAs base paired to a single pre-mRNA act synergistically, resulting in up to 700-fold inhibition of the expression of specific reporter genes and 25-fold inhibition of endogenous genes. Surprisingly, distance from the U1 snRNA binding site to the poly(A) signal is not critical for inhibition, instead the U1 snRNA must be targeted to the terminal exon of the pre-mRNA. This could reflect a disruption by the 5′ end-mutated U1 snRNA of the definition of the terminal exon as described by the exon definition model. PMID:12826613

  13. 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.

  14. 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

  15. Exon-Specific U1s Correct SPINK5 Exon 11 Skipping Caused by a Synonymous Substitution that Affects a Bifunctional Splicing Regulatory Element.

    PubMed

    Dal Mas, Andrea; Fortugno, Paola; Donadon, Irving; Levati, Lauretta; Castiglia, Daniele; Pagani, Franco

    2015-05-01

    The c.891C>T synonymous transition in SPINK5 induces exon 11 (E11) skipping and causes Netherton syndrome (NS). Using a specific RNA-protein interaction assay followed by mass spectrometry analysis along with silencing and overexpression of splicing factors, we showed that this mutation affects an exonic bifunctional splicing regulatory element composed by two partially overlapping silencer and enhancer sequences, recognized by hnRNPA1 and Tra2β splicing factors, respectively. The C-to-T substitution concomitantly increases hnRNPA1 and weakens Tra2β-binding sites, leading to pathological E11 skipping. In hybrid minigenes, exon-specific U1 small nuclear RNAs (ExSpe U1s) that target by complementarity intronic sequences downstream of the donor splice site rescued the E11 skipping defect caused by the c.891C>T mutation. ExSpe U1 lentiviral-mediated transduction of primary NS keratinocytes from a patient bearing the mutation recovered the correct full-length SPINK5 mRNA and the corresponding functional lympho-epithelial Kazal-type related inhibitor protein in a dose-dependent manner. This study documents the reliability of a mutation-specific, ExSpe U1-based, splicing therapy for a relatively large subset of European NS patients. Usage of ExSpe U1 may represent a general approach for correction of splicing defects affecting skin disease genes. PMID:25665175

  16. 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.

  17. Computational study of the energetics of charge and cation mixing in U1-xCexO₂

    DOE PAGESBeta

    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

  18. Constraints on abelian extensions of the Standard Model from two-loop vacuum stability and U(1) B- L

    NASA Astrophysics Data System (ADS)

    Corianò, Claudio; Rose, Luigi Delle; Marzo, Carlo

    2016-02-01

    We present a renormalization group study of the scalar potential in a minimal U(1) B- L extension of the Standard Model involving one extra heavier Higgs and three heavy right-handed neutrinos with family universal B-L charge assignments. We implement a type-I seesaw for the masses of the light neutrinos of the Standard Model. In particular, compared to a previous study, we perform a two-loop extension of the evolution, showing that two-loop effects are essential for the study of the stability of the scalar potential up to the Planck scale. The analysis includes the contribution of the kinetic mixing between the two abelian gauge groups, which is radiatively generated by the evolution, and the one-loop matching conditions at the electroweak scale. By requiring the stability of the potential up to the Planck mass, significant constraints on the masses of the heavy neutrinos, on the gauge couplings and the mixing in the Higgs sector are identified.

  19. Chiral quark model of nucleon spin-flavor structure with SU(3) and axial-U(1) breakings

    SciTech Connect

    Cheng, T.P.; Li, L.

    1998-01-01

    The chiral quark model with a nonet of Goldstone bosons can yield an adequate description of the observed proton flavor and spin structure. In a previous publication we have compared the results of an SU(3) symmetric calculation with the phenomenological findings based on experimental measurements and SU(3) symmetry relations. In this paper we discuss their SU(3) and axial U(1) breaking corrections. Our result demonstrates the broad consistency of the chiral quark model with the experimental observations of the proton spin-flavor structure. With two parameters, we obtain a very satifactory fit to the F/D ratios for the octet baryon masses and for their axial vector couplings, as well as the different quark flavor contributions to the proton spin. The result also can account for not only the light quark asymmetry {bar u}{minus}{bar d} but also the strange quark content {bar s} of the proton sea. SU(3) breaking is the key in reconciling the {bar s} value as measured in the neutrino charm production and that as deduced from the pion nucleon {sigma} term. {copyright} {ital 1997} {ital The American Physical Society}

  20. Scalar coupling limits and diphoton Higgs decay from LHC in an U (1 )' model with scalar dark matter

    NASA Astrophysics Data System (ADS)

    Martinez, R.; Nisperuza, J.; Ochoa, F.; Rubio, J. P.; Sierra, C. F.

    2015-08-01

    We explore constraints on the scalar coupling in a family nonuniversal U (1 )' extension of the standard model free from anomalies with a complex scalar dark matter particle. From unitarity and stability of the Higgs potential, we find the full set of bounds and order relations for the scalar coupling constants. Using recent data from the CERN-LHC collider, we study the signal strength of the diphoton Higgs decay, which imposes very stringent bounds to the scalar couplings and other scalar parameters, including parameters associated to the dark matter. Taking into account these constraints, the observable relic density of the Universe, and the limits from LUX collaboration for direct detection, we obtain allowed masses for the dark matter particle as low as 55 GeV. By assuming that the lightest scalar boson of the model corresponds to the observed Higgs boson, we evaluate deviations from the standard model of the trilineal Higgs self-coupling. The conditions from unitarity, stability and Higgs diphoton decay data allow trilineal deviations in the range 0 ≤δ g ≲-72 %.

  1. 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.

  2. 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.

  3. M48U1 CD4 mimetic has a sustained inhibitory effect on cell-associated HIV-1 by attenuating virion infectivity through gp120 shedding

    PubMed Central

    2013-01-01

    Background HIV-1 infected cells can establish new infections by crossing the vaginal epithelia and subsequently producing virus in a milieu that avoids the high microbicide concentrations of the vaginal lumen. Findings To address this problem, here, we report that pretreatment of HIV-infected peripheral blood mononuclear cells (PBMCs) with a 27 amino acid CD4-mimetic, M48U1, causes dramatic and prolonged reduction of infectious virus output, due to its induction of gp120 shedding. Conclusions M48U1 may, therefore, be valuable for prophylaxis of mucosal HIV-1 transmission. PMID:23375046

  4. 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.

  5. Identification of a putative RNA helicase (HRH1), a human homolog of yeast Prp22.

    PubMed Central

    Ono, Y; Ohno, M; Shimura, Y

    1994-01-01

    In the budding yeast Saccharomyces cerevisiae, a number of PRP genes known to be involved in pre-mRNA processing have been genetically identified and cloned. Three PRP genes (PRP2, PRP16, and PRP22) were shown to encode putative RNA helicases of the family of proteins with DEAH boxes. However, any such splicing factor containing the helicase motifs in vertebrates has not been identified. To identify human homologs of this family, we designed PCR primers corresponding to the highly conserved region of the DEAH box protein family and successfully amplified five cDNA fragments, using HeLa poly(A)+ RNA as a substrate. One fragment, designated HRH1 (human RNA helicase 1), is highly homologous to Prp22, which was previously shown to be involved in the release of spliced mRNAs from the spliceosomes. Expression of HRH1 in a S. cerevisiae prp22 mutant can partially rescue its temperature-sensitive phenotype. These results strongly suggest that HRH1 is a functional human homolog of the yeast Prp22 protein. Interestingly, HRH1 but not Prp22 contains an arginine- and serine-rich domain (RS domain) which is characteristic of some splicing factors, such as members of the SR protein family. We could show that HRH1 can interact in vitro and in the yeast two-hybrid system with members of the SR protein family through its RS domain. We speculate that HRH1 might be targeted to the spliceosome through this interaction. Images PMID:7935475

  6. Conservation of functional domains involved in RNA binding and protein-protein interactions in human and Saccharomyces cerevisiae pre-mRNA splicing factor SF1.

    PubMed Central

    Rain, J C; Rafi, Z; Rhani, Z; Legrain, P; Krämer, A

    1998-01-01

    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. PMID:9582097

  7. Stem-loop 1 of the U1 snRNP plays a critical role in the suppression of HIV-1 polyadenylation.

    PubMed Central

    Ashe, M P; Furger, A; Proudfoot, N J

    2000-01-01

    The inactivity or occlusion of the HIV-1 poly(A) signal when in the 5' long terminal repeat (LTR) has been mechanistically investigated. First we show that neither the homologous HIV-1 promoter nor the close proximity of this RNA processing signal to the transcript initiation site is required for the occlusion effect. Instead we demonstrate that the major splice donor (MSD) site positioned about 200 bp downstream maintains the poly(A) site in an inactive state. Although mutation of MSD results in activation of the 5' LTR poly(A) signal, this effect can be suppressed by targeting U1 snRNAs near to the mutated MSD by base pairing. We show that hybrid U7-U1 snRNAs can also suppress the poly(A) signal and that this suppression is dependent on the U1 stem-loop 1. In particular the binding site for the U1 snRNP protein 70K that binds to the loop structure of stem-loop 1 is associated with poly(A) site occlusion. These experiments were carried out with an HIV-1 proviral construct and as such emphasize the physiological importance of this splice donor-poly(A) site interaction. PMID:10688356

  8. 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.

  9. 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.

  10. Coexistence of anti-RNA polymerase III and anti-U1RNP antibodies in patients with systemic lupus erythematosus: two cases without features of scleroderma

    PubMed Central

    Satoh, M; Vazquez-Del Mercado, M; Krzyszczak, ME; Li, Y; Ceribelli, A; Burlingame, RW; Webb, TT; Sobel, ES; Reeves, WH; Chan, EKL

    2013-01-01

    Anti-RNA polymerase III (RNAP III) antibodies are highly specific for scleroderma (SSc) and associated with diffuse SSc and renal crisis. Coexistence of anti-RNAP III and other SSc autoantibodies is rarely documented. We report three cases with coexisting anti-RNAP III and anti-U1RNP. Autoantibodies in 3829 sera from rheumatology clinics were screened by immunoprecipitation. Anti-RNAP III-positive sera were also examined by immunofluorescence and anti-RNAP III ELISA. In total, 35 anti-RNAP III-positive sera were identified by immunoprecipitation, in which three had coexisting anti-U1RNP. All three were anti-RNAP III ELISA positive. Two had anti-RNAP I dominant (vs. RNAP III) reactivity and showed strong nucleolar staining. A case with anti-U1/U2RNP (U2RNP dominant) had systemic lupus erythematosus (SLE)–SSc overlap syndrome; however, the remaining two cases had SLE without signs of SSc. All three cases of anti-RNAP III + U1RNP fulfilled ACR SLE criteria but none in the group with anti-RNAP III alone (p = 0.0002). In contrast, only one case in the former group had sclerodermatous skin changes and Raynaud’s phenomenon, vs. 92% with scleroderma in the latter (p < 0.05). Although anti-RNAP III is highly specific for SSc, cases with coexisting anti-U1RNP are not so uncommon among anti-RNAP III positives (8%, 3/35) and may be SLE without features of SSc. PMID:22025191

  11. Low energy theorems and the unitarity bounds in the extra U(1) superstring inspired E{sub 6} models

    SciTech Connect

    Sharma, N.K.; Saxena, Pranav; Nagawat, Ashok K.; Singh, Sardar; Parashar, Prachi

    2005-11-01

    The conventional method using low energy theorems derived by Chanowitz et al. [Phys. Rev. Lett. 57, 2344 (1986);] does not seem to lead to an explicit unitarity limit in the scattering processes of longitudinally polarized gauge bosons for the high energy case in the extra U(1) superstring inspired models, commonly known as {eta} model, emanating from E{sub 6} group of superstring theory. We have made use of an alternative procedure given by Durand and Lopez [Phys. Lett. B 217, 463 (1989);], which is applicable to supersymmetric grand unified theories. Explicit unitarity bounds on the superpotential couplings (identified as Yukawa couplings) are obtained from both using unitarity constraints as well as using renormalization group equations (RGE) analysis at one-loop level utilizing critical couplings concepts implying divergence of scalar coupling at M{sub G}. These are found to be consistent with finiteness over the entire range M{sub Z}{<=}{radical}(s){<=}M{sub G} i.e. from grand unification scale to weak scale. For completeness, the similar approach has been made use of in other models i.e., {chi}, {psi}, and {nu} models emanating from E{sub 6} and it has been noticed that at weak scale, the unitarity bounds on Yukawa couplings do not differ among E{sub 6} extra U(1) models significantly except for the case of {chi} model in 16 representations. For the case of the E{sub 6}-{eta} model ({beta}{sub E} congruent with 9.64), the analysis using the unitarity constraints leads to the following bounds on various parameters: {lambda}{sub t(max.)}(M{sub Z})=1.294, {lambda}{sub b(max.)}(M{sub Z})=1.278, {lambda}{sub H(max.)}(M{sub Z})=0.955, {lambda}{sub D(max.)}(M{sub Z})=1.312. The analytical analysis of RGE at the one-loop level provides the following critical bounds on superpotential couplings: {lambda}{sub t,c}(M{sub Z}) congruent with 1.295, {lambda}{sub b,c}(M{sub Z}) congruent with 1.279, {lambda}{sub H,c}(M{sub Z}) congruent with 0.968, {lambda}{sub D,c}(M{sub Z

  12. Rotational line intensities of the c4‧1Σu+(1)-X1Σg+(0-2) bands of N2

    NASA Astrophysics Data System (ADS)

    C.; Lavín | A., M.; | I., Velasco; Martín

    2010-02-01

    Oscillator strengths and integrated cross-sections for rotational lines of the c4'1Σu+(1)-X1Σg+(0-2) bands of N 2 have been calculated with the molecular quantum defect orbital (MQDO) method. The known strong homogeneous interaction of the c4'1Σu+(1) Rydberg state with the b' 1Σu+(4) valence state has been presently dealt with through an interaction matrix for each value of the rotational quantum number, J. Because of perturbations, the intensity distribution of the rotational lines within each of the vibronic bands deviates from the predictions based on Hönl-London factors. Band oscillator strengths are also reported and their J-dependence has been analyzed.

  13. Semidirect product gauge group [SU(3){sub c}xSU(2){sub L}]xU(1){sub Y} and quantization of hypercharge

    SciTech Connect

    Hattori, Chuichiro; Matsunaga, Mamoru; Matsuoka, Takeo

    2011-01-01

    In the standard model the hypercharges of quarks and leptons are not determined by the gauge group SU(3){sub c}xSU(2){sub L}xU(1){sub Y} alone. We show that, if we choose the semidirect product group [SU(3){sub c}xSU(2){sub L}]xU(1){sub Y} as its gauge group, the hyperchages are settled to be n/6 mod Z(n=0,1,3,4). In addition, the conditions for gauge-anomaly cancellation give strong constraints. As a result, the ratios of the hypercharges are uniquely determined and the gravitational anomaly is automatically canceled. The standard charge assignment to quarks and leptons can be properly reproduced. For exotic matter fields their hypercharges are also discussed.

  14. 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

  15. SU(3){sub {ital L}}{circle_times} U(1){sub {ital N}} model for right-handed neutrino neutral currents

    SciTech Connect

    Long, H.N.

    1996-10-01

    A model based on the SU(3){sub {ital L}}{circle_times}U(1){sub {ital N}} gauge group in which neutrinos have right-handed neutral currents is considered. We argue that in order to have a result consistent with the low-energy one, the right-handed neutrino component must be treated as a correction instead of an equivalent spin state. {copyright} {ital 1996 The American Physical Society.}

  16. Quadratic Algebra Approach to the Dirac Equation with Spin and Pseudospin Symmetry for the 4D Harmonic Oscillator and U(1) Monopole

    NASA Astrophysics Data System (ADS)

    Aghaei, S.; Chenaghlou, A.

    2015-01-01

    In this paper, we study the Dirac equation with spin and pseudospin symmetry by the quadratic algebra approach for the 4-dimensional harmonic oscillator. By realization of the quadratic algebras in the deformed oscillator algebra, we obtain the relativistic energy spectrum. Also, by regarding the generalized Kustaanheimo-Stiefel transformation, we obtain the relativistic energy spectrum for the charge-dyon system with the U(1) monopole.

  17. ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP.

    PubMed

    Sun, Shuying; Ling, Shuo-Chien; Qiu, Jinsong; Albuquerque, Claudio P; Zhou, Yu; Tokunaga, Seiya; Li, Hairi; Qiu, Haiyan; Bui, Anh; Yeo, Gene W; Huang, Eric J; Eggan, Kevin; Zhou, Huilin; Fu, Xiang-Dong; Lagier-Tourenne, Clotilde; Cleveland, Don W

    2015-01-01

    The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their interaction with SMN and dysregulate its function, including loss of Gems and altered levels of small nuclear RNAs. The same mutants are found to have reduced association with U1-snRNP. Correspondingly, global RNA analysis reveals a mutant-dependent loss of splicing activity, with ALS-linked mutants failing to reverse changes caused by loss of wild-type FUS/TLS. Furthermore, a common FUS/TLS mutant-associated RNA splicing signature is identified in ALS patient fibroblasts. Taken together, these studies establish potentially converging disease mechanisms in ALS and spinal muscular atrophy, with ALS-causative mutants acquiring properties representing both gain (dysregulation of SMN) and loss (reduced RNA processing mediated by U1-snRNP) of function. PMID:25625564

  18. Wind-Tunnel Tests of a 0.182-Scale Model of an F4U-1 Airplane with External Stores

    NASA Technical Reports Server (NTRS)

    Silvers, H. Norman; Spreemann, Kenneth P.

    1947-01-01

    Tests were made in the Langley 7- by 10-foot tunnel on a 0.182-scale model of an F4U-1 airplane with external stores. This paper is concerned mainly with presenting the data obtained in this investigation and with a comparison of some of these data with flight-test results determining the feasibility of estimating flight buffet Mach number from tunnel data. The results of this investigation indicate that the incremental drag coefficient due to external stores may be used to estimate the maximum Mach number that the F4U-1 airplane may reach in flight when it is equipped with external stores. This estimation is conservative for the five configurations investigated by mounts varying from 0 to 10 percent of the flight limit Mach number. The free-stream tunnel Mach number corresponding to sonic flow over the lower surface of the wing in the region of the store is a good indication of the lower limit of buffet in flight of the F4U-1 airplane when equipped with external stores. The fluctuations of total pressure over the horizontal tail are not sufficiently large (maximum of 1 percent q(sub o) to cause buffeting of the airplane.

  19. Magnetism and structural chemistry of U1-xYxCu2±ySi2∓y, U1-xYxCr2Si2, and U(Cu1-xCrx)2Si2 alloys

    NASA Astrophysics Data System (ADS)

    Hiebl, K.; Rogl, P.; Horvath, C.; Remschnig, K.; Noël, H.

    1990-01-01

    Magnetic behavior for the three series of alloys U1-xYxCu2±ySi2∓y, U1-xYxCr2Si2, and U(Cu1-xCrx)2Si2 has been studied in the temperature range from 2 to 550 K. In all cases a complete solid solution with the ThCr2Si2 type of structure was observed from x-ray powder analysis with no ordering among the substituting atom species. Whereas YCu2Si2 did not reveal any homogeneous region on Si/Cu substitution, uranium-rich alloys show significant changes in the unit cell dimensions when comparing U1-xYxCu2Si2 and U1-xYxCu2+ySi2-y. In both latter alloy series a negative deviation of the c parameter from Vegard's rule is found almost compensated for by a positive deviation of a when Y is substituted for U. Substitution of Cu by Cr resulted in a linear dependence of the lattice dimensions. YCu2Si2 and YCr2Si2 are temperature independent Pauli paramagnets above 2 K, whereas the UCu2±ySi2∓y and the U(Cu1-xCrx)2Si2 systems are characterized by the onset of ferromagnetic ordering at TM =105 K. Above TM all samples are in the paramagnetic state in which the uranium atoms carry an effective moment larger than 2 μB. Saturation moments reveal a maximum for a copper deficiency of y˜0.1, whereas excess copper correlates with a strong magnetocrystalline anisotropy indicating the presence of narrow domain walls. Substitution of U by Y in U1-xYxCu2±ySi2∓y leads to a linear decrease of TM and for concentrations of 0.4≤x≤0.8 metamagnetic behavior is observed. The antiferromagnetic transition is followed by a ferromagnetic alignment of the U atoms below the Néel temperature. The maximum of the anisotropy energy coincides with the minimum in the c parameter at x˜0.65. The Y-rich alloys U1-xYxCu2∓ySi2±y display antiferromagnetism with a rather complex structure as indicated by the change of sign of the paramagnetic Curie-Weiss temperature θp. In the U1-xYxCr2Si2 alloys the antiferromagnetic coupling is destroyed by rather small amounts of Y.

  20. 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.

  1. Chiral symmetry breaking in monolayer graphene by strong coupling expansion of compact and non-compact U(1) lattice gauge theories

    SciTech Connect

    Araki, Yasufumi

    2011-06-15

    Research Highlights: > Monolayer graphene is treated by strong coupling expansion of lattice gauge theory. > Spontaneous gap generation is shown in the strong coupling regime. > Results from compact and non-compact gauge formulations are compared. > Dispersion relation of the collective excitations are derived. - Abstract: Due to effective enhancement of the Coulomb coupling strength in the vacuum-suspended graphene, the system may turn from a semimetal into an insulator by the formation of a gap in the fermionic spectrum. This phenomenon is analogous to the spontaneous breaking of chiral symmetry in the strong-coupling relativistic field theories. We study this 'chiral symmetry breaking' and associated collective excitations on graphene in the strong coupling regime by taking U(1) lattice gauge theory as an effective model for graphene. Both compact and non-compact formulations of the U(1) gauge action show chiral symmetry breaking with equal magnitude of the chiral condensate (exciton condensate) in the strong coupling limit, while they start to deviate from the next-to-leading order in the strong coupling expansion. Phase and amplitude fluctuations of the order parameter are also investigated: in particular, a mass formula for the pseudo-Nambu-Goldstone mode ({pi}-exciton), which is analogous to Gell-Mann-Oakes-Renner relation for the pion in quantum chromodynamics (QCD), is derived from the axial Ward-Takahashi identity. To check the applicability of the effective field theory description, typical energy scales of fermionic and bosonic excitations are estimated by identifying the lattice spacing of the U(1) gauge theory with that of the original honeycomb lattice of graphene.

  2. 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

  3. Isotopic production cross sections of spallation-evaporation residues from reactions of {sup 238}U(1A GeV) with deuterium

    SciTech Connect

    Casarejos, E.; Benlliure, J.; Pereira, J.; Armbruster, P.; Enqvist, T.; Schmidt, K.-H.; Bernas, M.; Mustapha, B.; Rejmund, F.; Stephan, C.; Taieb, J.; Tassan-Got, L.; Boudard, A.; Legrain, R.; Leray, S.; Volant, C.; Wlazlo, W.

    2006-10-15

    Isotopic production cross sections and momentum distributions of 602 residual nuclei produced in the collision of {sup 238}U(1A GeV) with deuterium have been measured. These data are relevant for a better understanding of spallation reactions for use as neutron sources for accelerator-driven systems or to produce radioactive nuclear beams. Access to primary residue production makes it possible to study the main reaction mechanisms involved: intranuclear cascade, particle evaporation, and fission. The characteristics of the reaction investigated and the high fissility of the {sup 238}U and the dinucleon projectile system are discussed and compared with other available experimental data.

  4. Experimental oxygen potentials of U1-yPryO2± x and thermodynamic assessment of the U-Pr-O system

    DOE PAGESBeta

    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.

  5. Experimental oxygen potentials for U1-yPryO2±x and thermodynamic assessment of the U-Pr-O system

    NASA Astrophysics Data System (ADS)

    McMurray, J. W.; Silva, C. M.

    2016-03-01

    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. 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. An SO(10) model with SU(3)⊗ SU(2) L ⊗ SU(2) R ⊗ U(1) B-L ⊗ D intermediate symmetry

    NASA Astrophysics Data System (ADS)

    Buccella, F.; Rosa, L.

    1987-09-01

    We construct a SO(10) model with intermediate symmetry 10052_2005_Article_BF01573937_TeX2GIFE1.gif SU(3) ⊗ SU(2)_L ⊗ SU(2)_R ⊗ U(1)_{B - L} ⊗ D and baryon and lepton number conserved between the two highest scales. The experimental values of sin2θ w and α s are consistent with the lower bound on τ p→ e ++π0 and with a mass value for v τ around 1 eV.

  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. Modern origin of numerous alternatively spliced human introns from tandem arrays

    PubMed Central

    Zhuo, Degen; Madden, Richard; Elela, Sherif Abou; Chabot, Benoit

    2007-01-01

    Despite the widespread occurrence of spliceosomal introns in the genomes of higher eukaryotes, their origin remains controversial. One model proposes that the duplication of small genomic portions could have provided the boundaries for new introns. If this mechanism has occurred recently, the 5′ and 3′ boundaries of each resulting intron should display distinctive sequence similarity. Here, we report that the human genome contains an excess of introns with perfect matching sequences at boundaries. One-third of these introns interrupt the protein-coding sequences of known genes. Introns with the best-matching boundaries are invariably found in tandem arrays of direct repeats. Sequence analysis of the arrays indicates that many intron-breeding repeats have disseminated in several genes at different times during human evolution. A comparison with orthologous regions in mouse and chimpanzee suggests a young age for the human introns with the most-similar boundaries. Finally, we show that these human introns are alternatively spliced with exceptionally high frequency. Our study indicates that genomic duplication has been an important mode of intron gain in mammals. The alternative splicing of transcripts containing these intron-breeding repeats may provide the plasticity required for the rapid evolution of new human proteins. PMID:17210920

  9. U1-RNP and Toll-like receptors in the pathogenesis of mixed connective tissue diseasePart II. Endosomal TLRs and their biological significance in the pathogenesis of mixed connective tissue disease

    PubMed Central

    2015-01-01

    Mixed connective tissue disease (MCTD) is a chronic autoimmune immunopathological disease of unknown etiology, which is characterized by the presence of various clinical symptoms and the presence of autoantibodies against U1-RNP particles. The U1-RNP component engages immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. The anti-U1-RNP autoantibodies form an immune complex with self-RNA, present in MCTD serum, which can act as endosomal Toll-like receptor (TLR) ligands. Inhibition of TLRs by nucleic acids is a promising area of research for the development of novel therapeutic strategies against pathogenic infection, tumorigenesis and autoimmunity. In this review we summarize current knowledge of endogenous TLRs and discuss their biological significance in the pathogenesis of MCTD. In part I we described the structure, biological function and significance of the U1-RNP complex in MCTD.

  10. Complementary test of the dark matter self-interaction in dark U(1) model by direct and indirect dark matter detection

    NASA Astrophysics Data System (ADS)

    Chen, Chian-Shu; Lin, Guey-Lin; Lin, Yen-Hsun

    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 mχ or the region opened up due to isospin violations.

  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. 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.

  13. Room-temperature oxidation of hypostoichiometric uranium-plutonium mixed oxides U1-yPuyO2-x - A depth-selective approach

    NASA Astrophysics Data System (ADS)

    Vauchy, Romain; Robisson, Anne-Charlotte; Belin, Renaud C.; Martin, Philippe M.; Scheinost, Andreas C.; Hodaj, Fiqiri

    2015-10-01

    In the present work, TGA, XAS and XRD were used to evidence the spontaneous oxidation of biphasic U1-yPuyO2-x samples, with y = 0.28 and 0.45, at room temperature and upon exposure to low moisture and oxygen contents. The oxidation occurs within very short timescales (e.g. O/M ratio increasing from 1.94 to 1.98 within ∼1 μm surface layer in ∼50 h). The combined use of these three complementary methods offered a depth-selective approach from the sample's bulk to its surface and allowed a thorough understanding of the underlying processes involved during the formation of the oxidized layer and of its thickening with time. We believe our results to be of interest in the prospect of fabricating hypo-stoichiometric uranium-plutonium mixed oxides since mastering the oxygen content is a crucial point for many of the fuel properties.

  14. Phenomenology of the SU(3){sub c}xSU(3){sub L}xU(1){sub X} model with exotic charged leptons

    SciTech Connect

    Salazar, Juan C.; Ponce, William A.; Gutierrez, Diego A.

    2007-04-01

    A phenomenological analysis of the three-family model based on the local gauge group SU(3){sub c}xSU(3){sub L}xU(1){sub X} with exotic charged leptons, is carried out. Instead of using the minimal scalar sector able to break the symmetry in a proper way, we introduce an alternative set of four Higgs scalar triplets, which combined with an anomaly-free discrete symmetry, produce quark and charged lepton mass spectrum without hierarchies in the Yukawa coupling constants. We also embed the structure into a simple gauge group and show some conditions to achieve a low energy gauge coupling unification, avoiding possible conflict with proton decay bounds. By using experimental results from the CERN-LEP, SLAC linear collider, and atomic parity violation data, we update constraints on several parameters of the model.

  15. 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.

  16. In situ study of the solid-state formation of U(1-x)Am(x)O(2±δ) solid solution.

    PubMed

    Lebreton, Florent; Belin, Renaud C; Prieur, Damien; Delahaye, Thibaud; Blanchart, Philippe

    2012-09-01

    In order to reduce the nuclear waste inventory and radiotoxicity, U(1-x)Am(x)O(2±δ) materials are promising fuels for heterogeneous transmutation. In this context, they are generally fabricated from UO(2+δ) and AmO(2-δ) dioxide powders. In the subsequent solid solution, americium is assumed to be trivalent whereas uranium exhibits a mixed-valence (+IV/+V) state. However, no formation mechanisms were ever evidenced and, more particularly, it was not possible to know whether the reduction of Am(IV) to Am(III) occurs before the solid-solution formation, or only once it is established. In this study, we used high-temperature X-ray diffraction on a UO(2±δ)/AmO(2-δ) (15 mol %) mixture to observe in situ the formation of the U(1-x)Am(x)O(2±δ) solid solution. We show that UO(2+δ) is, at relatively low temperature (<700 K), oxidized to U(4)O(9-δ), which is likely to be caused by oxygen release from the simultaneous AmO(2-δ) reduction to cubic Am(2)O(3±δ). Cubic Am(2)O(3+δ) then transforms to hexagonal Am(2)O(3) at 1300 K. Thus, the initial Am(IV) is fully reduced to Am(III) before the solid solution starts forming at 1740 K. The UO(2) fluorite phase vanishes after 4 h at 1970 K, indicating that the formation of the solid solution is completed, which proves that this solid solution is formed after the complete reduction of Am(IV) to Am(III). PMID:22908900

  17. 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

  18. 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

  19. 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

  20. 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

  1. Phosphoregulation of the human SMN complex.

    PubMed

    Husedzinovic, Alma; Oppermann, Felix; Draeger-Meurer, Stefanie; Chari, Ashwin; Fischer, Utz; Daub, Henrik; Gruss, Oliver J

    2014-03-01

    The survival motor neuron (SMN) complex is a macromolecular machine comprising 9 core proteins: SMN, Gemins2-8 and unrip in vertebrates. It performs tasks in RNA metabolism including the cytoplasmic assembly of spliceosomal small nuclear ribonucleoprotein particles (snRNPs). The SMN complex also localizes to the nucleus, where it accumulates in Cajal Bodies (CB) and may function in transcription and/or pre-mRNA splicing. The SMN complex is subject to extensive phosphorylation. Detailed understanding of SMN complex regulation necessitates a comprehensive analysis of these post-translational modifications. Here, we report on the first comprehensive phosphoproteome analysis of the intact human SMN complex, which identify 48 serine/threonine phosphosites in the complex. We find that 7 out of 9 SMN components of the intact complex are phosphoproteins and confidently place 29 phosphorylation sites, 12 of them in SMN itself. By the generation of multi non-phosphorylatable or phosphomimetic variants of SMN, respectively, we address to which extent phosphorylation regulates SMN complex function and localization. Both phosphomimetic and non-phosphorylatable variants assemble into intact SMN complexes and can compensate the loss of endogenous SMN in snRNP assembly at least to some extent. However, they partially or completely fail to target to nuclear Cajal bodies. Moreover, using a mutant of SMN, which cannot be phosphorylated on previously reported tyrosine residues, we provide first evidence that this PTM regulates SMN localization and nuclear accumulation. Our data suggest complex regulatory cues mediated by phosphorylation of serine/threonine and tyrosine residues, which control the subcellular localization of the SMN complex and its accumulation in nuclear CB. PMID:24602413

  2. 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

  3. In vitro transcription of a Drosophila U1 small nuclear RNA gene requires TATA box-binding protein and two proximal cis-acting elements with stringent spacing requirements.

    PubMed Central

    Zamrod, Z; Tyree, C M; Song, Y; Stumph, W E

    1993-01-01

    Transcription of a Drosophila U1 small nuclear RNA gene was functionally analyzed in cell extracts derived from 0- to 12-h embryos. Two promoter elements essential for efficient initiation of transcription in vitro by RNA polymerase II were identified. The first, termed PSEA, is located between positions -41 and -61 relative to the transcription start site, is crucial for promoter activity, and is the dominant element for specifying the transcription initiation site. PSEA thus appears to be functionally homologous to the proximal sequence element of vertebrate small nuclear RNA genes. The second element, termed PSEB, is located at positions -25 to -32 and is required for an efficient level of transcription initiation because mutation of PSEB, or alteration of the spacing between PSEA and PSEB, severely reduced transcriptional activity relative to that of the wild-type promoter. Although the PSEB sequence does not have any obvious sequence similarity to a TATA box, conversion of PSEB to the canonical TATA sequence dramatically increased the efficiency of the U1 promoter and simultaneously relieved the requirement for the upstream PSEA. Despite these effects, introduction of the TATA sequence into the U1 promoter had no effect on the choice of start site or on the RNA polymerase II specificity of the promoter. Finally, evidence is presented that the TATA box-binding protein is required for transcription from the wild-type U1 promoter as well as from the TATA-containing U1 promoter. Images PMID:8355718

  4. 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. PMID:26519451

  5. 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

  6. 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.

  7. Effects of quark family nonuniversality in SU(3){sub c} x SU(4){sub L} x U(1){sub X} models

    SciTech Connect

    Nisperuza, Jorge L.; Sanchez, Luis A.

    2009-08-01

    Flavor changing neutral currents arise in the SU(3){sub c} x SU(4){sub L} x U(1){sub X} extension of the standard model because anomaly cancellation among the fermion families requires one generation of quarks to transform differently from the other two under the gauge group. In the weak basis the distinction between quark families is meaningless. However, in the mass eigenstates basis, the Cabibbo-Kobayashi-Maskawa mixing matrix motivates us to classify left-handed quarks in families. In this sense there are, in principle, three different assignments of quark weak eigenstates into mass eigenstates. In this work, by using measurements at the Z pole, atomic parity violation data, and experimental input from neutral meson mixing, we examine two different models without exotic electric charges based on the 3-4-1 symmetry, and address the effects of quark family nonuniversality on the bounds on the mixing angle between two of the neutral currents present in the models and on the mass scales M{sub Z{sub 2}} and M{sub Z{sub 3}} of the new neutral gauge bosons predicted by the theory. The heaviest family of quarks must transform differently in order to keep lower bounds on M{sub Z{sub 2}} and M{sub Z{sub 3}} as low as possible without violating experimental constraints.

  8. Raman spectroscopy characterization of actinide oxides (U 1-yPu y)O 2: Resistance to oxidation by the laser beam and examination of defects

    NASA Astrophysics Data System (ADS)

    Jégou, C.; Caraballo, R.; Peuget, S.; Roudil, D.; Desgranges, L.; Magnin, M.

    2010-10-01

    Structural changes in four (U 1-yPu y)O 2 materials with very different plutonium concentrations (0 ⩽ y ⩽ 1) and damage levels (up to 110 dpa) were studied by Raman spectroscopy. The novel experimental approach developed for this purpose consisted in using a laser beam as a heat source to assess the reactivity and structural changes of these materials according to the power supplied locally by the laser. The experiments were carried out in air and in water with or without hydrogen peroxide. As expected, the material response to oxidation in air depends on the plutonium content of the test oxide. At the highest power levels U 3O 8 generally forms with UO 2 whereas no significant change in the spectra indicating oxidation is observed for samples with high plutonium content ( 239PuO 2). Samples containing 25 wt.% plutonium exhibit intermediate behavior, typified mainly by a higher-intensity 632 cm -1 peak and the disappearance of the 1LO peak at 575 cm -1. This can be attributed to the presence of anion sublattice defects without any formation of higher oxides. The range of materials examined also allowed us to distinguish partly the chemical effects of alpha self-irradiation. The results obtained with water and hydrogen peroxide (a water radiolysis product) on a severely damaged 238PuO 2 specimen highlight a specific behavior, observed for the first time.

  9. 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.

  10. 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.

  11. SU(3){sub C}xSU(3){sub L}xU(1){sub X} model with two Higgs triplets

    SciTech Connect

    Dong, P.V.; Long, H.N.; Nhung, D.T.; Soa, D.V.

    2006-02-01

    The SU(3){sub C}xSU(3){sub L}xU(1){sub X} gauge model with the minimal scalar sector (two Higgs triplets) is studied in detail. One of the vacuum expectation values u is a source of lepton-number violations and a reason for the mixing among the charged gauge bosons--the standard model W and the bilepton (with L=2) gauge bosons as well as among neutral non-Hermitian X{sup 0} and neutral gauge bosons: the photon, the Z, and the new Z{sup '}. Because of these mixings, the lepton-number violating interactions exist in both charged and neutral gauge boson sectors. An exact diagonalization of the neutral gauge boson sector is derived and bilepton mass splitting is also given. The lepton-number violation happens only in the neutrino but not in the charged lepton sector. In this model, lepton-number changing ({delta}L={+-}2) processes exist but only in the neutrino sector. Constraints on vacuum expectation values of the model are estimated and u{approx_equal}O(1) GeV, v{approx_equal}v{sub weak}=246 GeV, and {omega}{approx_equal}O(1) TeV.

  12. 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.

  13. Thermochemistry of rare earth doped uranium oxides LnxU1-xO2-0.5x+y (Ln = La, Y, Nd)

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Navrotsky, Alexandra

    2015-10-01

    Lanthanum, yttrium, and neodymium doped uranium dioxide samples in the fluorite structure have been synthesized, characterized in terms of metal ratio and oxygen content, and their enthalpies of formation measured by high temperature oxide melt solution calorimetry. For oxides doped with 10-50 mol % rare earth (Ln) cations, the formation enthalpies from constituent oxides (LnO1.5, UO2 and UO3 in a reaction not involving oxidation or reduction) become increasingly exothermic with increasing rare earth content, while showing no significant dependence on the varying uranium oxidation state. The oxidation enthalpy of LnxU1-xO2-0.5x+y is similar to that of UO2 to UO3 for all three rare earth doped systems. Though this may suggest that the oxidized uranium in these systems is energetically similar to that in the hexavalent state, thermochemical data alone can not constrain whether the uranium is present as U5+, U6+, or a mixture of oxidation states. The formation enthalpies from elements calculated from the calorimetric data are generally consistent with those from free energy measurements.

  14. Paleogeography of the Eosahabi River in Libya: New insights into the mineralogy, geochemistry and paleontology of Member U1 of the Sahabi Formation, northeastern Libya

    NASA Astrophysics Data System (ADS)

    Muftah, A. M.; Pavlakis, P.; Godelitsas, A.; Gamaletsos, P.; Boaz, N.

    2013-02-01

    A large paleo-river of Miocene age traversing Libya from south to north has been previously demonstrated by seismic, stratigraphic, paleontological, and remote sensing data. The depositional environment of As Sahabi Formation in north central Libya is this large and now extinct Eosahabi River. However, the source of this major African river has remained controversial. Dark-colored sedimentary material with magnetic properties suggested a source from the basaltic Haruj as Aswad massif in south central Libya. To test this hypothesis, mineralogical and geochemical study of clayey sediments from three localities, P25, P28 and P96c, from fossiliferous Member U1 of the As Sahabi Formation, were carried out. Results strongly indicate very mature and re-processed sediments of continental origin, and felsic sources with no basaltic contribution. Thus the origin can be traced to an upland area of outcrop of rocks of Precambrian continental origin in northeastern Chad. An alternative scenario is that the Sahabi sediments originated from Precambrian outcrops in Ethiopia through an east-west river connection with the Nile. We consider this hypothesis unlikely, since it is based only on remote sensing data, and lacks any time control or geological supporting evidence. The abundant vertebrate fauna from the Sahabi Formation shows strong similarities with penecontemporaneous fossil faunas in Chad and is supportive of an origin of the Eosahabi River in Neogene mega-Lake Chad.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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. PMID:24229268

  20. 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

  1. Langley Full-Scale Tunnel Investigation of a 1/3-Scale Model of the Chance Vought XF5U-1 Airplane

    NASA Technical Reports Server (NTRS)

    Lange, Roy H.; Cocke, Bennie W., Jr.; Proterra, Anthony J.

    1946-01-01

    The results of an investigation of a 1/3-scale model of the Chance Vought XF5U-1 airplane in the Langley full-scale tunnel are presented in this report. The maximum lift and stalling characteristics of several model configurations, the longitudinal stability characteristics of the model, and the effectiveness of the control surfaces were determined with the propellers removed. The propulsive characteristics, the effect of propeller operation on the lift, and the static thrust of the model propellers were determined at several propeller-blade angles. The results with the propellers removed showed that the maximum lift coefficient of the complete model configuration was only 0.97 was compared with the value of 1.31 for the model configuration in which the engine-air ducts and canopy are removed. The model with the propellers removed (normal center-of-gravity position) has a positive static margin, stick fixed, varying from 5 to 13 percent of the mean aerodynamic chord throughout the unstalled range of lift coefficients. The unit horizontal tail is sufficiently powerful to trim the airplane with the propellers removed throughout the unstalled range of lift coefficients. The peak propulsive efficiencies for beta = 20 degrees and beta = 30 degrees were increased 7 percent at C(sub L) congruent to 0.67 and 20 percent at C(sub L) congruent to 0.74, respectively, with the propellers rotating upward in the center than with the propellers rotating downward in the center. Indications are that the minimum forward-flight speed of the airplane for full-power operation at sea level will be about 90 miles per hour. Decreasing the weight and increasing the power reduced this value of minimum speed and there were no indications from the results of a lower limit to the minimum speed.

  2. Free-Spinning Tunnel Tests of a 1/20-Scale Model of the Chance Vought XF6U-1 Airplane, TED No. NACA 2390

    NASA Technical Reports Server (NTRS)

    Klinar, Walter J.

    1946-01-01

    A spin investigation has been conducted in the Langley 20-foot free-spinning tunnel on a 1/20-scale model of the Chance Vought XF6U-1 airplane, The effects of control settings and movements upon the erect and inverted spin and recovery characteristics of the model were determined for the normal-fighter condition. The investigation also included tests for the take-off fighter condition (wing-tip tanks plus fuel added) spin-recovery parachutes, and simulated pilot escape. In general, for the normal-fighter condition, the model was extremely oscillatory in roll, pitch, and yaw. The angles of the fuselage varied from extremely flat to inverted attitudes, and the model rotated with the rudder in a series of short turns and glides. Recoveries by rudder reversal were rapid but the model would immediately go into a spin in the other direction. Recoveries by merely neutralizing the rudder were satisfactory when the elevator and ailerons were set to neutral, the ensuing flight path being a steep glide. Thus, it is recommended that all controls be neutralized for safe recovery from spins obtained on the airplane. With the external wing-tip tanks installed, the spins were somewhat less oscillatory in roll but recovery could not be obtained unless full-down elevator was used in conjunction with the rudder. If a spin is entered inadvertently with the full-scale airplane with external wing-tip tanks installed and if recovery is not imminent after a recovery attempt is made, it is recommended that the tanks be jettisoned and the controls neutralized.

  3. Free-Spinning-Tunnel Tests of a 0.057-Scale Model of the Chance Vought XF7U-1 Airplane

    NASA Technical Reports Server (NTRS)

    Daughtridge, Lee T., Jr.

    1948-01-01

    An investigation of the spin and recovery characteristics of a 0.057-scale model of the Chance Vought XF7U-1 airplane has been conducted in the Langley 20-foot free-spinning tunnel. The effects of control settings and movements on the erect and inverted spin and recovery characteristics were determined, as were also the effects of extending the wing slats, of center-of-gravity movement, and-of variation in the mass distribution. The investigation also included wing-tip spin-recovery-parachute tests, pilot-escape tests, and rudder-control-force tests. The investigation indicated that the spin and recovery characteristics of the airplane will be satisfactory for all conditions. It was found that a single 4.24-foot (full-scale) parachute when opened alone from the outboard wing tip or two 8.77-foot (full-scale) parachutes when opened simultaneously, one from each wing tip, would effect satisfactory emergency recoveries (the drag coefficients of the parachutes, based on the surface area of the parachute, were 0.83 and 0.70 for the 4.24- and 8.77-foot parachutes, respectively). The towline length in both cases was 25 feet (full scale). Tests results showed that, if the pilot should have to leave the airplane during a spin, he should jump from the outboard side (left side in a right spin) of the cockpit. The rudder-control force necessary for recovery from a spin was found to be rather high but appeared to be within the upper limits of a pilot's capabilities.

  4. Free-Spinning-Tunnel Tests of a 1/16-Scale Model of the Chance Vought XF5U-1 Airplane, TED No. NACA 2349

    NASA Technical Reports Server (NTRS)

    White, Richard P.

    1947-01-01

    Spin tests of a 1/16-scale model of the Chance Vought XF5U-1 airplane have been performed in the Langley 20-foot free-spinning tunnel. The effect of control position and movement upon the erect and inverted spin and recovery characteristics ae well as the effects of propellers, of stability flaps, and of various revisions to the design configuration have been determined for the normal fighter loading. The investigation also included spin recovery parachute, tumbling, and pilot-escape tests. For the original design configuration, with or without windmilling propellers, the recovery characteristics of the model were considered unsatisfactory. Increasing the maximum upward deflection of the ailavators from 45 deg to 65 deg resulted in greatly improved recovery characteristics. Dimensional revisions to the original airplane configuration, which satisfactorily improved the general spin and recovery characteristics of the model, consisted of: (1) a supplementary vertical tail 34 inches by 59 inches (full-scale) attached to a boom 80 inches aft of the trailing edge of the airplane in the plane of symmetry, (2) a large semispan undersurface spoiler placed along the airplane quarter-chord line and opened on the outboard side in a spin, or (3) two additional vertical tails 64 inches by 52 inches (full-scale) located at the tips of the ailavators. A satisfactory parachute arrangement for emergency spin recovery from demonstration spins was found to be an arrangement consisting of a 13.3-foot parachute attached by a 30-foot towline to the arresting gear mast on the airplane and opened simultaneously with an 8-foot parachute on the outboard end of the wing attached by a 3-foot towline. Tests indicated that pilot escape from a spin would be extremely hazardous unless the pilot is mechanically ejected from the cockpit. Model tumbling tests indicated that the airplane would not tumble.

  5. 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

  6. Discrete torsion, de Sitter tunneling vacua and AdS brane: U(1) gauge theory on D 4-brane and an effective curvature

    NASA Astrophysics Data System (ADS)

    Singh, Abhishek K.; Pandey, K. Priyabrat; Singh, Sunita; Kar, Supriya

    2013-05-01

    The U(1) gauge dynamics on a D 4-brane is revisited, with a two form, to construct an effective curvature theory in a second order formalism. We exploit the local degrees in a two form, and modify its dynamics in a gauge invariant way, to incorporate a non-perturbative metric fluctuation in an effective D 4-brane. Interestingly, the near horizon D 4-brane is shown to describe an asymptotic Anti de Sitter (AdS) in a semi-classical regime. Using Weyl scaling(s), we obtain the emergent rotating geometries leading to primordial de Sitter (dS) and AdS vacua in a quantum regime. Under a discrete transformation, we re-arrange the mixed dS patches to describe a Schwazschild-like dS (SdS) and a topological-like dS (TdS) black holes. We analyze SdS vacuum for Hawking radiations to arrive at Nariai geometry, where a discrete torsion forms a condensate. We perform thermal analysis to identify Nariai vacuum with a TdS. Investigation reveals an AdS patch within a thermal dS brane, which may provide a clue to unfold dS/CFT. In addition, the role of dark energy, sourced by a discrete torsion, in the dS vacua is investigated using Painleve geometries. It is argued that a D-instanton pair is created by a discrete torsion, with a Big Bang/Crunch, at the past horizon in a pure dS. Nucleation, of brane/anti-brane pair(s), is qualitatively analyzed to construct an effective space-time on a D 4-brane and its anti brane. Analysis re-assures the significant role played by a non-zero mode, of NS-NS two form, to generalize the notion of branes within a brane.

  7. 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.

  8. 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.

  9. Z- Z' mixing and Z-mediated FCNCs in SU(3) C × SU(3) L × U(1) X models

    NASA Astrophysics Data System (ADS)

    Buras, Andrzej J.; De Fazio, Fulvia; Girrbach-Noe, Jennifer

    2014-08-01

    Most of the existing analyses of flavour changing neutral current processes (FCNC) in the 331 models, based on the gauge group SU(3) C × SU(3) L × U(1) X , are fully dominated by tree-level exchanges of a new heavy neutral gauge boson Z'. However, due to the Z - Z' mixing also corresponding contributions from Z boson are present. As the Z - Z' mixing is estimated generally in Z' models to be at most , the latter contributions are usually neglected. The paucity of relevant parameters in 331 models allows to check whether this neglect is really justified in these concrete models. We calculate the impact of these contributions on Δ F = 2 processes and rare K, B s and B d decays for different values of a parameter β, which distinguishes between various 331 models and for different fermion representations under the SU(3) L group. We find a general expression for the Z - Z' mixing in terms β, M Z , M Z' and tan , familiar from 2 Higgs Doublet models, that differs from the one quoted in the literature. We study in particular the models with β = ± n/ with n = 1 , 2 which have recently been investigated by us in the context of new data on B s, d → μ + μ - and B d → K *( K) μ + μ -. We find that these new contributions can indeed be neglected in the case of Δ F = 2 transitions and decays, like B d → K * μ + μ -, where they are suppressed by the small vectorial Z coupling to charged leptons. However, the contributions of tree-level Z exchanges to decays sensitive to axial-vector couplings, like B s, d → μ + μ - and B d → Kμ + μ -, and those with neutrinos in the final state, like b → sν transitions, K + → π + ν and K L → π 0 ν cannot be generally neglected with size of Z contributions depending on β, tan and M Z' . We analyze how our recent results on FCNCs in 331 models, in particular correlations between various observables, are modified by these new contributions. As a byproduct we analyze for the first time the ratio ɛ' /ɛ in

  10. Collision induced state-to-state energy transfer dynamics between the 2u ((1)D2) and 2g ((1)D2) ion-pair states of I2.

    PubMed

    Hoshino, Shoma; Nakano, Yukio; Araki, Mitsunori; Ishiwata, Takashi; Tsukiyama, Koichi

    2016-06-01

    We report the first observation of collision induced state-to-state energy transfer from the 2u ((1)D2) (v2u = 3-7) ion-pair state of I2 using a perturbation facilitated optical-optical double resonance technique through the c (1)Πg∼ B (3)Π(0) hyperfine mixed double-faced valence state as the intermediate state. The excitation of the 2u ((1)D2) state yielded the weak UV fluorescence from the wide range of vibrational levels in the nearby 2g ((1)D2) state. The vibrational distribution in the 2g ((1)D2) state derived by the Franck-Condon simulation of the UV fluorescence showed that the population in the 2u ((1)D2) state transfers mostly to the 2g ((1)D2) vibronic levels which are located energetically above the laser-prepared level. The radiative lifetimes and the self-quenching rate constants were determined to be 21.3 ± 0.1 and 44.6 ± 0.8 ns, and (1.30 ± 0.01) × 10(-9) and (2.26 ± 0.17) × 10(-9) cm(3) molecule(-1) s(-1) for the 2u ((1)D2) (v2u = 3) and 2g ((1)D2) (v2g = 5) states, respectively. The rate constant for the 2u ((1)D2) - 2g ((1)D2) collision induced state-to-state energy transfer was also evaluated to be (1.89 ± 0.01), (3.07 ± 0.07), and (3.77 ± 0.05) × 10(-10) cm(3) molecule(-1) s(-1) for the v2u = 3, 5, and 7 levels, respectively. The very large self-quenching cross sections for the ion-pair states of I2 could be explained by the harpoon mechanism. PMID:27165483

  11. The sequence complementarity between HIV-1 5' splice site SD4 and U1 snRNA determines the steady-state level of an unstable env pre-mRNA.

    PubMed Central

    Kammler, S; Leurs, C; Freund, M; Krummheuer, J; Seidel, K; Tange, T O; Lund, M K; Kjems, J; Scheid, A; Schaal, H

    2001-01-01

    HIV-1 env expression from certain subgenomic vectors requires the viral regulatory protein Rev, its target sequence RRE, and a 5' splice site upstream of the env open reading frame. To determine the role of this splice site in the 5'-splice-site-dependent Rev-mediated env gene expression, we have subjected the HIV-1 5' splice site, SD4, to a mutational analysis and have analyzed the effect of those mutations on env expression. The results demonstrate that the overall strength of hydrogen bonding between the 5' splice site, SD4, and the free 5' end of the U1 snRNA correlates with env expression efficiency, as long as env expression is suboptimal, and that a continuous stretch of 14 hydrogen bonds can lead to full env expression, as a result of stabilizing the pre-mRNA. The U1 snRNA-mediated stabilization is independent of functional splicing, as a mismatch in position +1 of the 5' splice site that led to loss of detectable amounts of spliced transcripts did not preclude stabilization and expression of the unspliced env mRNA, provided that Rev enables its nuclear export. The nucleotides capable of participating in U1 snRNA:pre-mRNA interaction include positions -3 to +8 of the 5' splice site and all 11 nt constituting the single-stranded 5' end of U1 snRNA. Moreover, env gene expression is significantly decreased upon the introduction of point mutations in several upstream GAR nucleotide motifs, which are mediating SF2/ASF responsiveness in an in vitro splicing assay. This suggests that the GAR sequences may play a role in stabilizing the pre-mRNA by sequestering U1 snRNP to SD4. PMID:11333022

  12. 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

  13. Thermosensitive and Mucoadhesive Pluronic-Hydroxypropylmethylcellulose Hydrogel Containing the Mini-CD4 M48U1 Is a Promising Efficient Barrier against HIV Diffusion through Macaque Cervicovaginal Mucus

    PubMed Central

    Aka-Any-Grah, Armelle; Dereuddre-Bosquet, Nathalie; Martin, Loïc; Lievin-Le-Moal, Vanessa; Le Grand, Roger; Nicolas, Valérie; Gibellini, Davide; Lembo, David; Poüs, Christian; Koffi, Armand; Ponchel, Gilles

    2015-01-01

    To be efficient, vaginal microbicide hydrogels should form a barrier against viral infections and prevent virus spreading through mucus. Multiple particle tracking was used to quantify the mobility of 170-nm fluorescently labeled COOH-modified polystyrene particles (COOH-PS) into thermosensitive hydrogels composed of amphiphilic triblock copolymers with block compositions EOn-POm-EOn (where EO refers to ethylene oxide and PO to propylene oxide) containing mucoadhesive hydroxypropylmethylcellulose (HPMC). COOH-PS were used to mimic the size and the surface charge of HIV-1. Analysis of COOH-PS trajectories showed that particle mobility was decreased by Pluronic hydrogels in comparison with cynomolgus macaque cervicovaginal mucus and hydroxyethylcellulose hydrogel (HEC; 1.5% by weight [wt%]) used as negative controls. Formulation of the peptide mini-CD4 M48U1 used as an anti-HIV-1 molecule into a mixture of Pluronic F127 (20 wt%) and HPMC (1 wt%) did not affect its anti-HIV-1 activity in comparison with HEC hydrogel. The 50% inhibitory concentration (IC50) was 0.53 μg/ml (0.17 μM) for M48U1-HEC and 0.58 μg/ml (0.19 μM) for M48U1-F127-HPMC. The present work suggests that hydrogels composed of F127-HPMC (20/1 wt%, respectively) can be used to create an efficient barrier against particle diffusion in comparison to conventional HEC hydrogels. PMID:25645853

  14. Structural basis for highly effective HIV-1 neutralization by CD4-mimetic miniproteins revealed by 1.5 Å co-crystal structure of gp120 and M48U1

    PubMed Central

    Acharya, Priyamvada; Luongo, Timothy; Louder, Mark K.; McKee, Krisha; Yang, Yongping; Kwon, Young Do; Mascola, John R.; Kessler, Pascal; Martin, Loïc; Kwong, Peter D.

    2014-01-01

    The interface between HIV-1 gp120 envelope glycoprotein and CD4 receptor contains an unusual interfacial cavity, the “Phe43 cavity”, which miniprotein mimetics of CD4 with non-natural extensions can potentially utilize to enhance their neutralization of HIV-1. Here we report co-crystal structures of HIV-1 gp120 with miniproteins M48U1 and M48U7, which insert cyclohexylmethoxy and 5-hydroxypentylmethoxy extensions, respectively, into the Phe43 cavity. Both inserts displayed flexibility and hydrophobic interactions, but the M48U1 insert showed better shape complementarity with the Phe43 cavity than the M48U7 insert. Subtle alteration in gp120 conformation played a substantial role in optimizing fit. With M48U1, these translated into a YU2-gp120 affinity of 0.015 nM and neutralization of all 180-circulating HIV-1 strains tested, except clade-A/E isolates with non-canonical Phe43 cavities. Ligand chemistry, shape complementary, surface burial, and gp120 conformation act in concert to modulate binding of ligands to the gp120-Phe43 cavity and, when optimized, can effect near pan-neutralization of HIV-1. PMID:23707685

  15. Purification of the individual snRNPs U1, U2, U5 and U4/U6 from HeLa cells and characterization of their protein constituents.

    PubMed Central

    Bringmann, P; Lührmann, R

    1986-01-01

    A procedure is described for the purification of the individual major small nuclear ribonucleoproteins (snRNPs) U1, U2, U5 and U4/U6 from HeLa cells. The salient feature of the method is the combined usage of antibodies against 2,2,7-trimethylguanosine (m3G) and 6-methyladenosine (m6A) for differential immune affinity chromatography of the snRNPs. While anti-m3G affinity columns allow the separation of snRNPs U1, U2 and U5 from U4/U6 RNPs, anti-m6A antibodies selectively react with snRNPs U2 and U4/U6. Our technique further incorporates immune affinity chromatography of snRNPs with antibodies against snRNP proteins in addition to ion exchange chromatography. The procedure avoids the usage of denaturing agents, so as to maintain the native structure of the particles. This is mainly provided for by the possibility of eluting the anti-m3G and anti-m6A bound snRNPs with excess of the respective nucleosides. We have so far identified 12 polypeptides as constituents of the major snRNPs U1 to U6. Seven proteins of approximate mol. wts 29 kd (B'), 28 kd (B), 16 kd (D), 15.5 kd (D'), 12 kd (E), 11 kd (F) and 9 kd (G) were present in each of the individual snRNPs U1, U2, U5 and U4/U6. In addition to the common proteins, U1 RNPs contain three unique polypeptides of mol. wts 70 kd, 34 kd (A) and 22 kd (C). U2 RNPs are characterized by the presence of a 33-kd and a 28.5-kd protein, denoted A' and B". We could not detect any unique polypeptide confined to the purified snRNPs U5 or U4/U6.(ABSTRACT TRUNCATED AT 250 WORDS) Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:2951249

  16. Human SPF45, a splicing factor, has limited expression in normal tissues, is overexpressed in many tumors, and can confer a multidrug-resistant phenotype to cells.

    PubMed

    Sampath, Janardhan; Long, Pandy R; Shepard, Robert L; Xia, Xiaoling; Devanarayan, Viswanath; Sandusky, George E; Perry, William L; Dantzig, Anne H; Williamson, Mark; Rolfe, Mark; Moore, Robert E

    2003-11-01

    Our effort to identify novel drug-resistant genes in cyclophosphamide-resistant EMT6 mouse mammary tumors led us to the identification of SPF45. Simultaneously, other groups identified SPF45 as a component of the spliceosome that is involved in alternative splicing. We isolated the human homologue and examined the normal human tissue expression, tumor expression, and the phenotype caused by overexpression of human SPF45. Our analyses revealed that SPF45 is expressed in many, but not all, normal tissues tested with predominant expression in normal ductal epithelial cells of the breast, liver, pancreas, and prostate. Our analyses using tissue microarrays and sausages of tumors indicated that SPF45 is highly expressed in numerous carcinomas including bladder, breast, colon, lung, ovarian, pancreatic, and prostate. Interestingly, this study revealed that overexpression of SPF45 in HeLa, a cervical carcinoma cell line, resulted in drug resistance to doxorubicin and vincristine, two chemotherapeutic drugs commonly used in cancer. To our knowledge, this is the first study showing tumor overexpression of an alternate splicing factor resulting in drug resistance. PMID:14578179

  17. Two Routes to Genetic Suppression of RNA Trimethylguanosine Cap Deficiency via C-Terminal Truncation of U1 snRNP Subunit Snp1 or Overexpression of RNA Polymerase Subunit Rpo26.

    PubMed

    Qiu, Zhicheng R; Schwer, Beate; Shuman, Stewart

    2015-07-01

    The trimethylguanosine (TMG) caps of small nuclear (sn) RNAs are synthesized by the enzyme Tgs1 via sequential methyl additions to the N2 atom of the m(7)G cap. Whereas TMG caps are inessential for Saccharomyces cerevisiae vegetative growth at 25° to 37°, tgs1∆ cells that lack TMG caps fail to thrive at 18°. The cold-sensitive defect correlates with ectopic stoichiometric association of nuclear cap-binding complex (CBC) with the residual m(7)G cap of the U1 snRNA and is suppressed fully by Cbc2 mutations that weaken cap binding. Here, we show that normal growth of tgs1∆ cells at 18° is also restored by a C-terminal deletion of 77 amino acids from the Snp1 subunit of yeast U1 snRNP. These results underscore the U1 snRNP as a focal point for TMG cap function in vivo. Casting a broader net, we conducted a dosage suppressor screen for genes that allowed survival of tgs1∆ cells at 18°. We thereby recovered RPO26 (encoding a shared subunit of all three nuclear RNA polymerases) and RPO31 (encoding the largest subunit of RNA polymerase III) as moderate and weak suppressors of tgs1∆ cold sensitivity, respectively. A structure-guided mutagenesis of Rpo26, using rpo26∆ complementation and tgs1∆ suppression as activity readouts, defined Rpo26-(78-155) as a minimized functional domain. Alanine scanning identified Glu89, Glu124, Arg135, and Arg136 as essential for rpo26∆ complementation. The E124A and R135A alleles retained tgs1∆ suppressor activity, thereby establishing a separation-of-function. These results illuminate the structure activity profile of an essential RNA polymerase component. PMID:25911228

  18. 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

  19. Repositioning of human interphase chromosomes by nucleolar dynamics in the reverse transformation of HT1080 fibrosarcoma cells.

    PubMed

    Krystosek, A

    1998-05-25

    An experimental system which should be valuable for studying the role of spatial positioning of the nuclear genome in human cell function has been developed. Reverse transformation of the malignant HT1080 fibrosarcoma cell line upon treatment with 8-chloro-cAMP results in growth inhibition, cytoskeletal reorganization, changes in nuclear shape and chromatin accessibility, and formation of prominent nucleoli. Fluorescent in situ hybridization was used to study DNA positioning during nuclear remodeling. Morphometric analysis of the hybridization sites for both repetitive sequences and "painting probes" for whole chromosomes indicated dispersal of acrocentric chromosomes in untreated cells and a highly organized central location of these ribosome gene-containing chromosomes in association with one or a few large nucleoli in nondividing treated cells. The results suggest that there was a directed movement of interphase chromosomes during a response which normalized a malignant cell line. These large-scale repositionings may serve two functions in restoring a normal transcriptional setup to the nucleus. First, ribosome genes are placed in the nucleolus, their transcriptional suborganelle. Second, nucleolar anchorings together with additional perinucleolar centromeric associations orient the domain shapes of entire chromosomes, installing gene-rich chromosomal regions into pockets of (accessible) DNAse I-sensitive chromatin populated by spliceosomes. PMID:9633529

  20. 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…

  1. 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

  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. 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.

  4. Interesting radiative patterns of neutrino mass in an SU(3){sub C}xSU(3){sub L}xU(1){sub X} model with right-handed neutrinos

    SciTech Connect

    Chang, Darwin; Hoang Ngoc Long

    2006-03-01

    We investigate a simple model of neutrino mass based on SU(3){sub C}xSU(3){sub L}xU(1){sub X} gauge unification. The Yukawa coupling of the model has automatic lepton-number symmetry which is broken only by the self-couplings of the Higgs boson. At tree level, the neutrino spectrum contains three Dirac fermions, one massless and two degenerate in mass. At the two-loop level, neutrinos obtain Majorana masses and correct the tree-level result which naturally gives rise to an inverted hierarchy mass pattern and interesting mixing which can fit the current data with minor fine-tuning. In another scenario, one can pick the scales such that the loop-induced Majorana mass matrix is bigger than the Dirac one and thus reproduces the usual seesaw mechanism.

  5. Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins

    PubMed Central

    Gonsalvez, Graydon B.; Tian, Liping; Ospina, Jason K.; Boisvert, François-Michel; Lamond, Angus I.; Matera, A. Gregory

    2007-01-01

    Small nuclear ribonucleoproteins (snRNPs) are core components of the spliceosome. The U1, U2, U4, and U5 snRNPs each contain a common set of seven Sm proteins. Three of these Sm proteins are posttranslationally modified to contain symmetric dimethylarginine (sDMA) residues within their C-terminal tails. However, the precise function of this modification in the snRNP biogenesis pathway is unclear. Several lines of evidence suggest that the methyltransferase protein arginine methyltransferase 5 (PRMT5) is responsible for sDMA modification of Sm proteins. We found that in human cells, PRMT5 and a newly discovered type II methyltransferase, PRMT7, are each required for Sm protein sDMA modification. Furthermore, we show that the two enzymes function nonredundantly in Sm protein methylation. Lastly, we provide in vivo evidence demonstrating that Sm protein sDMA modification is required for snRNP biogenesis in human cells. PMID:17709427

  6. 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.

  7. 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

  8. 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…

  9. 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- ...

  10. The Synthesis and Crystal Structure of Doped Uranium Brannerite Phases U 1- xM xTi 2O 6 ( M=Ca 2+, La 3+, and Gd 3+)

    NASA Astrophysics Data System (ADS)

    James, M.; Watson, J. N.

    2002-05-01

    Doped uranium brannerite phases (U1-xMxTi2O6; M=Ca2+, La3+ and Gd3+; x<0.5) were synthesized at 1400°C; the range of solid solution was found to vary depending on whether sintering took place in argon or air. Powder X-ray diffraction revealed that these phases crystallized to form monoclinic (C2/m) structures. In particular, the crystal structures of U0.74Ca0.26 Ti2O6 (1) (a=9.8008(2); b=3.7276(1); c=6.8745(1); β=118.38(1); V=220.97(1); Z=2; RP=7.3%; RB=4.6%) and U0.55La0.45Ti2O6 (2) (a=9.8002(7); b=3.7510(3); c=6.9990(5); β=118.37(4); V=226.40(3); Z=2; RP=4.5%; RB=2.9%) were refined from powder neutron diffraction data, revealing planes of corner and edge-sharing TiO6 octahedra separated by 8-fold coordinate U/M atoms. The oxygen sites within these structures were found to be fully occupied, confirming that the doping of lower valence M atoms occurs in conjunction with the oxidation of U(IV) to U(V).

  11. 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.

  12. 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.

  13. The synthesis, crystal chemistry and structures of Y-doped brannerite (U 1- xY xTi 2O 6) and thorutite (Th 1- xY xTi 2O 6- δ) phases

    NASA Astrophysics Data System (ADS)

    James, M.; Carter, M. L.; Watson, J. N.

    2003-09-01

    Yttrium-doped uranium brannerite (U 1- xY xTi 2O 6) and thorutite (Th 1- xY xTi 2O 6- δ) phases were synthesized in air at 1400°C. Powder X-ray diffraction revealed that these phases crystallized to form monoclinic ( C2/ m) structures. Crystal structures of U 0.54Y 0.46Ti 2O 6 ( 1) ( a=9.8008(2); b=3.7276(1); c=6.8745(1); β=118.38(1); V=220.97(1); Z=2; RP=7.3%; RB=4.6%) and Th 0.91Y 0.09Ti 2O 6- δ ( 2) ( a=9.8002(7); b=3.7510(3); c=6.9990(5); β=118.37(4); V=226.40(3); Z=2; RP=4.5%; RB=2.9%) were refined from powder neutron diffraction data. These two phases were isostructural, revealing planes of corner and edge-sharing TiO 6 octahedra separated by irregular eight-fold coordinate U/Y or Th/Y atoms. The oxygen sites within the structure of 1 were found to be fully occupied, confirming that the doping of lower valence Y atoms occurs in conjunction with the oxidation of U(IV) to U(V). Y doping of the thorutite phase 2 does not lead to oxidation but rather the formation of oxygen vacancies within the structure.

  14. 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.

  15. Human Trafficking

    MedlinePlus

    ... to debt bondage or peonage in which traffickers demand labor as a means repayment for a real ... human smuggling are two separate crimes under federal law. There are several important differences between them. Human ...

  16. 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 ...

  17. Effect of Various Modifications on Drag and Longitudinal Stability and Control Characteristics at Transonic Speeds of a Model of the XF7U-1 Tailless Airplane: NACA Wing-FLow Method, TED No. NACA DE 307

    NASA Technical Reports Server (NTRS)

    Sawyer, Richard H.; Trant, James P., Jr.

    1950-01-01

    An investigation was made by the NACA wing-flow method to determine the drag, pitching-moment, lift, and angle-of-attack characteristics at transonic speeds of various configurations of a semispan model of an early configuration of the XF7U-1 tailless airplane. The results of the tests indicated that for the basic configuration with undeflected ailavator, the zero-lift drag rise occurred at a Mach number of about 0.85 and that about a five-fold increase in drag occurred through the transonic speed range. The results of the tests also indicated that the drag increment produced by -8.0 degrees deflection of the ailavator increased with increase in normal-force coefficient and was smaller at speeds above than at speeds below the drag rise. The drag increment produced by 35 degree deflection of the speed brakes varied from 0.040 to 0.074 depending on the normal-force coefficient and Mach number. These values correspond to drag coefficients of about 0.40 and 0.75 based on speed-brake frontal area. Removal of the fin produced a small positive drag increment at a given normal-force coefficient at speeds during the drag rise. A large forward shift of the neutral-point location occurred at Mach numbers above about 0.90 upon removal of the fin, and also a considerable forward shift throughout the Mach number range occurred upon deflection of the speed brakes. Ailavator ineffectiveness or reversal at low deflections, similar to that determined in previous tests of the basic configuration of the model in the Mach number range from about 0.93 to 1.0, was found for the fin-off configuration and for the model equipped with skewed (more highly sweptback) hinge-line ailavators. With the speed brakes deflected, little or no loss in the incremental pitching moment produced by deflection of the ailavator from O degrees to -8.00 degrees occurred in the Mach number range from 0.85 to 1.0 in contrast to a considerable loss found in previous tests with the speed brakes off.

  18. 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

  19. 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)

  20. 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.

  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 II - Basic Lateral Stability Characteristics TED No. NACA DE308. Part 2; Basic Lateral Stability Charactistics, TED No. NACA DE308

    NASA Technical Reports Server (NTRS)

    Kemp, William B., Jr.; Goodson, Kenneth W.; Kuhn, Richard E.

    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 basic lateral stability characteristics of the complete model with undeflected control surfaces are presented 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 III - Longitudinal-Control Characteristics TED No. NACA DE308. Part 3; Longitudinal-Control Characteristics, TED No. NACA DE308

    NASA Technical Reports Server (NTRS)

    Kuhn, Richard E.; King, Thomas J., Jr.

    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 longitudinal-control characteristics of the complete model are presented in the present report with a limited analysis of the results.

  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. 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.

  4. Action, human.

    PubMed

    Russo, M T

    2010-01-01

    The term "human action" designates the intentional and deliberate movement that is proper and exclusive to mankind. Human action is a unified structure: knowledge, intention or volition, deliberation, decision or choice of means and execution. The integration between these dimensions appears as a task that demands strength of will to achieve the synthesis of self-possession and self-control that enables full personal realisation. Recently, the debate about the dynamism of human action has been enriched by the contribution of neurosciences. Thanks to techniques of neuroimaging, neurosciences have expanded the field of investigation to the nature of volition, to the role of the brain in decision-making processes and to the notion of freedom and responsibility. PMID:20393686

  5. 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…

  6. 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…

  7. Classical Humanities

    ERIC Educational Resources Information Center

    Goodwin, Donn; And Others

    1975-01-01

    This article reports on a pilot course in humanities team-taught by three teachers, two from a senior high-school and one from a junior high-school, in Brookfield, Wisconsin. The specific subject matter is Greek and Roman culture. The curriculum is outlined and the basic reading list is included. (CLK)

  8. [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

  9. 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…

  10. 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

  11. 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…

  12. 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

  13. Human Protothecosis

    PubMed Central

    Lass-Flörl, Cornelia; Mayr, Astrid

    2007-01-01

    Human protothecosis is a rare infection caused by members of the genus Prototheca. Prototheca species are generally considered to be achlorophyllic algae and are ubiquitous in nature. The occurrence of protothecosis can be local or disseminated and acute or chronic, with the latter being more common. Diseases have been classified as (i) cutaneous lesions, (ii) olecranon bursitis, or (iii) disseminated or systemic manifestations. Infections can occur in both immunocompetent and immunosuppressed patients, although more severe and disseminated infections tend to occur in immunocompromised individuals. Prototheca wickerhamii and Prototheca zopfii have been associated with human disease. Usually, treatment involves medical and surgical approaches; treatment failure is not uncommon. Antifungals such as ketoconazole, itraconazole, fluconazole, and amphotericin B are the most commonly used drugs to date. Among them, amphotericin B displays the best activity against Prototheca spp. Diagnosis is largely made upon detection of characteristic structures observed on histopathologic examination of tissue. PMID:17428884

  14. 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.

  15. Spliceosomal component Sf3b1 is essential for hematopoietic differentiation in zebrafish.

    PubMed

    De La Garza, Adriana; Cameron, Rosannah C; Nik, Sara; Payne, Sara G; Bowman, Teresa V

    2016-09-01

    SF3B1 (Splicing factor 3b, subunit 1) is one of the most commonly mutated factors in myelodysplastic syndrome (MDS). Although the genetic correlation between SF3B1 mutations and MDS etiology are quite strong, no in vivo model currently exists to explore how SF3B1 loss alters blood cell development. Using zebrafish mutants, we show here that proper function of Sf3b1 is required for all hematopoietic lineages. As in MDS patients, zebrafish sf3b1 mutants develop a macrocytic-anemia-like phenotype due to a block in maturation at a late progenitor stage. The mutant embryos also develop neutropenia, because their primitive myeloid cells fail to mature and turn on differentiation markers such as l-plastin and myeloperoxidase. In contrast, production of definitive hematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelial cells within the dorsal aorta is greatly diminished, whereas arterial endothelial cells are correctly fated. Notch signaling, imperative for the endothelial-to-hematopoietic transition, is also normal, indicating that HSPC induction is blocked in sf3b1 mutants downstream or independent of Notch signaling. The data demonstrate that Sf3b1 function is necessary during key differentiation fate decisions in multiple blood cell types. Zebrafish sf3b1 mutants offer a novel animal model with which to explore the role of splicing in hematopoietic development and provide an excellent in vivo system with which to delve into the question of why and how Sf3b1 dysfunction is detrimental to hematopoietic differentiation, which could improve MDS diagnosis and treatment. PMID:27260753

  16. 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

  17. Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3.

    PubMed

    Park, Joon Kyu; Das, Tanuza; Song, Eun Joo; Kim, Eunice EunKyeong

    2016-06-20

    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

  18. 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

  19. 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…

  20. 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)

  1. 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

  2. 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

  3. MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3) in cynomolgus macaques.

    PubMed

    Dereuddre-Bosquet, Nathalie; Morellato-Castillo, Laurence; Brouwers, Joachim; Augustijns, Patrick; Bouchemal, Kawthar; Ponchel, Gilles; Ramos, Oscar H P; Herrera, Carolina; Stefanidou, Martha; Shattock, Robin; Heyndrickx, Leo; Vanham, Guido; Kessler, Pascal; Le Grand, Roger; Martin, Loïc

    2012-01-01

    In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L) in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP) model of mucosal challenge with SHIV(162P3) after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control), the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50) of SHIV(162P3). All control animals were infected with a peak plasma viral load of 10(5)-10(6) viral RNA (vRNA) copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments. PMID:23236282

  4. Human abilities.

    PubMed

    Sternberg, R J; Kaufman, J C

    1998-01-01

    This chapter reviews recent literature, primarily from the 1990s, on human abilities. The review opens with a consideration of the question of what intelligence is, and then considers some of the major definitions of intelligence, as well as implicit theories of intelligence around the world. Next, the chapter considers cognitive approaches to intelligence, and then biological approaches. It proceeds to psychometric or traditional approaches to intelligence, and then to broad, recent approaches. The different approaches raise somewhat different questions, and hence produce somewhat different answers. They have in common, however, the attempt to understand what kinds of mechanisms lead some people to adapt to, select, and shape environments in ways that match particularly well the demands of those environments. PMID:9496630

  5. TT-seq maps the human transient transcriptome.

    PubMed

    Schwalb, Björn; Michel, Margaux; Zacher, Benedikt; Frühauf, Katja; Demel, Carina; Tresch, Achim; Gagneur, Julien; Cramer, Patrick

    2016-06-01

    Pervasive transcription of the genome produces both stable and transient RNAs. We developed transient transcriptome sequencing (TT-seq), a protocol that uniformly maps the entire range of RNA-producing units and estimates rates of RNA synthesis and degradation. Application of TT-seq to human K562 cells recovers stable messenger RNAs and long intergenic noncoding RNAs and additionally maps transient enhancer, antisense, and promoter-associated RNAs. TT-seq analysis shows that enhancer RNAs are short-lived and lack U1 motifs and secondary structure. TT-seq also maps transient RNA downstream of polyadenylation sites and uncovers sites of transcription termination; we found, on average, four transcription termination sites, distributed in a window with a median width of ~3300 base pairs. Termination sites coincide with a DNA motif associated with pausing of RNA polymerase before its release from the genome. PMID:27257258

  6. 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,…

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. [Human papillomaviruses].

    PubMed

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes. PMID:14610898

  12. 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.

  13. 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.

  14. Anomaly driven signatures of extra U(1)'s

    SciTech Connect

    Antoniadis, Ignatios; Boyarsky, Alexey; Ruchayskiy, Oleg

    2010-02-10

    Anomaly cancellation between different sectors of a theory may mediate new interactions between gauge bosons. Such interactions lead to observable effects both at precision laboratory experiments and at accelerators. Such experiments may reveal the presence of hidden sectors or hidden extra dimensions.

  15. 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.

  16. 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.

  17. Neutralinos in E 6 inspired supersymmetric U(1)' models

    NASA Astrophysics Data System (ADS)

    Hesselbach, S.; Franke, F.; Fraas, H.

    2002-03-01

    The neutralino sector in E_6 inspired supersymmetric models with extra neutral gauge bosons and singlet Higgs fields contains additional gaugino and singlino states compared to the MSSM. We discuss the neutralino mixing in rank-5 and rank-6 models and analyze the supersymmetric parameter space where the light neutralinos have mainly singlino or MSSM character. The neutralino character, resonance effects of the new gauge bosons and, assuming mSUGRA-type RGEs, different selectron masses lead to significant differences between the MSSM and the extended models in neutralino production at an e^+e^- linear collider. Beam polarization may improve the signatures to distinguish between the models. In an appendix, we present the mass terms of the gauge bosons, charginos and sfermions which show a significant different mass spectrum than in the MSSM and give all relevant neutralino couplings.

  18. 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.

  19. 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

  20. RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing

    PubMed Central

    Maatz, Henrike; Jens, Marvin; Liss, Martin; Schafer, Sebastian; Heinig, Matthias; Kirchner, Marieluise; Adami, Eleonora; Rintisch, Carola; Dauksaite, Vita; Radke, Michael H.; Selbach, Matthias; Barton, Paul J.R.; Cook, Stuart A.; Rajewsky, Nikolaus; Gotthardt, Michael; Landthaler, Markus; Hubner, Norbert

    2014-01-01

    Mutations in the gene encoding the RNA-binding protein RBM20 have been implicated in dilated cardiomyopathy (DCM), a major cause of chronic heart failure, presumably through altering cardiac RNA splicing. Here, we combined transcriptome-wide crosslinking immunoprecipitation (CLIP-seq), RNA-seq, and quantitative proteomics in cell culture and rat and human hearts to examine how RBM20 regulates alternative splicing in the heart. Our analyses revealed the presence of a distinct RBM20 RNA-recognition element that is predominantly found within intronic binding sites and linked to repression of exon splicing with RBM20 binding near 3′ and 5′ splice sites. Proteomic analysis determined that RBM20 interacts with both U1 and U2 small nuclear ribonucleic particles (snRNPs) and suggested that RBM20-dependent splicing repression occurs through spliceosome stalling at complex A. Direct RBM20 targets included several genes previously shown to be involved in DCM as well as genes not typically associated with this disease. In failing human hearts, reduced expression of RBM20 affected alternative splicing of several direct targets, indicating that differences in RBM20 expression may affect cardiac function. Together, these findings identify RBM20-regulated targets and provide insight into the pathogenesis of human heart failure. PMID:24960161