WorldWideScience

Sample records for u1 snrnp knockdown

  1. Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.

    Directory of Open Access Journals (Sweden)

    Helena Hernández

    2009-09-01

    Full Text Available Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post-translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B'. Results also show that unstructured post-translationally modified C-terminal tails are responsible for the dynamics of Sm-B/B' and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.

  2. U1 snRNP Alteration and Neuronal Cell Cycle Reentry in Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Bing Bai

    2018-03-01

    Full Text Available The aberrancy of U1 small nuclear ribonucleoprotein (snRNP complex and RNA splicing has been demonstrated in Alzheimer’s disease (AD. Importantly, the U1 proteopathy is AD-specific, widespread and early-occurring, thus providing a very unique clue to the AD pathogenesis. The prominent feature of U1 histopathology is its nuclear depletion and redistribution in the neuronal cytoplasm. According to the preliminary data, the initial U1 cytoplasmic distribution pattern is similar to the subcellular translocation of the spliceosome in cells undergoing mitosis. This implies that the U1 mislocalization might reflect the neuronal cell cycle-reentry (CCR which has been extensively evidenced in AD brains. The CCR phenomenon explains the major molecular and cellular events in AD brains, such as Tau and amyloid precursor protein (APP phosphorylation, and the possible neuronal death through mitotic catastrophe (MC. Furthermore, the CCR might be mechanistically linked to inflammation, a critical factor in the AD etiology according to the genetic evidence. Therefore, the discovery of U1 aberrancy might strengthen the involvement of CCR in the AD neuronal degeneration.

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

    Science.gov (United States)

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

    2010-12-15

    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.

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

    OpenAIRE

    Weber, G.; Trowitzsch, S.; Kastner, B.; Lührmann, R.; Wahl, M.

    2010-01-01

    The U1 small nuclear ribonucleoprotein initiates the assembly of the spliceosome. Here, the structure of the natively purified U1 small nuclear ribonucleoprotein particle reveals the core Sm protein ring and its interactions with the Sm site in the small nuclear RNA.

  5. B-CELL EPITOPE ON THE U1 SNRNP-C AUTOANTIGEN CONTAINS A SEQUENCE SIMILAR TO THAT OF THE HERPES-SIMPLEX VIRUS PROTEIN

    NARCIS (Netherlands)

    MISAKI, Y; YAMAMOTO, K; YANAGI, K; MIURA, H; ICHIJO, H; KATO, T; MATO, T; WELLINGWESTER, S; NISHIOKA, K; ITO, K

    The mechanism of autoantibody production in autoimmune diseases is not well understood. In the present study we performed the B cell epitope mapping of the U1 small nuclear ribonucleoprotein (snRNP)-C, one of the target molecules of anti-nRNP autoantibody to investigate how B cells respond to the

  6. Knocking Down Snrnp200 Initiates Demorphogenesis of Rod Photoreceptors in Zebrafish

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2015-01-01

    Full Text Available Purpose. The small nuclear ribonucleoprotein 200 kDa (SNRNP200 gene is a fundamental component for precursor message RNA (pre-mRNA splicing and has been implicated in the etiology of autosomal dominant retinitis pigmentosa (adRP. This study aims to determine the consequences of knocking down Snrnp200 in zebrafish. Methods. Expression of the Snrnp200 transcript in zebrafish was determined via whole mount in situ hybridization. Morpholino oligonucleotide (MO aiming to knock down the expression of Snrnp200 was injected into zebrafish embryos, followed by analyses of aberrant splicing and expression of the U4/U6-U5 tri-small nuclear ribonucleoproteins (snRNPs components and retina-specific transcripts. Systemic changes and retinal phenotypes were further characterized by histological study and immunofluorescence staining. Results. Snrnp200 was ubiquitously expressed in zebrafish. Knocking down Snrnp200 in zebrafish triggered aberrant splicing of the cbln1 gene, upregulation of other U4/U6-U5 tri-snRNP components, and downregulation of a panel of retina-specific transcripts. Systemic defects were found correlated with knockdown of Snrnp200 in zebrafish. Only demorphogenesis of rod photoreceptors was detected in the initial stage, mimicking the disease characteristics of RP. Conclusions. We conclude that knocking down Snrnp200 in zebrafish could alter regular splicing and expression of a panel of genes, which may eventually trigger rod defects.

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

    Directory of Open Access Journals (Sweden)

    Nicolas Tremblay

    2016-07-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  9. Spinal Muscular Atrophy: From Defective Chaperoning of snRNP Assembly to Neuromuscular Dysfunction

    Directory of Open Access Journals (Sweden)

    Maia Lanfranco

    2017-06-01

    Full Text Available Spinal Muscular Atrophy (SMA is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN protein. SMN is part of a multiprotein complex that also includes Gemins 2–8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5 complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs to generate small nuclear ribonucleoproteins (snRNPs, which are the operating components of the spliceosome. Molecular and structural studies have refined our knowledge of the key events taking place within the crowded environment of cells and the numerous precautions undertaken to ensure the faithful assembly of snRNPs. Nonetheless, it remains unclear whether a loss of chaperoning in snRNP assembly, considered as a “housekeeping” activity, is responsible for the selective neuromuscular phenotype in SMA. This review thus shines light on in vivo studies that point toward disturbances in snRNP assembly and the consequential transcriptome abnormalities as the primary drivers of the progressive neuromuscular degeneration underpinning the disease. Disruption of U1 snRNP or snRNP assembly factors other than SMN induces phenotypes that mirror aspects of SMN deficiency, and splicing defects, described in numerous SMA models, can lead to a DNA damage and stress response that compromises the survival of the motor system. Restoring the correct chaperoning of snRNP assembly is therefore predicted to enhance the benefit of SMA therapeutic modalities based on augmenting SMN expression.

  10. Cytoplasmic assembly of snRNP particles from stored proteins and newly transcribed snRNA's in L929 mouse fibroblasts

    International Nuclear Information System (INIS)

    Sauterer, R.A.; Feeney, R.J.; Zieve, G.W.

    1988-01-01

    Newly synthesized snRNAs appear transiently in the cytoplasm where they assemble into ribonucleoprotein particles, the snRNP particles, before returning permanently to the interphase nucleus. In this report, bona fide cytoplasmic fractions, prepared by cell enucleation, are used for a quantitative analysis of snRNP assembly in growing mouse fibroblasts. The half-lives and abundances of the snRNP precursors in the cytoplasm and the rates of snRNP assembly are calculated in L929 cells. With the exception of U6, the major snRNAs are stable RNA species; U1 is almost totally stable while U2 has a half-life of about two cell cycles. In contrast, the majority of newly synthesized U6 decays with a half-life of about 15 h. The relative abundances of the newly synthesized snRNA species U1, U2, U3, U4 and U6 in the cytoplasm are determined by Northern hybridization using cloned probes and are approximately 2% of their nuclear abundance. The half-lives of the two major snRNA precursors in the cytoplasm (U1 and U2) are approximately 20 min as determined by labeling to steady state. The relative abundance of the snRNP B protein in the cytoplasm is determined by Western blotting with the Sm class of autoantibodies and is approximately 25% of the nuclear abundance. Kinetic studies, using the Sm antiserum to immunoprecipitate the methionine-labeled snRNP proteins, suggest that the B protein has a half-life of 90 to 120 min in the cytoplasm. These data are discussed and suggest that there is a large pool of more stable snRNP proteins in the cytoplasm available for assembly with the less abundant but more rapidly turning-over snRNAs

  11. Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease.

    Science.gov (United States)

    Somarelli, J A; Mesa, A; Rodriguez, R; Avellan, R; Martinez, L; Zang, Y J; Greidinger, E L; Herrera, R J

    2011-03-01

    Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are autoimmune illnesses characterized by the presence of high titers of autoantibodies directed against a wide range of 'self ' antigens. Proteins of the U1 small nuclear ribonucleoprotein particle (U1 snRNP) are among the most immunogenic molecules in patients with SLE and MCTD. The recent release of a crystallized U1 snRNP provides a unique opportunity to evaluate the effects of tertiary and quaternary structures on autoantigenicity within the U1 snRNP. In the present study, an epitope map was created using the U1 snRNP crystal structure. A total of 15 peptides were tested in a cohort of 68 patients with SLE, 29 with MCTD and 26 healthy individuals and mapped onto the U1 snRNP structure. Antigenic sites were detected in a variety of structures and appear to include RNA binding domains, but mostly exclude regions necessary for protein-protein interactions. These data suggest that while some autoantibodies may target U1 snRNP proteins as monomers or apoptosis-induced, protease-digested fragments, others may recognize epitopes on assembled protein subcomplexes of the U1 snRNP. Although nearly all of the peptides are strong predictors of autoimmune illness, none were successful at distinguishing between SLE and MCTD. The antigenicity of some peptides significantly correlated with several clinical symptoms. This investigation implicitly highlights the complexities of autoimmune epitopes, and autoimmune illnesses in general, and demonstrates the variability of antigens in patient populations, all of which contribute to difficult clinical diagnoses.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities.

    Science.gov (United States)

    Didychuk, Allison L; Montemayor, Eric J; Carrocci, Tucker J; DeLaitsch, Andrew T; Lucarelli, Stefani E; Westler, William M; Brow, David A; Hoskins, Aaron A; Butcher, Samuel E

    2017-09-08

    U6 small nuclear ribonucleoprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood. Here, we report structures of the U6 RNA processing enzyme Usb1 from yeast and a substrate analog bound complex from humans. Unlike the human ortholog, we show that yeast Usb1 has cyclic phosphodiesterase activity that leaves a terminal 3' phosphate which prevents overprocessing. Usb1 processing of U6 RNA dramatically alters its affinity for cognate RNA-binding proteins. We reconstitute the post-transcriptional assembly of yeast U6 snRNP in vitro, which occurs through a complex series of handoffs involving 10 proteins (Lhp1, Prp24, Usb1 and Lsm2-8) and anti-cooperative interactions between Prp24 and Lhp1. We propose a model for U6 snRNP assembly that explains how evolutionarily divergent and seemingly antagonistic proteins cooperate to protect and chaperone the nascent snRNA during its journey to the spliceosome.The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.

  14. Dark U (1)

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  15. U(1) problem

    Energy Technology Data Exchange (ETDEWEB)

    McDougall, N.A. (Oxford Univ. (UK). Dept. of Theoretical Physics)

    1984-08-23

    The resolution of the U(1) problem requires the quark condensates to have a specific THETA dependence. We show that the required THETA dependence arises naturally upon application of the index theorem during the calculation of the dynamically generated quark mass.

  16. Shell Buckling Knockdown Factors

    Data.gov (United States)

    National Aeronautics and Space Administration — The Shell Buckling Knockdown Factor (SBKF) Project, NASA Engineering and Safety Center (NESC) Assessment #: 07-010-E, was established in March of 2007 by the NESC in...

  17. Gauged U(1) clockwork theory

    Science.gov (United States)

    Lee, Hyun Min

    2018-03-01

    We consider the gauged U (1) clockwork theory with a product of multiple gauge groups and discuss the continuum limit of the theory to a massless gauged U (1) with linear dilaton background in five dimensions. The localization of the lightest state of gauge fields on a site in the theory space naturally leads to exponentially small effective couplings of external matter fields localized away from the site. We discuss the implications of our general discussion with some examples, such as mediators of dark matter interactions, flavor-changing B-meson decays as well as D-term SUSY breaking.

  18. On the U(1) problem

    International Nuclear Information System (INIS)

    McDougall, N.A.

    1984-01-01

    The resolution of the U(1) problem requires the quark condensates to have a specific THETA dependence. We show that the required THETA dependence arises naturally upon application of the index theorem during the calculation of the dynamically generated quark mass. (orig.)

  19. The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression.

    Science.gov (United States)

    Egloff, Sylvain; Vitali, Patrice; Tellier, Michael; Raffel, Raoul; Murphy, Shona; Kiss, Tamás

    2017-04-03

    The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, regulates the mRNA elongation capacity of RNA polymerase II (RNAPII) through controlling the nuclear activity of positive transcription elongation factor b (P-TEFb). Here, we demonstrate that the human 7SK snRNP also functions as a canonical transcription factor that, in collaboration with the little elongation complex (LEC) comprising ELL, Ice1, Ice2, and ZC3H8, promotes transcription of RNAPII-specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. The 7SK snRNA specifically associates with a fraction of RNAPII hyperphosphorylated at Ser5 and Ser7, which is a hallmark of RNAPII engaged in snRNA synthesis. Chromatin immunoprecipitation (ChIP) and chromatin isolation by RNA purification (ChIRP) experiments revealed enrichments for all components of the 7SK snRNP on RNAPII-specific sn/snoRNA genes. Depletion of 7SK snRNA or Larp7 disrupts LEC integrity, inhibits RNAPII recruitment to RNAPII-specific sn/snoRNA genes, and reduces nascent snRNA and snoRNA synthesis. Thus, through controlling both mRNA elongation and sn/snoRNA synthesis, the 7SK snRNP is a key regulator of nuclear RNA production by RNAPII. © 2017 The Authors.

  20. Intronic PAH gene mutations cause a splicing defect by a novel mechanism involving U1snRNP binding downstream of the 5' splice site

    DEFF Research Database (Denmark)

    Martínez-Pizarro, Ainhoa; Dembic, Maja; Pérez, Belén

    2018-01-01

    Phenylketonuria (PKU), one of the most common inherited diseases of amino acid metabolism, is caused by mutations in the phenylalanine hydroxylase (PAH) gene. Recently, PAH exon 11 was identified as a vulnerable exon due to a weak 3' splice site, with different exonic mutations affecting exon 11 ...

  1. Vector coherent state representations of SO5 contains SU2 + SU2 contains U1 + U1 and SO5 contains U1 + U1

    International Nuclear Information System (INIS)

    Pan Feng

    1991-01-01

    VCS representations of SO 5 contains SU 2 + SU 2 contains U 1 + U 1 and SO 5 contains U 1 + U 1 are discussed. Reduced matrix elements for SO 5 contains SU 2 + SU 2 are derived. The multiplicity of a weight for SO 5 is determined by using the K-matrix technique

  2. The recruitment of the U5 snRNP to nascent transcripts requires internal loop 1 of U5 snRNA.

    Science.gov (United States)

    Kim, Rebecca; Paschedag, Joshua; Novikova, Natalya; Bellini, Michel

    2012-12-01

    In this study, we take advantage of the high spatial resolution offered by the nucleus and lampbrush chromosomes of the amphibian oocyte to investigate the mechanisms that regulate the intranuclear trafficking of the U5 snRNP and its recruitment to nascent transcripts. We monitor the fate of newly assembled fluorescent U5 snRNP in Xenopus oocytes depleted of U4 and/or U6 snRNAs and demonstrate that the U4/U6.U5 tri-snRNP is not required for the association of U5 snRNP with Cajal bodies, splicing speckles, and nascent transcripts. In addition, using a mutational analysis, we show that a non-functional U5 snRNP can associate with nascent transcripts, and we further characterize internal loop structure 1 of U5 snRNA as a critical element for licensing U5 snRNP to target both nascent transcripts and splicing speckles. Collectively, our data support the model where the recruitment of snRNPs onto pre-mRNAs is independent of spliceosome assembly and suggest that U5 snRNP may promote the association of the U4/U6.U5 tri-snRNP with nascent transcripts.

  3. Genome-wide analysis of KAP1, the 7SK snRNP complex, and RNA polymerase II

    Directory of Open Access Journals (Sweden)

    Ryan P. McNamara

    2016-03-01

    Full Text Available The transition of RNA polymerase II (Pol II from transcription initiation into productive elongation in eukaryotic cells is regulated by the P-TEFb kinase, which phosphorylates the C-terminal domain of paused Pol II at promoter-proximal regions. Our recent study found that P-TEFb (in an inhibited state bound to the 7SK snRNP complex interacts with the KAP1/TRIM28 transcriptional regulator, and that KAP1 and the 7SK snRNP co-occupy most gene promoters containing paused Pol II. Here we provide a detailed experimental description and analysis of the ChIP-seq datasets that have been deposited into Gene Expression Omnibus (GEO: GS72622, so that independent groups can replicate and expand upon these findings. We propose these datasets would provide valuable information for researchers studying mechanisms of transcriptional regulation including Pol II pausing and pause release. Keywords: P-TEFb/7SK snRNP, KAP1, RNA polymerase II, ChIP-seq, Transcription elongation

  4. U(1) x U(1) x U(1) symmetry of the Kimura 3ST model and phylogenetic branching processes

    International Nuclear Information System (INIS)

    Bashford, J D; Jarvis, P D; Sumner, J G; Steel, M A

    2004-01-01

    An analysis of the Kimura 3ST model of DNA sequence evolution is given on the basis of its continuous Lie symmetries. The rate matrix commutes with a U(1) x U(1) x U(1) phase subgroup of the group GL(4) of 4 x 4 invertible complex matrices acting on a linear space spanned by the four nucleic acid base letters. The diagonal 'branching operator' representing speciation is defined, and shown to intertwine the U(1) x U(1) x U(1) action. Using the intertwining property, a general formula for the probability density on the leaves of a binary tree under the Kimura model is derived, which is shown to be equivalent to established phylogenetic spectral transform methods. (letter to the editor)

  5. Tim50a, a nuclear isoform of the mitochondrial Tim50, interacts with proteins involved in snRNP biogenesis

    Directory of Open Access Journals (Sweden)

    Robinson Melvin L

    2005-07-01

    Full Text Available Abstract Background The Cajal body (CB is a nuclear suborganelle involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs, which are vital for pre-mRNA splicing. Newly imported Sm-class snRNPs traffic through CBs, where the snRNA component of the snRNP is modified, and then target to other nuclear domains such as speckles and perichromatin fibrils. It is not known how nascent snRNPs localize to the CB and are released from this structure after modification. The marker protein for CBs, coilin, may play a role in snRNP biogenesis given that it can interact with snRNPs and SMN, the protein mutated in Spinal Muscular Atrophy. Loss of coilin function in mice leads to significant viability and fertility problems and altered CB formation. Results In this report, we identify a minor isoform of the mitochondrial Tim50, Tim50a, as a coilin interacting protein. The Tim50a transcript can be detected in some cancer cell lines and normal brain tissue. The Tim50a protein differs only from Tim50 in that it contains an additional 103 aa N-terminal to the translation start of Tim50. Importantly, a putative nuclear localization signal is found within these 103 residues. In contrast to Tim50, which localizes to the cytoplasm and mitochondria, Tim50a is strictly nuclear and is enriched in speckles with snRNPs. In addition to coilin, Tim50a interacts with snRNPs and SMN. Competition binding experiments demonstrate that coilin competes with Sm proteins of snRNPs and SMN for binding sites on Tim50a. Conclusion Tim50a may play a role in snRNP biogenesis given its cellular localization and protein interaction characteristics. We hypothesize that Tim50a takes part in the release of snRNPs and SMN from the CB.

  6. Variability in clinical phenotypes of PRPF8-linked autosomal dominant retinitis pigmentosa correlates with differential PRPF8/SNRNP200 interactions.

    Science.gov (United States)

    Escher, Pascal; Passarin, Olga; Munier, Francis L; Tran, Viet H; Vaclavik, Veronika

    2018-01-01

    To expand the genotype/phenotype correlations in patients with autosomal dominant retinitis pigmentosa (adRP) harboring PRPF8 variants. Two patients, a father and his daughter, harboring a novel p.PRPF8-Glu2331* variant, underwent ophthalmic examination at 3-year-interval, including fundus photography, fundus autofluorescence, optical coherence tomography, and ISCEV standard full field ERGs. All reported disease-causing PRPF8 variants were collected and localized in the PRPF8 and PRPF8/SNRNP200 protein structures. The p.PRPF8-Glu2331* variant results in a truncated PRPF8 protein lacking the last five C-terminal amino acids and caused in the two patients a severe clinical phenotype, with the macula being affected from the second decade on. All but two adRP-linked variants are located in the last exon 43 encoding the C-terminal tail of the C-terminal PRPF8 Jab1 domain. The p.PRPF8-Ser2118Phe and -Asn2280Lys variants encoded by exons 39 and 42, respectively, are located at the basis of the C-terminal tail. Frame-shift mutations and nonconservative amino acid changes in PRPF8 typically cause severe clinical phenotypes. The conservative missense variant p.PRPF8-Arg2310Lys that is not altering the global charge of the C-terminal tail, and variants located at the basis of the C-terminal tail show milder clinical phenotypes, in accordance with functional data on PRPF8/SNRNP200 interactions in yeast.

  7. U(1) mediation of flux supersymmetry breaking

    Science.gov (United States)

    Grimm, Thomas W.; Klemm, Albrecht

    2008-10-01

    We study the mediation of supersymmetry breaking triggered by background fluxes in Type II string compactifications with Script N = 1 supersymmetry. The mediation arises due to an U(1) vector multiplet coupling to both a hidden supersymmetry breaking flux sector and a visible D-brane sector. The required internal manifolds can be constructed by non-Kähler resolutions of singular Calabi-Yau manifolds. The effective action encoding the U(1) coupling is then determined in terms of the global topological properties of the internal space. We investigate suitable local geometries for the hidden and visible sector in detail. This includes a systematic study of orientifold symmetries of del Pezzo surfaces realized in compact geometries after geometric transition. We construct compact examples admitting the key properties to realize flux supersymmetry breaking and U(1) mediation. Their toric realization allows us to analyze the geometry of curve classes and confirm the topological connection between the hidden and visible sector.

  8. U(1) mediation of flux supersymmetry breaking

    International Nuclear Information System (INIS)

    Grimm, Thomas W.; Klemm, Albrecht

    2008-01-01

    We study the mediation of supersymmetry breaking triggered by background fluxes in Type II string compactifications with N = 1 supersymmetry. The mediation arises due to an U(1) vector multiplet coupling to both a hidden supersymmetry breaking flux sector and a visible D-brane sector. The required internal manifolds can be constructed by non-Kaehler resolutions of singular Calabi-Yau manifolds. The effective action encoding the U(1) coupling is then determined in terms of the global topological properties of the internal space. We investigate suitable local geometries for the hidden and visible sector in detail. This includes a systematic study of orientifold symmetries of del Pezzo surfaces realized in compact geometries after geometric transition. We construct compact examples admitting the key properties to realize flux supersymmetry breaking and U(1) mediation. Their toric realization allows us to analyze the geometry of curve classes and confirm the topological connection between the hidden and visible sector.

  9. O(5) x U(1) electroweak theory

    International Nuclear Information System (INIS)

    Mukku, C.; Sayed, W.A.

    1980-12-01

    An anomaly free O(5) x U(1) theory of electroweak interactions is described which provides a unified description of electroweak phenomena for two families of standard leptons and quarks. No ''new'' non-sequential type fermions of the standard model are introduced as has been the case for all past studies based on this group. The present scheme requires the introduction of two further charged and three more neutral gauge fields over and above the Wsup(+-), Z and photon fields of SU(2) x U(1) giving rise to new neutral and charged currents. In this note we outline our reasons for proposing the present electroweak scheme, give the basic structure of the model, discuss the symmetry breaking pattern which ensures that SU(2)sub(L) x U(1) is the low energy symmetry, point out the new interactions present in the extended framework and obtain limits on the masses of all the gauge fields. (author)

  10. Topological excitations in U(1) -invariant theories

    International Nuclear Information System (INIS)

    Savit, R.

    1977-01-01

    A class of U(1) -invariant theories in d dimensions is introduced on a lattice. These theories are labeled by a simplex number s, with 1 < or = s < d. The case with s = 1 is the X-Y model; and s = 2 gives compact photodynamics. An exact duality transformation is applied to show that the U(1) -invariant theory in d dimensions with simplex number s is the same as a similar theory in d dimensions but which is Z /sub infinity/-invariant and has simplex number s = d-s. This dual theory describes the topological excitations of the original theory. These excitations are of dimension s - 1

  11. O(5) x U(1) electroweak theory

    International Nuclear Information System (INIS)

    Mukku, C.; Sayed, W.A.

    1981-01-01

    An anomaly-free O(5) x U(1) theory of electroweak interactions is described which provides a unified description of electroweak phenomena for two families of standard leptons and quarks. No ''new'' nonsequential-type fermions are introduced, unlike the case for all past studies based on this group. The present scheme requires the introduction of two further charged and three more neutral gauge fields over and above those of SU(2) x U(1) giving rise to new neutral and charged currents

  12. Two-dimensional gauge model with vector U(1) and axial-vector U(1) symmetries

    International Nuclear Information System (INIS)

    Watabiki, Y.

    1989-01-01

    We have succeeded in constructing a two-dimensional gauge model with both vector U(1) and axial-vector U(1) symmetries. This model is exactly solvable. The Schwinger term vanishes in this model as a consequence of the above symmetries, and negative-norm states appear. However, the norms of physical states are always positive semidefinite due to the gauge symmetries

  13. Deletion of SNURF/SNRPN U1B and U1B* upstream exons in a ...

    Indian Academy of Sciences (India)

    RESEARCH ARTICLE. Deletion of SNURF/SNRPN U1B and U1B* upstream exons in a child ... whereby genes are expressed in a parent-of-origin dependent manner. One of the ... lity, neurodevelopmental delay, features of attention deficit hyperactivity .... Received 16 December 2015; accepted 8 January 2016. Unedited ...

  14. Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients.

    Science.gov (United States)

    Yin, Shanye; Lopez-Gonzalez, Rodrigo; Kunz, Ryan C; Gangopadhyay, Jaya; Borufka, Carl; Gygi, Steven P; Gao, Fen-Biao; Reed, Robin

    2017-06-13

    Hexanucleotide repeat expansion in the C9ORF72 gene results in production of dipeptide repeat (DPR) proteins that may disrupt pre-mRNA splicing in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. At present, the mechanisms underlying this mis-splicing are not understood. Here, we show that addition of proline-arginine (PR) and glycine-arginine (GR) toxic DPR peptides to nuclear extracts blocks spliceosome assembly and splicing, but not other types of RNA processing. Proteomic and biochemical analyses identified the U2 small nuclear ribonucleoprotein particle (snRNP) as a major interactor of PR and GR peptides. In addition, U2 snRNP, but not other splicing factors, mislocalizes from the nucleus to the cytoplasm both in C9ORF72 patient induced pluripotent stem cell (iPSC)-derived motor neurons and in HeLa cells treated with the toxic peptides. Bioinformatic studies support a specific role for U2-snRNP-dependent mis-splicing in C9ORF72 patient brains. Together, our data indicate that DPR-mediated dysfunction of U2 snRNP could account for as much as ∼44% of the mis-spliced cassette exons in C9ORF72 patient brains. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients

    Directory of Open Access Journals (Sweden)

    Shanye Yin

    2017-06-01

    Full Text Available Hexanucleotide repeat expansion in the C9ORF72 gene results in production of dipeptide repeat (DPR proteins that may disrupt pre-mRNA splicing in amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD patients. At present, the mechanisms underlying this mis-splicing are not understood. Here, we show that addition of proline-arginine (PR and glycine-arginine (GR toxic DPR peptides to nuclear extracts blocks spliceosome assembly and splicing, but not other types of RNA processing. Proteomic and biochemical analyses identified the U2 small nuclear ribonucleoprotein particle (snRNP as a major interactor of PR and GR peptides. In addition, U2 snRNP, but not other splicing factors, mislocalizes from the nucleus to the cytoplasm both in C9ORF72 patient induced pluripotent stem cell (iPSC-derived motor neurons and in HeLa cells treated with the toxic peptides. Bioinformatic studies support a specific role for U2-snRNP-dependent mis-splicing in C9ORF72 patient brains. Together, our data indicate that DPR-mediated dysfunction of U2 snRNP could account for as much as ∼44% of the mis-spliced cassette exons in C9ORF72 patient brains.

  16. More modular invariant anomalous U(1) breaking

    International Nuclear Information System (INIS)

    Gaillard, Mary K.; Giedt, Joel

    2002-01-01

    We consider the case of several scalar fields, charged under a number of U(1) factors, acquiring vacuum expectation values due to an 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 upon 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 Kaehler 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

  17. U(1) textures and Lepton Flavor Violation

    CERN Document Server

    Gómez, M E; Lola, S; Vergados, J D

    1999-01-01

    U(1) family symmetries have led to successful predictions of the fermion mass spectrum and the mixing angles of the hadronic sector. In the context of the supersymmetric unified theories, they further imply a non-trivial mass structure for the scalar partners, giving rise to new sources of flavour violation. In the present work, lepton flavour non-conserving processes are examined in the context of the MSSM augmented by a U(1) family symmetry. We calculate the mixing effects on the mu -> e gamma and tau-> mu gamma rare decays. All supersymmetric scalar masses involved in the processes are determined at low energies using two loop renormalisation group analysis and threshold corrections. Further, various novel effects are considered and found to have important impact on the branching ratios. Thus, a rather interesting result is that when the see-saw mechanism is applied in the (12X12)-sneutrino mass matrix, the mixing effects of the Dirac matrix in the effective light sneutrino sector are canceled at first ord...

  18. Flipped SU(5) times U(1) in superconformal models

    Energy Technology Data Exchange (ETDEWEB)

    Bailin, D.; Katechou, E.K. (Sussex Univ., Brighton (United Kingdom). School of Mathematical and Physical Sciences); Love, A. (London Univ. (United Kingdom))

    1992-01-10

    This paper reports that flipped SU(5) {times} U(1) models are constructed in the framework of tensoring of N = 2 superconformal minimal models quotiented by discrete symmetries. Spontaneous breaking of flipped SU(5) {times} U(1) and extra U(1) factors in the gauge group along F-flat directions of the effective potential is studied.

  19. SU(2) x U(1) x U'(1) models which are slightly different from the Weinberg-Salam model

    International Nuclear Information System (INIS)

    Gao, C.; Wu, D.

    1981-01-01

    We discuss SU(2) x U(1) x U'(1) models by a uniform formula which is convenient for their comparison with the standard Weinberg-Salam model. As examples, we give three interesting models which are based on different grand unification models. In one model, U'(1) does not contribute to the electromagnetic interaction; in the other two, both U(1) and U'(1) do contribute to the electromagnetic interaction. Also, the first two models can approach the standard Weinberg-Salam model as close as one wants; but the third model has limitations on it

  20. Light hidden-sector U(1)s in string compactifications

    Energy Technology Data Exchange (ETDEWEB)

    Goodsell, Mark; Ringwald, Andreas

    2010-02-15

    We review the case for light U(1) gauge bosons in the hidden-sector of heterotic and type II string compactifications, present estimates of the size of their kinetic mixing with the visible-sector hypercharge U(1), and discuss their possibly very interesting phenomenological consequences in particle physics and cosmology. (orig.)

  1. Light hidden-sector U(1)s in string compactifications

    International Nuclear Information System (INIS)

    Goodsell, Mark; Ringwald, Andreas

    2010-02-01

    We review the case for light U(1) gauge bosons in the hidden-sector of heterotic and type II string compactifications, present estimates of the size of their kinetic mixing with the visible-sector hypercharge U(1), and discuss their possibly very interesting phenomenological consequences in particle physics and cosmology. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Corey Kownacki

    2016-09-01

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

  3. Supersymmetric U boson and the old U(1) problem

    International Nuclear Information System (INIS)

    Kim, B.R.

    1983-01-01

    In the supersymmetric SU(3)xSU(2)xU(1)xUsup(')(1) model the new gauge group Usup(')(1) enforces the introduction of mirror fermions. In this note we address the inverse question. If one starts with SU(3)xSU(2)xU(1) including mirror fermions, what physical arguments other than the supersymmetric require the introduction of a new gauge group Usup(')(1). It turns out that the old U(1) problem is closely related with this question. Further we give an estimate for the upper bound for the parameter of the supersymmetric U boson r and x. (orig.)

  4. A SU(3) x U(1) model for electroweak interactions

    International Nuclear Information System (INIS)

    Pisano, F.; Pleitez, V.

    1992-01-01

    We consider a gauge model based on a SU(3) vector U(1) symmetry in which the lepton number is violated explicitly by charged scalar and gauge boson, including a vector field with double electric charge. (author)

  5. Anomalous U(1) as a mediator of Supersymmetry Breaking

    CERN Document Server

    Dvali, Gia; Dvali, Gia; Pomarol, Alex

    1996-01-01

    We point out that an anomalous gauge U(1) symmetry is a natural candida= te for being the mediator and messenger of supersymmetry breaking. It facilitate= s dynamical supersymmetry breaking even in the flat limit. Soft masses are induced by both gravity and the U(1) gauge interactions giving an unusual= mass hierarchy in the sparticle spectrum which suppresses flavor violations. T= his scenario does not suffer from the Polonyi problem.

  6. Underground storage tank 291-D1U1: Closure plan

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. CERKL knockdown causes retinal degeneration in zebrafish.

    Directory of Open Access Journals (Sweden)

    Marina Riera

    Full Text Available The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration.

  8. Kinetics of the U-1% Mo alloy transformation during continual cooling; Kinetika transformacije legura U-1% Mo pri kontinuiranom hladjenju

    Energy Technology Data Exchange (ETDEWEB)

    Mihajlovic, A; Djuric, B; Tepavac, P [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Yugoslavia)

    1965-11-15

    Study of continuous cooling of the U-1% Mo alloy is significant if it could be used as fuel in the nuclear reactor. Previous studies were dealing with relatively low cooling rate up to 3 deg C/s{sup 1}, which produced alpha + gamma structure. This task was devoted to testing the U-1% Mo alloy properties at higher cooling rates in order to discover whether bainite reaction and favourable alpha grain could be achieved under certain conditions.

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

    CERN Document Server

    Antoniadis, I

    2014-01-01

    In this note we study the constraints on F-theory GUTs with extra $U(1)$'s in the context of elliptic fibrations with rational sections. We consider the simplest case of one abelian factor (Mordell-Weil rank one) and investigate the conditions that are induced on the coefficients of its Tate form. Converting the equation representing the generic hypersurface $P_{112}$ to this Tate's form we find that the presence of a U(1), already in this local description, is consistent with the exceptional ${\\cal E}_6$ and ${\\cal E}_7$ non-abelian singularities. We briefly comment on a viable ${\\cal E}_6\\times U(1)$ effective F-theory model.

  10. Minimal anomalous U(1) theories and collider phenomenology

    Science.gov (United States)

    Ekstedt, Andreas; Enberg, Rikard; Ingelman, Gunnar; Löfgren, Johan; Mandal, Tanumoy

    2018-02-01

    We study the collider phenomenology of a neutral gauge boson Z ' arising in minimal but anomalous U(1) extensions of the Standard Model (SM). To retain gauge invariance of physical observables, we consider cancellation of gauge anomalies through the Green-Schwarz mechanism. We categorize a wide class of U(1) extensions in terms of the new U(1) charges of the left-handed quarks and leptons and the Higgs doublet. We derive constraints on some benchmark models using electroweak precision constraints and the latest 13 TeV LHC dilepton and dijet resonance search data. We calculate the decay rates of the exotic and rare one-loop Z ' decays to ZZ and Z-photon modes, which are the unique signatures of our framework. If observed, these decays could hint at anomaly cancellation through the Green-Schwarz mechanism. We also discuss the possible observation of such signatures at the LHC and at future ILC colliders.

  11. A model with isospin doublet U(1)D gauge symmetry

    Science.gov (United States)

    Nomura, Takaaki; Okada, Hiroshi

    2018-05-01

    We propose a model with an extra isospin doublet U(1)D gauge symmetry, in which we introduce several extra fermions with odd parity under a discrete Z2 symmetry in order to cancel the gauge anomalies out. A remarkable issue is that we impose nonzero U(1)D charge to the Standard Model Higgs, and it gives the most stringent constraint to the vacuum expectation value of a scalar field breaking the U(1)D symmetry that is severer than the LEP bound. We then explore relic density of a Majorana dark matter candidate without conflict of constraints from lepton flavor violating processes. A global analysis is carried out to search for parameters which can accommodate with the observed data.

  12. A reduction of the globalization and U(1)-covering

    International Nuclear Information System (INIS)

    Tran Dao Dong.

    1993-03-01

    We suggest a reduction of the globalization and multidimensional quantization to the case of reductive Lie groups by lifting to U(1)-covering. our construction is connected with M. Duflo's third method for algebraic groups. From a reductive datum of the given real algebraic Lie group we firstly construct geometric complexes with respect to U(1)-covering by using the unipotent positive distributions. Then we describe in terms of local cohomology the maximal globalization of Harish-Chandra modules which correspond to the geometric complexes. (author). 9 refs

  13. Implications of Anomalous U(1) Symmetry in Unified Models the Flipped SU(5) x U(1) Paradigm

    CERN Document Server

    Ellis, Jonathan Richard; Rizos, J; Ellis, John

    2000-01-01

    A generic feature of string-derived models is the appearance of an anomalousAbelian U(1)_A symmetry which, among other properties, constrains the Yukawacouplings and distinguishes the three families from each other. In this paper,we discuss in a model-independent way the general constraints imposed by such aU(1)_A symmetry on fermion masses, R-violating couplings and proton-decayoperators in a generic flipped SU(5) x U(1)' model. We construct all possibleviable fermion mass textures and give various examples of effective low-energymodels which are distinguished from each other by their different predictionsfor B-, L- and R-violating effects. We pay particular attention to predictionsfor neutrino masses, in the light of the recent Super-Kamiokande data.

  14. Fractional winding numbers and the U(1) problem

    International Nuclear Information System (INIS)

    Rothe, K.D.; Swieca, J.A.; Pontificia Univ. Catolica do Rio de Janeiro

    1980-06-01

    The effective Lagrangian description of gauge theories with spontaneous mass generation is simulated by considering the chiral Gross-Neveu model embedded in a two-dimensional U(1) gauge theory. It is shown that in this hybrid model the non-vanishing expectation value of psi psi is due to the contribution of instanton configurations with fractional winding. (Author) [pt

  15. Rational conformal theories involving a U(1) current algebra

    International Nuclear Information System (INIS)

    Todorov, I.T.

    1989-01-01

    The problem of constructing and classifying rational conformal theories is illustrated on the example of extended chiral algebras involving a single U(1) current. The bulk of the paper is a self contained review (with some improvements) of recent work of R. Paunov and the author. (author)

  16. Anomalous U(1)A and electroweak symmetry breaking

    International Nuclear Information System (INIS)

    Gogoladze, I.; Tsulaya, M.

    2000-01-01

    A new mechanism for electroweak symmetry breaking in the supersymmetric Standard Model is suggested. Our suggestion is based on the presence of an anomalous U(1) A gauge symmetry, which naturally arises in the four-dimensional superstring theory, and heavily relies on the corresponding Fayet-Illiopoulos ξ-term

  17. Anomalous U(1)A and electroweak symmetry breaking

    International Nuclear Information System (INIS)

    Gogoladze, Ilia

    2000-10-01

    We suggest a mechanism for electroweak symmetry breaking in the Supersymmetric Standard Model. Our suggestion is based on the presence of an anomalous U(1) A gauge symmetry, which naturally arises in the four dimensional superstring theory, and heavily relies on the value of the corresponding Fayet-Illiopoulos ξ-term. (author)

  18. The U(1) Higgs model in an external electromagnetic field

    International Nuclear Information System (INIS)

    Damgaard, P.H.; Heller, U.M.

    1988-01-01

    An external electromagnetic field is coupled to the lattice-regularized U(1) Higgs model. We study the phase diagram of this model by both analytical and numerical techniques for different values of the external field strength tensor. The results are compared with expectations based on the analogy with superconducting systems, as described by the phenomenological Ginzburg-Landau theory. (orig.)

  19. Interactions between $U(1)$ Cosmic Strings: An Analytical Study

    OpenAIRE

    Bettencourt, L. M. A.; Rivers, R. J.

    1994-01-01

    We derive analytic expressions for the interaction energy between two general $U(1)$ cosmic strings as the function of their relative orientation and the ratio of the coupling constants in the model. The results are relevant to the statistic description of strings away from critical coupling and shed some light on the mechanisms involved in string formation and the evolution of string networks.

  20. Enhanced toxic cloud knockdown spray system for decontamination applications

    Science.gov (United States)

    Betty, Rita G [Rio Rancho, NM; Tucker, Mark D [Albuquerque, NM; Brockmann, John E [Albuquerque, NM; Lucero, Daniel A [Albuquerque, NM; Levin, Bruce L [Tijeras, NM; Leonard, Jonathan [Albuquerque, NM

    2011-09-06

    Methods and systems for knockdown and neutralization of toxic clouds of aerosolized chemical or biological warfare (CBW) agents and toxic industrial chemicals using a non-toxic, non-corrosive aqueous decontamination formulation.

  1. Kinetic Mixing of U(1)s in Heterotic Orbifolds

    CERN Document Server

    Goodsell, Mark; Ringwald, Andreas

    2012-01-01

    We study kinetic mixing between massless U(1) gauge symmetries in the bosonic formulation of heterotic orbifold compactifications. For non-prime Z_N factorisable orbifolds, we find a simple expression of the mixing in terms of the properties of the N=2 subsectors, which helps understand under what conditions mixing can occur. With this tool, we analyse Z_6-II heterotic orbifolds and find non-vanishing mixing even without including Wilson lines. We show that some semi-realistic models of the Mini-Landscape admit supersymmetric vacua with mixing between the hypercharge and an additional U(1), which can be broken at low energies. We finally discuss some phenomenologically appealing possibilities that hidden photons in heterotic orbifolds allow.

  2. SU(4) x U(1) gauge theory. II. CP nonconservation

    International Nuclear Information System (INIS)

    Deshpande, N.G.; Hwa, R.C.; Mannheim, P.D.

    1979-01-01

    We exploit the higher symmetry inherent in an SU(4) x U(1) gauge theory to construct a spontaneously broken theory of CP nonconservation. Higgs multiplets in the adjoint representation of SU(4) contain both even and odd CP fields; thus, requiring the simultaneous nonvanishing of the vacuum expectation values of these fields leads to CP noninvariance of the vacuum. We find that all the CP-nonconserving effects are mediated in our theory by the superheavy gauge bosons of the broken SU(4) x U(1) symmetry. In fact, the very existence of CP violation sets an upper limit on the masses of these bosons. In our model the dominant CP effect lies in the neutral kaon system and is found to arise through a direct (ΔS = 2) K 1 -K 2 transition. The model has all the features of a superweak theory, with a neutron electric dipole moment substantially smaller than 10 -24 e cm

  3. Kinetic mixing of U(1)s in heterotic orbifolds

    Energy Technology Data Exchange (ETDEWEB)

    Goodsell, Mark [European Organization for Nuclear Research (CERN), Geneva (Switzerland); Ramos-Sanchez, Saul [UNAM, Mexico (Mexico). Dept. of Theoretical Physics; Ringwald, Andreas [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2011-10-15

    We study kinetic mixing between massless U(1) gauge symmetries in the bosonic formulation of heterotic orbifold compactifications. For non-prime Z{sub N} factorisable orbifolds, we find a simple expression of the mixing in terms of the properties of the N=2 subsectors, which helps understand under what conditions mixing can occur. With this tool, we analyse Z{sub 6}-II heterotic orbifolds and find non-vanishing mixing even without including Wilson lines. We show that some semi-realistic models of the Mini-Landscape admit supersymmetric vacua with mixing between the hypercharge and an additional U(1), which can be broken at low energies. We finally discuss some phenomenologically appealing possibilities that hidden photons in heterotic orbifolds allow. (orig.)

  4. Underground storage tank 431-D1U1, Closure Plan

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. More flipped SU(5) x U(1) baryosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, J.; Hagelin, J.S.; Nanopoulos, D.V.; Olive, K.A.

    1988-06-30

    We supplement a previous discussion of baryosynthesis in flipped SU(5)xU(1) GUTs by including (1) the large incoherent field energy density which is likely when SU(5) is broken, and (2) the possibility of additional Higgs triplet fields suggested by four-dimensional string model-building. We consider strong (weak) reheating scenarios in which the Universe is (is not) SU(5) symmetric after inflation. We find an adequate baryon asymmetry subsequent to strong reheating, whatever the number of Higgs triplets (although beware of possible difficulties with quasi-stable relic particles), whereas weak reheating requires at least two Higgs triplets.

  6. Gaugino radiative decay in an anomalous U(1)' model

    International Nuclear Information System (INIS)

    Lionetto, Andrea; Racioppi, Antonio

    2010-01-01

    We study the neutralino radiative decay into the lightest supersymmetric particle (LSP) in the framework of a minimal anomalous U(1) ' extension of the MSSM. It turns out that in a suitable decoupling limit the axino, which is present in the Stueckelberg multiplet, is the LSP. We compute the branching ratio (BR) for the decay of a neutralino into an axino and a photon. We find that in a wide region of the parameter space, the BR is higher than 93% in contrast with the typical value (≤1%) in the CMSSM.

  7. Supersymmetric U(1)' model with multiple dark matters

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  8. Implications of hidden gauged U (1 ) model for B anomalies

    Science.gov (United States)

    Fuyuto, Kaori; Li, Hao-Lin; Yu, Jiang-Hao

    2018-06-01

    We propose a hidden gauged U (1 )H Z' model to explain deviations from the standard model (SM) values in lepton flavor universality known as RK and RD anomalies. The Z' only interacts with the SM fermions via their mixing with vectorlike doublet fermions after the U (1 )H symmetry breaking, which leads to b →s μ μ transition through the Z' at tree level. Moreover, introducing an additional mediator, inert-Higgs doublet, yields b →c τ ν process via charged scalar contribution at tree level. Using flavio package, we scrutinize adequate sizes of the relevant Wilson coefficients to these two processes by taking various flavor observables into account. It is found that significant mixing between the vectorlike and the second generation leptons is needed for the RK anomaly. A possible explanation of the RD anomaly can also be simultaneously addressed in a motivated situation, where a single scalar operator plays a dominant role, by the successful model parameters for the RK anomaly.

  9. Light U(1) gauge boson coupled to baryon number

    International Nuclear Information System (INIS)

    Carone, C.D.; Murayama, Hitoshi

    1995-06-01

    The authors discuss the phenomenology of a light U(1) gauge boson, γ B , that couples only to baryon number. Gauging baryon number at high energies can prevent dangerous baryon-number violating operators that may be generated by Planck scale physics. However, they assume at low energies that the new U(1) gauge symmetry is spontaneously broken and that the γ B mass m B is smaller than m z . They show for m Υ B z that the γB coupling α B can be as large as ∼ 0.1 without conflicting with the current experimental constraints. The authors argue that α B ∼ 0.1 is large enough to produce visible collider signatures and that evidence for the γ B could be hidden in existing LEP data. They show that there are realistic models in which mixing between the γ B and the electroweak gauge bosons occurs only as a radiative effect and does not lead to conflict with precision electroweak measurements. Such mixing may nevertheless provide a leptonic signal for models of this type at an upgraded Tevatron

  10. Confinement in dually transformed U(1) lattice gauge theory

    International Nuclear Information System (INIS)

    Zach, M.

    1997-10-01

    The aim of this work is a detailed investigation of the confinement mechanism in U(1) lattice gauge theory. In the first chapters we give a review on the definition of compact Abelian gauge theory on space-time lattices, the numerical calculation of physical observables for exploring confinement, and the interpretation of the results in terms of the dual superconductor picture, which is introduced at two levels of description. We work out that the electric field strength and the magnetic currents around a charge pair can be described very well by a classical effective model of Maxwell and London equations, if fluctuations of the occurring fluxoid string are considered. In order to obtain a deeper understanding of confinement in U(1), we extend the duality transformation of the path integral to the correlation functions which are used to calculate expectation values of fields and currents. This not only helps to interpret U(1) lattice gauge theory as a limit of the dual Higgs model, but also opens the possibility for efficient calculations of expectation values in the presence of static charges by simulating the dual model. Using this technique we are able to consider large flux tube lengths, low temperatures, and multiply charged systems without loss of numerical precision. The dual simulation is applied to flux tubes between static charges, to periodically closed flux tubes (torelons), and to doubly charged systems. We find that the behavior of flux tubes for large charge distances cannot be explained by the picture of a classical dual type-II superconductor; the observed roughening of the flux tube agrees very well with the prediction from the effective string description. We also analyze the different contributions to the total energy of the electromagnetic field. For torelons we calculate both the free energy and the total field energy, split the free energy into a string tension and a string fluctuation part, and apply lattice sum rules modified for finite

  11. e +e- modes and U(1) spontaneous chiral symmetry breaking

    International Nuclear Information System (INIS)

    Steininger, K.

    1992-01-01

    In this paper, motivated by evidence for a chiral phase transition in strong coupling lattice QED, the authors calculate the two-particle spectrum of the broken QED phase. This is done in the framework of a Nambu and Jona-Lasinio model with U(1) symmetry including chiral symmetry and symmetry breaking properties of QED. The second order chiral phase transition behavior in our model and in lattice QED are in excellent agreement. The authors then present a detailed analysis of the spectra of the e + e - modes in the broken phase. The authors examine whether these modes have any possible relationship to the narrow e + e - resonances found in soft heavy ion collisions at GSL. The authors' answer is negative

  12. U(1)' dark matter and R-parity violation

    International Nuclear Information System (INIS)

    Brahm, D.E.

    1990-04-01

    Attempts to understand physics beyond the Standard Model must face many phenomenological constraint, from recent Z 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)' gauge group, has a dark matter candidate which could soon be detected. The second, incorporating supersymmetry with R-parity violation, predicts rare Z 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

  13. Absence of U(1) anomalous superamplitudes in N≥5 supergravities

    Energy Technology Data Exchange (ETDEWEB)

    Freedman, Daniel Z. [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University,Stanford, CA 94305 (United States); Center for Theoretical Physics and Department of Mathematics,Massachusetts Institute of Technology,Cambridge, MA 02139 (United States); Kallosh, Renata; Murli, Divyanshu [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University,Stanford, CA 94305 (United States); Proeyen, Antoine Van [KU Leuven, Institute for Theoretical Physics,Celestijnenlaan 200D, B-3001, Leuven (Belgium); Yamada, Yusuke [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University,Stanford, CA 94305 (United States)

    2017-05-12

    We list all potential candidates for U(1) anomalous non-local 1-loop 4-point amplitudes and higher loop UV divergences in N≥5 supergravities. The relevant chiral superinvariants are constructed from linearized chiral superfields and define the corresponding superamplitudes. The anomalous amplitudes, of the kind present in N=4, are shown to be absent in N≥5. In N=6 supergravity the result is deduced from the double-copy (N=4){sub YM}×(N=2){sub YM} model, whereas in N=5,8 the result on absence of anomalous amplitudes is derived in supergravities as well as in the (N=4){sub YM}×(N−4){sub YM} double-copy models.

  14. On the BRST cohomology in U(1) gauge theory

    International Nuclear Information System (INIS)

    Malik, R.P.

    1998-08-01

    We discuss the Becchi-Rouet-Stora-Tyutin (BRST) cohomology in the case of two-dimensional free U(1) gauge theory. In addition to the usual BRST charge, we deduce a conserved and nilpotent dual-BRST charge under which the gauge-fixing term remains invariant. This charge is the analogue of the adjoint (dual) exterior derivative of differential geometry. The BRST extended Casimir operator, corresponding to the Laplacian operator of differential geometry, turns out to generate a symmetry under which the ghost term remains invariant. We take a single photon state in the Hilbert space and demonstrate the notion of gauge invariance, no-(anti)ghost theorem and transversality of photon by exploiting the refinement of cohomology by selecting the physical state as the harmonic state of the Hodge decomposition theorem. (author)

  15. Noncommutative U(1) gauge theory from a worldline perspective

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadiniaz, Naser [Facultad de Ciencias en Física y Matemáticas, Universidad Autónoma de Chiapas,Ciudad Universitaria, Tuxtla Gutiérrez 29050 (Mexico); Corradini, Olindo [Facultad de Ciencias en Física y Matemáticas, Universidad Autónoma de Chiapas,Ciudad Universitaria, Tuxtla Gutiérrez 29050 (Mexico); Dipartimento di Scienze Fisiche, Informatiche e Matematiche,Università di Modena e Reggio Emilia,Via Campi 213/A, I-41125 Modena (Italy); D’Ascanio, Daniela [Instituto de Física La Plata - CONICET, Universidad Nacional de La Plata,CC 67 (1900), La Plata (Argentina); Estrada-Jiménez, Sendic [Facultad de Ciencias en Física y Matemáticas, Universidad Autónoma de Chiapas,Ciudad Universitaria, Tuxtla Gutiérrez 29050 (Mexico); Pisani, Pablo [Instituto de Física La Plata - CONICET, Universidad Nacional de La Plata,CC 67 (1900), La Plata (Argentina)

    2015-11-10

    We study pure noncommutative U(1) gauge theory representing its one-loop effective action in terms of a phase space worldline path integral. We write the quadratic action using the background field method to keep explicit gauge invariance, and then employ the worldline formalism to write the one-loop effective action, singling out UV-divergent parts and finite (planar and non-planar) parts, and study renormalization properties of the theory. This amounts to employ worldline Feynman rules for the phase space path integral, that nicely incorporate the Fadeev-Popov ghost contribution and efficiently separate planar and non-planar contributions. We also show that the effective action calculation is independent of the choice of the worldline Green’s function, that corresponds to a particular way of factoring out a particle zero-mode. This allows to employ homogeneous string-inspired Feynman rules that greatly simplify the computation.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Holism and structuralism in U(1) gauge theory

    Science.gov (United States)

    Lyre, Holger

    After decades of neglect philosophers of physics have discovered gauge theories-arguably the paradigm of modern field physics-as a genuine topic for foundational and philosophical research. Incidentally, in the last couple of years interest from the philosophy of physics in structural realism-in the eyes of its proponents the best suited realist position towards modern physics-has also raised. This paper tries to connect both topics and aims to show that structural realism gains further credence from an ontological analysis of gauge theories-in particular U (1) gauge theory. In the first part of the paper the framework of fiber bundle gauge theories is briefly presented and the interpretation of local gauge symmetry will be examined. In the second part, an ontological underdetermination of gauge theories is carved out by considering the various kinds of non-locality involved in such typical effects as the Aharonov-Bohm effect. The analysis shows that the peculiar form of non-separability figuring in gauge theories is a variant of spatiotemporal holism and can be distinguished from quantum theoretic holism. In the last part of the paper the arguments for a gauge theoretic support of structural realism are laid out and discussed.

  18. Extended U(1) conformal field theories and Zk-parafermions

    International Nuclear Information System (INIS)

    Furlan, P.; Paunov, R.R.; Todorov, I.T.

    1992-01-01

    A constructive approach is developed for studying local chiral algebras generated by a pair of oppositely charged fields ψ(z, ±g) such that the operator product expansion (OPE) of ψ(z 1 ,g) ψ(z 2 , -g) involves a U (1) current. The main tool in the study is the factorization property of the charged fields (exhibited in [PT 2.3]) for Virasoro central charge c k -parafermions. The case Δ 2 =4(Δ 1 -1), where Δ sν =Δ K-ν (Δ 0 =0) ore conformal dimensions of the parafemionic currents, is studied in detail. For Δ Τ = 2Τ(1 - Δ/k) the theory is related to GEPNER'S [GE] Z 2 [SO (k)] parafermions and the corresponding quantum field theroretic (QFT) representations of the chiral algebra are displayed. The Coulomb gas method of [CR] is further developed to include an explicit construction of the basic parafermionic current φ of wight Δ = Δ 1 . The characters of the positive energy representations of the local chiral algebra are written as sums of products of Kac,s string functions and classical Θ-functions. (orig.)

  19. U(1) Wilson lattice gauge theories in digital quantum simulators

    Science.gov (United States)

    Muschik, Christine; Heyl, Markus; Martinez, Esteban; Monz, Thomas; Schindler, Philipp; Vogell, Berit; Dalmonte, Marcello; Hauke, Philipp; Blatt, Rainer; Zoller, Peter

    2017-10-01

    Lattice gauge theories describe fundamental phenomena in nature, but calculating their real-time dynamics on classical computers is notoriously difficult. In a recent publication (Martinez et al 2016 Nature 534 516), we proposed and experimentally demonstrated a digital quantum simulation of the paradigmatic Schwinger model, a U(1)-Wilson lattice gauge theory describing the interplay between fermionic matter and gauge bosons. Here, we provide a detailed theoretical analysis of the performance and the potential of this protocol. Our strategy is based on analytically integrating out the gauge bosons, which preserves exact gauge invariance but results in complicated long-range interactions between the matter fields. Trapped-ion platforms are naturally suited to implementing these interactions, allowing for an efficient quantum simulation of the model, with a number of gate operations that scales polynomially with system size. Employing numerical simulations, we illustrate that relevant phenomena can be observed in larger experimental systems, using as an example the production of particle-antiparticle pairs after a quantum quench. We investigate theoretically the robustness of the scheme towards generic error sources, and show that near-future experiments can reach regimes where finite-size effects are insignificant. We also discuss the challenges in quantum simulating the continuum limit of the theory. Using our scheme, fundamental phenomena of lattice gauge theories can be probed using a broad set of experimentally accessible observables, including the entanglement entropy and the vacuum persistence amplitude.

  20. Ribosomal protein gene knockdown causes developmental defects in zebrafish.

    Directory of Open Access Journals (Sweden)

    Tamayo Uechi

    Full Text Available The ribosomal proteins (RPs form the majority of cellular proteins and are mandatory for cellular growth. RP genes have been linked, either directly or indirectly, to various diseases in humans. Mutations in RP genes are also associated with tissue-specific phenotypes, suggesting a possible role in organ development during early embryogenesis. However, it is not yet known how mutations in a particular RP gene result in specific cellular changes, or how RP genes might contribute to human diseases. The development of animal models with defects in RP genes will be essential for studying these questions. In this study, we knocked down 21 RP genes in zebrafish by using morpholino antisense oligos to inhibit their translation. Of these 21, knockdown of 19 RPs resulted in the development of morphants with obvious deformities. Although mutations in RP genes, like other housekeeping genes, would be expected to result in nonspecific developmental defects with widespread phenotypes, we found that knockdown of some RP genes resulted in phenotypes specific to each gene, with varying degrees of abnormality in the brain, body trunk, eyes, and ears at about 25 hours post fertilization. We focused further on the organogenesis of the brain. Each knocked-down gene that affected the morphogenesis of the brain produced a different pattern of abnormality. Among the 7 RP genes whose knockdown produced severe brain phenotypes, 3 human orthologs are located within chromosomal regions that have been linked to brain-associated diseases, suggesting a possible involvement of RP genes in brain or neurological diseases. The RP gene knockdown system developed in this study could be a powerful tool for studying the roles of ribosomes in human diseases.

  1. DJ-1 KNOCK-DOWN IMPAIRS ASTROCYTE MITOCHONDRIAL FUNCTION

    Science.gov (United States)

    LARSEN, N. J.; AMBROSI, G.; MULLETT, S. J.; BERMAN, S. B.; HINKLE, D. A.

    2012-01-01

    Mitochondrial dysfunction has long been implicated in the pathogenesis of Parkinson’s disease (PD). PD brain tissues show evidence for mitochondrial respiratory chain Complex I deficiency. Pharmacological inhibitors of Complex I, such as rotenone, cause experimental parkinsonism. The cytoprotective protein DJ-1, whose deletion is sufficient to cause genetic PD, is also known to have mitochondria-stabilizing properties. We have previously shown that DJ-1 is over-expressed in PD astrocytes, and that DJ-1 deficiency impairs the capacity of astrocytes to protect co-cultured neurons against rotenone. Since DJ-1 modulated, astrocyte-mediated neuroprotection against rotenone may depend upon proper astrocytic mitochondrial functioning, we hypothesized that DJ-1 deficiency would impair astrocyte mitochondrial motility, fission/fusion dynamics, membrane potential maintenance, and respiration, both at baseline and as an enhancement of rotenone-induced mitochondrial dysfunction. In astrocyte-enriched cultures, we observed that DJ-1 knock-down reduced mitochondrial motility primarily in the cellular processes of both untreated and rotenone treated cells. In these same cultures, DJ-1 knock-down did not appreciably affect mitochondrial fission, fusion, or respiration, but did enhance rotenone-induced reductions in the mitochondrial membrane potential. In neuron–astrocyte co-cultures, astrocytic DJ-1 knock-down reduced astrocyte process mitochondrial motility in untreated cells, but this effect was not maintained in the presence of rotenone. In the same co-cultures, astrocytic DJ-1 knock-down significantly reduced mitochondrial fusion in the astrocyte cell bodies, but not the processes, under the same conditions of rotenone treatment in which DJ-1 deficiency is known to impair astrocyte-mediated neuroprotection. Our studies therefore demonstrated the following new findings: (i) DJ-1 deficiency can impair astrocyte mitochondrial physiology at multiple levels, (ii) astrocyte

  2. VG2 URA TRAJECTORY DERIVED SUMM U1 COORDS 48SEC V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains Voyager 2 spacecraft position vectors relative to Uranus in minus U1 coordinates. The U1 or Uranus West Longitude System coordinate system is a...

  3. U6 snRNA expression prevents toxicity in TDP-43-knockdown cells.

    Directory of Open Access Journals (Sweden)

    Masao Yahara

    Full Text Available Depletion of amyotrophic lateral sclerosis (ALS-associated transactivation response (TAR RNA/DNA-binding protein 43 kDa (TDP-43 alters splicing efficiency of multiple transcripts and results in neuronal cell death. TDP-43 depletion can also disturb expression levels of small nuclear RNAs (snRNAs as spliceosomal components. Despite this knowledge, the relationship between cell death and alteration of snRNA expression during TDP-43 depletion remains unclear. Here, we knocked down TDP-43 in murine neuroblastoma Neuro2A cells and found a time lag between efficient TDP-43 depletion and appearance of cell death, suggesting that several mechanisms mediate between these two events. The amount of U6 snRNA was significantly decreased during TDP-43 depletion prior to increase of cell death, whereas that of U1, U2, and U4 snRNAs was not. Downregulation of U6 snRNA led to cell death, whereas transient exogenous expression of U6 snRNA counteracted the effect of TDP-43 knockdown on cell death, and slightly decreased the mis-splicing rate of Dnajc5 and Sortilin 1 transcripts, which are assisted by TDP-43. These results suggest that regulation of the U6 snRNA expression level by TDP-43 is a key factor in the increase in cell death upon TDP-43 loss-of-function.

  4. Heritable and lineage-specific gene knockdown in zebrafish embryo.

    Directory of Open Access Journals (Sweden)

    Mei Dong

    Full Text Available BACKGROUND: Reduced expression of developmentally important genes and tumor suppressors due to haploinsufficiency or epigenetic suppression has been shown to contribute to the pathogenesis of various malignancies. However, methodology that allows spatio-temporally knockdown of gene expression in various model organisms such as zebrafish has not been well established, which largely limits the potential of zebrafish as a vertebrate model of human malignant disorders. PRINCIPAL FINDING: Here, we report that multiple copies of small hairpin RNA (shRNA are expressed from a single transcript that mimics the natural microRNA-30e precursor (mir-shRNA. The mir-shRNA, when microinjected into zebrafish embryos, induced an efficient knockdown of two developmentally essential genes chordin and alpha-catenin in a dose-controllable fashion. Furthermore, we designed a novel cassette vector to simultaneously express an intronic mir-shRNA and a chimeric red fluorescent protein driven by lineage-specific promoter, which efficiently reduced the expression of a chromosomally integrated reporter gene and an endogenously expressed gata-1 gene in the developing erythroid progenitors and hemangioblasts, respectively. SIGNIFICANCE: This methodology provides an invaluable tool to knockdown developmental important genes in a tissue-specific manner or to establish animal models, in which the gene dosage is critically important in the pathogenesis of human disorders. The strategy should be also applicable to other model organisms.

  5. Dark Matter candidate in Inert Doublet Model with additional local gauge symmetry U (1)

    International Nuclear Information System (INIS)

    Gaitán, R.; De Oca, J.H. Montes; Garcés, E. A.; Cabral-Rosetti, L. G.

    2016-01-01

    We consider the Inert Doublet Model (IDM) with an additional local gauge symmetry U (1) and a complex singlet scalar to break the symmetry U (1). The continuous symmetry U (1) is introduced to control the CP-conserving interaction instead of some discrete symmetries as usually. We present the mass spectrum for neutral scalar and gauge bosons and the values of the charges under U (1) for which the model could have a candidate to dark matter. (paper)

  6. Manipulating the in vivo immune response by targeted gene knockdown.

    Science.gov (United States)

    Lieberman, Judy

    2015-08-01

    Aptamers, nucleic acids selected for high affinity binding to proteins, can be used to activate or antagonize immune mediators or receptors in a location and cell-type specific manner and to enhance antigen presentation. They can also be linked to other molecules (other aptamers, siRNAs or miRNAs, proteins, toxins) to produce multifunctional compounds for targeted immune modulation in vivo. Aptamer-siRNA chimeras (AsiCs) that induce efficient cell-specific knockdown in immune cells in vitro and in vivo can be used as an immunological research tool or potentially as an immunomodulating therapeutic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Light sterile neutrinos, dark matter, and new resonances in a U(1) extension of the MSSM

    Science.gov (United States)

    Hebbar, A.; Lazarides, G.; Shafi, Q.

    2017-09-01

    We present ψ'MSSM, a model based on a U(1) ψ' extension of the minimal supersymmetric standard model. The gauge symmetry U(1)ψ', also known as U(1)N,is a linear combination of the U(1) χ and U(1)ψ subgroups of E6. The model predicts the existence of three sterile neutrinos with masses ≲0.1 eV , if the U(1)ψ' breaking scale is of order 10 TeV. Their contribution to the effective number of neutrinos at nucleosynthesis is Δ Nν≃0.29. The model can provide a variety of possible cold dark matter candidates including the lightest sterile sneutrino. If the U(1) ψ' breaking scale is increased to 1 03 TeV , the sterile neutrinos, which are stable on account of a Z2symmetry, become viable warm dark matter candidates. The observed value of the standard model Higgs boson mass can be obtained with relatively light stop quarks thanks to the D-term contribution from U(1)ψ'. The model predicts diquark and diphoton resonances which may be found at an updated LHC. The well-known μ problem is resolved and the observed baryon asymmetry of the universe can be generated via leptogenesis. The breaking of U(1)ψ' produces superconducting strings that may be present in our galaxy. A U(1) R symmetry plays a key role in keeping the proton stable and providing the light sterile neutrinos.

  8. Expression profile of CREB knockdown in myeloid leukemia cells

    International Nuclear Information System (INIS)

    Pellegrini, Matteo; Cheng, Jerry C; Voutila, Jon; Judelson, Dejah; Taylor, Julie; Nelson, Stanley F; Sakamoto, Kathleen M

    2008-01-01

    The cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution. To understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA. By combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA. We have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Heurtier, L. [Centre de Physique Théorique, École Polytechnique, CNRS, 91128 Palaiseau (France); Khalil, S.; Moursy, A., E-mail: lucien.heurtier@polytechnique.edu, E-mail: skhalil@zewailcity.edu.eg, E-mail: amoursy@zewailcity.edu.eg [Center for Fundamental Physics, Zewail City of Science and Technology, 6 October City, Cairo (Egypt)

    2015-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Heurtier, L. [Centre de Physique Théorique, École Polytechnique, CNRS,91128 Palaiseau (France); Khalil, S. [Center for Fundamental Physics, Zewail City of Science and Technology,6 October City, Cairo (Egypt); Department of Mathematics, Faculty of Science, Ain Shams University,Cairo, 11566 (Egypt); Moursy, A. [Center for Fundamental Physics, Zewail City of Science and Technology,6 October City, Cairo (Egypt)

    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.

  12. General U(1)xU(1) F-theory Compactifications and Beyond: Geometry of unHiggsings and novel Matter Structure

    CERN Document Server

    Cvetic, Mirjam; Piragua, Hernan; Taylor, Washington

    2015-01-01

    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(1)xU(1) gauge symmetry. Generic U(1)xU(1) models can be related to a Higgsed non-Abelian model with gauge group SU(2)xSU(2)xSU(3), SU(2)^3xSU(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 expl...

  13. Exploring the supersymmetric U(1 ) B -L×U(1 ) R model with dark matter, muon g - 2 , and Z' mass limits

    Science.gov (United States)

    Frank, Mariana; Özdal, Özer

    2018-01-01

    We study the low scale predictions of the supersymmetric standard model extended by U (1 )B -L×U (1 )R symmetry, obtained from S O (10 ) breaking via a left-right supersymmetric model, imposing universal boundary conditions. Two singlet Higgs fields are responsible for the radiative U (1 )B -L×U (1 )R symmetry breaking, and a singlet fermion S is introduced to generate neutrino masses through an inverse seesaw mechanism. The lightest neutralino or sneutrino emerge as dark matter candidates, with different low scale implications. We find that the composition of the neutralino lightest supersymmetric particle (LSP) changes considerably depending on the neutralino LSP mass, from roughly half U (1 )R bino, half minimal supersymmetric model (MSSM) bino, to a singlet higgsino, or completely dominated by the MSSM higgsino. The sneutrino LSP is statistically much less likely, and when it occurs it is a 50-50 mixture of right-handed sneutrino and the scalar S ˜. Most of the solutions consistent with the relic density constraint survive the XENON 1T exclusion curve for both LSP cases. We compare the two scenarios and investigate parameter space points and find consistency with the muon anomalous magnetic moment only at the edge of a 2 σ deviation from the measured value. However, we find that the sneutrino LSP solutions could be ruled out completely by the strict reinforcement of the recent Z' mass bounds. We finally discuss collider prospects for testing the model.

  14. Naturally light neutrinos in the flipped SU(5)xU(1) superstring model

    Energy Technology Data Exchange (ETDEWEB)

    Antoniadis, I.; Rizos, J. (Centre de Physique Theorique, Ecole Polytechnique, 91 - Palaiseau (France)); Tamvakis, K. (Physics Dept., Univ. Ioannina (Greece))

    1992-04-16

    We analyze the SU(5)xU(1)'xU(1){sup 4}xSO(10)xSU(4) superstring model, taking into account non-renormalizable superpotential interactions up to sixth order, and find that all neutrinos stay naturally light within the experimental mass bounds. (orig.).

  15. 46 CFR 54.01-10 - Steam-generating pressure vessels (modifies U-1(g)).

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 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 as...

  16. A Third-Rank Tensor Field Based on a U(1) Gauge Theory in Loop Space

    OpenAIRE

    Shinichi, DEGUCHI; Tadahito, NAKAJIMA; Department of Physics and Atomic Energy Research Institute College of Science and Technology; Department of Physics and Atomic Energy Research Institute College of Science and Technology

    1995-01-01

    We derive the Stueckelberg formalism extended to a third-rank tensor field from a U(1) gauge theory in loop space, the space of all loops in space-time. The third-rank tensor field is regarded as a constrained U(1) gauge field on the loop space.

  17. Baryon number generation in a flipped SU(5) x U(1) model

    International Nuclear Information System (INIS)

    Campbell, B.; Hagelin, J.; Nanopoulos, D.V.; Olive, K.A.

    1988-01-01

    We consider the possibilities for generating a baryon asymmetry in the early universe in a flipped SU(5) x U(1) model inspired by the superstring. Depending on the temperature of the radiation background after inflation we can distinguish between two scenarios for baryogenesis: (1) After reheating the original SU(5) x U(1) symmetry is restored, or there was no inflation at all; (2) reheating after inflation is rather weak and SU(5) x U(1) is broken. In either case the asymmetry is generated by the out-of-equilibrium decays of a massive SU(3) x SU(2) x U(1) singlet field φ m . In the flipped SU(5) x U(1) model, gauge symmetry breaking is triggered by strong coupling phenomena, and is in general accompanied by the production of entropy. We examine constraints on the reheating temperature and the strong coupling scale in each of the scenarios. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

  20. RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis

    International Nuclear Information System (INIS)

    Liu, Chang; Li, Chao-peng; Wang, Jia-Jian; Shan, Kun; Liu, Xin; Yan, Biao

    2016-01-01

    Retinal reactive gliosis is an important pathological feature of diabetic retinopathy. Identifying the underlying mechanisms causing reactive gliosis will be important for developing new therapeutic strategies for treating diabetic retinopathy. Herein, we show that long noncoding RNA-RNCR3 knockdown significantly inhibits retinal reactive gliosis. RNCR3 knockdown leads to a marked reduction in the release of several cytokines. RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration, as shown by less apoptotic retinal cells and ameliorative visual function. RNCR3 knockdown could also decrease Müller glial cell viability and proliferation, and reduce the expression of glial reactivity-related genes including GFAP and vimentin in vitro. Collectively, this study shows that RNCR3 knockdown may be a promising strategy for the prevention of diabetes mellitus-induced retinal neurodegeneration. - Highlights: • RNCR3 knockdown inhibits retinal reactive gliosis. • RNCR3 knockdown causes a significant change in cytokine profile. • RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration. • RNCR3 knockdown affects Müller glial cell function in vitro.

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

    Science.gov (United States)

    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

  2. Matrix models from localization of five-dimensional supersymmetric noncommutative U(1) gauge theory

    International Nuclear Information System (INIS)

    Lee, Bum-Hoon; Ro, Daeho; Yang, Hyun Seok

    2017-01-01

    We study localization of five-dimensional supersymmetric U(1) gauge theory on S 3 ×ℝ θ 2 where ℝ θ 2 is a noncommutative (NC) plane. The theory can be isomorphically mapped to three-dimensional supersymmetric U(N→∞) gauge theory on S 3 using the matrix representation on a separable Hilbert space on which NC fields linearly act. Therefore the NC space ℝ θ 2 allows for a flexible path to derive matrix models via localization from a higher-dimensional supersymmetric NC U(1) gauge theory. The result shows a rich duality between NC U(1) gauge theories and large N matrix models in various dimensions.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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 5̄ 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.

  4. Nonminimal quartic inflation in classically conformal U(1 ) X extended standard model

    Science.gov (United States)

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

    2018-03-01

    We propose quartic inflation with nonminimal gravitational coupling in the context of the classically conformal U(1 ) X extension of the standard model (SM). In this model, the U(1 ) X gauge symmetry is radiatively broken through the Coleman-Weinberg mechanism, by which the U(1 ) X gauge boson (Z' boson) and the right-handed Majorana neutrinos acquire their masses. We consider their masses in the range of O (10 GeV )-O (10 TeV ) , which are accessible to high-energy collider experiments. The radiative U(1 ) X gauge symmetry breaking also generates a negative mass squared for the SM Higgs doublet, and the electroweak symmetry breaking occurs subsequently. We identify the U(1 ) X Higgs field with inflaton and calculate the inflationary predictions. Because of the Coleman-Weinberg mechanism, the inflaton quartic coupling during inflation, which determines the inflationary predictions, is correlated to the U(1 ) X gauge coupling. With this correlation, we investigate complementarities between the inflationary predictions and the current constraint from the Z' boson resonance search at the LHC Run 2 as well as the prospect of the search for the Z' boson and the right-handed neutrinos at the future collider experiments.

  5. Tuned and non-Higgsable U(1)s in F-theory

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi-Nan [Center for Theoretical Physics, Department of Physics, Massachusetts Institute of Technology,77 Massachusetts Avenue, Cambridge, MA 02139 (United States)

    2017-03-27

    We study the tuning of U(1) gauge fields in F-theory models on a base of general dimension. We construct a formula that computes the change in Weierstrass moduli when such a U(1) is tuned, based on the Morrison-Park form of a Weierstrass model with an additional rational section. Using this formula, we propose the form of “minimal tuning” on any base, which corresponds to the case where the decrease in the number of Weierstrass moduli is minimal. Applying this result, we discover some universal features of bases with non-Higgsable U(1)s. Mathematically, a generic elliptic fibration over such a base has additional rational sections. Physically, this condition implies the existence of U(1) gauge group in the low-energy supergravity theory after compactification that cannot be Higgsed away. In particular, we show that the elliptic Calabi-Yau manifold over such a base has a small number of complex structure moduli. We also suggest that non-Higgsable U(1)s can never appear on any toric bases. Finally, we construct the first example of a threefold base with non-Higgsable U(1)s.

  6. Long-distance properties of frozen U(1) Higgs and axially U(1)-gauged four-Fermi models in 1 + 1 dimensions

    International Nuclear Information System (INIS)

    Yamamoto, Hisashi.

    1993-07-01

    We study the long-distance relevance of vortices (instantons) in an N-component axially U(1)-gauged four-Fermi theory in 1 + 1 dimensions, in which a naive use of 1/N expansion predicts the dynamical Higgs phenomenon. Its general effective lagrangian is found to be a frozen U(1) Higgs model with the gauge-field mass term proportional to an anomaly parameter (b). The dual-transformed versions of the effective theory are represented by sine-Gordon systems and recursion-relation analyses are performed. The results suggest that in the gauge-invariant scheme (b = 0) vortices are always relevant at long distances, while in non-invariant schemes (b > 0) there exists a critical N above which the long-distance behavior is dominated by a free massless scalar field. (author)

  7. SU(3)_C× SU(2)_L× U(1)_Y( × U(1)_X ) as a symmetry of division algebraic ladder operators

    Science.gov (United States)

    Furey, C.

    2018-05-01

    We demonstrate a model which captures certain attractive features of SU(5) theory, while providing a possible escape from proton decay. In this paper we show how ladder operators arise from the division algebras R, C, H, and O. From the SU( n) symmetry of these ladder operators, we then demonstrate a model which has much structural similarity to Georgi and Glashow's SU(5) grand unified theory. However, in this case, the transitions leading to proton decay are expected to be blocked, given that they coincide with presumably forbidden transformations which would incorrectly mix distinct algebraic actions. As a result, we find that we are left with G_{sm} = SU(3)_C× SU(2)_L× U(1)_Y / Z_6. Finally, we point out that if U( n) ladder symmetries are used in place of SU( n), it may then be possible to find this same G_{sm}=SU(3)_C× SU(2)_L× U(1)_Y / Z_6, together with an extra U(1)_X symmetry, related to B-L.

  8. Coenzyme O*U1*UO, Alpha-Tocopherol and Free Cholesterol in HDL and LDL Fractions

    DEFF Research Database (Denmark)

    Johansen, Kurt; Theorell, Henning; Karlsson, Jan

    1991-01-01

    Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL......Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL...

  9. Gravity/Fluid Correspondence and Its Application on Bulk Gravity with U(1) Gauge Field

    International Nuclear Information System (INIS)

    Hu, Ya-Peng; Zhang, Jian-Hui

    2014-01-01

    As the long wavelength limit of the AdS/CFT correspondence, the gravity/fluid correspondence has been shown to be a useful tool for extracting properties of the fluid on the boundary dual to the gravity in the bulk. In this paper, after briefly reviewing the algorithm of gravity/fluid correspondence, we discuss the results of its application on bulk gravity with a U(1) gauge field. In the presence of a U(1) gauge field, the dual fluid possesses more interesting properties such as its charge current. Furthermore, an external field A_μ"e"x"t could affect the charge current, and the U(1) Chern-Simons term also induces extra structures to the dual current giving anomalous transport coefficients.

  10. QCD sum rules for the gluon component of the U(1)sub(A) pseudoscalar meson

    International Nuclear Information System (INIS)

    Narison, S.; Centre National de la Recherche Scientifique, 13 - Marseille

    1981-01-01

    Using sum rules based on the positivity and the analyticity of the U(1)sub(A) spectral functions, and within the framework of QCD (quantum chromodynamics), we derive an upper bound Msub(p) approximately less than (0.6 approximately 0.75) GeV to the gluon component of the U(1)sub(A) meson mass. Such a bound could be identified as the exact value of Msub(p) if one accepts a QCD model for the ''continuum'' contribution to the U(1)sub(A) spectral functions. Comparing our result to the observed mass Msub(eta)' approximately equal to 0.96GeV, one could expect an important gluonic contribution to the eta'-mass. This experimental result could be reproduced, if one adds to our result, the quark contribution known to be Msub(q) approximately equal to root(3)msub(π). (author)

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

    Directory of Open Access Journals (Sweden)

    Shao-Long Chen

    2016-10-01

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

  12. Renormalization group aspects of 3-dimensional Pure U(1) lattice gauge theory

    International Nuclear Information System (INIS)

    Gopfert, M.; Mack, G.

    1983-01-01

    A few surprises in a recent study of the 3-dimensional pure U(1) lattice gauge theory model, from the point of view of the renormalization group theory, are discussed. Since the gauge group U(1) of this model is abelian, the model is subject to KramersWannier duality transformation. One obtains a ferromagnet with a global symmetry group Z. The duality transformation shows that the surface tension alpha of the model equals the strong tension of the U(1) gauge model. A theorem to represent the true asymptotic behaviour of alpha is derived. A second theorem considers the correlation functions. Discrepiancies between the theorems result in a solution that ''is regarded as a catastrophe'' in renormalization group theory. A lesson is drawn: To choose a good block spin in a renormalization group procedure, know what the low lying excitations of the theory are, to avoid integrating some of them by mischief

  13. F-theory GUTs with U(1) symmetries: Generalities and survey

    International Nuclear Information System (INIS)

    Dolan, Matthew J.; Marsano, Joseph; Saulina, Natalia; Schaefer-Nameki, Sakura

    2011-01-01

    We study the structure of SU(5) F-theory grand unified theory (GUT) models that engineer additional U(1) symmetries. These are highly constrained by a set of relations observed by Dudas and Palti (DP) that originate from the physics of four-dimensional anomaly cancellation. Using the DP relations, we describe a general tension between unification and the suppression of dimension 5 proton decay when one or more U(1)'s are Peccei-Quinn (PQ) symmetries and hypercharge flux is used to break the SU(5) GUT group. We then specialize to spectral cover models, whose global completions in F theory we know how to construct. In that setting, we provide a technical derivation of the DP relations, construct spectral covers that yield all possible solutions to them, and provide a complete survey of spectral cover models for SU(5) GUTs that exhibit two U(1) symmetries.

  14. Scalar dark matter interpretation of the DAMPE data with U(1) gauge interactions

    Science.gov (United States)

    Cao, Junjie; Feng, Lei; Guo, Xiaofei; Shang, Liangliang; Wang, Fei; Wu, Peiwen

    2018-05-01

    Recently, the Dark Matter Particle Explorer (DAMPE) experiment released the new measurement of the total cosmic e+e- flux between 25 GeV and 4.6 TeV, which indicates a spectral softening at around 0.9 TeV and a tentative peak at around 1.4 TeV. We utilize a scalar dark matter (DM) model to explain the DAMPE peak by χ χ →Z'Z'→ℓℓ ¯ ℓ'ℓ' ¯ with an additional anomaly-free gauged U (1 ) family symmetry, in which χ , Z', and ℓ(') denote, respectively, the scalar DM, the new gauge boson, and ℓ(')=e , μ , τ with mχ˜mZ'˜2 ×1.5 (TeV ) . We first illustrate that the minimal framework GSM×U (1 )Y' with the above mass choices can explain the DAMPE excess, which, however, be excluded by LHC constraints from the Z' searches. Then, we study a nonminimal framework GSM×U (1 )Y'×U (1 )Y'' in which U (1 )Y'' mixes with U (1)Y'. We show that such a framework can interpret the DAMPE data and at the same time survive all other constraints including the DM relic abundance, DM direct detection, and collider bounds. We also investigate the predicted e+e- spectrum in this framework and find that the mass splitting Δ m =mχ-mZ'' should be less than about 17 GeV to produce the peaklike structure.

  15. Knockdown of Pnpla6 protein results in motor neuron defects in zebrafish

    Directory of Open Access Journals (Sweden)

    Yang Song

    2013-03-01

    Mutations in patatin-like phospholipase domain containing 6 (PNPLA6, also known as neuropathy target esterase (NTE or SPG39, cause hereditary spastic paraplegia (HSP. Although studies on animal models, including mice and Drosophila, have extended our understanding of PNPLA6, its roles in neural development and in HSP are not clearly understood. Here, we describe the generation of a vertebrate model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio. Pnpla6 knockdown resulted in developmental abnormalities and motor neuron defects, including axon truncation and branching. The phenotypes in pnpla6 knockdown morphants were rescued by the introduction of wild-type, but not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP signaling in pnpla6 knockdown phenotypes. Taken together, these results demonstrate an important role of PNPLA6 in motor neuron development and implicate overexpression of BMP signaling as a possible mechanism underlying the developmental defects in pnpla6 morphants.

  16. Some comments on flipped SU(5) times U(1) and flipped unification in general

    Energy Technology Data Exchange (ETDEWEB)

    Barr, S.M. (Bartol Research Institute, University of Delaware, Newark, Delaware 19716 (US))

    1989-10-01

    A general group-theoretical discussion of flipped embeddings is given. In addition to the well-known flipped SU(5) and flipped SO(10), the existence of flipped E{sub 6} and E{sub 7} is shown, as well as several families and special cases of flipped embeddings. A possible physical reason, essentially based on the group theory of flipped embeddings, why nature prefers the low-energy group SU(3){times}SU(2){times}U(1) to alternatives such as SU(4){times}U(1) and SU(5) is pointed out.

  17. Some comments on flipped SU(5)xU(1) and flipped unification in general

    International Nuclear Information System (INIS)

    Barr, S.M.

    1989-01-01

    A general group-theoretical discussion of flipped embeddings is given. In addition to the well-known flipped SU(5) and flipped SO(10), the existence of flipped E 6 and E 7 is shown, as well as several families and special cases of flipped embeddings. A possible physical reason, essentially based on the group theory of flipped embeddings, why nature prefers the low-energy group SU(3)xSU(2)xU(1) to alternatives such as SU(4)xU(1) and SU(5) is pointed out

  18. Remarks on mass and angular momenta for U(1){sup 2}-invariant initial data

    Energy Technology Data Exchange (ETDEWEB)

    Alaee, Aghil, E-mail: aak818@mun.ca; Kunduri, Hari K., E-mail: hkkunduri@mun.ca [Department of Mathematics and Statistics, Memorial University of Newfoundland, St John’s, Newfoundland and Labrador NL A1C 4P5 (Canada)

    2016-03-15

    We extend Brill’s positive mass theorem to a large class of asymptotically flat, maximal, U(1){sup 2}-invariant initial data sets on simply connected four dimensional manifolds Σ. Moreover, we extend the local mass angular momenta inequality result [A. Alaee and H. K. Kunduri, Classical Quantum Gravity 32(16), 165020 (2015)] for U(1){sup 2} invariant black holes to the case with nonzero stress energy tensor with positive matter density and energy-momentum current invariant under the above symmetries.

  19. Duality invariance of non-anticommutative N = 1/2 supersymmetric U(1) gauge theory

    International Nuclear Information System (INIS)

    Dayi, Oemer F.; Kelleyane, Lara T.; Uelker, Kayhan

    2005-01-01

    A parent action is introduced to formulate (S-) dual of non-anticommutative N = 1/2 supersymmetric U(1) gauge theory. Partition function for parent action in phase space is utilized to establish the equivalence of partition functions of the theories which this parent action produces. Thus, duality invariance of non-anticommutative N = 1/2 supersymmetric U(1) gauge theory follows. The results which we obtained are valid at tree level or equivalently at the first order in the nonanticommutativity parameter C μν

  20. Dark Gauge U(1) symmetry for an alternative left-right model

    Science.gov (United States)

    Kownacki, Corey; Ma, Ernest; Pollard, Nicholas; Popov, Oleg; Zakeri, Mohammadreza

    2018-02-01

    An alternative left-right model of quarks and leptons, where the SU(2)_R lepton doublet (ν ,l)_R is replaced with (n,l)_R so that n_R is not the Dirac mass partner of ν _L, has been known since 1987. Previous versions assumed a global U(1)_S symmetry to allow n to be identified as a dark-matter fermion. We propose here a gauge extension by the addition of extra fermions to render the model free of gauge anomalies, and just one singlet scalar to break U(1)_S. This results in two layers of dark matter, one hidden behind the other.

  1. Lentivirus-mediated Knockdown of HDAC1 Uncovers Its Role in Esophageal Cancer Metastasis and Chemosensitivity

    OpenAIRE

    Song, Min; He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

    2016-01-01

    Histone deacetylationase 1 (HDAC1) is ubiquitously expressed in various cell lines and tissues and play an important role of regulation gene expression. Overexpression of HDAC1 has been observed in various types of cancers, which indicated that it might be a target for cancer therapy. To test HDAC1 inhibition for cancer treatment, the gene expression of HDAC1 was knockdown mediated by a lentivirus system. Our data showed the gene expression of HDAC1 could be efficiently knockdown by RNAi medi...

  2. Heavy charged scalars from c\\overline{s} fusion: a generic search strategy applied to a 3HDM with U(1) × U(1) family symmetry

    Science.gov (United States)

    Camargo-Molina, José Eliel; Mandal, Tanumoy; Pasechnik, Roman; Wessén, Jonas

    2018-03-01

    We describe a class of three Higgs doublet models (3HDMs) with a softly broken U(1) × U(1) family symmetry that enforces a Cabibbo-like quark mixing while forbidding tree-level flavour changing neutral currents. The hierarchy in the observed quark masses is partly explained by a softer hierarchy in the vacuum expectation values of the three Higgs doublets. As a consequence, the physical scalar spectrum contains a Standard Model (SM) like Higgs boson h 125 while exotic scalars couple the strongest to the second quark family, leading to rather unconventional discovery channels that could be probed at the Large Hadron Collider. In particular, we describe a search strategy for the lightest charged Higgs boson H ±, through the process c\\overline{s}\\to {H}+\\to {W}+{h}_{125} , using a multivariate analysis that leads to an excellent discriminatory power against the SM background. Although the analysis is applied to the proposed class of 3HDMs, we employ a model-independent formulation such that it can be applied to any other model with the same discovery channel.

  3. Dimensional Reduction of N=1, E_8 SYM over SU(3)/U(1) x U(1) x Z_3 and its four-dimensional effective action

    CERN Document Server

    Irges, Nikos; Zoupanos, George

    2011-01-01

    We present an extension of the Standard Model inspired by the E_8 x E_8 Heterotic String. In order that a reasonable effective Lagrangian is presented we neglect everything else other than the ten-dimensional N=1 supersymmetric Yang-Mills sector associated with one of the gauge factors and certain couplings necessary for anomaly cancellation. We consider a compactified space-time M_4 x B_0 / Z_3, where B_0 is the nearly-Kaehler manifold SU(3)/U(1) x U(1) and Z_3 is a freely acting discrete group on B_0. Then we reduce dimensionally the E_8 on this manifold and we employ the Wilson flux mechanism leading in four dimensions to an SU(3)^3 gauge theory with the spectrum of a N=1 supersymmetric theory. We compute the effective four-dimensional Lagrangian and demonstrate that an extension of the Standard Model is obtained with interesting features including a conserved baryon number and fixed tree level Yukawa couplings and scalar potential. The spectrum contains new states such as right handed neutrinos and heavy ...

  4. q-deformation of ''W3'', Virasoro and U(1)-Kac-Moody algebras

    International Nuclear Information System (INIS)

    El Hassouni, A.; Tahri, E.H.; Zakkari, M.

    1995-07-01

    A deformation of the algebra of infinite matrices gl(∞, C) is given. We show that this operation leads to the realization of a deformed ''W 3 '' like algebra. The central extension of the q-U(1) Kac-Moody and the q-Virasoro algebra is performed. (author). 10 refs

  5. The 17 MeV anomaly in beryllium decays and U(1) portal to dark matter

    Science.gov (United States)

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

    2017-11-01

    The experiment of Krasznahorkay et al. observed the transition of a 8Be excited state to its ground state and accompanied by an emission of an e+e‑ pair with 17 MeV invariant mass. This 6.8σ anomaly can be fitted by a new light gauge boson. We consider the new particle as a U(1) gauge boson, Z‧, which plays as a portal linking dark sector and visible sector. In particular, we study the new U(1) gauge symmetry as a hidden or nonhidden group separately. The generic hidden U(1) model, referred to as dark Z model, is excluded by imposing various experimental constraints. On the other hand, a nonhidden Z‧ is allowed due to the additional interactions between Z‧ and Standard Model fermions. We also study the implication of the dark matter direct search on such a scenario. We found that the search for the DM-nucleon scattering cannot probe the parameter space that is allowed by 8Be-anomaly for the range of DM mass above 500 MeV. However, the DM-electron scattering for DM between 20 MeV and 50 MeV can test the underlying U(1) portal model using the future Si and Ge detectors with the 5e‑ threshold charges.

  6. New fermion mass textures from anomalous U(1) symmetries with baryon and lepton number conservation

    CERN Document Server

    Leontaris, George K

    2000-01-01

    In this paper, we present solutions to the fermion mass hierarchy problem in the context of the minimal supersymmetric standard theory augmented by an anomalous family-dependent U(1)_X symmetry. The latter is spontaneously broken by non-zero vevs of a pair of singlet fields whose magnitude is determined through the D- and F-flatness conditions of the superpotential. We derive the general solutions to the anomaly cancellation conditions and show that they allow numerous choices for the U(1)_X fermion charges which give several fermion mass textures in agreement with the observed fermion mass hierarchy and mixing. Solutions with U(1)_X fermion charge assignments are found which forbid or substantially suppress the dangerous baryon and lepton number violating operators and the lepton-higgs mixing coupling while a higgs mixing mass classification of the fermion mass textures with respect to the sum of the doublet-higgs U(1)_X-charges and show that suppression of dimension-five operators naturally occurs for vario...

  7. Right-handed neutrino dark matter in a U(1) extension of the Standard Model

    Science.gov (United States)

    Cox, Peter; Han, Chengcheng; Yanagida, Tsutomu T.

    2018-01-01

    We consider minimal U(1) extensions of the Standard Model in which one of the right-handed neutrinos is charged under the new gauge symmetry and plays the role of dark matter. In particular, we perform a detailed phenomenological study for the case of a U(1)(B‑L)3 flavoured B‑L symmetry. If perturbativity is required up to high-scales, we find an upper bound on the dark matter mass of mχlesssim2 TeV, significantly stronger than that obtained in simplified models. Furthermore, if the U(1)(B‑L)3 breaking scalar has significant mixing with the SM Higgs, there are already strong constraints from direct detection. On the other hand, there remains significant viable parameter space in the case of small mixing, which may be probed in the future via LHC Z' searches and indirect detection. We also comment on more general anomaly-free symmetries consistent with a TeV-scale RH neutrino dark matter candidate, and show that if two heavy RH neutrinos for leptogenesis are also required, one is naturally led to a single-parameter class of U(1) symmetries.

  8. Electromagnetic mass differences in the SU(3) x U(1) gauge model

    International Nuclear Information System (INIS)

    Maharana, K.; Sastry, C.V.

    1975-01-01

    In this note we point out that the electromagnetic mass differences of the pion and kaon in the SU(3) times U(1) model are the same as in Weinberg's model except for the differences in the masses of the gauge bosons

  9. Higher-spin cluster algorithms: the Heisenberg spin and U(1) quantum link models

    Energy Technology Data Exchange (ETDEWEB)

    Chudnovsky, V

    2000-03-01

    I discuss here how the highly-efficient spin-1/2 cluster algorithm for the Heisenberg antiferromagnet may be extended to higher-dimensional representations; some numerical results are provided. The same extensions can be used for the U(1) flux cluster algorithm, but have not yielded signals of the desired Coulomb phase of the system.

  10. Higher-spin cluster algorithms: the Heisenberg spin and U(1) quantum link models

    International Nuclear Information System (INIS)

    Chudnovsky, V.

    2000-01-01

    I discuss here how the highly-efficient spin-1/2 cluster algorithm for the Heisenberg antiferromagnet may be extended to higher-dimensional representations; some numerical results are provided. The same extensions can be used for the U(1) flux cluster algorithm, but have not yielded signals of the desired Coulomb phase of the system

  11. Deep-inelastic lepton scattering in an SU(3) x U(1) gauge model

    International Nuclear Information System (INIS)

    Maharana, K.; Sastry, C.V.

    1976-01-01

    Linear relations and sum rules for deep-inelastic lepton scattering are derived in the light-cone algebra approach from a set of weak, neutral, and electromagnetic currents based on an SU(3) x U(1) gauge model proposed by Schechter and Ueda

  12. SU(5) x U(1) phenomenology: Theorems on neutral-current analysis

    International Nuclear Information System (INIS)

    Zee, A.; Kim, J.E.

    1980-01-01

    We embed the SU(5) unified theory of Georgi and Glashow in a U(5) theory. This may result from the breaking of an SU(N), N>5, theory or of a GL(5,c) theory. At low energy this leads to an SU(2) x U(1) x U(1) electroweak theory. We show that, with a suitable choice of Higgs representations, the predictions of this theory for neutral-current experiments are characterized by three parameters. For appropriate values of these parameters, the predictions are practically indistinguishable from the standard SU(2) x U(1) theory. Certain theorems on the analysis of neutral-current interactions are proved. (Section V is independent for readers who are interested only in the theorems.) More accurate neutral-current measurement might answer the question of whether SU(5) x U(1) is relevant. Possible verification of the present electroweak theory can result from (roughly) an order suppression relative to the standard prediction on the asymmetries in e + e - → μ + μ - and discovery of two Z bosons around 90 --100 GeV. GL(n,c) gauge theories are formulated in the Appendix

  13. Asymptotic behaviour in polarized and half-polarized U(1) symmetric vacuum spacetimes

    International Nuclear Information System (INIS)

    Isenberg, James; Moncrief, Vincent

    2002-01-01

    We use the Fuchsian algorithm to study the behaviour near the singularity of certain families of U(1) symmetric solutions of the vacuum Einstein equations (with the U(1) isometry group acting spatially). We consider an analytic family of polarized solutions with the maximum number of arbitrary functions consistent with the polarization condition (one of the 'gravitational degrees of freedom' is turned off) and show that all members of this family are asymptotically velocity term dominated (AVTD) as one approaches the singularity. We show that the same AVTD behaviour holds for a family of 'half-polarized' solutions, which is defined by adding one extra arbitrary function to those characterizing the polarized solutions. (The full set of nonpolarized solutions involves two extra arbitrary functions.) Using SL(2, R) Geroch transformations, we produce a further class of U(1) symmetric solutions with AVTD behaviour. We begin to address the issue of whether AVTD behaviour is independent of the choice of time foliation by showing that indeed AVTD behaviour is seen for a wide class of choices of harmonic time in the polarized and half-polarized (U(1) symmetric vacuum) solutions discussed here

  14. Duality in the U(1) Higgs model with an external field

    International Nuclear Information System (INIS)

    Damgaard, P.H.

    1988-07-01

    An external electromagnetic field is coupled to the lattice U(1) Higgs model in a Villain form. Duality transformations are then used to express the partition function in terms of an effective Lagrangian of topological excitations and their couplings to the external field. Consequences for the phase diagram are derived. (orig.)

  15. Quark seesaw mechanism, dark U (1 ) symmetry, and the baryon-dark matter coincidence

    Science.gov (United States)

    Gu, Pei-Hong; Mohapatra, Rabindra N.

    2017-09-01

    We attempt to understand the baryon-dark matter coincidence problem within the quark seesaw extension of the standard model where parity invariance is used to solve the strong C P problem. The S U (2 )L×S U (2 )R×U (1 )B -L gauge symmetry of this model is extended by a dark U (1 )X group plus inclusion of a heavy neutral vector-like fermion χL ,R charged under the dark group which plays the role of dark matter. All fermions are Dirac type in this model. Decay of heavy scalars charged under U (1 )X leads to simultaneous asymmetry generation of the dark matter and baryons after sphaleron effects are included. The U (1 )X group not only helps to stabilize the dark matter but also helps in the elimination of the symmetric part of the dark matter via χ -χ ¯ annihilation. For dark matter mass near the proton mass, it explains why the baryon and dark matter abundances are of similar magnitude (the baryon-dark matter coincidence problem). This model is testable in low threshold (sub-keV) direct dark matter search experiments.

  16. The flipped SU(5)xU(1) string model revamped

    Energy Technology Data Exchange (ETDEWEB)

    Antoniadis, I.; Ellis, J.; Hagelin, J.S.; Nanopoulos, D.V. (European Organization for Nuclear Research, Geneva (Switzerland))

    1989-11-02

    We present a refined version of our three-generation flipped SU(5)xU(1) string model with the following properties. The complete massless spectrum is derived and shown to be free of all gauge and mixed anomalies apart from a single anomalous U(1). The imaginary part of the dilaton supermultiplet is eaten by the anomalous U(1) gauge boson, and the corresponding D-term is cancelled by large VEVs for singlet fields that break surplus U(1) gauge factors, leaving a supersymmetric vacuum with an SU(5)xU(1) visible gauge group and an SO(10)xSO(6) hidden gauge group. There are sufficient Higgs multiplets to break the visible gauge symmetry down to the standard model in an essentially unique way. All trilinear superpotential couplings have been calculated and there are in particular some giving m{sub t}, m{sub b}, m{sub tau}ne0. A renormalization group analysis shows that m{sub t}<190 GeV and m{sub b}{approx equal}3m{sub tau}. Light Higgs doublets are split automatically from heavy Higgs triplets, leaving no residual dimension-five operators for baryon decay, and the baryon lifetime tau{sub B} {approx equal} 2x10{sup 34{plus minus}2} yr. There are no tree-level flavour-changing neutral currents, but muyieldsegamma may occur at a detectable level: B(muyieldsegamma){proportional to} 10{sup -11}-10{sup -14}. (orig.).

  17. Flipped SU(5)xU(1){sub X} models from F-theory

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Jing [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Li Tianjun, E-mail: tjli@physics.rutgers.ed [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, TX 77843 (United States); Key Laboratory of Frontiers in Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190 (China); Nanopoulos, Dimitri V. [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, TX 77843 (United States); Astroparticle Physics Group, Houston Advanced Research Center (HARC), Mitchell Campus, Woodlands, TX 77381 (United States); Academy of Athens, Division of Natural Sciences, 28 Panepistimiou Avenue, Athens 10679 (Greece); Xie Dan [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, TX 77843 (United States)

    2010-05-01

    We systematically construct flipped SU(5)xU(1){sub X} models without and with bulk vector-like particles from F-theory. To realize the decoupling scenario, we introduce sets of vector-like particles in complete SU(5)xU(1) multiplets at the TeV scale, or at the intermediate scale, or at the TeV scale and high scale. To avoid the Landau pole problem for the gauge couplings, we can only introduce five sets of vector-like particles around the TeV scale. These vector-like particles can couple to the Standard Model singlet fields, and obtain suitable masses by Higgs mechanism. We study gauge coupling unification in detail. We show that the U(1){sub X} flux contributions to the gauge couplings preserve the SU(5)xU(1){sub X} gauge coupling unification. We calculate the SU(3){sub C}xSU(2){sub L} unification scales, and the SU(5)xU(1){sub X} unification scales and unified couplings. In most of our models, the high-scale or bulk vector-like particles can be considered as string-scale threshold corrections since their masses are close to the string scale. Furthermore, we discuss the phenomenological consequences of our models. In particular, in the models with TeV-scale vector-like particles, the vector-like particles can be observed at the Large Hadron Collider, the proton decay is within the reach of the future Hyper-Kamiokande experiment, the lightest CP-even Higgs boson mass can be increased, the hybrid inflation can be naturally realized, and the correct cosmic primordial density fluctuations can be generated.

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

    Science.gov (United States)

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

    2016-07-01

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

  19. Knockdown of ZFR suppresses cell proliferation and invasion of human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Xiaolan Zhao

    Full Text Available BACKGROUND: Zinc finger RNA binding protein (ZFR is involved in the regulation of growth and cancer development. However, little is known about ZFR function in pancreatic cancer. METHODS: Herein, to investigate whether ZFR is involved in tumor growth, Oncomine microarray data was firstly used to evaluate ZFR gene expression in human pancreatic tumors. Then short hairpin RNA (shRNA targeting ZFR was designed and delivered into PANC-1 pancreatic cancer cells to knock down ZFR expression. Cell viability, cell proliferation and cell cycle analysis after ZFR knockdown were determined by MTT, colony forming and FACS, respectively. In addition, cell migration and invasion were assessed using the Transwell system. RESULTS: The expression of ZFR was significantly higher in pancreatic tumors than normal pancreas tissues by Oncomine database analysis. Knockdown of ZFR by shRNA-expressing lentivirus significantly decreased the viability and invasion ability of pancreatic cancer cells. Moreover, FACS analysis showed that knockdown of ZFR in PANC-1 cells caused a significant cell cycle arrest at G0/G1 phase. Furthermore, knockdown of ZFR decreased the levels of CDK2, CDK4, CyclinA and CyclinD1 and enhanced the expression of p27, which has evidenced by qRT-PCR and Western blot analysis. CONCLUSIONS: Knockdown of ZFR might provide a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation.

  20. Transcription factor Runx2 knockdown regulates colon cancer transplantation tumor growth in vitro: an experimental study

    Directory of Open Access Journals (Sweden)

    Bin Xu1

    2017-05-01

    Full Text Available Objective: To study the effect of transcription factor Runx2 knockdown on colon cancer transplantation tumor growth in vitro. Methods: Colon cancer cell lines HT29 were cultured and transfected with negative control (NC - shRNA plasmids and Runx2-shRNA plasmids respectively, the colon cancer cells transfected with shRNA were subcutaneously injected into C57 nude mice, and they were included in NC group and Runx2 knockdown group respectively. 1 week, 2 weeks and 3 weeks after model establishment, serum was collected to determine the contents of tumor markers, and tumor lesions were collected to determine proliferation and apoptosis gene expression. Results: CCSA-2, CEA and CA19-9 levels in serum as well as Rac1, Wnt3a, PLD2 and FAM96B protein expression in transplantation tumor lesions of Runx2 knockdown group were significantly lower than those of NC group while MS4A12, ASPP2 and Fas protein expression in transplantation tumor lesions of Runx2 knockdown group were significantly higher than those of NC group. Conclusion: Transcription factor Runx2 knockdown could inhibit the colon cancer transplantation tumor growth in vitro.

  1. Knockdown of p53 suppresses Nanog expression in embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Abdelalim, Essam Mohamed, E-mail: emohamed@qf.org.qa [Qatar Biomedical Research Institute, Qatar Foundation, Doha 5825 (Qatar); Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia (Egypt); Tooyama, Ikuo [Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan)

    2014-01-10

    Highlights: •We investigate the role of p53 in ESCs in the absence of DNA damage. •p53 knockdown suppresses ESC proliferation. •p53 knockdown downregulates Nanog expression. •p53 is essential for mouse ESC self-renewal. -- Abstract: Mouse embryonic stem cells (ESCs) express high levels of cytoplasmic p53. Exposure of mouse ESCs to DNA damage leads to activation of p53, inducing Nanog suppression. In contrast to earlier studies, we recently reported that chemical inhibition of p53 suppresses ESC proliferation. Here, we confirm that p53 signaling is involved in the maintenance of mouse ESC self-renewal. RNA interference-mediated knockdown of p53 induced downregulation of p21 and defects in ESC proliferation. Furthermore, p53 knockdown resulted in a significant downregulation in Nanog expression at 24 and 48 h post-transfection. p53 knockdown also caused a reduction in Oct4 expression at 48 h post-transfection. Conversely, exposure of ESCs to DNA damage caused a higher reduction of Nanog expression in control siRNA-treated cells than in p53 siRNA-treated cells. These data show that in the absence of DNA damage, p53 is required for the maintenance of mouse ESC self-renewal by regulating Nanog expression.

  2. Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jie [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Yang, Xi-fei [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Ren, Xiao-hu [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Meng, Xiao-jing [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Huang, Hai-yan [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zhao, Qiong-hui [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen (China); Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Liu, Jian-jun, E-mail: bio-research@hotmail.com [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zou, Fei, E-mail: zoufei616@163.com [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China)

    2014-10-10

    Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.

  3. Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

    International Nuclear Information System (INIS)

    Li, Jie; Yang, Xi-fei; Ren, Xiao-hu; Meng, Xiao-jing; Huang, Hai-yan; Zhao, Qiong-hui; Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li; Liu, Jian-jun; Zou, Fei

    2014-01-01

    Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer

  4. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Quan He

    2014-01-01

    Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

  5. Retracing the phenomenology of the flipped SU(5)xU(1) superstring model

    Energy Technology Data Exchange (ETDEWEB)

    Rizos, J.; Tamvakis, K. (Ioannina Univ. (Greece). Dept. of Physics)

    1990-11-22

    We study in detail gauge symmetry breaking in the SU(5)xU(1)'xU(1){sup 4}xSO(10)xSO(6) superstring model, solving the D- and F-flatness conditions and taking into account quartic and quintic superpotential terms. We find that, to this order, the model describes two massive generations of quarks and leptons as well as a massless generation expected to receive naturally suppressed masses from higher order non-renormalizable terms. We show that D-flatness restricts the number of massless isodoublets to four. We also extract an inequality relating the top quark mass to M{sub W}. (orig.).

  6. Neutrino masses from U(1) symmetries and the Super-Kamiokande data

    CERN Document Server

    Lola, S; Lola, Smaragda; Ross, Graham G.

    1999-01-01

    Motivated by the Super-Kamiokande data, we revisit models with U(1) symmetries and discuss the origin of neutrino masses and mixings in such theories. We show that, in models with just three light neutrinos and a hierarchy of neutrino masses, large (2-3) mixing fixes the lepton doublet U(1) charges and is thus related to the structure of the charged lepton mass matrix. We discuss the fermion mass structure that follows from the abelian family symmetry with an extended gauge group. Requiring that the quark and lepton masses be ordered by the family symmetry, we identify the most promising scheme. This requires large, but not necessarily maximal, mixing in the mu tau sector and gives e mu mixing in the range that is required for the small angle solution of the solar neutrino deficit.

  7. Geometrical origin of tricritical points of various U(1) lattice models

    International Nuclear Information System (INIS)

    Janke, W.; Kleiert, H.

    1989-01-01

    The authors review the dual relationship between various compact U(1) lattice models and Abelian Higgs models, the latter being the disorder field theories of line-like topological excitations in the system. The authors point out that the predicted first-order transitions in the Abelian Higgs models (Coleman-Weinberg mechanism) are, in three dimensions, in contradiction with direct numerical investigations in the compact U(1) formulation since these yield continuous transitions in the major part of the phase diagram. In four dimensions, there are indications from Monte Carlo data for a similar situation. Concentrating on the strong-coupling expansion in terms of geometrical objects, surfaces or lines, with certain statistical weights, the authors present semi-quantitative arguments explaining the observed cross-over from first-order to continuous transitions by the balance between the lowest two weights (2:1 ratio) of these geometrical objects

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

    Directory of Open Access Journals (Sweden)

    Fuminobu Takahashi

    2016-09-01

    Full Text Available 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(1Y. With the large kinetic mixing, the standard model gauge couplings unify around 1017 GeV, suggesting the grand unified theory without too rapid proton decay. Our scenario predicts events with a photon and missing transverse momentum, and its cross section is related to that for the diphoton excess through the kinetic mixing. We also discuss other possible collider signatures and cosmology, including various ways to evade constraints on exotic stable charged particles. In some cases where the 750 GeV diphoton excess is due to diaxion decays, our scenario also predicts triphoton and tetraphoton signals.

  9. Dirac dark matter and b →s ℓ+ℓ- with U(1) gauge symmetry

    Science.gov (United States)

    Celis, Alejandro; Feng, Wan-Zhe; Vollmann, Martin

    2017-02-01

    We revisit the possibility of a Dirac fermion dark matter candidate in the light of current b →s ℓ+ℓ- anomalies by investigating a minimal extension of the Standard Model with a horizontal U(1 ) ' local symmetry. Dark matter stability is protected by a remnant Z2 symmetry arising after spontaneous symmetry breaking of U(1 ) '. The associated Z' gauge boson can accommodate current hints of new physics in b →s ℓ+ℓ- decays, and acts as a vector portal between dark matter and the visible sector. We find that the model is severely constrained by a combination of precision measurements at flavor factories, LHC searches for dilepton resonances, as well as direct and indirect dark matter searches. Despite this, viable regions of the parameter space accommodating the observed dark matter relic abundance and the b →s ℓ+ℓ-anomalies still persist for dark matter and Z ' masses in the TeV range.

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

    Science.gov (United States)

    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

  11. New hierarchy in GUTs based on SU(n,1)/SU(n)U(1) SUGRA

    International Nuclear Information System (INIS)

    Hayashi, M.J.; Murayama, Akihiro

    1985-01-01

    Grand unified theories (GUTs) in the framework of SU(n, 1)/SU(n) x U(1) supergravity are discussed which naturally generate a new hierarchy, Msub(P) (Planck mass): Msub(X) (GUT scale):msub(3/2) (gravitino mass):m (explicit supersymmetry breaking scale)=1:epsilon:epsilon 3 :epsilon 5 α(Msub(X)) with Msub(P) as the only input mass scale. The SUSY breaking scale m is expected to be fixed radiatively as mproportionalMsub(W), i.e., epsilonproportional10 -3 . Our method would be applicable to any GUT based on SU(n, 1)/SU(n) x U(1) supergravity. (orig.)

  12. Dark gauge U(1) symmetry for an alternative left-right model

    Energy Technology Data Exchange (ETDEWEB)

    Kownacki, Corey; Ma, Ernest; Pollard, Nicholas; Popov, Oleg; Zakeri, Mohammadreza [University of California, Department of Physics and Astronomy, Riverside, CA (United States)

    2018-02-15

    An alternative left-right model of quarks and leptons, where the SU(2){sub R} lepton doublet (ν, l){sub R} is replaced with (n, l){sub R} so that n{sub R} is not the Dirac mass partner of ν{sub L}, has been known since 1987. Previous versions assumed a global U(1){sub S} symmetry to allow n to be identified as a dark-matter fermion. We propose here a gauge extension by the addition of extra fermions to render the model free of gauge anomalies, and just one singlet scalar to break U(1){sub S}. This results in two layers of dark matter, one hidden behind the other. (orig.)

  13. Non(anti)commutative N = (1,1/2) supersymmetric U(1) gauge theory

    International Nuclear Information System (INIS)

    Araki, Takeo; Ito, Katsushi; Ohtsuka, Akihisa

    2005-01-01

    We study a reduction of deformation parameters in non(anti)commutative N = 2 harmonic superspace to those in non(anti)commutative N = 1 superspace. By this reduction we obtain the exact gauge and supersymmetry transformations in the Wess-Zumino gauge of non(anti)commutative N = 2 supersymmetric U(1) gauge theory defined in the deformed harmonic superspace. We also find that the action with the first order correction in the deformation parameter reduces to the one in the N = 1 superspace by some field redefinition. We construct deformed N = (1,1/2) supersymmetry in N = 2 supersymmetric U(1) gauge theory in non(anti)commutative N = 1 superspace

  14. Testable flipped SU(5)xU(1){sub X} models

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Jing [Institute of Theoretical Science, University of Oregon, Eugene, OR 97403 (United States); Li Tianjun [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, TX 77843 (United States) and Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100080 (China) and Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854 (United States)]. E-mail: tjli@physics.rutgers.edu; Nanopoulos, Dimitri V. [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, TX 77843 (United States); Astroparticle Physics Group, Houston Advanced Research Center (HARC), Mitchell Campus, Woodlands, TX 77381 (United States); Academy of Athens, Division of Natural Sciences, 28 Panepistimiou Avenue, Athens 10679 (Greece)

    2007-06-11

    The little hierarchy between the GUT scale and the string scale may give us some hints that can be tested at the LHC. To achieve string-scale gauge coupling unification, we introduce additional vector-like particles. We require that these vector-like particles be standard, form complete GUT multiplets, and have masses around the TeV scale or close to the string scale. Interestingly, only the flipped SU(5)xU(1){sub X} models can work elegantly. We consider all possible sets of vector-like particles with masses around the TeV scale. And we introduce vector-like particles with masses close to the string scale which can mimic the string-scale threshold corrections. We emphasize that all of these vector-like particles can be obtained in the interesting flipped SU(5)xU(1){sub X} string models from the four-dimensional free fermionic string construction. Assuming the low-energy supersymmetry, high-scale supersymmetry, and split supersymmetry, we show that the string-scale gauge coupling unification can indeed be achieved in the flipped SU(5)xU(1){sub X} models. These models can be tested at the LHC by observing simple sets of vector-like particles at the TeV scale. Moreover, we discuss a simple flipped SU(5)xU(1){sub X} model with string-scale gauge coupling unification and high-scale supersymmetry by introducing only one pair of the vector-like particles at the TeV scale, and we predict the corresponding Higgs boson masses. Also, we briefly comment on the string-scale gauge coupling unification in the model with low-energy supersymmetry by introducing only one pair of the vector-like particles at the intermediate scale. And we briefly comment on the mixings among the SM fermions and the corresponding extra vector-like particles.

  15. Neutrino masses, dark matter and leptogenesis with U(1) B - L gauge symmetry

    Science.gov (United States)

    Geng, Chao-Qiang; Okada, Hiroshi

    2018-06-01

    We propose a model with an U(1) B - L gauge symmetry, in which small neutrino masses, dark matter and the matter-antimatter asymmetry in the Universe can be simultaneously explained. In particular, the neutrino masses are generated radiatively, while the matter-antimatter asymmetry is led by the leptogenesis mechanism, at TeV scale. We also explore allowed regions of the model parameters and discuss some phenomenological effects, including lepton flavor violating processes.

  16. Radiative corrections in SU2 x U1 LEP/SLC

    International Nuclear Information System (INIS)

    Lynn, B.W.; Peskin, M.E.; Stuart, R.G.

    1985-06-01

    We show the sensitivity of various experimental measurements to one-loop radiative corrections in SU 2 x U 1 . Models considered are the standard GSW model as well as extensions of it which include extra quarks and leptons, SUSY and certain technicolor models. The observation of longitudinal polarization is a great help in seeing these effects in asymmetries in e + e - → μ + μ - , tau + tau - on Z 0 resonance. 25 refs., 22 figs., 10 tabs

  17. On bound states of photons in noncommutative U(1) gauge theory

    International Nuclear Information System (INIS)

    Fatollahi, A.H.; Jafari, A.

    2006-01-01

    We consider the possibility that photons of noncommutative U(1) gauge theory can make bound states. Using the potential model, developed based on the constituent gluon picture of QCD glue-balls, arguments are presented in favor of the existence of these bound states. The basic ingredient of the potential model is that the self-interacting massless gauge particles may get mass by the inclusion of non-perturbative effects. (orig.)

  18. Nuclear matter saturation in a U(1) circle-times chiral model

    International Nuclear Information System (INIS)

    Lin, Wei

    1989-01-01

    The mean-field approximation in the U(1) circle-times chiral model for nuclear matter maturation is reviewed. Results show that it cannot be the correct saturation mechanism. It is argued that in this chiral model, other than the fact the ω mass can depend on the density of nuclear matter, saturation is still quite like the Walecka picture. 16 refs., 3 figs

  19. Dilatometric Study Of U1-xAmxO2±δ Transmutation Fuels

    International Nuclear Information System (INIS)

    Lebreton, Florent; Horlait, Denis; Delahaye, Thibaud; Blanchart, P.

    2013-01-01

    Conclusions - Dilatometric study results: • Reactive sintering: competition between solidsolution formation and densification process → the latter is slowed down and final density limited; • Conventional sintering: avoids this competition → higher densities are reached. - New homogeneous U 1-x Am x O 2±δ precursors: • Powders synthesized by oxalate co-conversion; • Microspheres formed using the CRMP (WAR-like) process

  20. Slavnov and Gaudin-Korepin Formulas for Models without U(1) Symmetry: the Twisted XXX Chain

    Science.gov (United States)

    Belliard, Samuel; Pimenta, Rodrigo A.

    2015-12-01

    We consider the XXX spin-1/2 Heisenberg chain on the circle with an arbitrary twist. We characterize its spectral problem using the modified algebraic Bethe anstaz and study the scalar product between the Bethe vector and its dual. We obtain modified Slavnov and Gaudin-Korepin formulas for the model. Thus we provide a first example of such formulas for quantum integrable models without U(1) symmetry characterized by an inhomogenous Baxter T-Q equation.

  1. Heavy charged leptons in an SU(3)L x U(1)N model

    International Nuclear Information System (INIS)

    Pleitez, V.; Tonasse, M.D.

    1992-12-01

    An SU(3) L x U(1) N model for the electroweak interactions which includes additional heavy charged leptons is considered. These leptons have not strong constraints on their masses since they do not couple in the same way as the lightest leptons to the neutral-currents and also because new contributions to the muon g-2 factor already suppressed because of the massive new vector boson present in this model. (author)

  2. Zee-Babu type model with U (1 )Lμ-Lτ gauge symmetry

    Science.gov (United States)

    Nomura, Takaaki; Okada, Hiroshi

    2018-05-01

    We extend the Zee-Babu model, introducing local U (1 )Lμ-Lτ symmetry with several singly charged bosons. We find a predictive neutrino mass texture in a simple hypothesis in which mixings among singly charged bosons are negligible. Also, lepton-flavor violations are less constrained compared with the original model. Then, we explore the testability of the model, focusing on doubly charged boson physics at the LHC and the International Linear Collider.

  3. New scotogenic model of neutrino mass with U(1){sub D} gauge interaction

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Ernest [Department of Physics and Astronomy, University of California, Riverside, CA 92521 (United States); Picek, Ivica; Radovčić, Branimir [Department of Physics, Faculty of Science, University of Zagreb, P.O.B. 331, HR-10002 Zagreb (Croatia)

    2013-11-04

    We propose a new realization of the one-loop radiative model of neutrino mass generated by dark matter (scotogenic), where the particles in the loop have an additional U(1){sub D} gauge symmetry, which may be exact or broken to Z{sub 2}. This model is relevant to a number of astrophysical observations, including AMS-02 and the dark-matter distribution in dwarf galactic halos.

  4. Neutrinoless double beta decay in an SU(3)L x U(1)N model

    International Nuclear Information System (INIS)

    Pleitez, V.; Tonasse, M.D.

    1993-01-01

    A model for the electroweak interactions with SU (3) L x U(1) N gauge symmetry is considered. It is shown that, it is the conservation of F = L + B which forbids massive neutrinos and the neutrinoless double beta decay, (β β) On u. Explicit and spontaneous breaking of F imply that the neutrinos have an arbitrary mass and (β β) On u proceeds also with some contributions that do not depend explicitly on the neutrino mass. (author)

  5. Kinetic mixing of the photon with hidden U(1)s in string phenomenology

    International Nuclear Information System (INIS)

    Abel, S.A.; Khoze, V.V.; Jaeckel, J.

    2008-03-01

    Embeddings of the standard model in type II string theory typically contain a variety of U(1) gauge factors arising from D-branes in the bulk. In general, there is no reason why only one of these - the one corresponding to weak hypercharge - should be massless. Observations require that standard model particles must be neutral (or have an extremely small charge) under additional massless U(1)s, i.e. the latter have to belong to a so called hidden sector. The exchange of heavy messengers, however, can lead to a kinetic mixing between the hypercharge and the hidden-sector U(1)s, that is testable with near future experiments. This provides a powerful probe of the hidden sectors and, as a consequence, of the string theory realisation itself. In the present paper, we show, using a variety of methods, how the kinetic mixing can be derived from the underlying type II string compactification, involving supersymmetric and nonsupersymmetric configurations of D-branes, both in large volumes and in warped backgrounds with fluxes. We first demonstrate by explicit example that kinetic mixing occurs in a completely supersymmetric set-up where we can use conformal field theory techniques. We then develop a supergravity approach which allows us to examine the phenomenon in more general backgrounds, where we find that kinetic mixing is natural in the context of flux compactifications. We discuss the phenomenological consequences for experiments at the low-energy frontier, searching for signatures of light, sub-electronvolt or even massless hidden-sector U(1) gauge bosons and minicharged particles. (orig.)

  6. Kinetic mixing of the photon with hidden U(1)s in string phenomenology

    Energy Technology Data Exchange (ETDEWEB)

    Abel, S.A.; Khoze, V.V. [Durham Univ. (United Kingdom). Inst. for Particle Physics Phenomenology; Goodsell, M.D. [Laboratoire de Physique Theorique et Hautes Energies, Paris (France); Jaeckel, J. [Durham Univ. (United Kingdom). Inst. for Particle Physics Phenomenology]|[Heidelberg Univ. (Germany). Inst. fuer Theoretische Physik; Ringwald, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2008-03-15

    Embeddings of the standard model in type II string theory typically contain a variety of U(1) gauge factors arising from D-branes in the bulk. In general, there is no reason why only one of these - the one corresponding to weak hypercharge - should be massless. Observations require that standard model particles must be neutral (or have an extremely small charge) under additional massless U(1)s, i.e. the latter have to belong to a so called hidden sector. The exchange of heavy messengers, however, can lead to a kinetic mixing between the hypercharge and the hidden-sector U(1)s, that is testable with near future experiments. This provides a powerful probe of the hidden sectors and, as a consequence, of the string theory realisation itself. In the present paper, we show, using a variety of methods, how the kinetic mixing can be derived from the underlying type II string compactification, involving supersymmetric and nonsupersymmetric configurations of D-branes, both in large volumes and in warped backgrounds with fluxes. We first demonstrate by explicit example that kinetic mixing occurs in a completely supersymmetric set-up where we can use conformal field theory techniques. We then develop a supergravity approach which allows us to examine the phenomenon in more general backgrounds, where we find that kinetic mixing is natural in the context of flux compactifications. We discuss the phenomenological consequences for experiments at the low-energy frontier, searching for signatures of light, sub-electronvolt or even massless hidden-sector U(1) gauge bosons and minicharged particles. (orig.)

  7. Crystallo-chemistry of actinide nitrides (U1-yPuy)N and effect of impurities

    International Nuclear Information System (INIS)

    Beauvy, M.; Coulon-Picard, E.; Pelletier, M.

    2004-01-01

    Investigations on actinide nitrides has been done in our Laboratories for Fast Breeder Reactors since the seventies and some properties are reported to show the interest for these fuels. Today, the actinide nitrides are reconsidered as possible fuels for the future fission reactors (GFR and LMFR selected by the international forum Generation IV). The results of new investigations on crystal structure of mixed mono-nitrides (U,Pu)N, and the effects of oxygen and carbon contaminations on this structure are presented. The cubic 'NaCl-fcc' type structure of actinide nitrides AnN with space group O5/h-Fm3m does not respect the 'Vegard law' model for the mixed nitrides (U 1-y Pu y )N. These nitrides are usually considered with strong metallic character associated with partial ionic bonding, but the ionic contribution in the An-N bonding determined in this work is very important and near 41.6% for UN and PuN. From results published on resistivity of mixed nitrides, the data on bonding must be also modified for partial covalence. This is in good agreement with the experimental lattice parameters which are not compatible with dominant metallic bonding. The numbers of bonding electrons in the nitrides (U 1-y Pu y )N are reevaluated and the low values proposed comparatively with those previously published confirm the strong ionic character with high concentration of An 3+ ions. The solubility of oxygen and carbon in actinide nitrides (U 1-y Pu y )N are discussed from measurements on volume concentration of actinide oxide phase, total oxygen and carbon contents, and lattice parameter of nitrides. The oxygen solubility limit in UN is near 1000 ppm, with a lightly higher value of 1200 ppm for the mixed nitride (U 0.8 Pu 0.2 )N. The effects of oxygen or carbon atoms in the lattice of (U 1-y Pu y )N are analysed

  8. Phenomenological implications of the flipped SU(5) x U(1) superstring model

    Energy Technology Data Exchange (ETDEWEB)

    Tamvakis, K. (Physics Dept., Univ. of Ioannina (Greece))

    1991-07-01

    We study in detail gauge symmetry breaking in the SU(5)xU(1)'xU(1){sup 4}xSO(10)xSO(6) superstring model, solving the D and F-flatness conditions and taking into account quartic and quintic superpotential terms. We find that, to this order, the model describes two massive generations of quarks and leptons as well as a massless generation expected to receive naturally suppressed masses from higher order non-renormalizable terms. D and F-flatness restricts the number of massless isodoublets to four. We solve the coupled renormalization group equations for the gauge and Yukawa couplings in the two-loop approximation and obtain the top-quark mass as a function of two parameters of the model which could be chosen to be ratios of singlet v.e.v's associated with the surplus (U(1)){sup 4} breaking. We obtain a heavy top-quark with 150GeV {<=} m{sub 1} < 200GeV, for most part of the parameter space, while lower values are possible only in a very small extermal region. We also compute the allowed range of unification parameters (M{sub x}, sin{sup 2} {theta}{sub w}, {alpha}{sub 3}(M{sub w})) in the presence of a heavy top quark. (orig.).

  9. Neutrino mass, leptogenesis and FIMP dark matter in a U(1){sub B-L} model

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Anirban; Khan, Sarif [Harish-Chandra Research Institute, Allahabad (India); Homi Bhabha National Institute, Training School Complex, Mumbai (India); Choubey, Sandhya [Harish-Chandra Research Institute, Allahabad (India); Homi Bhabha National Institute, Training School Complex, Mumbai (India); AlbaNova University Center, Department of Theoretical Physics, School of Engineering Sciences, KTH Royal Institute of Technology, Stockholm (Sweden)

    2017-12-15

    The Standard Model (SM) is inadequate to explain the origin of tiny neutrino masses, the dark matter (DM) relic abundance and the baryon asymmetry of the Universe. In this work, to address all three puzzles, we extend the SM by a local U(1){sub B-L} gauge symmetry, three right-handed (RH) neutrinos for the cancellation of gauge anomalies and two complex scalars having non-zero U(1){sub B-L} charges. All the newly added particles become massive after the breaking of the U(1){sub B-L} symmetry by the vacuum expectation value (VEV) of one of the scalar fields φ{sub H}. The other scalar field, φ{sub DM}, which does not have any VEV, becomes automatically stable and can be a viable DM candidate. Neutrino masses are generated using the Type-I seesaw mechanism, while the required lepton asymmetry to reproduce the observed baryon asymmetry can be attained from the CP violating out of equilibrium decays of the RH neutrinos in TeV scale. More importantly within this framework, we study in detail the production of DM via the freeze-in mechanism considering all possible annihilation and decay processes. Finally, we find a situation when DM is dominantly produced from the annihilation of the RH neutrinos, which are at the same time also responsible for neutrino mass generation and leptogenesis. (orig.)

  10. Neutrino mass, leptogenesis and FIMP dark matter in a U(1)_{B-L} model

    Science.gov (United States)

    Biswas, Anirban; Choubey, Sandhya; Khan, Sarif

    2017-12-01

    The Standard Model (SM) is inadequate to explain the origin of tiny neutrino masses, the dark matter (DM) relic abundance and the baryon asymmetry of the Universe. In this work, to address all three puzzles, we extend the SM by a local U(1)_{B-L} gauge symmetry, three right-handed (RH) neutrinos for the cancellation of gauge anomalies and two complex scalars having non-zero U(1)_{B-L} charges. All the newly added particles become massive after the breaking of the U(1)_{B-L} symmetry by the vacuum expectation value (VEV) of one of the scalar fields φ _H. The other scalar field, φ _DM, which does not have any VEV, becomes automatically stable and can be a viable DM candidate. Neutrino masses are generated using the Type-I seesaw mechanism, while the required lepton asymmetry to reproduce the observed baryon asymmetry can be attained from the CP violating out of equilibrium decays of the RH neutrinos in TeV scale. More importantly within this framework, we study in detail the production of DM via the freeze-in mechanism considering all possible annihilation and decay processes. Finally, we find a situation when DM is dominantly produced from the annihilation of the RH neutrinos, which are at the same time also responsible for neutrino mass generation and leptogenesis.

  11. Supersymmetric codimension-two branes and U(1)R mediation in 6D gauged supergravity

    International Nuclear Information System (INIS)

    Lee, Hyun Min

    2008-01-01

    We construct a consistent supersymmetric action for brane chiral and vector multiplets in a six-dimensional chiral gauged supergravity. A nonzero brane tension can be accommodated by allowing for a brane-localized Fayet-Iliopoulos term proportional to the brane tension. When the brane chiral multiplet is charged under the bulk U(1) R , we obtain a nontrivial coupling to the extra component of the U(1) R gauge field strength and a singular scalar self-interaction term. Dimensionally reducing to 4D on a football supersymmetric solution, we discuss the implication of such interactions for obtaining the U(1) R D-term in the 4D effective supergravity. By assuming the bulk gaugino condensates and nonzero brane F- and/or D-term for the uplifting potential, we have all the moduli stabilized with a vanishing cosmological constant. The brane scalar with nonzero R charge then gets a soft mass of order the gravitino mass. The overall sign of the soft mass squared depends on the sign of the R charge as well as whether the brane F- or D-term dominates.

  12. Quantitative SRXRF analysis on the BL15U1 beamline at SSRF

    International Nuclear Information System (INIS)

    Zhang Yanle; Yu Xiaohan

    2010-01-01

    In this paper, we give an introduction first to two quantification methods for synchrotron radiation X-ray fluorescence analysis (SRXRF), namely fundamental parameters method and Monte-Carlo simulation method, for their application on the BL15U1 beamline (hard X-ray microprobe) at SSRF (Shanghai Synchrotron Radiation Facility). Effectiveness of the two methods is demonstrated and the XRF detection limits of the BL15U1 beamline are calculated. The results show that, quantitative analysis at the ppm level can be done using the two methods, with an accuracy of better than 10%. Although both the methods are valid for the SRXRF data analysis,the Monte Carlo method gives better analysis result, as it compares the simulated spectrum with the experiment spectrum, and this helps the determination of experiment parameters and thus minimizes the error caused by incorrect parameters. Finally, the detection limits shows that the BL15U1 beamline is capable of carrying out standard-of-the-art XRF experiment. (authors)

  13. Critical behavior of the compact 3D U(1) gauge theory on isotropic lattices

    International Nuclear Information System (INIS)

    Borisenko, O; Fiore, R; Papa, A; Gravina, M

    2010-01-01

    We report on the computation of the critical point of the deconfinement phase transition, critical indices and the string tension in the compact three-dimensional U(1) lattice gauge theory at finite temperatures. The critical indices govern the behavior across the deconfinement phase transition in the pure gauge U(1) model and are generally expected to coincide with the critical indices of the two-dimensional XY model. We studied numerically the U(1) model for N t = 8 on lattices with spatial extension ranging from L = 32 to 256. Our determination of the infinite volume critical point on the lattice with N t = 8 differs substantially from the pseudo-critical coupling at L = 32, found earlier in the literature and implicitly assumed as the onset value of the deconfined phase. The critical index ν computed from the scaling of the pseudo-critical couplings with the extension of the spatial lattice agrees well with the XY value ν = 1/2. On the other hand, the index η shows large deviation from the expected universal value. The possible reasons for such behavior are discussed in detail

  14. B-meson anomalies and Higgs physics in flavored U(1)' model

    Science.gov (United States)

    Bian, Ligong; Lee, Hyun Min; Park, Chan Beom

    2018-04-01

    We consider a simple extension of the Standard Model with flavor-dependent U(1)', that has been proposed to explain some of B-meson anomalies recently reported at LHCb. The U(1)' charge is chosen as a linear combination of anomaly-free B_3-L_3 and L_μ -L_τ . In this model, the flavor structure in the SM is restricted due to flavor-dependent U(1)' charges, in particular, quark mixings are induced by a small vacuum expectation value of the extra Higgs doublet. As a result, it is natural to get sizable flavor-violating Yukawa couplings of heavy Higgs bosons involving the bottom quark. In this article, we focus on the phenomenology of the Higgs sector of the model including extra Higgs doublet and singlet scalars. We impose various bounds on the extended Higgs sector from Higgs and electroweak precision data, B-meson mixings and decays as well as unitarity and stability bounds, then discuss the productions and decays of heavy Higgs bosons at the LHC.

  15. Mixed Mediation of Supersymmetry Breaking in Models with Anomalous U(1) Gauge Symmetry

    International Nuclear Information System (INIS)

    Choi, Kiwoon

    2010-01-01

    There can be various built-in sources of supersymmetry breaking in models with anomalous U(1) gauge symmetry, e.g. the U(1) D-term, the F-components of the modulus superfield required for the Green-Schwarz anomaly cancellation mechanism and the chiral matter superfields required to cancel the Fayet-Iliopoulos term, and finally the supergravity auxiliary component which can be parameterized by the F-component of chiral compensator. The relative strength between these supersymmetry breaking sources depends crucially on the characteristics of D-flat direction and also on how the D-flat direction is stabilized at a vacuum with nearly vanishing cosmological constant. We examine the possible pattern of the mediation of supersymmetry breaking in models with anomalous U(1) gauge symmetry, and find that various different mixed mediation scenarios can be realized, including the mirage mediation which corresponds to a mixed modulus-anomaly mediation, D-term domination giving a split sparticle spectrum, and also a mixed gauge-D-term mediation scenario.

  16. Knockdown of Pokemon protein expression inhibits hepatocellular carcinoma cell proliferation by suppression of AKT activity.

    Science.gov (United States)

    Zhu, Xiaosan; Dai, Yichen; Chen, Zhangxin; Xie, Junpei; Zeng, Wei; Lin, Yuanyuan

    2013-01-01

    Overexpression of Pokemon, which is an erythroid myeloid ontogenic factor protein, occurs in different cancers, including hepatocellular carcinoma (HCC). Pokemon is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of Pokemon knockdown on the regulation of HCC growth. POK shRNA suppressed the expression of Pokemon protein in HepG2 cells compared to the negative control vector-transfected HCC cells. Pokemon knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. AKT activation and the expression of various cell cycle-related genes were inhibited following Pokemon knockdown. These data demonstrate that Pokemon may play a role in HCC progression, suggesting that inhibition of Pokemon expression using Pokemon shRNA should be further evaluated as a novel target for the control of HCC.

  17. Neurobasal media facilitates increased specificity of siRNA-mediated knockdown in primary cerebellar cultures

    DEFF Research Database (Denmark)

    Gustafsson, Julie Ry; Katsioudi, Georgia; Issazadeh-Navikas, Shohreh

    2016-01-01

    be effectively grown in Neurobasal™ media. NEW METHOD: We tested the efficiency of siRNA from the Accell range from Dharmacon™ when delivered in Neurobasal™ media in contrast to the recommended Accell Delivery media provided by the manufacturer. RESULTS: We observed a more specific knockdown of target...... in Neurobasal™ media, than in Accell Delivery media when using cerebellar granule neurons. Transfection efficiency and cell viability was comparable between the two media. COMPARISON WITH EXISTING METHODS: Delivery of siRNA in Neurobasal™ media facilitates increased specificity of the knockdown compared...... to delivery in Accell Delivery media. The off-target effect observed in Accell Delivery media was not a secondary biological response to downregulation of target, but rather a mixture of specific and non-specific off-target effects. CONCLUSIONS: Specific knockdown of target can be achieved in primary...

  18. Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction

    Science.gov (United States)

    Poerschke, Robyn L.; Moos, Philip J.

    2010-01-01

    Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to anticancer treatments, as well as certain selenocompounds. However, it is unknown if TR1 knockdown produces similar effect on the sensitivity of human lung cancer cells. To further elucidate the role of TR1 in the mechanism of selenocompounds in lung cancer, a lentiviral microRNA delivery system to knockdown TR1 expression in A549 human lung adenocarcinoma cells was utilized. Cell viability was assessed after 48 hr treatment with the selenocysteine prodrug selenazolidines 2-butylselenazolidine-4(R)-carboxylic acid (BSCA) and 2-cyclohexylselenazolidine-4-(R)-carboxylic acid (ChSCA), selenocystine (SECY), methylseleninic acid (MSA), 1,4-phenylenebis(methylene)selenocyanate (p-XSC), and selenomethionine (SEM). TR1 knockdown increased the cytotoxicity of BSCA, ChSCA, and SECY but did not sensitize cells to MSA, SEM, or p-XSC. GSH and TR1 depletion together decreased cell viability, while no change was observed with GSH depletion alone. Reactive oxygen species generation was induced only in TR1 knockdown cells treated with the selenazolidines or SECY. These three compounds also decreased total intracellular glutathione levels and oxidized thioredoxin, but in a TR1 independent manner. TR1 knockdown increased selenazolidine and SECY-induced mitochondrial membrane depolarization, as well as DNA strand breaks and AIF translocation from the mitochondria. These results indicate the ability of TR1 to modulate the cytotoxic effects of BSCA, ChSCA and SECY in human lung cancer cells through mitochondrial dysfunction. PMID:20920480

  19. Brain gene expression changes elicited by peripheral vitellogenin knockdown in the honey bee.

    Science.gov (United States)

    Wheeler, M M; Ament, S A; Rodriguez-Zas, S L; Robinson, G E

    2013-10-01

    Vitellogenin (Vg) is best known as a yolk protein precursor. Vg also functions to regulate behavioural maturation in adult honey bee workers, but the underlying molecular mechanisms by which it exerts this novel effect are largely unknown. We used abdominal vitellogenin (vg) knockdown with RNA interference (RNAi) and brain transcriptomic profiling to gain insights into how Vg influences honey bee behavioural maturation. We found that vg knockdown caused extensive gene expression changes in the bee brain, with much of this transcriptional response involving changes in central biological functions such as energy metabolism. vg knockdown targeted many of the same genes that show natural, maturation-related differences, but the direction of change for the genes in these two contrasts was not correlated. By contrast, vg knockdown targeted many of the same genes that are regulated by juvenile hormone (JH) and there was a significant correlation for the direction of change for the genes in these two contrasts. These results indicate that the tight coregulatory relationship that exists between JH and Vg in the regulation of honey bee behavioural maturation is manifest at the genomic level and suggest that these two physiological factors act through common pathways to regulate brain gene expression and behaviour. © 2013 Royal Entomological Society.

  20. Gene knockdown of CENPA reduces sphere forming ability and stemness of glioblastoma initiating cells

    Directory of Open Access Journals (Sweden)

    Jinan Behnan

    2016-09-01

    Knockdown of CENPA reduced sphere forming ability, proliferation and cell viability of GICs. We also detected significant reduction in the expression of stemness marker SOX2 and the proliferation marker Ki67. These results indicate that CENPA might represent a promising therapeutic target for GBM treatment.

  1. Genetic and chemical knockdown: a complementary strategy for evaluating an anti-infective target

    Directory of Open Access Journals (Sweden)

    Ramachandran V

    2013-02-01

    Full Text Available Vasanthi Ramachandran,1,* Ragini Singh,2,* Xiaoyu Yang,1 Ragadeepthi Tunduguru,1 Subrat Mohapatra,2 Swati Khandelwal,2 Sanjana Patel,2 Santanu Datta21AstraZeneca India R&D, Bangalore, India; 2Cellworks India, Bangalore, India *These authors contributed equally to this workAbstract: The equity of a drug target is principally evaluated by its genetic vulnerability with tools ranging from antisense- and microRNA-driven knockdowns to induced expression of the target protein. In order to upgrade the process of antibacterial target identification and discern its most effective type of inhibition, an in silico toolbox that evaluates its genetic and chemical vulnerability leading either to stasis or cidal outcome was constructed and validated. By precise simulation and careful experimentation using enolpyruvyl shikimate-3-phosphate synthase and its specific inhibitor glyphosate, it was shown that genetic knockdown is distinct from chemical knockdown. It was also observed that depending on the particular mechanism of inhibition, viz competitive, uncompetitive, and noncompetitive, the antimicrobial potency of an inhibitor could be orders of magnitude different. Susceptibility of Escherichia coli to glyphosate and the lack of it in Mycobacterium tuberculosis could be predicted by the in silico platform. Finally, as predicted and simulated in the in silico platform, the translation of growth inhibition to a cidal effect was able to be demonstrated experimentally by altering the carbon source from sorbitol to glucose.Keywords: knockdown, inhibition, in silico, vulnerability

  2. Dual knockdown of N-ras and epiregulin synergistically suppressed the growth of human hepatoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Meng; He, Hong-wei; Sun, Huan-xing; Ren, Kai-huan [Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050 (China); Shao, Rong-guang, E-mail: shaor@bbn.cn [Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050 (China)

    2009-09-18

    Hepatocellular carcinoma (HCC) is a major challenge because of its resistance to conventional cytotoxic chemotherapy and radiotherapy. Multi-targeted therapy might be a new option for HCC treatment. Our previous study showed that N-ras gene was activated in HCC and was inhibited by RNA interference. In the present study, we investigated the alternation of gene expression by microarray in N-Ras-siRNA-treated HepG2 cells. The results revealed that the EREG gene, encoding epiregulin, was dramatically up-regulated in response to silence of N-ras. We speculated that the up-regulation of epiregulin was involved in the compensatory mechanism of N-ras knockdown for cell growth. Therefore, we evaluated whether dual silence of N-ras and epiregulin display a greater suppression of cell growth. The results confirmed that dual knockdown of N-ras and epiregulin synergistically inhibited cell growth. Our results also showed that dual knockdown of N-ras and epiregulin significantly induced cell arrest at G0/G1 phase. Furthermore, Western blot assay showed that dual knockdown of N-ras and epiregulin markedly reduced the phosphorylations of ERK1/2, Akt and Rb, and inhibited the expression of cyclin D1. Our findings imply that multi-targeted silence of oncogenes might be an effective treatment for HCC.

  3. TET1 knockdown inhibits the odontogenic differentiation potential of human dental pulp cells.

    Science.gov (United States)

    Rao, Li-Jia; Yi, Bai-Cheng; Li, Qi-Meng; Xu, Qiong

    2016-06-30

    Human dental pulp cells (hDPCs) possess the capacity to differentiate into odontoblast-like cells and generate reparative dentin in response to exogenous stimuli or injury. Ten-eleven translocation 1 (TET1) is a novel DNA methyldioxygenase that plays an important role in the promotion of DNA demethylation and transcriptional regulation in several cell lines. However, the role of TET1 in the biological functions of hDPCs is unknown. To investigate the effect of TET1 on the proliferation and odontogenic differentiation potential of hDPCs, a recombinant shRNA lentiviral vector was used to knock down TET1 expression in hDPCs. Following TET1 knockdown, TET1 was significantly downregulated at both the mRNA and protein levels. Proliferation of the hDPCs was suppressed in the TET1 knockdown groups. Alkaline phosphatase activity, the formation of mineralized nodules, and the expression levels of DSPP and DMP1 were all reduced in the TET1-knockdown hDPCs undergoing odontogenic differentiation. Based on these results, we concluded that TET1 knockdown can prevent the proliferation and odontogenic differentiation of hDPCs, which suggests that TET1 may play an important role in dental pulp repair and regeneration.

  4. Peccei-Quinn invariant singlet extended SUSY with anomalous U(1) gauge symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Im, Sang Hui; Seo, Min-Seok [Center for Theoretical Physics of the Universe, Institute for Basic Science (IBS),Daejeon 305-811 (Korea, Republic of)

    2015-05-13

    Recent discovery of the SM-like Higgs boson with m{sub h}≃125 GeV motivates an extension of the minimal supersymmetric standard model (MSSM), which involves a singlet Higgs superfield with a sizable Yukawa coupling to the doublet Higgs superfields. We examine such singlet-extended SUSY models with a Peccei-Quinn (PQ) symmetry that originates from an anomalous U(1){sub A} gauge symmetry. We focus on the specific scheme that the PQ symmetry is spontaneously broken at an intermediate scale v{sub PQ}∼√(m{sub SUSY}M{sub Pl}) by an interplay between Planck scale suppressed operators and tachyonic soft scalar mass m{sub SUSY}∼√(D{sub A}) induced dominantly by the U(1){sub A}D-term D{sub A}. This scheme also results in spontaneous SUSY breaking in the PQ sector, generating the gaugino masses M{sub 1/2}∼√(D{sub A}) when it is transmitted to the MSSM sector by the conventional gauge mediation mechanism. As a result, the MSSM soft parameters in this scheme are induced mostly by the U(1){sub A}D-term and the gauge mediated SUSY breaking from the PQ sector, so that the sparticle masses can be near the present experimental bounds without causing the SUSY flavor problem. The scheme is severely constrained by the condition that a phenomenologically viable form of the low energy operators of the singlet and doublet Higgs superfields is generated by the PQ breaking sector in a way similar to the Kim-Nilles solution of the μ problem, and the resulting Higgs mass parameters allow the electroweak symmetry breaking with small tan β. We find two minimal models with two singlet Higgs superfields, satisfying this condition with a relatively simple form of the PQ breaking sector, and briefly discuss some phenomenological aspects of the model.

  5. Superheavy contributions to FCNC in the flipped SU(5) x U(1)

    Energy Technology Data Exchange (ETDEWEB)

    Gabbiani, F.; Masiero, A.

    1988-08-04

    In the supersymmetric GUT's the presence of the superheavy fields yields new contributions to flavour-changing neutral-current effects at low energy. We analyse this phenomenon in the context of the flipped SU(5) x U(1) superstring (-inspired) model. We show that possibly sizeable flavour leptonic changes (..mu.. -> e..gamma.., ..mu.. -> eeanti e, ..mu..-e conversion in nuclei) are generated. K-anti K, B-anti B mixings and b -> s..gamma.. constrain new couplings at the superlarge scale, which are unrelated to the standard Yukawa coefficients.

  6. Constraints from proton decay in the flipped SU(5)xU(1) superstring model

    Energy Technology Data Exchange (ETDEWEB)

    Leontaris, G.K.; Tamvakis, K. (Ioannina Univ. (Greece). Theoretical Physics Div.)

    1991-05-16

    We discuss the constraints the emerge from the existence of dimension-5 baryon-violating operators in the flipped SU(5) x U(1) superstring model. These are constraints on matter field assignments and on singlet VEV values. Although baryon-violating dimension-5 operators that appear as quintic non-renormalizable terms vanish as has been proven before and as we verify here, effective dimension-5 operators resulting from Higgs exchange put non-trivial but feasible constraints on the model. Constraints are also extracted from the presence of higher order non-renormalizable terms that generate such operators which do not a priori vanish. (orig.).

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

    Energy Technology Data Exchange (ETDEWEB)

    Bu, Yanyan [Department of Physics, Ben-Gurion University of the Negev, Beer-Sheva 84105 (Israel); Lublinsky, Michael [Department of Physics, Ben-Gurion University of the Negev, Beer-Sheva 84105 (Israel); Physics Department, University of Connecticut, 2152 Hillside Road, Storrs, CT 06269-3046 (United States); Sharon, Amir [Department of Physics, Ben-Gurion University of the Negev, Beer-Sheva 84105 (Israel)

    2016-04-21

    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.

  8. Study on renormalization transformation for U(1) gauge theory in the neighbourhood of gaussian fixed point

    International Nuclear Information System (INIS)

    Neves, A.G.M.

    1988-01-01

    The renormalization transformation e sup(-S 1) sup((B)) const. ζ e sup(-S o (A) - V(A)) δ (B-C sub(1) A) δ sub(Ax) (A)DA for the U(1) lattice gauge theory, where S sub(o) (A) is the gaussian fixed point of the transformation, V(A) is a gauge invariant perturbation, C sub(1) is the averaging operator and δ sub(Ax) (A) fixes the local axial gauge is studied via an equivalent renormalization transformation on the 2-forms F = dA. The transformation is linearized in the neighborhood of the fixed point and then diagonalized. (author)

  9. Constructive tensorial group field theory I: The {U(1)} -{T^4_3} model

    Science.gov (United States)

    Lahoche, Vincent

    2018-05-01

    The loop vertex expansion (LVE) is a constructive technique using canonical combinatorial tools. It works well for quantum field theories without renormalization, which is the case of the field theory studied in this paper. Tensorial group field theories (TGFTs) are a new class of field theories proposed to quantize gravity. This paper is devoted to a very simple TGFT for rank three tensors with U(1) group and quartic interactions, hence nicknamed -. It has no ultraviolet divergence, and we show, with the LVE, that it is Borel summable in its coupling constant.

  10. U(1)R mediation from the flux compactification in six dimensions

    International Nuclear Information System (INIS)

    Lee, Hyun Min

    2008-01-01

    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) R mediation can be a dominant source of SUSY breaking for a brane scalar with nonzero R charge.

  11. Bistate t-expansion study of U(1) lattice gauge theory in 2+1 dimensions

    International Nuclear Information System (INIS)

    Morningstar, C.J.

    1992-01-01

    The compact formulation of U(1) Hamiltonian lattice gauge theory in 2+1 dimensions is studied using the t expansion. The ground-state energy, average plaquette, specific heat, photon mass gap, and the ratio of the two lowest masses are investigated. Two contraction techniques are applied: a unistate scheme which uses only the strong-coupling vacuum for the trial state, and a bistate scheme which allows the introduction of variational parameters and arbitrarily large loops of electric flux in one of the trial states. The mass ratio obtained from the bistate contraction scheme exhibits precocious scaling. No evidence of a stable scalar glueball is found

  12. Hairy black hole solutions in U(1) gauge-invariant scalar-vector-tensor theories

    Science.gov (United States)

    Heisenberg, Lavinia; Tsujikawa, Shinji

    2018-05-01

    In U (1) gauge-invariant scalar-vector-tensor theories with second-order equations of motion, we study the properties of black holes (BH) on a static and spherically symmetric background. In shift-symmetric theories invariant under the shift of scalar ϕ → ϕ + c, we show the existence of new hairy BH solutions where a cubic-order scalar-vector interaction gives rise to a scalar hair manifesting itself around the event horizon. In the presence of a quartic-order interaction besides the cubic coupling, there are also regular BH solutions endowed with scalar and vector hairs.

  13. Flux tubes in U(1) - Do they attract or repel each other?

    International Nuclear Information System (INIS)

    Zach, M.; Faber, M.; Skala, P.

    1998-01-01

    The dually transformed path integral of four-dimensional U(1) lattice gauge theory is used for a numerical investigation of multiply charged systems and the interaction between flux tubes. For this aim, it is convenient to implement periodically closed flux tubes (torelons) in the dual formulation. We calculate the free energy as well as the total electro-magnetic energy of doubly charged flux tubes as a function of the coupling β. The main results are that the string tension scales proportionally to the charge (contrary to the Coulomb potential) and in the range 0.9<β<1.0 we find a clear signal for attraction between flux tubes. (orig.)

  14. A radiative neutrino mass model in light of DAMPE excess with hidden gauged U(1) symmetry

    Science.gov (United States)

    Nomura, Takaaki; Okada, Hiroshi; Wu, Peiwen

    2018-05-01

    We propose a one-loop induced neutrino mass model with hidden U(1) gauge symmetry, in which we successfully involve a bosonic dark matter (DM) candidate propagating inside a loop diagram in neutrino mass generation to explain the e+e‑ excess recently reported by the DArk Matter Particle Explorer (DAMPE) experiment. In our scenario dark matter annihilates into four leptons through Z' boson as DM DM → Z' Z' (Z' → l+ l‑) and Z' decays into leptons via one-loop effect. We then investigate branching ratios of Z' taking into account lepton flavor violations and neutrino oscillation data.

  15. Loop calculations for the non-commutative U*(1) gauge field model with oscillator term

    International Nuclear Information System (INIS)

    Blaschke, Daniel N.; Grosse, Harald; Kronberger, Erwin; Schweda, Manfred; Wohlgenannt, Michael

    2010-01-01

    Motivated by the success of the non-commutative scalar Grosse-Wulkenhaar model, a non-commutative U * (1) gauge field theory including an oscillator-like term in the action has been put forward in (Blaschke et al. in Europhys. Lett. 79:61002, 2007). The aim of the current work is to analyze whether that action can lead to a fully renormalizable gauge model on non-commutative Euclidean space. In a first step, explicit one-loop graph computations are hence presented, and their results as well as necessary modifications of the action are successively discussed. (orig.)

  16. Loop suppressed light fermion masses with U (1 )R gauge symmetry

    Science.gov (United States)

    Nomura, Takaaki; Okada, Hiroshi

    2017-07-01

    We propose a model with a two-Higgs doublet, where quark and charged-lepton masses in the first and second families are induced at one-loop level, and neutrino masses are induced at the two-loop level. In our model, we introduce an extra U (1 )R gauge symmetry that plays a crucial role in achieving desired terms in no conflict with anomaly cancellation. We show the mechanism to generate fermion masses, the resultant mass matrices, and Yukawa interactions in mass eigenstates, and we discuss several interesting phenomenologies such as the muon anomalous magnetic dipole moment and the dark matter candidate that arise from this model.

  17. Hidden U (1 ) gauge symmetry realizing a neutrinophilic two-Higgs-doublet model with dark matter

    Science.gov (United States)

    Nomura, Takaaki; Okada, Hiroshi

    2018-04-01

    We propose a neutrinophilic two-Higgs-doublet model with hidden local U (1 ) symmetry, where active neutrinos are Dirac type, and a fermionic dark matter (DM) candidate is naturally induced as a result of remnant symmetry even after the spontaneous symmetry breaking. In addition, a physical Goldstone boson arises as a consequence of two types of gauge singlet bosons and contributes to the DM phenomenologies as well as an additional neutral gauge boson. Then, we analyze the relic density of DM within the safe range of direct detection searches and show the allowed region of dark matter mass.

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

    International Nuclear Information System (INIS)

    Bu, Yanyan; Lublinsky, Michael; Sharon, Amir

    2016-01-01

    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.

  19. Generalized permutation symmetry and the flavour problem in SU(2)sub(L)xU(1)

    International Nuclear Information System (INIS)

    Ecker, G.

    1984-01-01

    A generalized permutation group is introduced as a possible horizontal symmetry for SU(2)sub(L)xU(1) gauge theories. It leads to the unique two generation quark mass matrices with a correct prediction for the Cabibbo angle. For three generations the model exhibits spontaneous CP violation, correlates the Kobayashi-Maskawa mixing parameters s 1 and s 3 and predicts an upper bound for the running top quark mass of approximately 45 GeV. The hierarchy of generations is due to a hierarchy of vacuum expectation values rather than of Yukawa coupling constants. (orig.)

  20. Knockdown of HSPA9 induces TP53-dependent apoptosis in human hematopoietic progenitor cells.

    Directory of Open Access Journals (Sweden)

    Tuoen Liu

    Full Text Available Myelodysplastic syndromes (MDS are the most common adult myeloid blood cancers in the US. Patients have increased apoptosis in their bone marrow cells leading to low peripheral blood counts. The full complement of gene mutations that contribute to increased apoptosis in MDS remains unknown. Up to 25% of MDS patients harbor and acquired interstitial deletion on the long arm of chromosome 5 [del(5q], creating haploinsufficiency for a large set of genes including HSPA9. Knockdown of HSPA9 in primary human CD34+ hematopoietic progenitor cells significantly inhibits growth and increases apoptosis. We show here that HSPA9 knockdown is associated with increased TP53 expression and activity, resulting in increased expression of target genes BAX and p21. HSPA9 protein interacts with TP53 in CD34+ cells and knockdown of HSPA9 increases nuclear TP53 levels, providing a possible mechanism for regulation of TP53 by HSPA9 haploinsufficiency in hematopoietic cells. Concurrent knockdown of TP53 and HSPA9 rescued the increased apoptosis observed in CD34+ cells following knockdown of HSPA9. Reduction of HSPA9 below 50% results in severe inhibition of cell growth, suggesting that del(5q cells may be preferentially sensitive to further reductions of HSPA9 below 50%, thus providing a genetic vulnerability to del(5q cells. Treatment of bone marrow cells with MKT-077, an HSPA9 inhibitor, induced apoptosis in a higher percentage of cells from MDS patients with del(5q compared to non-del(5q MDS patients and normal donor cells. Collectively, these findings indicate that reduced levels of HSPA9 may contribute to TP53 activation and increased apoptosis observed in del(5q-associated MDS.

  1. Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

    Directory of Open Access Journals (Sweden)

    Pham Phuc V

    2011-12-01

    Full Text Available Abstract Background Breast cancer stem cells (BCSCs are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs. Methods We isolated a breast cancer cell population (CD44+CD24- cells from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Results Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Conclusions Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.

  2. Knockdown of Heparanase Suppresses Invasion of Human Trophoblasts by Activating p38 MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Guanglu Che

    2018-01-01

    Full Text Available Preeclampsia is a pregnancy-related disease with increasing maternal and perinatal morbidity and mortality worldwide. Defective trophoblast invasion is considered to be a major factor in the pathophysiological mechanism of preeclampsia. Heparanase, the only endo-β-glucuronidase in mammalian cells, has been shown to be abnormally expressed in the placenta of preeclampsia patients in our previous study. The biological role and potential mechanism of heparanase in trophoblasts remain unclear. In the present study, stably transfected HTR8/SVneo cell lines with heparanase overexpression or knockdown were constructed. The effect of heparanase on cellular proliferation, apoptosis, invasion, tube formation, and potential pathways in trophoblasts was explored. Our results showed that overexpression of heparanase promoted proliferation and invasion. Knockdown of heparanase suppressed proliferation, invasion, and tube formation but induced apoptosis. These findings reveal that downregulation of heparanase may contribute to defective placentation and plays a crucial role in the pathogenesis of preeclampsia. Furthermore, increased activation of p38 MAPK in heparanase-knockdown HTR8/SVneo cell was shown by MAPK pathway phosphorylation array and Western blotting assay. After pretreatment with 3 specific p38 MAPK inhibitors (BMS582949, SB203580, or BIRB796, inadequate invasion in heparanase-knockdown HTR8/SVneo cell was rescued. That indicates that knockdown of heparanase decreases HTR8/SVneo cell invasion through excessive activation of the p38 MAPK signaling pathway. Our study suggests that heparanase can be a potential predictive biomarker for preeclampsia at an early stage of pregnancy and represents a promising therapeutic target for the treatment of preeclampsia.

  3. Knockdown of TFIIS by RNA silencing inhibits cancer cell proliferation and induces apoptosis

    International Nuclear Information System (INIS)

    Hubbard, Kyle; Catalano, Jennifer; Puri, Raj K; Gnatt, Averell

    2008-01-01

    A common element among cancer cells is the presence of improperly controlled transcription. In these cells, the degree of specific activation of some genes is abnormal, and altering the aberrant transcription may therefore directly target cancer. TFIIS is a transcription elongation factor, which directly binds the transcription motor, RNA Polymerase II and allows it to read through various transcription arrest sites. We report on RNA interference of TFIIS, a transcription elongation factor, and its affect on proliferation of cancer cells in culture. RNA interference was performed by transfecting siRNA to specifically knock down TFIIS expression in MCF7, MCF10A, PL45 and A549 cells. Levels of TFIIS expression were determined by the Quantigene method, and relative protein levels of TFIIS, c-myc and p53 were determined by C-ELISA. Induction of apoptosis was determined by an enzymatic Caspase 3/7 assay, as well as a non-enzymatic assay detecting cytoplasmic mono- and oligonucleosomes. A gene array analysis was conducted for effects of TFIIS siRNA on MCF7 and MCF10A cell lines. Knockdown of TFIIS reduced cancer cell proliferation in breast, lung and pancreatic cancer cell lines. More specifically, TFIIS knockdown in the MCF7 breast cancer cell line induced cancer cell death and increased c-myc and p53 expression whereas TFIIS knockdown in the non-cancerous breast cell line MCF10A was less affected. Differential effects of TFIIS knockdown in MCF7 and MCF10A cells included the estrogenic, c-myc and p53 pathways, as observed by C-ELISA and gene array, and were likely involved in MCF7 cell-death. Although transcription is a fundamental process, targeting select core transcription factors may provide for a new and potent avenue for cancer therapeutics. In the present study, knockdown of TFIIS inhibited cancer cell proliferation, suggesting that TFIIS could be studied as a potential cancer target within the transcription machinery

  4. SU(2) x U(1) unified theory for charge, orbit and spin currents

    International Nuclear Information System (INIS)

    Jin Peiqing; Li Youquan; Zhang Fuchun

    2006-01-01

    Spin and charge currents in systems with Rashba or Dresselhaus spin-orbit couplings are formulated in a unified version of four-dimensional SU(2) x U(1) gauge theory, with U(1) being the Maxwell field and SU(2) being the Yang-Mills field. While the bare spin current is non-conserved, it is compensated by a contribution from the SU(2) gauge field, which gives rise to a spin torque in the spin transport, consistent with the semi-classical theory of Culcer et al. Orbit current is shown to be non-conserved in the presence of electromagnetic fields. Similar to the Maxwell field inducing forces on charge and charge current, we derive forces acting on spin and spin current induced by the Yang-Mills fields such as the Rashba and Dresselhaus fields and the sheer strain field. The spin density and spin current may be considered as a source generating Yang-Mills field in certain condensed matter systems

  5. The neutralino sector in the U(1)-extended supersymmetric standard model

    Energy Technology Data Exchange (ETDEWEB)

    Choi, S.Y. [Chonbuk National Univ., Jeonju (Korea). Dept. of Physics and RIPC]|[Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Haber, H.E. [California Univ., Santa Cruz, CA (United States). SCIPP; Kalinowski, J. [Warsaw Univ. (Poland). Inst. of Theoretical Physics; Zerwas, P.M. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)]|[California Univ., Santa Cruz, CA (United States). SCIPP

    2006-12-15

    Motivated by grand unified theories and string theories we analyze the general structure of the neutralino sector in the USSM, an extension of the Minimal Supersymmetric Standard Model that involves a broken extra U(1) gauge symmetry. This supersymmetric U(1)-extended model includes an Abelian gauge superfield and a Higgs singlet superfield in addition to the standard gauge and Higgs superfields of the MSSM. The interactions between the MSSM fields and the new fields are in general weak and the mixing is small, so that the coupling of the two subsystems can be treated perturbatively. As a result, the mass spectrum and mixing matrix in the neutralino sector can be analyzed analytically and the structure of this 6-state system is under good theoretical control. We describe the decay modes of the new states and the impact of this extension on decays of the original MSSM neutralinos, including radiative transitions in cross-over zones. Production channels in cascade decays at the LHC and pair production at e{sup +}e{sup -} colliders are also discussed. (orig.)

  6. Resolutions of Cn/Zn orbifolds, their U(1) bundles, and applications to string model building

    International Nuclear Information System (INIS)

    Nibbelink, Stefan Groot; Trapletti, Michele; Walter, Martin G.A.

    2007-01-01

    We describe blowups of C n /Z n orbifolds as complex line bundles over CP n-1 . We construct some gauge bundles on these resolutions. Apart from the standard embedding, we describe U(1) bundles and an SU(n-1) bundle. Both blowups and their gauge bundles are given explicitly. We investigate ten dimensional SO(32) super Yang-Mills theory coupled to supergravity on these backgrounds. The integrated Bianchi identity implies that there are only a finite number of U(1) bundle models. We describe how the orbifold gauge shift vector can be read off from the gauge background. In this way we can assert that in the blow down limit these models correspond to heterotic C 2 /Z 2 and C 3 /Z 3 orbifold models. (Only the Z 3 model with unbroken gauge group SO(32) cannot be reconstructed in blowup without torsion.) This is confirmed by computing the charged chiral spectra on the resolutions. The construction of these blowup models implies that the mismatch between type-I and heterotic models on T 6 /Z 3 does not signal a complication of S-duality, but rather a problem of type-I model building itself: The standard type-I orbifold model building only allows for a single model on this orbifold, while the blowup models give five different models in blow down

  7. 750 GeV resonance in the gauged U(1′-extended MSSM

    Directory of Open Access Journals (Sweden)

    Yun Jiang

    2016-08-01

    Full Text Available 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.

  8. Z-Z' mass hierarchy in a supersymmetric model with a secluded U(1)'-breaking sector

    International Nuclear Information System (INIS)

    Erler, Jens; Langacker, Paul; Li Tianjun

    2002-01-01

    We consider the Z ' /Z mass hierarchy in a supersymmetric model in which the U(1) ' is broken in a secluded sector coupled to the ordinary sector only by gauge and possibly soft terms. A large mass hierarchy can be achieved while maintaining the normal sparticle spectra if there is a direction in which the tree level potential becomes flat when a particular Yukawa coupling vanishes. We describe the conditions needed for the desired breaking pattern, to avoid unwanted global symmetries, and for an acceptable effective μ parameter. The electroweak breaking is dominated by A terms rather than scalar masses, leading to tan β≅1. The spectrum of the symmetry breaking sector is displayed. There is significant mixing between the MSSM particles and new standard model singlets, for both the Higgs scalars and the neutralinos. A larger Yukawa coupling for the effective μ parameter is allowed than in the NMSSM because of the U(1) ' contribution to the running from a high scale. The upper bound on the tree-level mass of the lightest CP even Higgs doublet mass is about cx174 GeV, where c is of order unity, but the actual mass eigenvalues are generally smaller because of singlet mixing

  9. Hidden gauginos of an unbroken U(1): Cosmological constraints and phenomenological prospects

    Energy Technology Data Exchange (ETDEWEB)

    Ibarra, A. [Technische Univ. Muenchen, Garching (Germany). Physik-Department]|[Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Ringwald, A.; Weniger, C. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2008-09-15

    We study supersymmetric scenarios where the dark matter is the gaugino of an unbroken hidden U(1) which interacts with the visible world only via a small kinetic mixing with the hypercharge. Strong constraints on the parameter space can be derived from avoiding overclosure of the Universe and from requiring successful Big Bang Nucleosynthesis and structure formation. We find that for typical values of the mixing parameter, scenarios with neutralino NLSP are excluded, while scenarios with slepton NLSP are allowed when the mixing parameter lies in the range {chi} {proportional_to}O(10{sup -13}-10{sup -10}). We also show that if the gravitino is the LSP and the hidden U(1) gaugino the NLSP, the bounds on the reheating temperature from long lived charged MSSM relics can be considerably relaxed and we comment on the signatures of these scenarios at future colliders. Finally, we discuss the case of an anomalously small mixing, {chi} <<10{sup -16}, where the neutralino becomes a decaying dark matter candidate, and derive constraints from gamma ray experiments. (orig.)

  10. Closing the SU(3)LxU(1)X symmetry at the electroweak scale

    International Nuclear Information System (INIS)

    Dias, Alex G.; Montero, J. C.; Pleitez, V.

    2006-01-01

    We show that some models with SU(3) C xSU(3) L xU(1) X gauge symmetry can be realized at the electroweak scale and that this is a consequence of an approximate global SU(2) L+R symmetry. This symmetry implies a condition among the vacuum expectation value of one of the neutral Higgs scalars, the U(1) X 's coupling constant, g X , the sine of the weak mixing angle sinθ W , and the mass of the W boson, M W . In the limit in which this symmetry is valid it avoids the tree level mixing of the Z boson of the standard model with the extra Z ' boson. We have verified that the oblique T parameter is within the allowed range indicating that the radiative corrections that induce such a mixing at the 1-loop level are small. We also show that a SU(3) L+R custodial symmetry implies that in some of the models we have to include sterile (singlets of the 3-3-1 symmetry) right-handed neutrinos with Majorana masses, since the seesaw mechanism is mandatory to obtain light active neutrinos. Moreover, the approximate SU(2) L+R subset of SU(3) L+R symmetry implies that the extra nonstandard particles of these 3-3-1 models can be considerably lighter than it had been thought before so that new physics can be really just around the corner

  11. Why is Interstellar Object 1I/2017 U1 (`Oumuamua) Rocky, Tumbling and Possibly Very Prolate?

    Science.gov (United States)

    Katz, J. I.

    2018-05-01

    The recently discovered first interstellar object 1I/2017 U1 (`Oumuamua) has brightness that varies by a factor of 10, a range greater than that of any Solar System asteroid, a spectrum characteristic of Type D asteroids, and no evidence of evaporating volatiles, contrary to expectation for exo-Oort clouds. `Oumuamua is possibly the first example of the proposed "Jurads", objects depleted in volatiles and ejected from planetary systems during the post-main sequence evolution of their parent stars. I suggest that heating by the star's giant stage fluidized a precursor object as well as driving off any volatiles, causing it to assume the Jacobi ellipsoidal shape of a self-gravitating incompressible liquid. The collision that produced the inferred tumbling motion may have occurred thousands of years after the formation of 1I/2017 U1 `Oumuamua. Jacobi ellipsoids have a unique relation among rotation rate, density and axial ratio. The inferred axial ratio ⪆ 5 suggests a lower bound on the density of 1.6 g/cm3, apparently excluding an icy interior unless it is almost entirely frozen CO2. `Oumuamua may be related to accreting objects that pollute white dwarf atmospheres and that may make Soft Gamma Repeaters.

  12. Yeast Interacting Proteins Database: YGR013W, YKL012W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available tion U1 snRNP protein involved in splicing, interacts with the branchpoint-binding protein during the formation of the second commitm... PRP40 U1 snRNP protein involved in splicing, interacts with the branchpoint-binding protein during the form...ation of the second commitment complex Rows with this prey as prey (1) Rows with

  13. Knockdown of CDK2AP1 in human embryonic stem cells reduces the threshold of differentiation.

    Directory of Open Access Journals (Sweden)

    Khaled N Alsayegh

    Full Text Available Recent studies have suggested a role for the Cyclin Dependent Kinase-2 Associated Protein 1 (CDK2AP1 in stem cell differentiation and self-renewal. In studies with mouse embryonic stem cells (mESCs derived from generated mice embryos with targeted deletion of the Cdk2ap1 gene, CDK2AP1 was shown to be required for epigenetic silencing of Oct4 during differentiation, with deletion resulting in persistent self-renewal and reduced differentiation potential. Differentiation capacity was restored in these cells following the introduction of a non-phosphorylatible form of the retinoblastoma protein (pRb or exogenous Cdk2ap1. In this study, we investigated the role of CDK2AP1 in human embryonic stem cells (hESCs. Using a shRNA to reduce its expression in hESCs, we found that CDK2AP1 knockdown resulted in a significant reduction in the expression of the pluripotency genes, OCT4 and NANOG. We also found that CDK2AP1 knockdown increased the number of embryoid bodies (EBs formed when differentiation was induced. In addition, the generated EBs had significantly higher expression of markers of all three germ layers, indicating that CDK2AP1 knockdown enhanced differentiation. CDK2AP1 knockdown also resulted in reduced proliferation and reduced the percentage of cells in the S phase and increased cells in the G2/M phase of the cell cycle. Further investigation revealed that a higher level of p53 protein was present in the CDK2AP1 knockdown hESCs. In hESCs in which p53 and CDK2AP1 were simultaneously downregulated, OCT4 and NANOG expression was not affected and percentage of cells in the S phase of the cell cycle was not reduced. Taken together, our results indicate that the knockdown of CDK2AP1 in hESCs results in increased p53 and enhances differentiation and favors it over a self-renewal fate.

  14. U(1) x SU(2) Chern-Simons gauge theory of underdoped cuprate superconductors

    International Nuclear Information System (INIS)

    Marchetti, P.A.; Su Zhao-Bin; Yu Lu

    1998-05-01

    The Chern-Simons bosonization with U(1)xSU(2) gauge field is applied to the 2-D t-J model in the limit t>>J, to study the normal state properties of underdoped cuprate superconductors. We prove the existence of an upper bound on the partition function for holons in a spinon background, and we find the optimal spinon configuration saturating the upper bound on average - a coexisting flux phase and s+id-like RVB state. After neglecting the feedback of holon fluctuations on the U(1) field B and spinon fluctuations on the SU(2) field V, the holon field is a fermion and the spinon field is a hard-core boson. Within this approximation we show that the B field produces a π flux phase for the holons, converting them into Dirac-like fermions, while the V field, taking into account the feedback of holons produces a gap for the spinons vanishing in the zero doping limit. The nonlinear σ-model with a mass term describes the crossover from the short-ranged antiferromagnetic (AF) state in doped samples to long range AF order in reference compounds. Moreover, we derive a low-energy effective action in terms of spinons holons and a self-generated U(1) gauge field. Neglecting the gauge fluctuations, the holons are described by the Fermi liquid theory with a Fermi surface consisting of 4 ''half-pockets'' centered at (+-π/2,+-π/2) and one reproduces the results for the electron spectral function obtained in the mean field approximation, in agreement with the photoemission data on underdoped cuprates. The gauge fluctuations are not confining due to coupling to holons, but nevertheless yield an attractive interaction between spinons and holons leading to a bound state with electron quantum numbers. The renormalisation effects due to gauge fluctuations give rise to non-Fermi liquid behaviour for the composite electron, in certain temperature range showing the linear in T resistivity. This formalism provides a new interpretation of the spin gap in the underdoped superconductors

  15. Lifting scalar-quark and -lepton masses with sideways U(1)-II

    International Nuclear Information System (INIS)

    McCabe, J.F.; Wada, W.W.

    1984-01-01

    We investigate the phenomenological consequences of an SUSY model with a gauged O'Raifeartaigh sector on scalar partner masses. The model has the gauge symmetry SU(5) x U(1). We find that this form of spontaneous SUSY breaking leads to large scalar partner masses through one loop graphs without changing quark and lepton masses from tree values, and without breaking SU(5) symmetries by the scalar partner sector. To calculate the scalar partner masses we extend previous work on supergraph techniques to include cases when SUSY is broken at tree level. We are able to sum exactly the corrections to unbroken propagators with the aid of a supersymmetric version of tree-level Dyson equations. We show how the same ideas can be implemented in an SU(5) gauge model where the normal Higgs give large masses radiatively to the scalar-quarks and -leptons. 7 references

  16. Flavor violations in no-scale flipped SU(5)xU(1)

    Energy Technology Data Exchange (ETDEWEB)

    Faraggi, A.E.; Lopez, J.L.; Nonopoulos, D.V.; Yuan, K.

    1989-05-04

    We study lepton-number violations in the flipped SU(5)xU(1) model in the context of no-scale supergravity. We find that the experimental limits on ..mu..->e..gamma.., ..mu..->eeanti e, and ..mu.. conversion in nuclei generally imply an upper bound on the top quark mass and a lower bound on the gaugino mass. We conclude that the seed of supersymmetry breaking in no-scale models (gaugino masses) radically changes some results obtained in ''minimal'' N=1 supergravity in the leptonic sector, while results in the hadronic sector (e.g. K-anti K, B-anti B mixings, and b->s..gamma..) remain essentially unchanged.

  17. Nano and micro U1-xThxO2 solid solutions: From powders to pellets

    Science.gov (United States)

    Balice, Luca; Bouëxière, Daniel; Cologna, Marco; Cambriani, Andrea; Vigier, Jean-François; De Bona, Emanuele; Sorarù, Gian Domenico; Kübel, Christian; Walter, Olaf; Popa, Karin

    2018-01-01

    Nuclear fuels production, structural materials, separation techniques, and waste management, all may benefit from an extensive knowledge in the nano-nuclear technology. In this line, we present here the production of U1-xThxO2 (x = 0 to 1) mixed oxides nanocrystals (NC's) through the hydrothermal decomposition of the oxalates in hot compressed water at 250 °C. Particles of spherical shape and size of about 5.5-6 nm are obtained during the hydrothermal decomposition process. The powdery nanocrystalline products were consolidated by spark plasma sintering into homogeneous mixed oxides pellets with grain sizes in the 0.4 to 5.5 μm range. Grain growth and mechanical properties were studied as a function of composition and size. No grain size effect was observed on the hardness or elastic modulus.

  18. Renormalization of a tensorial field theory on the homogeneous space SU(2)/U(1)

    Science.gov (United States)

    Lahoche, Vincent; Oriti, Daniele

    2017-01-01

    We study the renormalization of a general field theory on the homogeneous space (SU(2)/ ≤ft. U(1)\\right){{}× d} with tensorial interaction and gauge invariance under the diagonal action of SU(2). We derive the power counting for arbitrary d. For the case d  =  4, we prove perturbative renormalizability to all orders via multi-scale analysis, study both the renormalized and effective perturbation series, and establish the asymptotic freedom of the model. We also outline a general power counting for the homogeneous space {{≤ft(SO(D)/SO(D-1)\\right)}× d} , of direct interest for quantum gravity models in arbitrary dimension, and point out the obstructions to the direct generalization of our results to these cases.

  19. Study of higher order cumulant expansion of U(1) lattice gauge model at finite temperature

    International Nuclear Information System (INIS)

    Zheng Xite; Lei Chunhong; Li Yuliang; Chen Hong

    1993-01-01

    The order parameter, Polyakov line , of the U(1) gauge model on N σ 3 x N τ (N τ = 1) lattice by using the cumulant expansion is calculated to the 5-th order. The emphasis is put on the behaviour of the cumulant expansion in the intermediate coupling region. The necessity of higher order expansion is clarified from the connection between the cumulant expansion and the correlation length. The variational parameter in the n-th order calculation is determined by the requirement that corrections of the n-th order expansion to the zeroth order expansion finish. The agreement with the Monte Carlo simulation is obtained not only in the weak and strong coupling regions, but also in the intermediate coupling region except in the very vicinity of the phase transition point

  20. Horizontal, anomalous U(1) symmetry for the more minimal supersymmetric standard model

    International Nuclear Information System (INIS)

    Nelson, A.E.; Wright, D.

    1997-01-01

    We construct explicit examples with a horizontal, open-quotes anomalousclose quotes U(1) gauge group, which, in a supersymmetric extension of the standard model, reproduce qualitative features of the fermion spectrum and CKM matrix, and suppress FCNC and proton decay rates without the imposition of global symmetries. We review the motivation for such open-quotes moreclose quotes minimal supersymmetric standard models and their predictions for the sparticle spectrum. There is a mass hierarchy in the scalar sector which is the inverse of the fermion mass hierarchy. We show in detail why ΔS=2 FCNCs are greatly suppressed when compared with naive estimates for nondegenerate squarks. copyright 1997 The American Physical Society

  1. Yeast endoribonuclease stimulated by Novikoff Hepatoma small nuclear RNAS U1 and U2

    International Nuclear Information System (INIS)

    Stevens, A.

    1982-01-01

    Using [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) from yeast as a substrate, an endoribonuclease has been detected in enzyme fractions derived from a high salt wash of ribonucleoprotein particles of Saccharomyces cerevisiae. The [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) seems to be a preferred substrate since other polyribonucleotides are hydrolyzed more slowly, if at all. The enzyme is inhibited by ethidium bromide, but fully double-stranded polyribonucleotides are not hydrolyzed. The hydrolysis of [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) is stimulated about 2.5-fold by the addition of small nuclear RNAs U1 and U2 of Novikoff hepatoma cells. Results show that the stimulation involves an interaction of the labeled RNA with the small nuclear RNA

  2. Spitzer DDT observations of the interstellar comet A/2017 U1

    Science.gov (United States)

    Trilling, David; Hora, Joe; Mommert, Michael; Carey, Sean; Lisse, Carey; Werner, Mike; Chesley, Steve; Emery, Josh; Fazio, Giovanni; Fernandez, Yan; Harris, Alan; Marengo, Massimo; Mueller, Migo; Roegge, Alissa; Smith, Howard; Smith, Nathan; Weaver, Hal

    2017-11-01

    We propose to observe the newly discovered interstellar comet A/2017 U1 to measure its diameter and albedo. Little is known about this object, which presumably formed in another planetary system. This is the only opportunity *ever* to determine the albedo of this object, which will help us understand how planetary system formation in other systems compares to what occurred in our Solar System. The proposed observations -- requiring 32.6 hours in late November -- are the last telescopic observations that will ever be made of this object. The return from these proposed observations would be tremendous -- characterizing the first ever known object from beyond our Solar System. Because the object is faint and fading, these observations must be made as soon as possible.

  3. New approach to high energy SU/sub 2L/ /times/ U1 radiative corrections

    International Nuclear Information System (INIS)

    Ward, B.F.L.

    1988-07-01

    We present a new approach to SU/sub 2L/ /times/ U 1 radiative corrections at high energies. Our approach is based on the infrared summation methods of Yennie, Frautschi and Suura, taken together with the Weinberg-'t Hooft renormalization group equation. Specific processes which have been realized via explicit Monte Carlo algorithms are e + e/sup /minus// → f/bar f/' + n(γ), f = μ, /tau/, d, s, u, c, b or t and e + e/sup /minus// → e + e/sup /minus// + n(γ), where n(γ), denotes multiple photo emission on an event-by-event basis. Exemplary Monte Carlo data are presented. 16 refs., 4 figs

  4. The SU(3)xU(1) invariant breaking of gauged N=8 supergravity

    International Nuclear Information System (INIS)

    Nicolai, H.; Warner, N.P.

    1985-01-01

    The SU(3) x U(1) invariant stationary point of N=8 supergravity is described in some detail. This vacuum has N=2 supersymmetry, and it is shown how the fields of N=8 supergravity may be collected into multiplets of SU(3) x Osp(2, 4). A new kind of shortened massive multiplet is described, and the multiplet shortening conditions for this and other multiplets are used to determine, by the use of group theory alone, the masses of many of the fields in the vacuum. The remaining masses are determined by explicit calculation. The critical point realizes Gell-Mann's scheme for relating the spin-1/2 fermions of the theory to the observed quarks and leptons. (orig.)

  5. A yeast endoribonuclease stimulated by Novikoff hepatoma small nuclear RNAs U1 and U2

    International Nuclear Information System (INIS)

    Stevens, A.

    1982-01-01

    Using [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) from yeast as a substrate, an endoribonuclease has been detected in enzyme fractions derived from a high salt wash of ribonucleoprotein particles of Saccharomyces cerevisiae. The [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) seems to be a preferred substrate since other polyribonucleotides are hydrolyzed more slowly, if at all. The enzyme is inhibited by ethidium bromide, but fully double-stranded polyribonucleotides are not hydrolyzed. The hydrolysis of [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) is stimulated about 2.5-fold by the addition of small nuclear RNAs U1 and U2 of Novikoff hepatoma cells. Results show that the stimulation involves an interaction of the labeled RNA with the small nuclear RNA

  6. Two-color quark matter: U(1)A restoration, superfluidity, and quarkyonic phase

    International Nuclear Information System (INIS)

    Brauner, Tomas; Fukushima, Kenji; Hidaka, Yoshimasa

    2009-01-01

    We discuss the phase structure of quantum chromodynamics (QCD) with two colors and two flavors of light quarks. This is motivated by the increasing interest in the QCD phase diagram as follows: (1) The QCD critical point search has been under intensive dispute and its location and existence suffer from uncertainty of effective U(1) A symmetry restoration. (2) A new phase called quarkyonic matter is drawing theoretical and experimental attention but it is not clear whether it can coexist with diquark condensation. We point out that two-color QCD is nontrivial enough to contain essential ingredients for (1) and (2) both, and most importantly, is a system without the sign problem in numerical simulations on the lattice. We adopt the two-flavor Nambu-Jona-Lasinio model extended with the two-color Polyakov loop and make quantitative predictions that can be tested by lattice simulations.

  7. Global analysis of general SU(2) x SU(2) x U(1) models with precision data

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Ken; Yu, Jiang-Hao; Yuan, C.P. [Michigan State Univ., East Lansing, MI (United States). Dept. of Physics and Astronomy; Schmitz, Kai [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Michigan State Univ., East Lansing, MI (United States). Dept. of Physics and Astronomy

    2010-05-15

    We present the results of a global analysis of a class of models with an extended electroweak gauge group of the form SU(2) x SU(2) x U(1), often denoted as G(221) models, which include as examples the left-right, the lepto-phobic, the hadro-phobic, the fermio-phobic, the un-unified, and the non-universal models. Using an effective Lagrangian approach, we compute the shifts to the coeffcients in the electroweak Lagrangian due to the new heavy gauge bosons, and obtain the lower bounds on the masses of the Z' and W' 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. (orig.)

  8. Global analysis of general SU(2) x SU(2) x U(1) models with precision data

    International Nuclear Information System (INIS)

    Hsieh, Ken; Yu, Jiang-Hao; Yuan, C.P.; Schmitz, Kai; Michigan State Univ., East Lansing, MI

    2010-05-01

    We present the results of a global analysis of a class of models with an extended electroweak gauge group of the form SU(2) x SU(2) x U(1), often denoted as G(221) models, which include as examples the left-right, the lepto-phobic, the hadro-phobic, the fermio-phobic, the un-unified, and the non-universal models. Using an effective Lagrangian approach, we compute the shifts to the coeffcients in the electroweak Lagrangian due to the new heavy gauge bosons, and obtain the lower bounds on the masses of the Z' and W' 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. (orig.)

  9. Hanford facility RCRA permit condition II.U.1 report: mapping of underground piping

    Energy Technology Data Exchange (ETDEWEB)

    Hays, C.B.

    1996-09-27

    The purpose of this report is to fulfill Condition Il.U.1. of the Hanford Facility (HF) Resource Conservation and Recovery Act (RCRA) Permit. The HF RCRA Permit, Number WA7890008967, became effective on September 28, 1994 (Ecology 1994). Permit Conditions Il.U. (mapping) and II.V. (marking) of the HF RCRA Permit, Dangerous Waste (OW) Portion, require the mapping and marking of dangerous waste underground pipelines subject to the provisions of the Washington Administrative Code (WAC) Chapter 173-303. Permit Condition Il.U.I. requires the submittal of a report describing the methodology used to generate pipeline maps and to assure their quality. Though not required by the Permit, this report also documents the approach used for the field marking of dangerous waste underground pipelines.

  10. The U(1)-Higgs model: critical behaviour in the confining-Higgs region

    International Nuclear Information System (INIS)

    Alonso, J.L.; Azcoiti, V.; Campos, I.; Ciria, J.C.; Cruz, A.; Iniguez, D.; Lesmes, F.; Piedrafita, C.; Rivero, A.; Tarancon, A.; Badoni, D.; Fernandez, L.A.; Munoz Sudupe, A.; Ruiz-Lorenzo, J.J.; Gonzalez-Arroyo, A.; Martinez, P.; Pech, J.; Tellez, P.

    1993-01-01

    We study numerically the critical properties of the U(1)-Higgs lattice model, with fixed Higgs modulus, in the region of small gauge coupling where the Higgs and confining phases merge. We find evidence for a first-order transition line that ends in a second-order point. By means of a rotation in parameter space we introduce thermodynamic magnitudes and critical exponents in close resemblance with simple models that show analogous critical behaviour. The measured data allow us to fit the critical exponents finding values in agreement with the mean-field prediction. The location of the critical point and the slope of the first-order line are accurately measured. (orig.)

  11. The factorized F-matrices for arbitrary U(1)(N-1) integrable vertex models

    International Nuclear Information System (INIS)

    Martins, M.J.; Pimenta, R.A.; Zuparic, M.

    2012-01-01

    We discuss the F-matrices associated to the R-matrix of a general N-state vertex model whose statistical configurations encode N-1U(1) symmetries. The factorization condition is shown for arbitrary weights being based only on the unitarity property and the Yang-Baxter relation satisfied by the R-matrix. Focusing on the N=3 case we are able to conjecture the structure of some relevant twisted monodromy matrix elements for general weights. We apply this result providing the algebraic expressions of the domain wall partition functions built up in terms of the creation and annihilation monodromy fields. For N=3 we also exhibit a R-matrix whose weights lie on a del Pezzo surface and have a rather general structure.

  12. Paramagnetic properties of the (U1-xTbx)Co2Ge2 solid solutions

    International Nuclear Information System (INIS)

    Kuznietz, Moshe; Pinto, Haim; Ettedgui, Hanania

    1995-01-01

    Polycrystalline (U 1-x Tb x )Co 2 Ge 2 solid solutions have the ThCr 2 Si 2 -type crystal structure and order antiferromagnetically. AC-susceptibility at 80-295 K yields paramagnetic Curie temperatures θ=-350±50, -15±5, -50±15, -12±5, and -80±5 K, and effective magnetic moments μ eff =4.5, 5.9, 7.3, 8.5, and 12.0 (±0.5)μ B , for samples with x=0, 0.25, 0.50, 0.75 and 1, respectively. The high μ eff values are related to occurrence of paramagnetic moments on U, Tb and Co, of which only U and Tb moments order magnetically. ((orig.))

  13. b → s transitions in family-dependent U(1)(prime) models

    International Nuclear Information System (INIS)

    Barger, V.; Everett, L.; Jiang, J.; Langacker, P.; Liu, T.; Wagner, C.E.M.

    2009-01-01

    We analyze flavor-changing-neutral-current (FCNC) effects in the b → 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 ΔB = 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 s -(bar B) mixing and the time-dependent CP asymmetries of the penguin-dominated B d → (π,φ, η(prime), ρ,ω,f0)K 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. Interstellar Interloper 1I/2017 U1: Observations from the NOT and WIYN Telescopes

    Science.gov (United States)

    Jewitt, David; Luu, Jane; Rajagopal, Jayadev; Kotulla, Ralf; Ridgway, Susan; Liu, Wilson; Augusteijn, Thomas

    2017-12-01

    We present observations of the interstellar interloper 1I/2017 U1 (’Oumuamua) taken during its 2017 October flyby of Earth. The optical colors B - V = 0.70 ± 0.06, V - R = 0.45 ± 0.05, overlap those of the D-type Jovian Trojan asteroids and are incompatible with the ultrared objects that are abundant in the Kuiper Belt. With a mean absolute magnitude H V = 22.95 and assuming a geometric albedo p V = 0.1, we find an average radius of 55 m. No coma is apparent; we deduce a limit to the dust mass production rate of only ˜2 × 10-4 kg s-1, ruling out the existence of exposed ice covering more than a few m2 of the surface. Volatiles in this body, if they exist, must lie beneath an involatile surface mantle ≳0.5 m thick, perhaps a product of prolonged cosmic-ray processing in the interstellar medium. The light curve range is unusually large at ˜2.0 ± 0.2 mag. Interpreted as a rotational light curve the body has axis ratio ≥ {6.3}-1.1+1.3:1 and semi-axes ˜230 m × 35 m. A ≳6:1 axis ratio is extreme relative to most small solar system asteroids and suggests that albedo variations may additionally contribute to the variability. The light curve is consistent with a two-peaked period ˜8.26 hr, but the period is non-unique as a result of aliasing in the data. Except for its unusually elongated shape, 1I/2017 U1 is a physically unremarkable, sub-kilometer, slightly red, rotating object from another planetary system. The steady-state population of similar, ˜100 m scale interstellar objects inside the orbit of Neptune is ˜104, each with a residence time of ˜10 years.

  15. 'L=R' -- $U(1)_R$ Lepton Number at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Frugiuele, Claudia [Fermilab; Gregoire, Thomas [Ottawa Carleton Inst. Phys.; Kumar, Piyush [Yale U.; Ponton, Eduardo [ISCAP, New York

    2013-05-03

    We perform a detailed study of a variety of LHC signals in supersymmetric models where lepton number is promoted to an (approximate) U(1)( )R( ) symmetry. Such a symmetry has interesting implications for naturalness, as well as flavor- and CP-violation, among others. Interestingly, it makes large sneutrino vacuum expectation values phenomenologically viable, so that a slepton doublet can play the role of the down-type Higgs. As a result, (some of) the leptons and neutrinos are incorporated into the chargino and neutralino sectors. This leads to characteristic decay patterns that can be experimentally tested at the LHC. The corresponding collider phenomenology is largely determined by the new approximately conserved quantum number, which is itself closely tied to the presence of “leptonic R-parity violation”. We find rather loose bounds on the first and second generation squarks, arising from a combination of suppressed production rates together with relatively small signal efficiencies of the current searches. Naturalness would indicate that such a framework should be discovered in the near future, perhaps through spectacular signals exhibiting the lepto-quark nature of the third generation squarks. The presence of fully visible decays, in addition to decay chains involving large missing energy (in the form of neutrinos) could give handles to access the details of the spectrum of new particles, if excesses over SM background were to be observed. The scale of neutrino masses is intimately tied to the source of U(1)( )R( ) breaking, thus opening a window into the R-breaking sector through neutrino physics. Further theoretical aspects of the model have been presented in the companion paper [1].

  16. Knockdown of the placental growth factor gene inhibits laser induced choroidal neovascularization in a murine model.

    Science.gov (United States)

    Nourinia, Ramin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Akrami, Hassan; Rezaei Kanavi, Mozhgan; Samiei, Shahram

    2013-01-01

    To evaluate the effect of placental growth factor (PlGF) gene knockdown in a murine model of laser-induced choroidal neovascularization. Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl) corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

  17. Knockdown of the Placental Growth Factor Gene Inhibits Laser Induced Choroidal Neovascularization in a Murine Model

    Directory of Open Access Journals (Sweden)

    Ramin Nourinia

    2013-01-01

    Full Text Available Purpose: To evaluate the effect of placental growth factor (PlGF gene knockdown in a murine model of laser-induced choroidal neovascularization. Methods: Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. Results: No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Conclusion: Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

  18. A realisation of q-deformed of U(1)-Kac Moody and Virasoro algebras through the a-bar∞ algebra

    International Nuclear Information System (INIS)

    El Hassouni, A.; Zakkari, M.

    1995-11-01

    A representation of one parameter deformation of U(1)-Kac Moody and Virasoro algebras is obtained through the infinite matrix algebra a-bar ∞ . Their central extensions are also investigated. (author). 19 refs

  19. Goat activin receptor type IIB knockdown by muscle specific promoter driven artificial microRNAs.

    Science.gov (United States)

    Patel, Amrutlal K; Shah, Ravi K; Patel, Utsav A; Tripathi, Ajai K; Joshi, Chaitanya G

    2014-10-10

    Activin receptor type IIB (ACVR2B) is a transmembrane receptor which mediates signaling of TGF beta superfamily ligands known to function in regulation of muscle mass, embryonic development and reproduction. ACVR2B antagonism has shown to enhance the muscle growth in several disease and transgenic models. Here, we show ACVR2B knockdown by RNA interference using muscle creatine kinase (MCK) promoter driven artificial microRNAs (amiRNAs). Among the various promoter elements tested, the ∼1.26 kb MCK promoter region showed maximum transcriptional activity in goat myoblasts cells. We observed up to 20% silencing in non-myogenic 293T cells and up to 32% silencing in myogenic goat myoblasts by MCK directed amiRNAs by transient transfection. Goat myoblasts stably integrated with MCK directed amiRNAs showed merely 8% silencing in proliferating myoblasts which was increased to 34% upon induction of differentiation at transcript level whereas up to 57% silencing at protein level. Knockdown of ACVR2B by 5'-UTR derived amiRNAs resulted in decreased SMAD2/3 signaling, increased expression of myogenic regulatory factors (MRFs) and enhanced proliferation and differentiation of myoblasts. Unexpectedly, knockdown of ACVR2B by 3'-UTR derived amiRNAs resulted in increased SMAD2/3 signaling, reduced expression of MRFs and suppression of myogenesis. Our study offers muscle specific knockdown of ACVR2B as a potential strategy to enhance muscle mass in the farm animal species. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Stable knockdown of Kif5b in MDCK cells leads to epithelial–mesenchymal transition

    International Nuclear Information System (INIS)

    Cui, Ju; Jin, Guoxiang; Yu, Bin; Wang, Zai; Lin, Raozhou; Huang, Jian-Dong

    2015-01-01

    Polarization of epithelial cells requires vectorial sorting and transport of polarity proteins to apical or basolateral domains. Kif5b is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). To investigate the function of Kif5b in epithelial cells, we examined the phenotypes of Kif5b-deficient MDCK cells. Stable knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate, profound changes in cell morphology, loss of epithelial cell marker, and gain of mesenchymal marker, as well as increased cell migration, invasion, and tumorigenesis abilities. E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells, and their expression levels were decreased in Kif5b-deficient MDCK cells. Overexpression of E-cadherin and NMMIIA in Kif5b depleted MDCK cells could decrease mesenchymal marker expression and cell migration ability. These results indicate that stable knockdown of Kif5b in MDCK cells can lead to epithelial–mesenchymal transition, which is mediated by defective E-cadherin and NMMIIA expression. - Highlights: • Knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate. • Kif5b deficient MDCK cells underwent epithelial–mesenchymal transition. • E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells. • Decreased E-cadherin and NMMIIA levels mediate EMT in Kif5b deficient MDCK cells. • Overexpression of E-cadherin and NMMIIA reverse the effects of Kif5b knockdown

  1. RNAi-mediated double gene knockdown and gustatory perception measurement in honey bees (Apis mellifera).

    Science.gov (United States)

    Wang, Ying; Baker, Nicholas; Amdam, Gro V

    2013-07-25

    This video demonstrates novel techniques of RNA interference (RNAi) which downregulate two genes simultaneously in honey bees using double-stranded RNA (dsRNA) injections. It also presents a protocol of proboscis extension response (PER) assay for measuring gustatory perception. RNAi-mediated gene knockdown is an effective technique downregulating target gene expression. This technique is usually used for single gene manipulation, but it has limitations to detect interactions and joint effects between genes. In the first part of this video, we present two strategies to simultaneously knock down two genes (called double gene knockdown). We show both strategies are able to effectively suppress two genes, vitellogenin (vg) and ultraspiracle (usp), which are in a regulatory feedback loop. This double gene knockdown approach can be used to dissect interrelationships between genes and can be readily applied in different insect species. The second part of this video is a demonstration of proboscis extension response (PER) assay in honey bees after the treatment of double gene knockdown. The PER assay is a standard test for measuring gustatory perception in honey bees, which is a key predictor for how fast a honey bee's behavioral maturation is. Greater gustatory perception of nest bees indicates increased behavioral development which is often associated with an earlier age at onset of foraging and foraging specialization in pollen. In addition, PER assay can be applied to identify metabolic states of satiation or hunger in honey bees. Finally, PER assay combined with pairing different odor stimuli for conditioning the bees is also widely used for learning and memory studies in honey bees.

  2. Stable knockdown of Kif5b in MDCK cells leads to epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ju, E-mail: juzi.cui@gmail.com [The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing (China); Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Jin, Guoxiang; Yu, Bin [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Wang, Zai [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing (China); Lin, Raozhou [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen (China)

    2015-07-17

    Polarization of epithelial cells requires vectorial sorting and transport of polarity proteins to apical or basolateral domains. Kif5b is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). To investigate the function of Kif5b in epithelial cells, we examined the phenotypes of Kif5b-deficient MDCK cells. Stable knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate, profound changes in cell morphology, loss of epithelial cell marker, and gain of mesenchymal marker, as well as increased cell migration, invasion, and tumorigenesis abilities. E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells, and their expression levels were decreased in Kif5b-deficient MDCK cells. Overexpression of E-cadherin and NMMIIA in Kif5b depleted MDCK cells could decrease mesenchymal marker expression and cell migration ability. These results indicate that stable knockdown of Kif5b in MDCK cells can lead to epithelial–mesenchymal transition, which is mediated by defective E-cadherin and NMMIIA expression. - Highlights: • Knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate. • Kif5b deficient MDCK cells underwent epithelial–mesenchymal transition. • E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells. • Decreased E-cadherin and NMMIIA levels mediate EMT in Kif5b deficient MDCK cells. • Overexpression of E-cadherin and NMMIIA reverse the effects of Kif5b knockdown.

  3. Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis.

    Science.gov (United States)

    Wang, Xiaoyu; Zhang, Yiting; Lin, Haiyingjie; Liu, Yan; Tan, Yi; Lin, Jie; Gao, Fenze; Lin, Shaoqiang

    2017-01-22

    Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin. We found that the expression of ST3Gal3 has reverse correlation with the dosage of cisplatin used in both SKOV3 and HO8910PM cells, and high dose of cisplatin could down-regulate ST3Gal3 expression. We then examined the functional effects of ST3Gal3 knockdown in cancer cell lines using FACS analysis. The number of apoptotic cells was much higher in cells if ST3Gal3 expression was knocked down by siRNA and/or by treating cells with higher dosage of cisplatin in comparison to control cells. Interestingly, in HO8910PM cells with ST3Gal3 knockdown, the levels of caspase 8 and caspase 3 proteins increased, which was more obvious in cells treated with both ST3Gal3 knockdown and cisplatin, suggesting that ST3Gal3 knockdown synergistically enhanced cisplatin-induced apoptosis in ovarian cancer cells. Taken together, these results uncover an alternative mechanism of cisplatin-resistance through ST3Gal3 and open a window for effective prevention of chemoresistance and relapse of ovarian cancer by targeting ST3Gal3. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Short Hairpin RNA (shRNA): Design, Delivery, and Assessment of Gene Knockdown

    Science.gov (United States)

    Moore, Chris B.; Guthrie, Elizabeth H.; Huang, Max Tze-Han; Taxman, Debra J.

    2013-01-01

    Shortly after the cellular mechanism of RNA interference (RNAi) was first described, scientists began using this powerful technique to study gene function. This included designing better methods for the successful delivery of small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) into mammalian cells. While the simplest method for RNAi is the cytosolic delivery of siRNA oligonucleotides, this technique is limited to cells capable of transfection and is primarily utilized during transient in vitro studies. The introduction of shRNA into mammalian cells through infection with viral vectors allows for stable integration of shRNA and long-term knockdown of the targeted gene; however, several challenges exist with the implementation of this technology. Here we describe some well-tested protocols which should increase the chances of successful design, delivery, and assessment of gene knockdown by shRNA. We provide suggestions for designing shRNA targets and controls, a protocol for sequencing through the secondary structure of the shRNA hairpin structure, and protocols for packaging and delivery of shRNA lentiviral particles. Using real-time PCR and functional assays we demonstrate the successful knockdown of ASC, an inflammatory adaptor molecule. These studies demonstrate the practicality of including two shRNAs with different efficacies of knockdown to provide an additional level of control and to verify dose dependency of functional effects. Along with the methods described here, as new techniques and algorithms are designed in the future, shRNA is likely to include further promising application and continue to be a critical component of gene discovery. PMID:20387148

  5. CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells.

    Science.gov (United States)

    Xiong, Lijuan; Ding, Li; Ning, Haoyong; Wu, Chenglin; Fu, Kaifei; Wang, Yuxiao; Zhang, Yan; Liu, Yan; Zhou, Lijun

    2016-09-06

    Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types of cancer cells. Whether CD147 alters the effect of trastuzumab on HER2-positive breast cancer cells has not been previously reported. Our study confirmed that CD147 suppression enhances the effects of trastuzumab both in vitro and in vivo. CD147 suppression increased the inhibitory rate of trastuzumab and cell apoptosis in SKBR3, BT474, HCC1954 and MDA-MB453 cells compared with the controls. Furthermore, CD147 knockdown increased expression of cleaved Caspase-3/9 and poly (ADP-ribose) polymerase (PARP) and decreased both mitogen-activated protein kinase (MAPK) and Akt phosphorylation in the four cell lines. In an HCC1954 xenograft model, trastuzumab achieved greater suppression of tumor growth in the CD147-knockdown group than in the shRNA negative control (NC) group. These data indicated that enhancement of the effect of trastuzumab on HER2-positive cells following CD147 knockdown might be attributed to increased apoptosis and decreased phosphorylation of signaling proteins. CD147 may be a key protein for enhancing the clinical efficacy of trastuzumab.

  6. In Vivo Testing of MicroRNA-Mediated Gene Knockdown in Zebrafish

    Directory of Open Access Journals (Sweden)

    Ivone Un San Leong

    2012-01-01

    Full Text Available The zebrafish (Danio rerio has become an attractive model for human disease modeling as there are a large number of orthologous genes that encode similar proteins to those found in humans. The number of tools available to manipulate the zebrafish genome is limited and many currently used techniques are only effective during early development (such as morpholino-based antisense technology or it is phenotypically driven and does not offer targeted gene knockdown (such as chemical mutagenesis. The use of RNA interference has been met with controversy as off-target effects can make interpreting phenotypic outcomes difficult; however, this has been resolved by creating zebrafish lines that contain stably integrated miRNA constructs that target the desired gene of interest. In this study, we show that a commercially available miRNA vector system with a mouse-derived miRNA backbone is functional in zebrafish and is effective in causing eGFP knockdown in a transient in vivo eGFP sensor assay system. We chose to apply this system to the knockdown of transcripts that are implicated in the human cardiac disorder, Long QT syndrome.

  7. MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrea Turner

    Full Text Available The Map kinase Activating Death Domain containing protein (MADD isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.

  8. ETV4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion

    International Nuclear Information System (INIS)

    Moss, Alan C.; Lawlor, Garrett; Murray, David; Tighe, Donal; Madden, Stephen F.; Mulligan, Anne-Marie; Keane, Conor O.; Brady, Hugh R.; Doran, Peter P.; MacMathuna, Padraic

    2006-01-01

    We have identified novel colorectal cancer-associated genes using NCBI's UNIGENE cDNA libraries. Colon cancer libraries were examined using Digital Differential Display and disease-associated genes were selected. Among these were ETV4 and MYEOV, novel colorectal cancer-associated genes. Samples of matched normal and neoplastic colon were obtained from human subjects and gene expression was quantified using real-time PCR. ETV4 gene expression was significantly increased in colonic neoplasia in comparison to matched normal colonic tissue (p < 0.05). Myeov expression was also increased in colon neoplasia in comparison to matched normal tissue. The effect of siRNA-mediated knockdown of ETV4 and Myeov on cell proliferation and invasion was assessed. ETV4 knockdown resulted in a 90% decrease in cell proliferation (p < 0.05) and a 67% decrease in cell invasion. Myeov knockdown resulted in a 48% decrease in cell proliferation (p < 0.05) and a 36% decrease in cell invasion. These data suggest that ETV4 and Myeov may provide novel targets for therapeutic intervention

  9. Promising Noninvasive Cellular Phenotype in Prostate Cancer Cells Knockdown of Matrix Metalloproteinase 9

    Directory of Open Access Journals (Sweden)

    Aditi Gupta

    2013-01-01

    Full Text Available Cell surface interaction of CD44 and MMP9 increases migration and invasion of PC3 cells. We show here that stable knockdown of MMP9 in PC3 cells switches CD44 isoform expression from CD44s to CD44v6 which is more glycosylated. These cells showed highly adhesive morphology with extensive cell spreading which is due to the formation of focal adhesions and well organized actin-stress fibers. MMP9 knockdown blocks invadopodia formation and matrix degradation activity as well. However, CD44 knockdown PC3 cells failed to develop focal adhesions and stress fibers; hence these cells make unstable adhesions. A part of the reason for these changes could be caused by silencing of CD44v6 as well. Immunostaining of prostate tissue microarray sections illustrated significantly lower levels of CD44v6 in adenocarcinoma than normal tissue. Our results suggest that interaction between CD44 and MMP9 is a potential mechanism of invadopodia formation. CD44v6 expression may be essential for the protection of non-invasive cellular phenotype. CD44v6 decrease may be a potential marker for prognosis and therapeutics.

  10. A family-universal anomalous U(1) in string models as the origin of supersymmetry breaking and squark degeneracy

    International Nuclear Information System (INIS)

    Faraggi, A.E.; Pati, J.C.

    1997-12-01

    Recently a promising mechanism for supersymmetry breaking that utilizes both an anomalous U(1) gauge symmetry and an effective mass term m ∼ 1TeV of certain relevant fields has been proposed. In this paper we examine whether such a mechanism can emerge in superstring derived free fermionic models. We observe that certain three generation string solutions, though not all, lead to an anomalous U(1) which couples universally to all three families. The advantages of this three-family universality of U(1) A , compared to the two-family case, proposed in earlier works, in yielding squark degeneracy, while avoiding radiative breaking of color and charge, are noted. The root cause of the flavor universality of U(1) A is the cyclic permutation symmetry that characterizes the Z 2 x Z 2 orbifold compactification with standard embedding, realized in the free fermionic models by the NAHE set. It is shown that nonrenormalizable terms which contain hidden-sector condensates, generate the required suppression of the relevant mass term m, compared to the Planck scale. While the D-term of the family universal U(1) A leads to squark degeneracy, those of the family dependent U(1)'s, remarkably enough, are found to vanish for the solutions considered, owing to minimization of the potential

  11. U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo

    Directory of Open Access Journals (Sweden)

    Rafal Goraczniak

    2013-01-01

    Full Text Available U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2 and metabotropic glutamate receptor 1 (GRM1, in a human melanoma cell xenograft mouse model system. Using a newly developed dendrimer delivery system, anti-BCL2 U1 Adaptors were very potent and suppressed tumor growth at doses as low as 34 µg/kg with twice weekly intravenous (iv administration. Anti-GRM1 U1 Adaptors suppressed tumor xenograft growth with similar potency. Mechanism of action was demonstrated by showing target gene suppression in tumors and by observing that negative control U1 Adaptors with just one functional domain show no tumor suppression activity. The anti-BCL2 and anti-GRM1 treatments were equally effective against cell lines harboring either wild-type or a mutant V600E B-RAF allele, the most common mutation in melanoma. Treatment of normal immune-competent mice (C57BL6 indicated no organ toxicity or immune stimulation. These proof-of-concept studies represent an in-depth (over 800 mice in ~108 treatment groups validation that U1 Adaptors are a highly potent gene-silencing therapeutic and open the way for their further development to treat other human diseases.

  12. Large (g-2)$_{\\mu}$ in SU(5) x U(1) supergravity models

    CERN Document Server

    López, J L; Wang, X

    1994-01-01

    We compute the supersymmetric contribution to the anomalous magnetic moment of the muon within the context of $SU(5)\\times U(1)$ supergravity models. The largest possible contributions to $a^{susy}_\\mu$ occur for the largest allowed values of $\\tan\\beta$ and can easily exceed the present experimentally allowed range, even after the LEP lower bounds on the sparticle masses are imposed. Such $\\tan\\beta$ enhancement implies that $a^{susy}_\\mu$ can greatly exceed both the electroweak contribution ($\\approx1.95\\times10^{-9}$) and the present hadronic uncertainty ($\\approx\\pm1.75\\times10^{-9}$). Therefore, the new E821 Brookhaven experiment (with an expected accuracy of $0.4\\times10^{-9}$) should explore a large fraction (if not all) of the parameter space of these models, corresponding to slepton, chargino, and squarks masses as high as 200, 300, and 1000 GeV respectively. Moreover, contrary to popular belief, the $a^{susy}_\\mu$ contribution can have either sign, depending on the sign of the Higgs mixing parameter...

  13. Collective modes of the Nambu--Jona-Lasinio model with an external U(1) gauge field

    International Nuclear Information System (INIS)

    Klevansky, S.P.; Jaenicke, J.; Lemmer, R.H.

    1991-01-01

    The effect of external color fields on the collective modes of the SU L (2)xSU R (2) chiral flavor version of the Nambu--Jona-Lasinio model is studied analytically in a U(1) approximation to the gauge fields. We show that the scalar and pseudoscalar modes respond differently to external chromomagnetic and -electric fields. In the former case, in which chiral asymmetry is enhanced, the modes remain well separated and vary slowly with the field, while in the latter case the scalar mode drops rapidly to become degenerate with the pseudoscalar mode in the chiral limit. In this regime, both modes are weakly coupled to quark matter, and the pseudoscalar pion mode in particular survives as a well-defined excitation as it enters the pair continuum. The Goldberger-Treiman relation, which is shown to hold in the presence of external fields, is responsible for this behavior. Chromoelectric and -magnetic polarizabilities are seen to be equal and opposite with absolute values β σ =2.0α s and β π =0.03α s for the scalar and pseudoscalar modes respectively

  14. Study on Surface Structure of U1-yGdyO2-x Using Raman Spectroscopy

    International Nuclear Information System (INIS)

    Lee, Jeong Mook; Kim, Jan Dee; Youn, Young Sang; Kim, Jong Goo; Ha, Yeong Keong; Kim, Jong Yun

    2016-01-01

    To understand the structural character of the spent nuclear fuel, rare earth element (REE) doped UO 2±x have been studied as simulated spent fuel. The REE doping effect has influence on the phase stability in U-FP-O system, thermal conductivity and the relevant fuel performance. Raman spectroscopy has been used to investigate surface structure of the nuclear fuel materials, because of its sensitivity, convenience and non-destructive sample preparation. The Raman studies on trivalent-doped UO 2 directly show the defect due to oxygen vacancy that could be created by loss of oxygen for charge compensation. This defect has significant effect on the kinetics of fuel oxidation. In this study, we have been investigated the effect on Gd-doping on the UO 2 structure with Raman spectroscopy to characterize the defect structure of nuclear fuel material. The oxygen deficiencies of pellets were estimated by the relation between the doping concentration and a lattice parameter evaluated from XRD spectra. The Raman spectra of U 1-y GdyO 2-x solid solution pellets show the distorted fluorite structure with defect structure due to oxygen vacancies with increasing Gd contents.

  15. Entanglement entropy in (3+1)-d free U(1) gauge theory

    Energy Technology Data Exchange (ETDEWEB)

    Soni, Ronak M.; Trivedi, Sandip P. [Department of Theoretical Physics, Tata Institute of Fundamental Research,Colaba, Mumbai, 400005 (India)

    2017-02-21

    We consider the entanglement entropy for a free U(1) theory in 3+1 dimensions in the extended Hilbert space definition. By taking the continuum limit carefully we obtain a replica trick path integral which calculates this entanglement entropy. The path integral is gauge invariant, with a gauge fixing delta function accompanied by a Faddeev -Popov determinant. For a spherical region it follows that the result for the logarithmic term in the entanglement, which is universal, is given by the a anomaly coefficient. We also consider the extractable part of the entanglement, which corresponds to the number of Bell pairs which can be obtained from entanglement distillation or dilution. For a spherical region we show that the coefficient of the logarithmic term for the extractable part is different from the extended Hilbert space result. We argue that the two results will differ in general, and this difference is accounted for by a massless scalar living on the boundary of the region of interest.

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

    Directory of Open Access Journals (Sweden)

    T. Pichler

    2016-03-01

    Full Text Available 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.

  17. The origin of interstellar asteroidal objects like 1I/2017 U1 'Oumuamua

    Science.gov (United States)

    Zwart, S. Portegies; Torres, S.; Pelupessy, I.; Bédorf, J.; Cai, Maxwell X.

    2018-05-01

    We study the origin of the interstellar object 1I/2017 U1 'Oumuamua by juxtaposing estimates based on the observations with simulations. We speculate that objects like 'Oumuamua are formed in the debris disc as left over from the star and planet formation process, and subsequently liberated. The liberation process is mediated either by interaction with other stars in the parental star-cluster, by resonant interactions within the planetesimal disc or by the relatively sudden mass loss when the host star becomes a compact object. Integrating 'Oumuamua backward in time in the Galactic potential together with stars from the Gaia-TGAS catalogue we find that about 1.3 Myr ago 'Oumuamua passed the nearby star HIP 17288 within a mean distance of 1.3 pc. By comparing nearby observed L-dwarfs with simulations of the Galaxy we conclude that the kinematics of 'Oumuamua is consistent with relatively young objects of 1.1-1.7 Gyr. We just met 'Oumuamua by chance, and with a derived mean Galactic density of ˜3 × 105 similarly sized objects within 100 au from the Sun or ˜1014 per cubic parsec we expect about 2 to 12 such visitors per year within 1 au from the Sun.

  18. Matter fields near quantum critical point in (2+1)-dimensional U(1) gauge theory

    International Nuclear Information System (INIS)

    Liu Guozhu; Li Wei; Cheng Geng

    2010-01-01

    We study chiral phase transition and confinement of matter fields in (2+1)-dimensional U(1) gauge theory of massless Dirac fermions and scalar bosons. The vanishing scalar boson mass, r=0, defines a quantum critical point between the Higgs phase and the Coulomb phase. We consider only the critical point r=0 and the Coulomb phase with r>0. The Dirac fermion acquires a dynamical mass when its flavor is less than certain critical value N f c , which depends quantitatively on the flavor N b and the scalar boson mass r. When N f f c , the matter fields carrying internal gauge charge are all confined if r≠0 but are deconfined at the quantum critical point r=0. The system has distinct low-energy elementary excitations at the critical point r=0 and in the Coulomb phase with r≠0. We calculate the specific heat and susceptibility of the system at r=0 and r≠0, which can help to detect the quantum critical point and to judge whether dynamical fermion mass generation takes place.

  19. Sterile neutrino portal to Dark Matter I: the U(1){sub B−L} case

    Energy Technology Data Exchange (ETDEWEB)

    Escudero, Miguel; Rius, Nuria [Departamento de Física Teórica and IFIC, Universidad de Valencia-CSIC,C/ Catedrático José Beltrán, 2, E-46980 Paterna (Spain); Sanz, Verónica [Department of Physics and Astronomy, University of Sussex,Falmer Campus, Brighton BN1 9QH (United Kingdom)

    2017-02-08

    In this paper we explore the possibility that the sterile neutrino and Dark Matter sectors in the Universe have a common origin. We study the consequences of this assumption in the simple case of coupling the dark sector to the Standard Model via a global U(1){sub B−L}, broken down spontaneously by a dark scalar. This dark scalar provides masses to the dark fermions and communicates with the Higgs via a Higgs portal coupling. We find an interesting interplay between Dark Matter annihilation to dark scalars — the CP-even that mixes with the Higgs and the CP-odd which becomes a Goldstone boson, the Majoron — and heavy neutrinos, as well as collider probes via the coupling to the Higgs. Moreover, Dark Matter annihilation into sterile neutrinos and its subsequent decay to gauge bosons and quarks, charged leptons or neutrinos lead to indirect detection signatures which are close to current bounds on the gamma ray flux from the galactic center and dwarf galaxies.

  20. On the renormalizability of noncommutative U(1) gauge theory-an algebraic approach

    International Nuclear Information System (INIS)

    Vilar, L C Q; Tedesco, D G; Lemes, V E R; Ventura, O S

    2010-01-01

    We investigate the quantum effects of the nonlocal gauge invariant operator 1/D 2 F μν * 1/D 2 F μν in the noncommutative U(1) action and its consequences to the infrared sector of the theory. Nonlocal operators of such kind were proposed to solve the infrared problem of the noncommutative gauge theories evading the questions on the explicit breaking of the Lorentz invariance. More recently, a first step in the localization of this operator was accomplished by means of the introduction of an extra tensorial matter field, and the first loop analysis was carried out (Blaschke et al (2009 Eur. Phys. J. C 62 433-43)). We will complete this localization avoiding the introduction of new degrees of freedom beyond those of the original action by using only BRST doublets. This will allow us to conduct a complete BRST algebraic study of the renormalizability of the theory, following Zwanziger's method of localization of nonlocal operators in QFT.

  1. Explaining the DAMPE data with scalar dark matter and gauged U(1)Le-Lμ interaction

    International Nuclear Information System (INIS)

    Cao, Junjie; Feng, Lei; Guo, Xiaofei; Shang, Liangliang; Wang, Fei; Wu, Peiwen; Zu, Lei

    2018-01-01

    Inspired by the peak structure observed by recent DAMPE experiment in e + e - cosmic-ray spectrum, we consider a scalar dark matter (DM) model with gauged U(1) L e -L μ symmetry, which is the most economical anomaly-free theory to potentially explain the peak by DM annihilation in nearby subhalo. We utilize the process χχ → Z ' Z ' → l anti ll ' anti l ' , where χ, Z ' , l (') denote the scalar DM, the new gauge boson and l (') = e, μ, respectively, to generate the e + e - spectrum. By fitting the predicted spectrum to the experimental data, we obtain the favored DM mass range m χ ≅ 3060 +80 -100 GeV and Δm ≡ m χ - m Z'

  2. Algebraic Bethe ansatz for U(1) invariant integrable models: Compact and non-compact applications

    International Nuclear Information System (INIS)

    Martins, M.J.; Melo, C.S.

    2009-01-01

    We apply the algebraic Bethe ansatz developed in our previous paper [C.S. Melo, M.J. Martins, Nucl. Phys. B 806 (2009) 567] to three different families of U(1) integrable vertex models with arbitrary N bond states. These statistical mechanics systems are based on the higher spin representations of the quantum group U q [SU(2)] for both generic and non-generic values of q as well as on the non-compact discrete representation of the SL(2,R) algebra. We present for all these models the explicit expressions for both the on-shell and the off-shell properties associated to the respective transfer matrices eigenvalue problems. The amplitudes governing the vectors not parallel to the Bethe states are shown to factorize in terms of elementary building blocks functions. The results for the non-compact SL(2,R) model are argued to be derived from those obtained for the compact systems by taking suitable N→∞ limits. This permits us to study the properties of the non-compact SL(2,R) model starting from systems with finite degrees of freedom.

  3. Algebraic Bethe ansatz for U(1) invariant integrable models: Compact and non-compact applications

    Science.gov (United States)

    Martins, M. J.; Melo, C. S.

    2009-10-01

    We apply the algebraic Bethe ansatz developed in our previous paper [C.S. Melo, M.J. Martins, Nucl. Phys. B 806 (2009) 567] to three different families of U(1) integrable vertex models with arbitrary N bond states. These statistical mechanics systems are based on the higher spin representations of the quantum group U[SU(2)] for both generic and non-generic values of q as well as on the non-compact discrete representation of the SL(2,R) algebra. We present for all these models the explicit expressions for both the on-shell and the off-shell properties associated to the respective transfer matrices eigenvalue problems. The amplitudes governing the vectors not parallel to the Bethe states are shown to factorize in terms of elementary building blocks functions. The results for the non-compact SL(2,R) model are argued to be derived from those obtained for the compact systems by taking suitable N→∞ limits. This permits us to study the properties of the non-compact SL(2,R) model starting from systems with finite degrees of freedom.

  4. Sterile neutrino portal to Dark Matter I: the U(1)B−L case

    International Nuclear Information System (INIS)

    Escudero, Miguel; Rius, Nuria; Sanz, Verónica

    2017-01-01

    In this paper we explore the possibility that the sterile neutrino and Dark Matter sectors in the Universe have a common origin. We study the consequences of this assumption in the simple case of coupling the dark sector to the Standard Model via a global U(1) B−L , broken down spontaneously by a dark scalar. This dark scalar provides masses to the dark fermions and communicates with the Higgs via a Higgs portal coupling. We find an interesting interplay between Dark Matter annihilation to dark scalars — the CP-even that mixes with the Higgs and the CP-odd which becomes a Goldstone boson, the Majoron — and heavy neutrinos, as well as collider probes via the coupling to the Higgs. Moreover, Dark Matter annihilation into sterile neutrinos and its subsequent decay to gauge bosons and quarks, charged leptons or neutrinos lead to indirect detection signatures which are close to current bounds on the gamma ray flux from the galactic center and dwarf galaxies.

  5. Hamiltonian study of improved U(1) lattice gauge theory in three dimensions

    International Nuclear Information System (INIS)

    Loan, Mushtaq; Hamer, Chris

    2004-01-01

    A comprehensive analysis of the Symanzik improved anisotropic three-dimensional U(1) lattice gauge theory in the Hamiltonian limit is made. Monte Carlo techniques are used to obtain numerical results for the static potential, ratio of the renormalized and bare anisotropies, the string tension, lowest glueball masses and the mass ratio. Evidence that rotational symmetry is established more accurately for the Symanzik improved anisotropic action is presented. The discretization errors in the static potential and the renormalization of the bare anisotropy are found to be only a few percent compared to errors of about 20-25 % for the unimproved gauge action. Evidence of scaling in the string tension, antisymmetric mass gap and the mass ratio is observed in the weak coupling region and the behavior is tested against analytic and numerical results obtained in various other Hamiltonian studies of the theory. We find that more accurate determination of the scaling coefficients of the string tension and the antisymmetric mass gap has been achieved, and the agreement with various other Hamiltonian studies of the theory is excellent. The improved action is found to give faster convergence to the continuum limit. Very clear evidence is obtained that in the continuum limit the glueball ratio M S /M A approaches exactly 2, as expected in a theory of free, massive bosons

  6. Entanglement entropy in (3 + 1)-d free U(1) gauge theory

    Science.gov (United States)

    Soni, Ronak M.; Trivedi, Sandip P.

    2017-02-01

    We consider the entanglement entropy for a free U(1) theory in 3+1 dimensions in the extended Hilbert space definition. By taking the continuum limit carefully we obtain a replica trick path integral which calculates this entanglement entropy. The path integral is gauge invariant, with a gauge fixing delta function accompanied by a Faddeev -Popov determinant. For a spherical region it follows that the result for the logarithmic term in the entanglement, which is universal, is given by the a anomaly coefficient. We also consider the extractable part of the entanglement, which corresponds to the number of Bell pairs which can be obtained from entanglement distillation or dilution. For a spherical region we show that the coefficient of the logarithmic term for the extractable part is different from the extended Hilbert space result. We argue that the two results will differ in general, and this difference is accounted for by a massless scalar living on the boundary of the region of interest.

  7. Spliceosomal protein U1A is involved in alternative splicing and salt stress tolerance in Arabidopsis thaliana

    KAUST Repository

    Gu, Jinbao

    2017-12-01

    Soil salinity is a significant threat to sustainable agricultural production worldwide. Plants must adjust their developmental and physiological processes to cope with salt stress. Although the capacity for adaptation ultimately depends on the genome, the exceptional versatility in gene regulation provided by the spliceosome-mediated alternative splicing (AS) is essential in these adaptive processes. However, the functions of the spliceosome in plant stress responses are poorly understood. Here, we report the in-depth characterization of a U1 spliceosomal protein, AtU1A, in controlling AS of pre-mRNAs under salt stress and salt stress tolerance in Arabidopsis thaliana. The atu1a mutant was hypersensitive to salt stress and accumulated more reactive oxygen species (ROS) than the wild-type under salt stress. RNA-seq analysis revealed that AtU1A regulates AS of many genes, presumably through modulating recognition of 5′ splice sites. We showed that AtU1A is associated with the pre-mRNA of the ROS detoxification-related gene ACO1 and is necessary for the regulation of ACO1 AS. ACO1 is important for salt tolerance because ectopic expression of ACO1 in the atu1a mutant can partially rescue its salt hypersensitive phenotype. Our findings highlight the critical role of AtU1A as a regulator of pre-mRNA processing and salt tolerance in plants.

  8. OAZ1 knockdown enhances viability and inhibits ER and LHR transcriptions of granulosa cells in geese.

    Directory of Open Access Journals (Sweden)

    Bo Kang

    Full Text Available An increasing number of studies suggest that ornithine decarboxylase antizyme 1 (OAZ1, which is regarded as a tumor suppressor gene, regulates follicular development, ovulation, and steroidogenesis. The granulosa cells in the ovary play a critical role in these ovarian functions. However, the action of OAZ1 mediating physiological functions of granulosa cells is obscure. OAZ1 knockdown in granulosa cells of geese was carried out in the current study. The effect of OAZ1 knockdown on polyamine metabolism, cell proliferation, apoptosis, and hormone receptor transcription of primary granulosa cells in geese was measured. The viability of granulosa cells transfected with the shRNA OAZ1 at 48 h was significantly higher than the control (p<0.05. The level of putrescine and spermidine in granulosa cells down-regulating OAZ1 was 7.04- and 2.11- fold higher compared with the control, respectively (p<0.05. The CCND1, SMAD1, and BCL-2 mRNA expression levels in granulosa cells down-regulating OAZ1 were each significantly higher than the control, respectively (p<0.05, whereas the PCNA and CASPASE 3 expression levels were significantly lower than the control (p<0.05. The estradiol concentration, ER and LHR mRNA expression levels were significantly lower in granulosa cells down-regulating OAZ1 compared with the control (p<0.05. Taken together, our results indicated that OAZ1 knockdown elevated the putrescine and spermidine contents and enhanced granulosa cell viability and inhibited ER and LHR transcriptions of granulosa cells in geese.

  9. Shp2 knockdown and Noonan/LEOPARD mutant Shp2-induced gastrulation defects.

    Directory of Open Access Journals (Sweden)

    Chris Jopling

    2007-12-01

    Full Text Available Shp2 is a cytoplasmic protein-tyrosine phosphatase that is essential for normal development. Activating and inactivating mutations have been identified in humans to cause the related Noonan and LEOPARD syndromes, respectively. The cell biological cause of these syndromes remains to be determined. We have used the zebrafish to assess the role of Shp2 in early development. Here, we report that morpholino-mediated knockdown of Shp2 in zebrafish resulted in defects during gastrulation. Cell tracing experiments demonstrated that Shp2 knockdown induced defects in convergence and extension cell movements. In situ hybridization using a panel of markers indicated that cell fate was not affected by Shp2 knock down. The Shp2 knockdown-induced defects were rescued by active Fyn and Yes and by active RhoA. We generated mutants of Shp2 with mutations that were identified in human patients with Noonan or LEOPARD Syndrome and established that Noonan Shp2 was activated and LEOPARD Shp2 lacked catalytic protein-tyrosine phosphatase activity. Expression of Noonan or LEOPARD mutant Shp2 in zebrafish embryos induced convergence and extension cell movement defects without affecting cell fate. Moreover, these embryos displayed craniofacial and cardiac defects, reminiscent of human symptoms. Noonan and LEOPARD mutant Shp2s were not additive nor synergistic, consistent with the mutant Shp2s having activating and inactivating roles in the same signaling pathway. Our results demonstrate that Shp2 is required for normal convergence and extension cell movements during gastrulation and that Src family kinases and RhoA were downstream of Shp2. Expression of Noonan or LEOPARD Shp2 phenocopied the craniofacial and cardiac defects of human patients. The finding that defective Shp2 signaling induced cell movement defects as early as gastrulation may have implications for the monitoring and diagnosis of Noonan and LEOPARD syndrome.

  10. Aldolase B knockdown prevents high glucose-induced methylglyoxal overproduction and cellular dysfunction in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Jianghai Liu

    Full Text Available We used cultured endothelial cells as a model to examine whether up-regulation of aldolase B and enhanced methylglyoxal (MG formation play an important role in high glucose-induced overproduction of advanced glycosylation endproducts (AGEs, oxidative stress and cellular dysfunction. High glucose (25 mM incubation up-regulated mRNA levels of aldose reductase (an enzyme converting glucose to fructose and aldolase B (a key enzyme that catalyzes MG formation from fructose and enhanced MG formation in human umbilical vein endothelial cells (HUVECs and HUVEC-derived EA. hy926 cells. High glucose-increased MG production in EA. hy926 cells was completely prevented by siRNA knockdown of aldolase B, but unaffected by siRNA knockdown of aldolase A, an enzyme responsible for MG formation during glycolysis. In addition, inhibition of cytochrome P450 2E1 or semicarbazide-sensitive amine oxidase which produces MG during the metabolism of lipid and proteins, respectively, did not alter MG production. Both high glucose (25 mM and MG (30, 100 µM increased the formation of N(ε-carboxyethyl-lysine (CEL, a MG-induced AGE, oxidative stress (determined by the generation of oxidized DCF, H(2O(2, protein carbonyls and 8-oxo-dG, O-GlcNAc modification (product of the hexosamine pathway, membrane protein kinase C activity and nuclear translocation of NF-κB in EA. hy926 cells. However, the above metabolic and signaling alterations induced by high glucose were completely prevented by knockdown of aldolase B and partially by application of aminoguanidine (a MG scavenger or alagebrium (an AGEs breaker. In conclusion, efficient inhibition of aldolase B can prevent high glucose-induced overproduction of MG and related cellular dysfunction in endothelial cells.

  11. Lifespan and reproduction in brain-specific miR-29-knockdown mouse.

    Science.gov (United States)

    Takeda, Toru; Tanabe, Hiroyuki

    2016-03-18

    The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post-reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR-29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice.

    Directory of Open Access Journals (Sweden)

    Naoto Hayasaka

    Full Text Available Regulators of G protein signaling (RGS are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs of G protein α-subunits to terminate G protein signaling. Previous studies have demonstrated that the Rgs16 transcripts exhibit robust circadian rhythms both in the suprachiasmatic nucleus (SCN, the master circadian light-entrainable oscillator (LEO of the hypothalamus, and in the liver. To investigate the role of RGS16 in the circadian clock in vivo, we generated two independent transgenic mouse lines using lentiviral vectors expressing short hairpin RNA (shRNA targeting the Rgs16 mRNA. The knockdown mice demonstrated significantly shorter free-running period of locomotor activity rhythms and reduced total activity as compared to the wild-type siblings. In addition, when feeding was restricted during the daytime, food-entrainable oscillator (FEO-driven elevated food-anticipatory activity (FAA observed prior to the scheduled feeding time was significantly attenuated in the knockdown mice. Whereas the restricted feeding phase-advanced the rhythmic expression of the Per2 clock gene in liver and thalamus in the wild-type animals, the above phase shift was not observed in the knockdown mice. This is the first in vivo demonstration that a common regulator of G protein signaling is involved in the two separate, but interactive circadian timing systems, LEO and FEO. The present study also suggests that liver and/or thalamus regulate the food-entrained circadian behavior through G protein-mediated signal transduction pathway(s.

  13. Insecticidal potency of RNAi-based catalase knockdown in Rhynchophorus ferrugineus (Oliver) (Coleoptera: Curculionidae).

    Science.gov (United States)

    Al-Ayedh, Hassan; Rizwan-Ul-Haq, Muhammad; Hussain, Abid; Aljabr, Ahmed M

    2016-11-01

    Palm trees around the world are prone to notorious Rhynchophorus ferrugineus, which causes heavy losses of palm plantations. In Middle Eastern countries, this pest is a major threat to date palm orchards. Conventional pest control measures with the major share of synthetic insecticides have resulted in insect resistance and environmental issues. Therefore, in order to explore better alternatives, the RNAi approach was employed to knock down the catalase gene in fifth and tenth larval instars with different dsRNA application methods, and their insecticidal potency was studied. dsRNA of 444 bp was prepared to knock down catalase in R. ferrugineus. Out of the three dsRNA application methods, dsRNA injection into larvae was the most effective, followed by dsRNA application by artificial feeding. Both methods resulted in significant catalase knockdown in various tissues, especially the midgut. As a result, the highest growth inhibition of 123.49 and 103.47% and larval mortality of 80 and 40% were observed in fifth-instar larvae, whereas larval growth inhibition remained at 86.83 and 69.08% with larval mortality at 30 and 10% in tenth-instar larvae after dsRNA injection and artificial diet treatment. The topical application method was the least efficient, with the lowest larval growth inhibition of 57.23 and 45.61% and 0% mortality in fifth- and tenth-instar larvae. Generally, better results were noted at the high dsRNA dose of 5 µL. Catalase enzyme is found in most insect body tissues, and thus its dsRNA can cause broad-scale gene knockdown within the insect body, depending upon the application method. Significant larval mortality and growth inhibition after catalase knockdown in R. ferrugineus confirms its insecticidal potency and suggests a bright future for RNAi-based bioinsecticides in pest control. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  14. Vivo-morpholinos induced transient knockdown of physical activity related proteins.

    Directory of Open Access Journals (Sweden)

    David P Ferguson

    Full Text Available Physical activity is associated with disease prevention and overall wellbeing. Additionally there has been evidence that physical activity level is a result of genetic influence. However, there has not been a reliable method to silence candidate genes in vivo to determine causal mechanisms of physical activity regulation. Vivo-morpholinos are a potential method to transiently silence specific genes. Thus, the aim of this study was to validate the use of Vivo-morpholinos in a mouse model for voluntary physical activity with several sub-objectives. We observed that Vivo-morpholinos achieved between 60-97% knockdown of Drd1-, Vmat2-, and Glut4-protein in skeletal muscle, the delivery moiety of Vivo-morpholinos (scramble did not influence physical activity and that a cocktail of multiple Vivo-morpholinos can be given in a single treatment to achieve protein knockdown of two different targeted proteins in skeletal muscle simultaneously. Knocking down Drd1, Vmat2, or Glut4 protein in skeletal muscle did not affect physical activity. Vivo-morpholinos injected intravenously alone did not significantly knockdown Vmat2-protein expression in the brain (p = 0.28. However, the use of a bradykinin analog to increase blood-brain-barrier permeability in conjunction with the Vivo-morpholinos significantly (p = 0.0001 decreased Vmat2-protein in the brain with a corresponding later over-expression of Vmat2 coincident with a significant (p = 0.0016 increase in physical activity. We conclude that Vivo-morpholinos can be a valuable tool in determining causal gene-phenotype relationships in whole animal models.

  15. A Simple Retroelement Based Knock-Down System in Dictyostelium: Further Insights into RNA Interference Mechanisms.

    Science.gov (United States)

    Friedrich, Michael; Meier, Doreen; Schuster, Isabelle; Nellen, Wolfgang

    2015-01-01

    We have previously shown that the most abundant Dictyostelium discoideum retroelement DIRS-1 is suppressed by RNAi mechanisms. Here we provide evidence that both inverted terminal repeats have strong promoter activity and that bidirectional expression apparently generates a substrate for Dicer. A cassette containing the inverted terminal repeats and a fragment of a gene of interest was sufficient to activate the RNAi response, resulting in the generation of ~21 nt siRNAs, a reduction of mRNA and protein expression of the respective endogene. Surprisingly, no transitivity was observed on the endogene. This was in contrast to previous observations, where endogenous siRNAs caused spreading on an artificial transgene. Knock-down was successful on seven target genes that we examined. In three cases a phenotypic analysis proved the efficiency of the approach. One of the target genes was apparently essential because no knock-out could be obtained; the RNAi mediated knock-down, however, resulted in a very slow growing culture indicating a still viable reduction of gene expression. ADVANTAGES OF THE DIRS-1–RNAI SYSTEM: The knock-down system required a short DNA fragment (~400 bp) of the target gene as an initial trigger. Further siRNAs were generated by RdRPs since we have shown some siRNAs with a 5'-triphosphate group. Extrachromosomal vectors facilitate the procedure and allowed for molecular and phenotypic analysis within one week. The system provides an efficient and rapid method to reduce protein levels including those of essential genes.

  16. [Effect of NOR1 gene knockdown on the biological behavior of HeLa cells].

    Science.gov (United States)

    Tan, Yixin; Li, Wenjuan; Yi, Mei; Wang, Wei; Zheng, Pan; Zhang, Haijing; Xiang, Bo; Li, Guiyuan

    2014-08-01

    To explore the effect of the oxidored nitro domain containing protein 1 (NOR1) gene knockdown on the biological behavior of HeLa cells in cervical carcinoma. The recombinant plasmids pSUPER-shNOR1-1, pSUPER-shNOR1-2 and pSUPERscramble, which targeted to NOR1 gene, were constructed by pSUPER.neo+GFP vector, transfected into HeLa cells respectively using Lipofectamine 2000 reagent, and followed by G418 selection. The expression level of NOR1 mRNA and protein were determined by RT-PCR and Western blotting, respectively. Methyl thiazolyl tetrazolium (MTT) assay was performed to determine the growth curve of cell viability. The stable transfectants were treated with H₂O₂ and cell apoptosis was determined by Hoechst 33258 staining and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay. The expression levels of Bcl-2, cleaved caspase 9 and poly ADP-ribose polymerase (PARP) were measured by Western blot. NOR1- knockdown HeLa cells were successfully constructed by transfection of pSUPER-shNOR1-1 or pSUPER-shNOR1-2 plasmids into HeLa cells. MTT assay showed that the silence of endogenous NOR1 in HeLa cells could lead to the increase in cell viability and proliferation, and the inhibition of H₂O₂-induced apoptosis compared with the negative control. Western blot showed that the expression level of active caspase 9 and cleaved PARP was inhibited in NOR1-knockdown cells when they were treated with H₂O₂ while the expression level of Bcl-2 protein increased. Silence of endogenous NOR1 facilitates the cell viability and growth of HeLa cells, and attenuates HeLa cells apoptosis induced by H₂O₂, which might be mediated by up-regulation of Bcl-2 level and down-regulation of the cleaved caspase 9 cascade.

  17. Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction.

    Directory of Open Access Journals (Sweden)

    Enise Bagci

    Full Text Available Thyroid hormone (TH balance is essential for vertebrate development. Deiodinase type 1 (D1 and type 2 (D2 increase and deiodinase type 3 (D3 decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray, biochemistry, morphology and physiology using morpholino (MO knockdown. Knockdown of D1+D2 (D1D2MO and knockdown of D3 (D3MO both resulted in transcriptional regulation of energy metabolism and (muscle development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct

  18. Selective knockdown of ceramide synthases reveals complex interregulation of sphingolipid metabolism[S

    OpenAIRE

    Mullen, Thomas D.; Spassieva, Stefka; Jenkins, Russell W.; Kitatani, Kazuyuki; Bielawski, Jacek; Hannun, Yusuf A.; Obeid, Lina M.

    2011-01-01

    Mammalian ceramide synthases 1 to 6 (CerS1–6) generate Cer in an acyl-CoA-dependent manner, and expression of individual CerS has been shown to enhance the synthesis of ceramides with particular acyl chain lengths. However, the contribution of each CerS to steady-state levels of specific Cer species has not been evaluated. We investigated the knockdown of individual CerS in the MCF-7 human breast adenocarcinoma cell line by using small-interfering RNA (siRNA). We found that siRNA-induced down...

  19. Elucidating the role of free polycations in gene knockdown by siRNA polyplexes

    DEFF Research Database (Denmark)

    Klauber, Thomas Christopher Bogh; Søndergaard, Rikke Vicki; Sawant, Rupa R.

    2016-01-01

    capability, but are very different regarding siRNA decondensation, cellular internalization and induction of reporter gene knockdown. Lipid conjugation of bPEI 1.8. kDa improves the siRNA delivery properties, but with markedly different formulation requirements and mechanisms of action compared...... today.A major reason for the lack of progress is insufficient understanding of cell-polyplex interaction. We investigate siRNA delivery using polyethyleneimine (PEI) based vectors and examine how crucial formulation parameters determine the challenges associated with PEI as a delivery vector. We further...

  20. Phenomenological constraints imposed by the hidden sector in the flipped SU(5)xU(1) superstring model

    Energy Technology Data Exchange (ETDEWEB)

    Leontaris, G.K.; Rizos, J.; Tamvakis, K. (Ioannina Univ. (Greece). Theoretical Physics Div.)

    1990-06-28

    We calculate the trilinear superpotential of the hidden sector of the three generation flipped SU(5)xU(1)xU(1){sup 4}xSO(10)xSU(4) superstring model. We perform a renormalization group analysis of the model taking into account the hidden sector. We find that, in all relevant cases, fractionally charged tetraplets of the hidden SO(6) gauge group are confined at a high scale. Nevertheless, their contribution to the observable U(1) gauge coupling evolution results in a drastic reduction of the available freedom in the values of a{sub 3}(m{sub w}), sin{sup 2}{theta}{sub w} and M{sub x} that allow superunification. (orig.).

  1. Boson-fermion mass splittings in four-dimensional heterotic string models with anomalous U(1) gauge groups

    International Nuclear Information System (INIS)

    Yamaguchi, Masahiro; Yamamoto, Hisashi; Onogi, Tetsuya

    1989-01-01

    In four-dimensional heterotic string models with anomalous U(1) gauge groups, space-time supersymmetry (SUSY) breaks down spontaneously at one loop. In this paper, the Ward-Takahashi identity of broken SUSY in one-loop two-point amplitudes is investigated in all generalities. The boson-fermion mass splitting of any supersymmetric pair in an arbitrary model is proportional to the product of the D-term expectation value (the sum of (chirality)x(U(1) charge) of massless fermions in the model) and the U(1) charge of the external particle. In order to give a better understanding of the results, we present some examples of the mass splittings in a simple Z 3 orbifold model. (orig.)

  2. TH-A-BRC-01: AAPM TG-135U1 QA for Robotic Radiosurgery

    International Nuclear Information System (INIS)

    Dieterich, S.

    2016-01-01

    AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance - Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline

  3. TH-A-BRC-01: AAPM TG-135U1 QA for Robotic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Dieterich, S. [UC Davis Medical Center (United States)

    2016-06-15

    AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance - Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline

  4. Investigations on the renormalizability of a non-commutative u(1) gauge theory

    International Nuclear Information System (INIS)

    Rofner, A.

    2009-01-01

    standard model is formulated via gauge field theories. It is therefore crucial to find their non-commutative, renormalizable counterparts. Having said this we have already addressed the goal and content of this dissertation, which consists in finding a potentially renormalizable theta-deformed u(1) gauge theory. In a first step, we studied in detail a localized version of a model, which represents an extension of ordinary u(1) gauge theory (formulated on Euclidean space) to the non-commutative setting, and is based on adding a term similar to the one of Gurau et. al., leading to an IR-damped gauge boson propagator. In the course of one-loop calculations, we have shown that it implements additional degrees of freedom and hence modifies the original physical content of the theory. A way out was found by implementing the modification of the IR sector through the introduction of a soft breaking term similar to the approach of Gribov and Zwanziger known from commutative Yang Mills theory. However, when trying to show renormalizability at one-loop level, it turned out that the action does not contain the appropriate terms for absorbing the IR divergences. usually, in such cases one constructs an effective renormalizable action via application of renormalization schemes such as Algebraic Renormalization, which in this case fails, due to the inherent non-locality of the star product. As a consequence, some ideas regarding the applicability and possible extension of traditional renormalization schemes to non-commutative GFTs have been discussed. Finally a new action (the BRSW model) was constructed. It could be shown to be renormalizable to one-loop order. Although a rigorous proof is still missing, we expect it to be a very promising candidate for the first fully renormalizable non-commutative gauge field theory.(author) [de

  5. Matter, dark matter and gravitational waves from a GUT-scale U(1) phase transition

    Energy Technology Data Exchange (ETDEWEB)

    Domcke, Valerie

    2013-09-15

    The cosmological realization of the spontaneous breaking of B-L, the difference of baryon and lepton number, can generate the initial conditions for the hot early universe. In particular, we show that entropy, dark matter and a matter-antimatter asymmetry can be produced in accordance with current observations. If B-L is broken at the grand unification scale, F-term hybrid inflation can be realized in the false vacuum of unbroken B-L. The phase transition at the end of inflation, governed by tachyonic preheating, spontaneously breaks the U(1){sub B-L} symmetry and sets the initial conditions for the following perturbative reheating phase. We provide a detailed, time-resolved picture of the reheating process. The competition of cosmic expansion and entropy production leads to an intermediate plateau of constant temperature, which controls both the generated lepton asymmetry and the dark matter abundance. This enables us to establish relations between the neutrino and superparticle mass spectrum, rendering this mechanism testable. Moreover, we calculate the entire gravitational wave spectrum for this setup. This yields a promising possibility to probe cosmological B - L breaking with forthcoming gravitational wave detectors such as eLISA, advanced LIGO and BBO/DECIGO. The largest contribution is obtained from cosmic strings which is, for typical parameter values, at least eight orders of magnitude higher then the contribution from inflation. Finally, we study the possibility of realizing hybrid inflation in a superconformal framework. We find that superconformal D-term inflation is an interesting possibility generically leading to a two-field inflation model, but in its simplest version disfavoured by the recently published Planck data.

  6. Matter, dark matter and gravitational waves from a GUT-scale U(1) phase transition

    International Nuclear Information System (INIS)

    Domcke, Valerie

    2013-09-01

    The cosmological realization of the spontaneous breaking of B-L, the difference of baryon and lepton number, can generate the initial conditions for the hot early universe. In particular, we show that entropy, dark matter and a matter-antimatter asymmetry can be produced in accordance with current observations. If B-L is broken at the grand unification scale, F-term hybrid inflation can be realized in the false vacuum of unbroken B-L. The phase transition at the end of inflation, governed by tachyonic preheating, spontaneously breaks the U(1) B-L symmetry and sets the initial conditions for the following perturbative reheating phase. We provide a detailed, time-resolved picture of the reheating process. The competition of cosmic expansion and entropy production leads to an intermediate plateau of constant temperature, which controls both the generated lepton asymmetry and the dark matter abundance. This enables us to establish relations between the neutrino and superparticle mass spectrum, rendering this mechanism testable. Moreover, we calculate the entire gravitational wave spectrum for this setup. This yields a promising possibility to probe cosmological B - L breaking with forthcoming gravitational wave detectors such as eLISA, advanced LIGO and BBO/DECIGO. The largest contribution is obtained from cosmic strings which is, for typical parameter values, at least eight orders of magnitude higher then the contribution from inflation. Finally, we study the possibility of realizing hybrid inflation in a superconformal framework. We find that superconformal D-term inflation is an interesting possibility generically leading to a two-field inflation model, but in its simplest version disfavoured by the recently published Planck data.

  7. Gauge symmetry breaking in the hidden sector of the flipped SU(5)xU(1) superstring model

    Energy Technology Data Exchange (ETDEWEB)

    Antoniadis, I.; Rizos, J. (Centre de Physique Theorique, Ecole Polytechnique, 91 - Palaiseau (France)); Tamvakis, K. (Theoretical Physics Div., Univ. Ioannina (Greece))

    1992-03-26

    We analyze the SU(5)xU(1)'xU(1){sup 4}xSO(10)xSU(4) superstring model with a spontaneously broken hidden sector down to SO(7)xSO(5) taking into account non-renormalizable superpotential terms up to eight order. As a result of the hidden sector breaking the 'exotic' states get a mass and the 'observable' spectrum is composed of the standard three families. In addition, Cabibbo mixing arises at sixth order and an improved fermion mass hierarchy emerges. (orig.).

  8. Critical behavior of the compact 3D U(1) theory in the limit of zero spatial coupling

    International Nuclear Information System (INIS)

    Borisenko, O; Gravina, M; Papa, A

    2008-01-01

    Critical properties of the compact three-dimensional U(1) lattice gauge theory are explored at finite temperatures on an asymmetric lattice. For vanishing value of the spatial gauge coupling one obtains an effective two-dimensional spin model which describes the interaction between Polyakov loops. We study numerically the effective spin model for N t = 1,4,8 on lattices with spatial extent ranging from L = 64 to 256. Our results indicate that the finite temperature U(1) lattice gauge theory belongs to the universality class of the two-dimensional XY model, thus supporting the Svetitsky–Yaffe conjecture

  9. Multi-parameter variational calculations for the (2+1)-dimensional U(1) lattice gauge theory and the XY model

    International Nuclear Information System (INIS)

    Heys, D.W.; Stump, D.R.

    1987-01-01

    Variational calculations are described that use multi-parameter trial wave functions for the U(1) lattice gauge theory in two space dimensions, and for the XY model. The trial functions are constructed as the exponential of a linear combination of states from the strong-coupling basis of the model, with the coefficients treated as variational parameters. The expectation of the hamiltonian is computed by the Monte Carlo method, using a reweighting technique to evaluate expectation values in finite patches of the parameter space. The trial function for the U(1) gauge theory involves six variational parameters, and its weak-coupling behaviour is in reasonable agreement with theoretical expectations. (orig.)

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

    International Nuclear Information System (INIS)

    Jia Yin; Huang Rijun; Liu Changyong

    2010-01-01

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

  11. Analysis of the 3 and 4 cycles with extensions in the operation of the CNLV U-1; Analisis de los ciclos 3 y 4 con extensiones en la operacion de la CNLV U-1

    Energy Technology Data Exchange (ETDEWEB)

    Montes T, J.L.; Torres A, C.; Perusquia C, R. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    1992-08-15

    The objective of the report is the comparison of the radial distributions of burned in the core among the results of the simulation of the Laguna Verde Central U-1 reactor during the operation of the cycles 1 to 4 and the data of the operation with information provided by the fuel supplier. (Author)

  12. Hypersensitivity of mouse NEIL1-knockdown cells to hydrogen peroxide during S phase

    International Nuclear Information System (INIS)

    Yamamoto, Ryohei; Ohshiro, Yukari; Shimotani, Tatsuhiko; Yamamoto, Mizuki; Matsuyama, Satoshi; Ide, Hiroshi; Kubo, Kihei

    2014-01-01

    Oxidative base damage occurs spontaneously due to reactive oxygen species generated as byproducts of respiration and other pathological processes in mammalian cells. Many oxidized bases are mutagenic and/or toxic, and most are repaired through the base excision repair pathway. Human endonuclease VIII-like protein 1 (hNEIL1) is thought to play an important role during the S phase of the cell cycle by removing oxidized bases in DNA replication fork-like (bubble) structures, and the protein level of hNEIL1 is increased in S phase. Compared with hNEIL1, there is relatively little information on the properties of the mouse ortholog mNEIL1. Since mouse cell nuclei lack endonuclease III-like protein (NTH) activity, in contrast to human cell nuclei, mNEIL1 is a major DNA glycosylase for repair of oxidized pyrimidines in mouse nuclei. In this study, we made mNEIL1-knockdown cells using an shRNA expression vector and examined the cell cycle-related variation in hydrogen peroxide (H 2 O 2 ) sensitivity. Hypersensitivity to H 2 O 2 caused by mNEIL1 knockdown was more significant in S phase than in G1 phase, suggesting that mNEIL1 has an important role during S phase, similarly to hNEIL1

  13. REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Kaushali Thakore-Shah

    Full Text Available REST (RE1 silencing transcription factor, also known as NRSF (neuron-restrictive silencer factor, is a well-known transcriptional repressor of neural genes in non-neural tissues and stem cells. Dysregulation of REST activity is thought to play a role in diverse diseases including epilepsy, cancer, Down's syndrome and Huntington's disease. The role of REST/NRSF in control of human embryonic stem cell (hESC fate has never been examined. To evaluate the role of REST in hESCs we developed an inducible REST knockdown system and examined both growth and differentiation over short and long term culture. Interestingly, we have found that altering REST levels in multiple hESC lines does not result in loss of self-renewal but instead leads to increased survival. During differentiation, REST knockdown resulted in increased MAPK/ERK and WNT signaling and increased expression of mesendoderm differentiation markers. Therefore we have uncovered a new role for REST in regulation of growth and early differentiation decisions in human embryonic stem cells.

  14. Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Dehu Chen

    2017-06-01

    Full Text Available Background/Aims: Gastric cancer (GC is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5 has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

  15. The knockdown of OsVIT2 and MIT affects iron localization in rice seed.

    Science.gov (United States)

    Bashir, Khurram; Takahashi, Ryuichi; Akhtar, Shamim; Ishimaru, Yasuhiro; Nakanishi, Hiromi; Nishizawa, Naoko K

    2013-11-20

    The mechanism of iron (Fe) uptake in plants has been extensively characterized, but little is known about how Fe transport to different subcellular compartments affects Fe localization in rice seed. Here, we discuss the characterization of a rice vacuolar Fe transporter 2 (OsVIT2) T-DNA insertion line (osvit2) and report that the knockdown of OsVIT2 and mitochondrial Fe transporter (MIT) expression affects seed Fe localization. osvit2 plants accumulated less Fe in their shoots when grown under normal or excess Fe conditions, while the accumulation of Fe was comparable to that in wild-type (WT) plants under Fe-deficient conditions. The accumulation of zinc, copper, and manganese also changed significantly in the shoots of osvit2 plants. The growth of osvit2 plants was also slow compared to that of WT plants. The concentration of Fe increased in osvit2 polished seeds. Previously, we reported that the expression of OsVIT2 was higher in MIT knockdown (mit-2) plants, and in this study, the accumulation of Fe in mit-2 seeds decreased significantly. These results suggest that vacuolar Fe trafficking is important for plant Fe homeostasis and distribution, especially in plants grown in the presence of excess Fe. Moreover, changes in the expression of OsVIT2 and MIT affect the concentration and localization of metals in brown rice as well as in polished rice seeds.

  16. Knockdown of autophagy enhances innate immune response in hepatitis C virus infected hepatocytes

    Science.gov (United States)

    Shrivastava, Shubham; Raychoudhuri, Amit; Steele, Robert; Ray, Ranjit; Ray, Ratna B.

    2010-01-01

    The role of autophagy in disease pathogenesis following viral infection is beginning to be elucidated. We have previously reported that hepatitis C virus (HCV) infection in hepatocytes induces autophagy. However, the biological significance of HCV induced autophagy has not been clarified. Autophagy has recently been identified as a novel component of innate immune system against viral infection. In the present study, we have shown that knockdown of autophagy related protein Beclin1 or ATG7 in immortalized human hepatocytes (IHH) inhibited HCV growth. Beclin1 or ATG7 knockdown IHH when infected with HCV exhibited an increased expression of IFN-β, OAS-1, IFN-α and IFI27 mRNAs of the interferon signaling pathways as compared to infection of control IHH. Subsequent study demonstrated that HCV infection in autophagy impaired IHH displayed caspase activation, PARP cleavage and apoptotic cell death. Conclusion The disruption of autophagy machinery in HCV infected hepatocytes activated IFN signaling pathway, and induced apoptosis. Together, these results suggest that HCV induced autophagy impairs innate immune response. PMID:21274862

  17. Acute sterol o-acyltransferase 2 (SOAT2 knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

    Directory of Open Access Journals (Sweden)

    Stephanie M Marshall

    Full Text Available The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE. We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2 increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD, the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.

  18. Novel siRNA formulation to effectively knockdown mutant p53 in osteosarcoma.

    Science.gov (United States)

    Kundu, Anup K; Iyer, Swathi V; Chandra, Sruti; Adhikari, Amit S; Iwakuma, Tomoo; Mandal, Tarun K

    2017-01-01

    The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318-1, a murine osteosarcoma cell line. The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP) and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer. A series of studies that include using different nanoparticles, different amount of siRNAs, cell numbers, incubation time, transfection media volume, and storage temperature was performed to optimize the gene silencing efficiency. Replacement of lipids by PLGA or PLGA-PEG decreased the particle size and overall cytotoxicity. Among all lipid-polymer nanoformulations, nanoparticles with 10% PLGA showed highest mutant p53 knockdown efficiency while maintaining higher cell viability when a nanoparticle to siRNA ratio equal to 6.8:0.66 and 75 nM siRNA was used. With long term storage the mutant p53 knockdown efficiency decreased to a greater extent. This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.

  19. Novel siRNA formulation to effectively knockdown mutant p53 in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Anup K Kundu

    Full Text Available The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318-1, a murine osteosarcoma cell line.The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer. A series of studies that include using different nanoparticles, different amount of siRNAs, cell numbers, incubation time, transfection media volume, and storage temperature was performed to optimize the gene silencing efficiency.Replacement of lipids by PLGA or PLGA-PEG decreased the particle size and overall cytotoxicity. Among all lipid-polymer nanoformulations, nanoparticles with 10% PLGA showed highest mutant p53 knockdown efficiency while maintaining higher cell viability when a nanoparticle to siRNA ratio equal to 6.8:0.66 and 75 nM siRNA was used. With long term storage the mutant p53 knockdown efficiency decreased to a greater extent.This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.

  20. Knockdown of RMI1 impairs DNA repair under DNA replication stress.

    Science.gov (United States)

    Xu, Chang; Fang, Lianying; Kong, Yangyang; Xiao, Changyan; Yang, Mengmeng; Du, Li-Qing; Liu, Qiang

    2017-12-09

    RMI1 (RecQ-mediated genome instability protein 1) forms a conserved BTR complex with BLM, Topo IIIα, and RMI2, and its absence causes genome instability. It has been revealed that RMI1 localizes to nuclear foci with BLM and Topo IIIα in response to replication stress, and that RMI1 functions downstream of BLM in promoting replication elongation. However, the precise functions of RMI1 during replication stress are not completely understood. Here we report that RMI1 knockdown cells are hypersensitive to hydroxyurea (HU). Using comet assay, we show that RMI1 knockdown cells exhibit accumulation of broken DNAs after being released from HU treatment. Moreover, we demonstrate that RMI1 facilitates the recovery from activated checkpoint and resuming the cell cycle after replicative stress. Surprisingly, loss of RMI1 results in a failure of RAD51 loading onto DNA damage sites. These findings reveal the importance of RMI1 in response to replication stress, which could explain the molecular basis for its function in maintaining genome integrity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts.

    Science.gov (United States)

    Xu, Lu-lu; Lu, Yun-tao; Zhang, Jing; Wu, Lian; Merrilees, Mervyn J; Qu, Jie-ming

    2015-08-15

    COPD lung is characterized by loss of alveolar elastic fibers and an increase in the chondroitin sulfate (CS) matrix proteoglycan versican V1 (V1). V1 is a known inhibitor of elastic fiber deposition and this study investigates the effects of knockdown of V1, and add-back of CS, on CCL-210 lung fibroblasts treated with cigarette smoke extract (CSE) as a model for COPD. CSE inhibited fibroblast proliferation, viability, tropoelastin synthesis, and elastin deposition, and increased V1 synthesis and secretion. V1 siRNA decreased V1 and constituent CS, did not affect tropoelastin production, but blocked the CSE-induced loss in insoluble elastin. Exogenous CS reduced insoluble elastin, even in the presence of V1 siRNA. These findings confirm that V1 and CS impair the assembly of tropoelastin monomers into insoluble fibers, and further demonstrate that specific knockdown of V1 alleviates the impaired assembly of elastin seen in cultures of pulmonary fibroblasts exposed to CSE, indicating a regulatory role for this protein in the pathophysiology of COPD. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence

    Energy Technology Data Exchange (ETDEWEB)

    Byrne, Ann; McLaren, Rajashree P.; Mason, Paul; Chai, Lilly; Dufault, Michael R.; Huang, Yinyin; Liang, Beirong; Gans, Joseph D.; Zhang, Mindy; Carter, Kara; Gladysheva, Tatiana B.; Teicher, Beverly A.; Biemann, Hans-Peter N.; Booker, Michael; Goldberg, Mark A.; Klinger, Katherine W.; Lillie, James [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Madden, Stephen L., E-mail: steve.madden@genzyme.com [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Jiang, Yide, E-mail: yide.jiang@genzyme.com [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)

    2010-01-15

    The PSMD14 (POH1, also known as Rpn11/MPR1/S13/CepP1) protein within the 19S complex (19S cap; PA700) is responsible for substrate deubiquitination during proteasomal degradation. The role of PSMD14 in cell proliferation and senescence was explored using siRNA knockdown in carcinoma cell lines. Our results reveal that down-regulation of PSMD14 by siRNA transfection had a considerable impact on cell viability causing cell arrest in the G0-G1 phase, ultimately leading to senescence. The molecular events associated with decreased cell proliferation, cell cycle arrest and senescence include down-regulation of cyclin B1-CDK1-CDC25C, down-regulation of cyclin D1 and up-regulation of p21{sup /Cip} and p27{sup /Kip1}. Most notably, phosphorylation of the retinoblastoma protein was markedly reduced in PSMD14 knockdown cells. A comparative study with PSMB5, a subunit of the 20S proteasome, revealed that PSMB5 and PSMD14 have different effects on cell cycle, senescence and associated molecular events. These data support the view that the 19S and 20S subunits of the proteasome have distinct biological functions and imply that targeting 19S and 20S would have distinct molecular consequences on tumor cells.

  3. Knockdown of Zebrafish Blood Vessel Epicardial Substance Results in Incomplete Retinal Lamination

    Directory of Open Access Journals (Sweden)

    Yu-Ching Wu

    2014-01-01

    Full Text Available Cell polarity during eye development determines the normal retinal lamination and differentiation of photoreceptor cells in the retina. In vertebrates, blood vessel epicardial substance (Bves is known to play an important role in the formation and maintenance of the tight junctions essential for epithelial cell polarity. In the current study, we generated a transgenic zebrafish Bves (zbves promoter-EGFP zebrafish line to investigate the expression pattern of Bves in the retina and to study the role of zbves in retinal lamination. Immunostaining with different specific antibodies from retinal cells and transmission electron microscopy were used to identify the morphological defects in normal and Bves knockdown zebrafish. In normal zebrafish, Bves is located at the apical junctions of embryonic retinal neuroepithelia during retinogenesis; later, it is strongly expressed around inner plexiform layer (IPL and retinal pigment epithelium (RPE. In contrast, a loss of normal retinal lamination and cellular polarity was found with undifferentiated photoreceptor cells in Bves knockdown zebrafish. Herein, our results indicated that disruption of Bves will result in a loss of normal retinal lamination.

  4. CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jiajia [Department of Laboratory Medicine, Peking University Third Hospital, Beijing (China); Zhu, Xi [Department of Urology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing (China); Zhang, Jie, E-mail: zhangjiebjmu@163.com [Department of Laboratory Medicine, Peking University Third Hospital, Beijing (China)

    2014-03-28

    Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCR and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy.

  5. Multiple origins of knockdown resistance mutations in the Afrotropical mosquito vector Anopheles gambiae.

    Directory of Open Access Journals (Sweden)

    João Pinto

    2007-11-01

    Full Text Available How often insecticide resistance mutations arise in natural insect populations is a fundamental question for understanding the evolution of resistance and also for modeling its spread. Moreover, the development of resistance is regarded as a favored model to study the molecular evolution of adaptive traits. In the malaria vector Anopheles gambiae two point mutations (L1014F and L1014S in the voltage-gated sodium channel gene, that confer knockdown resistance (kdr to DDT and pyrethroid insecticides, have been described. In order to determine whether resistance alleles result from single or multiple mutation events, genotyping of the kdr locus and partial sequencing of the upstream intron-1 was performed on a total of 288 A. gambiae S-form collected from 28 localities in 15 countries. Knockdown resistance alleles were found to be widespread in West Africa with co-occurrence of both 1014S and 1014F in West-Central localities. Differences in intron-1 haplotype composition suggest that kdr alleles may have arisen from at least four independent mutation events. Neutrality tests provided evidence for a selective sweep acting on this genomic region, particularly in West Africa. The frequency and distribution of these kdr haplotypes varied geographically, being influenced by an interplay between different mutational occurrences, gene flow and local selection. This has important practical implications for the management and sustainability of malaria vector control programs.

  6. Use of zebrafish and knockdown technology to define proprotein convertase activity.

    Science.gov (United States)

    Chitramuthu, Babykumari P; Bennett, Hugh P J

    2011-01-01

    The Zebrafish (Danio rerio) is a powerful and well-established tool used extensively for the study of early vertebrate development and as a model of human diseases. Zebrafish genes orthologous to their mammalian counterparts generally share conserved biological function. Protein knockdown or overexpression can be effectively achieved by microinjection of morpholino antisense oligonucleotides (MOs) or mRNA, respectively, into developing embryos at the one- to two-cell stage. Correlating gene expression patterns with the characterizing of phenotypes resulting from over- or underexpression can reveal the function of a particular protein. The microinjection technique is simple and results are reproducible. We defined the expression pattern of the proprotein convertase PCSK5 within the lateral line neuromasts and various organs including the liver, gut and otic vesicle by whole-mount in situ hybridization (ISH) and immunofluorescence (IF). MO-mediated knockdown of zebrafish PCSK5 expression generated embryos that display abnormal neuromast deposition within the lateral line system resulting in uncoordinated patterns of swimming.

  7. TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Lee Adam Wheeler

    2016-05-01

    Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

  8. Raman spectroscopic study of keratin 8 knockdown oral squamous cell carcinoma derived cells

    Science.gov (United States)

    Singh, S. P.; Alam, Hunain; Dmello, Crismita; Vaidya, Milind M.; Krishna, C. Murali

    2012-03-01

    Keratins are one of most widely used markers for oral cancers. Keratin 8 and 18 are expressed in simple epithelia and perform both mechanical and regulatory functions. Their expression are not seen in normal oral tissues but are often expressed in oral squamous cell carcinoma. Aberrant expression of keratins 8 and 18 is most common change in human oral cancer. Optical-spectroscopic methods are sensitive to biochemical changes and being projected as novel diagnostic tools for cancer diagnosis. Aim of this study was to evaluate potentials of Raman spectroscopy in detecting minor changes associated with differential level of keratin expression in tongue-cancer-derived AW13516 cells. Knockdown clones for K8 were generated and synchronized by growing under serum-free conditions. Cell pellets of three independent experiments in duplicate were used for recording Raman spectra with fiberoptic-probe coupled HE-785 Raman-instrument. A total of 123 and 96 spectra from knockdown clones and vector controls respectively in 1200-1800 cm-1 region were successfully utilized for classification using LDA. Two separate clusters with classification-efficiency of ~95% were obtained. Leave-one-out cross-validation yielded ~63% efficiency. Findings of the study demonstrate the potentials of Raman spectroscopy in detecting even subtle changes such as variations in keratin expression levels. Future studies towards identifying Raman signals from keratin in oral cells can help in precise cancer diagnosis.

  9. CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

    International Nuclear Information System (INIS)

    Zheng, Jiajia; Zhu, Xi; Zhang, Jie

    2014-01-01

    Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCR and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy

  10. [Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

    Science.gov (United States)

    Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

    2016-12-01

    Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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 http://dx.doi.org/10.1007/JHEP09(2015)144. 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.

  12. Composite fields, generalized hypergeometric functions and the U(1)Y symmetry in the AdS/CFT correspondence

    International Nuclear Information System (INIS)

    Hoffmann, L.; Leonhardt, T.; Mesref, L.; Ruehl, W.

    2001-01-01

    We discuss the concept of composite fields in flat CFT as well as in the context of AdS/CFT. Furthermore we show how to represent Green functions using generalized hypergeometric functions and apply these techniques to four-point functions. Finally we prove an identity of U(1) Y symmetry for four-point functions

  13. Composite fields, generalized hypergeometric functions and the U(1)Y symmetry in the AdS/CFT correspondence

    Science.gov (United States)

    Hoffmann, L.; Leonhardt, T.; Mesref, L.; Rühl, W.

    2001-09-01

    We discuss the concept of composite fields in flat CFT as well as in the context of AdS/CFT. Furthermore we show how to represent Green functions using generalized hypergeometric functions and apply these techniques to four-point functions. Finally we prove an identity of U(1)Y symmetry for four-point functions.

  14. Analysis of the 3 and 4 cycles with extensions in the operation of the CNLV U-1

    International Nuclear Information System (INIS)

    Montes T, J.L.; Torres A, C.; Perusquia C, R.

    1992-08-01

    The objective of the report is the comparison of the radial distributions of burned in the core among the results of the simulation of the Laguna Verde Central U-1 reactor during the operation of the cycles 1 to 4 and the data of the operation with information provided by the fuel supplier. (Author)

  15. AHR2 morpholino knockdown reduces the toxicity of total particulate matter to zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Massarsky, Andrey, E-mail: andrey.massarsky@duke.edu [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Bone, Audrey J. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Dong, Wu [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); School of Animal Science and Technology, Inner Mongolia Provincial Key Laboratory for Toxicants and Animal Disease, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028000 (China); Hinton, David E. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Prasad, G.L. [RAI Services Company, Winston-Salem, NC 27101 (United States); Di Giulio, Richard T. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States)

    2016-10-15

    The zebrafish embryo has been proposed as a ‘bridge model’ to study the effects of cigarette smoke on early development. Previous studies showed that exposure to total particulate matter (TPM) led to adverse effects in developing zebrafish, and suggested that the antioxidant and aryl hydrocarbon receptor (AHR) pathways play important roles. This study investigated the roles of these two pathways in mediating TPM toxicity. The study consisted of four experiments. In experiment I, zebrafish embryos were exposed from 6 h post fertilization (hpf) until 96 hpf to TPM{sub 0.5} and TPM{sub 1.0} (corresponding to 0.5 and 1.0 μg/mL equi-nicotine units) in the presence or absence of an antioxidant (N-acetyl cysteine/NAC) or a pro-oxidant (buthionine sulfoximine/BSO). In experiment II, TPM exposures were performed in embryos that were microinjected with nuclear factor erythroid 2-related factor 2 (Nrf2), AHR2, cytochrome P450 1A (CYP1A), or CYP1B1 morpholinos, and deformities were assessed. In experiment III, embryos were exposed to TPM, and embryos/larvae were collected at 24, 48, 72, and 96 hpf to assess several genes associated with the antioxidant and AHR pathways. Lastly, experiment IV assessed the activity and protein levels of CYP1A and CYP1B1 after exposure to TPM. We demonstrate that the incidence of TPM-induced deformities was generally not affected by NAC/BSO treatments or Nrf2 knockdown. In contrast, AHR2 knockdown reduced, while CYP1A or CYP1B1 knockdowns elevated the incidence of some deformities. Moreover, as shown by gene expression the AHR pathway, but not the antioxidant pathway, was induced in response to TPM exposure, providing further evidence for its importance in mediating TPM toxicity. - Highlights: • Total particulate matter (TPM) is the particulate phase of cigarette smoke. • Zebrafish is proposed as a ‘bridge model’ to study the effects of TPM. • We investigate the roles of antioxidant and aryl hydrocarbon receptor (AHR) pathways.

  16. Simultaneous analysis of multiple Mycobacterium tuberculosis knockdown mutants in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Antje Blumenthal

    2010-12-01

    Full Text Available Mycobacterium tuberculosis (Mtb represents one of the most persistent bacterial threats to human health and new drugs are needed to limit its impact. Conditional knockdown mutants can help validate new drug targets, but the analysis of individual mutants is laborious and time consuming. Here, we describe quantitative DNA tags (qTags and their use to simultaneously analyze conditional Mtb knockdown mutants that allowed silencing the glyoxylate and methylcitrate cycles (via depletion of isocitrate lyase, ICL, the serine protease Rv3671c, and the core subunits of the mycobacterial proteasome, PrcB and PrcA. The impact of gene silencing in multi-strain cultures was determined by measuring the relative abundance of mutant-specific qTags with real-time PCR. This achieved accurate quantification over a broad range of qTag abundances and depletion of ICL, Rv3671c, or PrcBA resulted in the expected impairment of growth of Mtb with butyrate as the primary carbon source, survival during oxidative stress, acid stress and starvation. The impact of depleting ICL, Rv3671c, or PrcBA in multi-strain mouse infections was analyzed with two approaches. We first measured the relative abundance of mutant-specific qTags in total chromosomal DNA isolated from bacteria that were recovered from infected lungs on agar plates. We then developed a two-step amplification procedure, which allowed us to measure the abundances of individual mutants directly in infected lung tissue. Both strategies confirmed that inactivation of Rv3671c and PrcBA severely reduced persistence of Mtb in mice. The multi-strain infections furthermore suggested that silencing ICL not only prevented growth of Mtb during acute infections but also prevented survival of Mtb during chronic infections. Analyses of the ICL knockdown mutant in single-strain infections confirmed this and demonstrated that silencing of ICL during chronic infections impaired persistence of Mtb to the extent that the pathogen

  17. Diminished exercise capacity and mitochondrial bc1 complex deficiency in tafazzin-knockdown mice.

    Directory of Open Access Journals (Sweden)

    Corey ePowers

    2013-04-01

    Full Text Available The phospholipid, cardiolipin, is essential for maintaining mitochondrial structure and optimal function. Cardiolipin-deficiency in humans, Barth syndrome, is characterized by exercise intolerance, dilated cardiomyopathy, neutropenia and 3-methyl-glutaconic aciduria. The causative gene is the mitochondrial acyl-transferase, tafazzin that is essential for remodeling acyl chains of cardiolipin. We sought to determine metabolic rates in tafazzin-deficient mice during resting and exercise, and investigate the impact of cardiolipin deficiency on mitochondrial respiratory chain activities. Tafazzin knockdown in mice markedly impaired oxygen consumption rates during an exercise, without any significant effect on resting metabolic rates. CL-deficiency resulted in significant reduction of mitochondrial respiratory reserve capacity in neonatal cardiomyocytes that is likely to be caused by diminished activity of complex-III, which requires CL for its assembly and optimal activity. Our results may provide mechanistic insights of Barth syndrome pathogenesis.

  18. Knockdown of cytosolic NADP(+) -dependent isocitrate dehydrogenase enhances MPP(+) -induced oxidative injury in PC12 cells.

    Science.gov (United States)

    Yang, Eun Sun; Park, Jeen-Woo

    2011-05-01

    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolite 1-methyl-4-phenylpyridium ion (MPP(+)) have been shown to induce Parkinson's disease-like symptoms as well as neurotoxicity in humans and animal species. Recently, we reported that maintenance of redox balance and cellular defense against oxidative damage are primary functions of the novel antioxidant enzyme cytosolic NADP(+) -dependent isocitrate dehydrogenase (IDPc). In this study, we examined the role of IDPc in cellular defense against MPP(+) -induced oxidative injury using PC12 cells transfected with IDPc small interfering RNA (siRNA). Our results demonstrate that MPP(+) -mediated disruption of cellular redox status, oxidative damage to cells, and apoptotic cell death were significantly enhanced by knockdown of IDPc.

  19. Novel liposomal combination treatments using dual genes knockdown in oral cancer treatment

    Science.gov (United States)

    Wu, Jyun-Sian; Yeh, Chia-Hsien; Huang, Leaf; Hsu, Yih-Chih

    2018-02-01

    Small interfering RNA (siRNA) can be used to treat tumor because it can effectively knockdown target oncoprotein expression and it leads to cancer cell death and apoptosis. Hypoxia-inducible factors-1 (HIF-1) is a transcription factor gene. Its high expression of tumor hypoxia cells, activation of transcription factor HIF-1α and angiogenesis found in most cancerous tissues. HIF-1α protein in cancer cells are critical to cell survival, tumor growth and proliferation. Epidermal growth factor receptor (EGFR) gene is another common head and neck oncogene. The dual self-designed siRNA sequences were encapsulated in the lipid-calcium-phosphate (LCP) and targeted to sigma receptors on the surface of cancer cells via binding to amino ethyl anisamide (AEAA). We used human oral cancer cells to establish the xenograft animal model to study the combination therapy for therapeutic results.

  20. Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis

    Directory of Open Access Journals (Sweden)

    Lv MT

    2016-11-01

    Full Text Available Mutian Lv,1 Yaming Li,1 Xin Tian,2 Shundong Dai,3,4 Jing Sun,5 Guojiang Jin,6 Shenyi Jiang7 1Department of Nuclear Medicine, 2Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, 3Department of Pathology, The First Affiliated Hospital, College of Basic Medical Sciences of China Medical University, 4Department of Pathology, Institute of Pathology and Pathophysiology, 5Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute, 6Department of Laboratory Medicine, 7Department of Rheumatology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: Nemo-like kinase (NLK, an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC, which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro. Moreover, knockdown of NLK led to cell cycle arrest at the S-phase via suppression of Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition. Furthermore, knockdown of NLK decreased the migration of NCI-H446 cells and downregulated matrix metalloproteinase 9. Treatment with NLK short hairpin RNA significantly reduced SCLC tumor growth in vivo. In conclusion, this study suggests that NLK plays an important role in the growth and metastasis of SCLC and may serve as a potential therapeutic target for the treatment of SCLC. Keywords: NLK, SCLC, RNAi, proliferation, migration

  1. Knockdown of hypocretin attenuates extended access of cocaine self-administration in rats.

    Science.gov (United States)

    Schmeichel, Brooke E; Matzeu, Alessandra; Koebel, Pascale; Vendruscolo, Leandro F; Sidhu, Harpreet; Shahryari, Roxana; Kieffer, Brigitte L; Koob, George F; Martin-Fardon, Rémi; Contet, Candice

    2018-04-06

    The hypocretin/orexin (HCRT) neuropeptide system regulates feeding, arousal state, stress responses, and reward, especially under conditions of enhanced motivational relevance. In particular, HCRT neurotransmission facilitates drug-seeking behavior in circumstances that demand increased effort and/or motivation to take the drug. The present study used a shRNA-encoding adeno-associated viral vector to knockdown Hcrt expression throughout the dorsal hypothalamus in adult rats and determine the role of HCRT in cocaine self-administration. Chronic Hcrt silencing did not impact cocaine self-administration under short-access conditions, but robustly attenuated cocaine intake under extended access conditions, a model that mimics key features of compulsive cocaine taking. In addition, Hcrt silencing decreased motivation for both cocaine and a highly palatable food reward (i.e., sweetened condensed milk; SCM) under a progressive ratio schedule of reinforcement, but did not alter responding for SCM under a fixed ratio schedule. Importantly, Hcrt silencing did not affect food or water consumption, and had no consequence for general measures of arousal and stress reactivity. At the molecular level, chronic Hcrt knockdown reduced the number of neurons expressing dynorphin (DYN), and to a smaller extent melanin-concentrating hormone (MCH), in the dorsal hypothalamus. These original findings support the hypothesis that HCRT neurotransmission promotes operant responding for both drug and non-drug rewards, preferentially under conditions requiring a high degree of motivation. Furthermore, the current study provides compelling evidence for the involvement of the HCRT system in cocaine self-administration also under low-effort conditions in rats allowed extended access, possibly via functional interactions with DYN and MCH signaling.

  2. A protein knockdown strategy to study the function of β-catenin in tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhou Pengbo

    2003-09-01

    Full Text Available Abstract Background The Wnt signaling pathway plays critical roles in cell proliferation and cell fate determination at many stages of development. A critical downstream target of Wnt signaling is the cytosolic β-catenin, which is stabilized upon Wnt activation and promotes transcription of a variety of target genes including c-myc and cyclin D. Aberrant Wnt signaling, which results from mutations of either β-catenin or adenomatous polyposis coli (APC, renders β-catenin resistant to degradation, and has been associated with multiple types of human cancers. Results A protein knockdown strategy was designed to reduce the cytosolic β-catenin levels through accelerating its turnover rate. By engineering a chimeric protein with the β-catenin binding domain of E-cadherin fused to βTrCP ubiquitin-protein ligase, the stable β-catenin mutant was recruited to the cellular SCF (Skp1, Cullin 1, and F-box-containing substrate receptor ubiquitination machinery for ubiquitination and degradation. The DLD1 colon cancer cells express wild type β-catenin at abnormally high levels due to loss of APC. Remarkably, conditional expression of βTrCP-E-cadherin under the control of a tetracycline-repressive promoter in DLD1 cells selectively knocked down the cytosolic, but not membrane-associated subpopulation of β-catenin. As a result, DLD1 cells were impaired in their growth and clonogenic ability in vitro, and lost their tumorigenic potential in nude mice. Conclusion We have designed a novel approach to induce degradation of stabilized/mutated β-catenin. Our results suggest that a high concentration of cytoplasmic β-catenin is critical for the growth of colorectal tumor cells. The protein knockdown strategy can be utilized not only as a novel method to dissect the role of oncoproteins in tumorigenesis, but also as a unique tool to delineate the function of a subpopulation of proteins localized to a specific subcellular compartment.

  3. Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding.

    Science.gov (United States)

    More, Vijay R; Xu, Jialin; Shimpi, Prajakta C; Belgrave, Clyde; Luyendyk, James P; Yamamoto, Masayuki; Slitt, Angela L

    2013-08-01

    The nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the progression of metabolic syndrome with long-term high-fat diet (HFD) feeding. C57BL/6 and Keap1-knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene expression. HFD feeding increased hepatic steatosis and inflammation to a greater extent in Keap1-KD mice compared to C57BL/6 mice, which was associated with increased liver Cd36, fatty acid-binding protein 4, and monocyte chemoattractant protein 1 mRNA expression, as well as increased acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1 protein expression. The HFD altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice, which was accompanied by downregulation of insulin receptor substrate 1 mRNA expression in skeletal muscle. Together, the results indicate that Keap1 knockdown, on treatment with HFD, increases certain markers of metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Expression and knockdown of zebrafish folliculin suggests requirement for embryonic brain morphogenesis.

    Science.gov (United States)

    Kenyon, Emma J; Luijten, Monique N H; Gill, Harmeet; Li, Nan; Rawlings, Matthew; Bull, James C; Hadzhiev, Yavor; van Steensel, Maurice A M; Maher, Eamonn; Mueller, Ferenc

    2016-07-08

    Birt-Hogg-Dubé syndrome (BHD) is a dominantly inherited familial cancer syndrome characterised by the development of benign skin fibrofolliculomas, multiple lung and kidney cysts, spontaneous pneumothorax and susceptibility to renal cell carcinoma. BHD is caused by mutations in the gene encoding Folliculin (FLCN). Little is known about what FLCN does in a healthy individual and how best to treat those with BHD. As a first approach to developing a vertebrate model for BHD we aimed to identify the temporal and spatial expression of flcn transcripts in the developing zebrafish embryo. To gain insights into the function of flcn in a whole organism system we generated a loss of function model of flcn by the use of morpholino knockdown in zebrafish. flcn is expressed broadly and upregulated in the fin bud, somites, eye and proliferative regions of the brain of the Long-pec stage zebrafish embryos. Together with knockdown phenotypes, expression analysis suggest involvement of flcn in zebrafish embryonic brain development. We have utilised the zFucci system, an in vivo, whole organism cell cycle assay to study the potential role of flcn in brain development. We found that at the 18 somite stage there was a significant drop in cells in the S-M phase of the cell cycle in flcn morpholino injected embryos with a corresponding increase of cells in the G1 phase. This was particularly evident in the brain, retina and somites of the embryo. Timelapse analysis of the head region of flcn morpholino injected and mismatch control embryos shows the temporal dynamics of cell cycle misregulation during development. In conclusion we show that zebrafish flcn is expressed in a non-uniform manner and is likely required for the maintenance of correct cell cycle regulation during embryonic development. We demonstrate the utilisation of the zFucci system in testing the role of flcn in cell proliferation and suggest a function for flcn in regulating cell proliferation in vertebrate embryonic

  5. Quantification of Functionalised Gold Nanoparticle-Targeted Knockdown of Gene Expression in HeLa Cells

    Science.gov (United States)

    Jiwaji, Meesbah; Sandison, Mairi E.; Reboud, Julien; Stevenson, Ross; Daly, Rónán; Barkess, Gráinne; Faulds, Karen; Kolch, Walter; Graham, Duncan; Girolami, Mark A.; Cooper, Jonathan M.; Pitt, Andrew R.

    2014-01-01

    Introduction Gene therapy continues to grow as an important area of research, primarily because of its potential in the treatment of disease. One significant area where there is a need for better understanding is in improving the efficiency of oligonucleotide delivery to the cell and indeed, following delivery, the characterization of the effects on the cell. Methods In this report, we compare different transfection reagents as delivery vehicles for gold nanoparticles functionalized with DNA oligonucleotides, and quantify their relative transfection efficiencies. The inhibitory properties of small interfering RNA (siRNA), single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA) sequences targeted to human metallothionein hMT-IIa are also quantified in HeLa cells. Techniques used in this study include fluorescence and confocal microscopy, qPCR and Western analysis. Findings We show that the use of transfection reagents does significantly increase nanoparticle transfection efficiencies. Furthermore, siRNA, ssRNA and ssDNA sequences all have comparable inhibitory properties to ssDNA sequences immobilized onto gold nanoparticles. We also show that functionalized gold nanoparticles can co-localize with autophagosomes and illustrate other factors that can affect data collection and interpretation when performing studies with functionalized nanoparticles. Conclusions The desired outcome for biological knockdown studies is the efficient reduction of a specific target; which we demonstrate by using ssDNA inhibitory sequences targeted to human metallothionein IIa gene transcripts that result in the knockdown of both the mRNA transcript and the target protein. PMID:24926959

  6. [Knockdown of PRDX6 in microglia reduces neuron viability after OGD/R injury].

    Science.gov (United States)

    Tan, Li; Zhao, Yong; Jiang, Beibei; Yang, Bo; Zhang, Hui

    2016-08-01

    Objective To observe the effects of peroxiredoxin 6 (PRDX6) knockdown in the microglia on neuron viability after oxygen-glucose deprivation and reoxygenation (OGD/R). Methods Microglia was treated with lentivirus PRDX6-siRNA and Ca(2+)-independent phospholipase A2 (iPLA2) inhibitor, 1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol (MJ33). Twenty-four hours later, it was co-cultured with primary neuron to establish the microglia-neuron co-culture OGD/R model. According to the different treatment of microglia, the cells were divided into normal group, OGD/R group, negative control-siRNA treated OGD/R group, PRDX6-siRNA treated OGD/R group and PRDX6-siRNA combined with MJ33 treated OGD/R group. Western blot analysis and real-time quantitative PCR were respectively performed to detect PRDX6 protein and mRNA levels after knockdown of PRDX6 in microglia. The iPLA2 activity was measured by ELISA. MTS and lactate dehydrogenase (LDH) assay were used to measure neuron viability and cell damage. The oxidative stress level of neuron was determined by measuring superoxide dismutase (SOD) and malonaldehyde (MDA) content. Results In PRDX6-siRNA group, neuron viability was inhibited and oxidative stress damage was aggravated compared with OGD/R group. In PRDX6-siRNA combined with MJ33 group, cell viability was promoted and oxidative stress damage was alleviated compared with PRDX6-siRNA group. Conclusion PRDX6 in microglia protects neuron against OGD/R-induced injury, and iPLA2 activity has an effect on PRDX6.

  7. Keratin23 (KRT23) knockdown decreases proliferation and affects the DNA damage response of colon cancer cells

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Hahn, Stephan; Mansilla, Francisco

    2013-01-01

    correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed...... response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced......Keratin 23 (KRT23) is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation...

  8. Calculation of the top quark mass in the flipped SU(5)xU(1) superstring model

    Energy Technology Data Exchange (ETDEWEB)

    Leontaris, G.K.; Rizos, J.; Tamvakis, K. (Ioannina Univ. (Greece). Dept. of Physics)

    1990-11-08

    We present a complete renormalization group calculation of the top-quark mass in the SU(5)xU(1) superstring model. We solve the coupled renormalization group equations for the gauge and Yukawa couplings in the two-loop approximation and obtain the top-quark mass as a function of two parameters of the model which could be chosen to be ratios of singlet VEVs associated with the surplus (U(1)){sup 4} breaking. We obtain a heavy top-quark with 150 GeV{le}m{sub t}<200 GeV, for most part of the parameter space, while lower values are possible only in a very small extremal region. We also compute the allowed range of unification parameters (M{sub x}, sin{sup 2}{theta}{sub w}, {alpha}{sub 3}(M{sub W})) in the presence of a heavy top-quark. (orig.).

  9. The maximal U(1){sub L} inverse seesaw from d = 5 operator and oscillating asymmetric Sneutrino dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Zhaofeng [Korea Institute for Advanced Study, School of Physics, Seoul (Korea, Republic of); Institute of Theoretical Physics, Chinese Academy of Sciences, Key Laboratory of Frontiers in Theoretical Physics, Beijing (China); Li, Jinmian [Institute of Theoretical Physics, Chinese Academy of Sciences, Key Laboratory of Frontiers in Theoretical Physics, Beijing (China); University of Adelaide, ARC Centre of Excellence for Particle Physics at the Terascale and CSSM, Department of Physics, Adelaide, SA (Australia); Li, Tianjun [Institute of Theoretical Physics, Chinese Academy of Sciences, Key Laboratory of Frontiers in Theoretical Physics, Beijing (China); University of Electronic Science and Technology of China, School of Physical Electronics, Chengdu (China); Liu, Tao [University of Alberta, Department of Physics, Edmonton, Alberta (Canada); Yang, Jin Min [Institute of Theoretical Physics, Chinese Academy of Sciences, Key Laboratory of Frontiers in Theoretical Physics, Beijing (China)

    2016-05-15

    The maximal U(1){sub L} supersymmetric inverse seesaw mechanism (MLSIS) provides a natural way to relate asymmetric darkmatter (ADM)with neutrino physics. In this paper we point out that MLSIS is a natural outcome if one dynamically realizes the inverse seesaw mechanism in the next-to minimal supersymmetric standard model (NMSSM) via the dimension-five operator (N){sup 2}S{sup 2}/M{sub *}, with S the NMSSM singlet developing TeV scale VEV; it slightly violates lepton number due to the suppression by the fundamental scale M{sub *}, thus preserving U(1){sub L} maximally. The resulting sneutrino is a distinguishable ADM candidate, oscillating and favored to have weak scale mass. A fairly large annihilating cross section of such a heavy ADM is available due to the presence of singlet. (orig.)

  10. Semidirect product gauge group [SU(3)cxSU(2)L]xU(1)Y and quantization of hypercharge

    International Nuclear Information System (INIS)

    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) c xSU(2) L xU(1) Y alone. We show that, if we choose the semidirect product group [SU(3) c xSU(2) L ]xU(1) 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.

  11. SU(n)c x SU(m)L x U(1)N generalizations of the standard model

    International Nuclear Information System (INIS)

    Pleitez, V.

    1993-01-01

    Generalizations of the Standard Model which are based on the gauge symmetry SU(n) c x SU(m) L x U(1) N are considered. Although the most interesting possibility occurs when n = 3, it will be considered also the cases n = 4,5, both with m = 3,4. It will also be given possible grand unification scenarios. (author). 18 refs

  12. Some new contributions to neutrinoless double β-decay in an SU(2)xU(1) model

    International Nuclear Information System (INIS)

    Escobar, C.O.

    1982-11-01

    An SU(2) x U(1) model having both Dirac and Majorana mass terms for the neutrinos, with an extended Higgs sector without natural flavor conservation is considered. Under these conditions, it is shown that for a certain range of the mass parameters of the model, some new contributions become important for the neutrinoless double β-decay (ββ)oν. (Author) [pt

  13. SU(5)×U(1)X grand unification with minimal seesaw and Z‧-portal dark matter

    Science.gov (United States)

    Okada, Nobuchika; Okada, Satomi; Raut, Digesh

    2018-05-01

    We propose a grand unified SU (5) × U(1)X model, where the standard SU(5) grand unified theory is supplemented by minimal seesaw and a right-handed neutrino dark matter with an introduction of a global Z2-parity. In the presence of three right-handed neutrinos (RHNs), the model is free from all gauge and mixed-gravitational anomalies. The SU(5) symmetry is broken into the Standard Model (SM) gauge group at MGUT ≃ 4 ×1016GeV in the standard manner, while the U(1)X symmetry breaking occurs at the TeV scale, which generates the TeV-scale mass of the U(1)X gauge boson (Z‧ boson) and the three Majorana RHNs. A unique Z2-odd RHN is stable and serves as the dark matter (DM) in the present Universe, while the remaining two RHNs work to generate the SM neutrino masses through the minimal seesaw. We investigate the Z‧-portal RHN DM scenario in this model context. We find that the constraints from the DM relic abundance, and the Z‧ boson search at the Large Hadron Collider (LHC), and the perturbativity bound on the U(1)X gauge coupling are complementary to narrow down the allowed parameter region in the range of 3.0 ≤mZ‧ [TeV ] ≤ 9.2 for the Z‧ boson mass. The allowed region for mZ‧ ≤ 5TeV will be fully covered by the future LHC experiments. We also briefly discuss the successful implementation of Baryogenesis and cosmological inflation scenarios in the present model.

  14. SU(2) X SU(2) X U(1) basis for symmetric SO(6) representations: matrix elements of the generators

    International Nuclear Information System (INIS)

    Piepenbring, R.; Silvestre-Brac, B.; Szymanski, Z.

    1987-01-01

    Matrix elements of the group generators for the symmetric irreducible representations of SO(6) are explicitly calculated in a closed form employing thedecomposition chain SO(6) is contained in SU(2) X SU(2) X U(1) (which is different from the well known Wigner supermultiplet scheme). The relation to the Gel'fand Tsetlin method using SO(6) contained in SO(5) up to ... SO(2) is indicated. An example of a physical application is given

  15. Anomalous leptonic U(1) symmetry: Syndetic origin of the QCD axion, weak-scale dark matter, and radiative neutrino mass

    Science.gov (United States)

    Ma, Ernest; Restrepo, Diego; Zapata, Óscar

    2018-01-01

    The well-known leptonic U(1) symmetry of the Standard Model (SM) of quarks and leptons is extended to include a number of new fermions and scalars. The resulting theory has an invisible QCD axion (thereby solving the strong CP problem), a candidate for weak-scale dark matter (DM), as well as radiative neutrino masses. A possible key connection is a color-triplet scalar, which may be produced and detected at the Large Hadron Collider.

  16. Phenomenology of the spontaneous C P violation in SU(3)L x U(1)Y electroweak models

    International Nuclear Information System (INIS)

    Epele, Luis N.; Gomez Dumm, Daniel A.

    1994-01-01

    This work studies the phenomenological consequence of the spontaneous C P violation in a SU(3) L x U(1) Y model with three Higgs triplets and one sextuplet, which has been recently proposed. Since this C P-violating effects are due to the presence of complex vacuum expectation values in the Higgs sector, our analysis requires a detailed study of the enlarged potential

  17. Dark matter contribution to b → sμ+μ- anomaly in local U(1) Lμ -Lτ model

    Science.gov (United States)

    Baek, Seungwon

    2018-06-01

    We propose a local U(1) Lμ -Lτ model to explain b → sμ+μ- anomaly observed at the LHCb and Belle experiments. The model also has a natural dark matter candidate N. We introduce SU(2)L-doublet colored scalar q ˜ to mediate b → s transition at one-loop level. The U(1) Lμ -Lτ gauge symmetry is broken spontaneously by the scalar S. All the new particles are charged under U(1) Lμ -Lτ. We can obtain C9μ , NP ∼ - 1 to solve the b → sμ+μ- anomaly and can explain the correct dark matter relic density of the universe, ΩDMh2 ≈ 0.12, simultaneously, while evading constraints from electroweak precision tests, neutrino trident experiments and other quark flavor-changing loop processes such as b → sγ and Bs -B‾s mixing. Our model can be tested by searching for Z‧ and new colored scalar at the LHC and B →K* ν ν ‾ process at Belle-II.

  18. FIMP and muon (g−2) in a U(1){sub L{sub μ−L{sub τ}}} model

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Anirban [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 019 (India); Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India); Choubey, Sandhya [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 019 (India); Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India); Department of Theoretical Physics, School of Engineering Sciences, KTH Royal Institute of Technology, AlbaNova University Center, 106 91 Stockholm (Sweden); Khan, Sarif [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 019 (India); Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094 (India)

    2017-02-23

    The tightening of the constraints on the standard thermal WIMP scenario has forced physicists to propose alternative dark matter (DM) models. One of the most popular alternate explanations of the origin of DM is the non-thermal production of DM via freeze-in. In this scenario the DM never attains thermal equilibrium with the thermal soup because of its feeble coupling strength (∼ 10{sup −12}) with the other particles in the thermal bath and is generally called the Feebly Interacting Massive Particle (FIMP). In this work, we present a gauged U(1){sub L{sub μ−L{sub τ}}} extension of the Standard Model (SM) which has a scalar FIMP DM candidate and can consistently explain the DM relic density bound. In addition, the spontaneous breaking of the U(1){sub L{sub μ−L{sub τ}}} gauge symmetry gives an extra massive neutral gauge boson Z{sub μτ} which can explain the muon (g−2) data through its additional one-loop contribution to the process. Lastly, presence of three right-handed neutrinos enable the model to successfully explain the small neutrino masses via the Type-I seesaw mechanism. The presence of the spontaneously broken U(1){sub L{sub μ−L{sub τ}}} gives a particular structure to the light neutrino mass matrix which can explain the peculiar mixing pattern of the light neutrinos.

  19. NLRC5 knockdown in chicken macrophages alters response to LPS and poly (I:C stimulation

    Directory of Open Access Journals (Sweden)

    Lian Ling

    2012-03-01

    Full Text Available Abstract Background NLRC5 is a member of the CARD domain containing, nucleotide-binding oligomerization (NOD-like receptor (NLR family, which recognizes pathogen-associated molecular patterns (PAMPs and initiates an innate immune response leading to inflammation and/or cell death. However, the specific role of NLRC5 as a modulator of the inflammatory immune response remains controversial. It has been reported to be a mediator of type I IFNs, NF-kB, and MHC class I gene. But no study on NLRC5 function has been reported to date in chickens. In the current study, we investigated the role of NLRC5 in the regulation of IFNA, IFNB, IL-6, and MHC class I in the chicken HD11 macrophage cell line, by using RNAi technology. HD11 cells were transfected with one of five siRNAs (s1, s2, s3, negative-siRNA, or a mixture of s1, s2, s3-siRNAs. After 24 hours, cells were exposed to LPS or poly (I:C or a vehicle control. Gene expression of NLRC5, IFNA, IFNB, IL-6, and MHC class I at 2, 4, 6, and 8 hours post stimulation (hps was quantified by qPCR. Results The expression of NLRC5, IFNA, IFNB, and IL-6 genes in negative irrelevant transfection controls was up-regulated at 2 hps after LPS treatment compared to the vehicle controls. S3-siRNA effectively knocked down NLRC5 expression at 4 hps, and the expression of IFNA and IFNB (but not IL-6 and MHC class I was also down-regulated at 4 hps in s3-siRNA transfected cells, compared to negative irrelevant transfection controls. Stimulation by LPS appeared to relatively restore the decrease in NLRC5, IFNA, and IFNB expression, but the difference is not significant. Conclusions Functional characterization of chicken NLRC5 in an in vitro system demonstrated its importance in regulating intracellular molecules involved in inflammatory response. The knockdown of NLRC5 expression negatively mediates gene expression of IFNA and IFNB in the chicken HD11 cell line; therefore, NLRC5 likely has a role in positive regulation of

  20. Knockdown of HIF-1α and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells.

    Science.gov (United States)

    Choi, Sung Hoon; Park, Jun Yong; Kang, Wonseok; Kim, Seung Up; Kim, Do Young; Ahn, Sang Hoon; Ro, Simon Wonsang; Han, Kwang-Hyub

    2016-01-01

    A local hypoxic microenvironment is one of the most important characteristics of solid tumors. Hypoxia inducible factor-1α (HIF-1α) and Interleukin-8 (IL-8) activate tumor survival from hypoxic-induced apoptosis in each pathway. This study aimed to evaluate whether knockdown of HIF-1α and IL-8 induced apoptosis of the hepatocellular carcinoma (HCC) and endothelial cell lines. HCC cell lines were infected with adenovirus-expressing shRNA for HIF-1α and IL-8 and maintained under hypoxic conditions (1% O2, 24 h). The expression levels of HIF-1α and both apoptotic and growth factors were examined by real-time quantitative PCR and western blot. We also investigated apoptosis by TUNEL assay (FACS and Immunofluorescence) and measured the concentration of cytochrome C. Inhibition of HIF-1α and IL-8 up-regulated the expression of apoptotic factors while downregulating anti-apoptotic factors simultaneously. Knockdown of HIF-1α and IL-8 increased the concentration of cytochrome C and enhanced DNA fragmentation in HCC cell lines. Moreover, culture supernatant collected from the knockdown of HIF-1α and IL-8 in HCC cell lines induced apoptosis in human umbilical vein endothelial cells under hypoxia, and the expression of variable apoptotic ligand increased from HCC cell lines, time-dependently. These data suggest that adenovirus-mediated knockdown of HIF-1α and IL-8 induced apoptosis in HCC cells and triggered apoptosis of vascular endothelial cells.

  1. Knockdown of angiopoietin-like 2 mimics the benefits of intermittent fasting on insulin responsiveness and weight loss.

    Science.gov (United States)

    Martel, Cécile; Pinçon, Anthony; Bélanger, Alexandre Maxime; Luo, Xiaoyan; Gillis, Marc-Antoine; de Montgolfier, Olivia; Thorin-Trescases, Nathalie; Thorin, Éric

    2018-01-01

    Angiopoietin-like 2 (ANGPTL2) is an inflammatory adipokine linking obesity to insulin resistance. Intermittent fasting, on the other hand, is a lifestyle intervention able to prevent obesity and diabetes but difficult to implement and maintain. Our objectives were to characterize a link between ANGPTL2 and intermittent fasting and to investigate whether the knockdown of ANGPTL2 reproduces the benefits of intermittent fasting on weight gain and insulin responsiveness in knockdown and wild-type littermates mice. Intermittent fasting, access to food ad libitum once every other day, was initiated at the age of three months and maintained for four months. Intermittent fasting decreased by 63% (p < 0.05) gene expression of angptl2 in adipose tissue of wild-type mice. As expected, intermittent fasting improved insulin sensitivity (p < 0.05) and limited weight gain (p < 0.05) in wild-type mice. Knockdown mice fed ad libitum, however, were comparable to wild-type mice following the intermittent fasting regimen: insulin sensitivity and weight gain were identical, while intermittent fasting had no additional impact on these parameters in knockdown mice. Energy intake was similar between both wild-type fed intermittent fasting and ANGPTL2 knockdown mice fed ad libitum, suggesting that intermittent fasting and knockdown of ANGPTL2 equally lower feeding efficiency. These results suggest that the reduction of ANGPTL2 could be a useful and promising strategy to prevent obesity and insulin resistance, although further investigation of the mechanisms linking ANGPTL2 and intermittent fasting is warranted. Impact statement Intermittent fasting is an efficient diet pattern to prevent weight gain and improve insulin sensitivity. It is, however, a difficult regimen to follow and compliance is expected to be very low. In this work, we demonstrate that knockdown of ANGPTL2 in mice fed ad libitum mimics the beneficial effects of intermittent fasting on weight gain and insulin

  2. MRP4 knockdown enhances migration, suppresses apoptosis, and produces aggregated morphology in human retinal vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Tagami, Mizuki [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Kusuhara, Sentaro, E-mail: kusu@med.kobe-u.ac.jp [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Imai, Hisanori [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Uemura, Akiyoshi [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Department of Vascular Biology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Honda, Shigeru; Tsukahara, Yasutomo; Negi, Akira [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-10-01

    Research highlights: {yields} Exogenous VEGF decreases MRP4 expression in a dose-dependent manner. {yields} MRP4 knockdown leads to enhanced cell migration. {yields} MRP4 knockdown suppresses caspase-3-mediated cell apoptosis. {yields} MRP4 knockdown produces cell assembly and cell aggregation. -- Abstract: The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly understood so far. This study aims to explore the angiogenic properties of MRP4 in human retinal microvascular endothelial cells (HRECs) utilizing the RNA interference (RNAi) technique. MRP4 expression was decreased at the mRNA and protein levels after stimulation with exogenous vascular endothelial growth factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not affect cell proliferation but enhances cell migration. Moreover, cell apoptosis induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation assay, although MRP4 knockdown did not lead to a significant change in the total tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive tube-like structure, which was not observed in control siRNA-treated HRECs. These results suggest that MRP4 is uniquely involved in retinal angiogenesis.

  3. Optimization of Critical Hairpin Features Allows miRNA-based Gene Knockdown Upon Single-copy Transduction

    Directory of Open Access Journals (Sweden)

    Renier Myburgh

    2014-01-01

    Full Text Available Gene knockdown using micro RNA (miRNA-based vector constructs is likely to become a prominent gene therapy approach. It was the aim of this study to improve the efficiency of gene knockdown through optimizing the structure of miRNA mimics. Knockdown of two target genes was analyzed: CCR5 and green fluorescent protein. We describe here a novel and optimized miRNA mimic design called mirGE comprising a lower stem length of 13 base pairs (bp, positioning of the targeting strand on the 5′ side of the miRNA, together with nucleotide mismatches in upper stem positions 1 and 12 placed on the passenger strand. Our mirGE proved superior to miR-30 in four aspects: yield of targeting strand incorporation into RNA-induced silencing complex (RISC; incorporation into RISC of correct targeting strand; precision of cleavage by Drosha; and ratio of targeting strand over passenger strand. A triple mirGE hairpin cassette targeting CCR5 was constructed. It allowed CCR5 knockdown with an efficiency of over 90% upon single-copy transduction. Importantly, single-copy expression of this construct rendered transduced target cells, including primary human macrophages, resistant to infection with a CCR5-tropic strain of HIV. Our results provide new insights for a better knockdown efficiency of constructs containing miRNA. Our results also provide the proof-of-principle that cells can be rendered HIV resistant through single-copy vector transduction, rendering this approach more compatible with clinical applications.

  4. Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK cells

    Directory of Open Access Journals (Sweden)

    Akira Marine

    2014-01-01

    Full Text Available Superoxide is widely regarded as the primary reactive oxygen species (ROS which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1α expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ, a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS inhibitor demonstrated that peroxynitrite (at low micromolar levels induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation.

  5. Effects of vivo morpholino knockdown of lateral hypothalamus orexin/hypocretin on renewal of alcohol seeking.

    Science.gov (United States)

    Prasad, Asheeta A; McNally, Gavan P

    2014-01-01

    Two experiments used vivo morpholinos to assess the role of orexin/hypocretin in ABA renewal of extinguished alcohol seeking. Rats were trained to respond for alcoholic beer in a distinctive context, A, and then extinguished in a second distinctive context, B. When rats were tested in the extinction context, ABB, responding was low but when they were tested in the training context, ABA, responding was significantly higher. Microinjection of an orexin/hypocretin antisense vivo morpholino into LH significantly reduced orexin/hypocretin protein expression but had no effect on the ABA renewal of alcohol seeking (Experiment 1). Microinjection of a higher dose of the antisense vivo morpholino into LH also significantly reduced orexin/hypocretin protein expression but this was not selective and yielded significant reduction in melanin-concentrating hormone (MCH) protein expression. This non-selective knockdown did significantly reduce ABA renewal as well as reduce the reacquisition of alcohol seeking. Taken together, these findings show an important role for LH in the ABA renewal of alcohol seeking but that orexin/hypocretin is not necessary for this renewal.

  6. Effects of vivo morpholino knockdown of lateral hypothalamus orexin/hypocretin on renewal of alcohol seeking.

    Directory of Open Access Journals (Sweden)

    Asheeta A Prasad

    Full Text Available Two experiments used vivo morpholinos to assess the role of orexin/hypocretin in ABA renewal of extinguished alcohol seeking. Rats were trained to respond for alcoholic beer in a distinctive context, A, and then extinguished in a second distinctive context, B. When rats were tested in the extinction context, ABB, responding was low but when they were tested in the training context, ABA, responding was significantly higher. Microinjection of an orexin/hypocretin antisense vivo morpholino into LH significantly reduced orexin/hypocretin protein expression but had no effect on the ABA renewal of alcohol seeking (Experiment 1. Microinjection of a higher dose of the antisense vivo morpholino into LH also significantly reduced orexin/hypocretin protein expression but this was not selective and yielded significant reduction in melanin-concentrating hormone (MCH protein expression. This non-selective knockdown did significantly reduce ABA renewal as well as reduce the reacquisition of alcohol seeking. Taken together, these findings show an important role for LH in the ABA renewal of alcohol seeking but that orexin/hypocretin is not necessary for this renewal.

  7. Sex determination in beetles: Production of all male progeny by Parental RNAi knockdown of transformer

    Science.gov (United States)

    Shukla, Jayendra Nath; Palli, Subba Reddy

    2012-01-01

    Sex in insects is determined by a cascade of regulators ultimately controlling sex-specific splicing of a transcription factor, Doublesex (Dsx). We recently identified homolog of dsx in the red flour beetle, Tribolium castaneum (Tcdsx). Here, we report on the identification and characterization of a regulator of Tcdsx splicing in T. castaneum. Two male-specific and one female-specific isoforms of T. castaneum transformer (Tctra) were identified. RNA interference-aided knockdown of Tctra in pupa or adults caused a change in sex from females to males by diverting the splicing of Tcdsx pre-mRNA to male-specific isoform. All the pupa and adults developed from Tctra dsRNA injected final instar larvae showed male-specific sexually dimorphic structures. Tctra parental RNAi caused an elimination of females from the progeny resulting in production of all male progeny. Transformer parental RNAi could be used to produce all male population for use in pest control though sterile male release methods. PMID:22924109

  8. Analysis of changes to mRNA levels and CTCF occupancy upon TFII-I knockdown

    Directory of Open Access Journals (Sweden)

    Maud Marques

    2015-06-01

    Full Text Available CTCF is a key regulator of nuclear chromatin structure, chromatin organization and gene regulation. The impact of CTCF on transcriptional output is quite varied, ranging from repression, to transcriptional pausing and transactivation. The multifunctional nature of CTCF is mediated, in part, through differential association with protein partners having unique properties. We identified the general transcription factor TFII-I as an interacting partner of CTCF. To gain an understanding of the function of TFII-I in regulating gene expression and CTCF binding genome wide, we conducted microarray experiments following TFII-I knockdown and chromatin immunoprecipitation of CTCF followed by next generation sequencing (ChIP-seq from the same TFII-I depleted cells. Here, we described the experimental design and the quality control and analysis that were performed on the dataset. The data is publicly available through the GEO database with accession number GSE60918. The interpretation and description of these data are included in a manuscript in revision (1.

  9. Efficient and specific gene knockdown by small interfering RNAs produced in bacteria

    Science.gov (United States)

    Huang, Linfeng; Jin, Jingmin; Deighan, Padraig; Kiner, Evgeny; McReynolds, Larry; Lieberman, Judy

    2013-01-01

    Synthetic small interfering RNAs (siRNAs) are an indispensable tool to investigate gene function in eukaryotic cells1,2 and may be used for therapeutic purposes to knockdown genes implicated in disease3. Thus far, most synthetic siRNAs have been produced by chemical synthesis. Here we present a method to produce highly potent siRNAs in E. coli. This method relies on ectopic expression of p19, a siRNA-binding protein found in a plant RNA virus4, 5. When expressed in E. coli, p19 stabilizes ~21 nt siRNA-like species produced by bacterial RNase III. Transfection of mammalian cells with siRNAs, generated in bacteria expressing p19 and a hairpin RNA encoding 200 or more nucleotides of a target gene, at low nanomolar concentrations reproducibly knocks down gene expression by ~90% without immunogenicity or off-target effects. Because bacterially produced siRNAs contain multiple sequences against a target gene, they may be especially useful for suppressing polymorphic cellular or viral genes. PMID:23475073

  10. Cofilin Knockdown Attenuates Hemorrhagic Brain Injury-induced Oxidative Stress and Microglial Activation in Mice.

    Science.gov (United States)

    Alhadidi, Qasim; Nash, Kevin M; Alaqel, Saleh; Sayeed, Muhammad Shahdaat Bin; Shah, Zahoor A

    2018-05-08

    Intracerebral hemorrhage (ICH) resulting from the rupture of the blood vessels in the brain is associated with significantly higher mortality and morbidity. Clinical studies focused on alleviating the primary injury, hematoma formation and expansion, were largely ineffective, suggesting that secondary injury-induced inflammation and the formation of reactive species also contribute to the overall injury process. In this study, we explored the effects of cofilin knockdown in a mouse model of ICH. Animals given stereotaxic injections of cofilin siRNA, 72-h prior to induction of ICH by collagenase injection within the area of siRNA administration showed significantly decreased cofilin expression levels and lower hemorrhage volume and edema, and the animals performed significantly better in neurobehavioral tasks i.e., rotarod, grip strength and neurologic deficit scores. Cofilin siRNA knocked-down mice had reduced ICH-induced DNA fragmentation, blood-brain barrier disruption and microglial activation, with a concomitant increase in astrocyte activation. Increased expression of pro-survival proteins and decreased markers of oxidative stress were also observed in cofilin siRNA-treated mice possibly due to the reduced levels of cofilin. Our results suggest that cofilin plays a major role in ICH-induced secondary injury, and could become a potential therapeutic target. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. The anomalous U(1){sub anom} symmetry and flavors from an SU(5) x SU(5){sup '} GUT in Z{sub 12-I} orbifold compactification

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihn E. [Kyung Hee University, Department of Physics, Seoul (Korea, Republic of); Center for Axion and Precision Physics Research (IBS), Daejeon (Korea, Republic of); Kyae, Bumseok [Pusan National University, Department of Physics, Busan (Korea, Republic of); Nam, Soonkeon [Kyung Hee University, Department of Physics, Seoul (Korea, Republic of)

    2017-12-15

    In string compactifications, frequently the anomalous U(1) gauge symmetry appears which belongs to E{sub 8} x E{sub 8}{sup '} of the heterotic string. This anomalous U(1) gauge boson obtains mass at the compactification scale (∼ 10{sup 18} GeV) by absorbing one pseudoscalar (corresponding to the model-independent axion) from the second rank antisymmetric tensor field B{sub MN}. Below the compactification scale a global symmetry U(1){sub anom} results whose charge Q{sub anom} is the original gauge U(1) charge. This is the most natural global symmetry, realizing the ''invisible'' axion. This global symmetry U(1){sub anom} is suitable for a flavor symmetry. In the simplest compactification model with the flipped SU(5) grand unification, all the low energy parameters are calculated in terms of the vacuum expectation values of the standard model singlets. (orig.)

  12. The anomalous U(1)_{anom} symmetry and flavors from an SU(5) × SU(5)' GUT in Z_{12-I} orbifold compactification

    Science.gov (United States)

    Kim, Jihn E.; Kyae, Bumseok; Nam, Soonkeon

    2017-12-01

    In string compactifications, frequently the anomalous U(1) gauge symmetry appears which belongs to E_8 × E_8' of the heterotic string. This anomalous U(1) gauge boson obtains mass at the compactification scale (≈ 10^{18 } {GeV}) by absorbing one pseudoscalar (corresponding to the model-independent axion) from the second rank antisymmetric tensor field B_{MN}. Below the compactification scale a global symmetry U(1)_{anom} results whose charge Q_anom is the original gauge U(1) charge. This is the most natural global symmetry, realizing the "invisible" axion. This global symmetry U(1)_{anom} is suitable for a flavor symmetry. In the simplest compactification model with the flipped SU(5) grand unification, all the low energy parameters are calculated in terms of the vacuum expectation values of the standard model singlets.

  13. Freeze-in production of sterile neutrino dark matter in U(1){sub B−L} model

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Anirban; Gupta, Aritra [Harish-Chandra Research Institute,Chhatnag Road, Jhunsi, Allahabad 211 019 (India)

    2016-09-27

    With the advent of new and more sensitive direct detection experiments, scope for a thermal WIMP explanation of dark matter (DM) has become extremely constricted. The non-observation of thermal WIMP in these experiments has put a strong upper bound on WIMP-nucleon scattering cross section and within a few years it is likely to overlap with the coherent neutrino-nucleon cross section. Hence in all probability, DM may have some non-thermal origin. In this work we explore in detail this possibility of a non-thermal sterile neutrino DM within the framework of U(1){sub B−L} model. The U(1){sub B−L} model on the other hand is a well-motivated and minimal way of extending the standard model so that it can explain the neutrino masses via Type-I see-saw mechanism. We have shown, besides explaining the neutrino mass, it can also accommodate a non-thermal sterile neutrino DM with correct relic density. In contrast with the existing literature, we have found that W{sup ±} decay can also be a dominant production mode of the sterile neutrino DM. To obtain the comoving number density of dark matter, we have solved here a coupled set of Boltzmann equations considering all possible decay as well as annihilation production modes of the sterile neutrino dark matter. The framework developed here though has been done for a U(1){sub B−L} model, can be applied quite generally for any models with an extra neutral gauge boson and a fermionic non-thermal dark matter.

  14. Experimentally verifiable Yang-Mills spin 2 gauge theory of gravity with group U(1) x SU(2)

    International Nuclear Information System (INIS)

    Peng, H.

    1988-01-01

    In this work, a Yang-Mills spin 2 gauge theory of gravity is proposed. Based on both the verification of the helicity 2 property of the SU(2) gauge bosons of the theory and the agreement of the theory with most observational and experimental evidence, the authors argues that the theory is truly a gravitational theory. An internal symmetry group, the eigenvalues of its generators are identical with quantum numbers, characterizes the interactions of a given class. The author demonstrates that the 4-momentum P μ of a fermion field generates the U(1) x SU(2) internal symmetry group for gravity, but not the transformation group T 4 . That particles are classified by mass and spin implies that the U(1) x SU(2), instead of the Poincare group, is a symmetry group of gravity. It is shown that the U(1) x SU(2) group represents the time displacement and rotation in ordinary space. Thereby internal space associated with gravity is identical with Minkowski spacetime, so a gauge potential of gravity carries two space-time indices. Then he verifies that the SU(2) gravitational boson has helicity 2. It is this fact, spin from internal spin, that explains alternatively why the gravitational field is the only field which is characterized by spin 2. The Physical meaning of gauge potentials of gravity is determined by comparing theory with the results of experiments, such as the Collella-Overhauser-Werner (COW) experiment and the Newtonian limit, etc. The gauge potentials this must identify with ordinary gravitational potentials

  15. Neutrino masses in the flipped SU(5) x U(1) and the SU(4) x O(4) GUT models

    Energy Technology Data Exchange (ETDEWEB)

    Ranfone, S.; Papageorgiu, E.

    1992-03-01

    We classify the different neutrino-mass pattern arising in string-inspired Grand Universal Theory (GUT) and supersymmetric GUT models based on the flipped SU(5)xU(1) and the SU(4)xO(4) gauge groups. Phenomenologically interesting spectra are obtained through the interplay of the two seesaw mechanisms present, with typical neutrino masses {approx}10{sup -3} eV in the supersymmetric GUT models and of order 0.1 - 10 KeV in the ordinary GUTs. (author).

  16. Phenomenology of the hierarchical lepton mass spectrum in the flipped SU(5)xU(1) string model

    Energy Technology Data Exchange (ETDEWEB)

    Leontaris, G.K.; Nanopoulos, D.V.

    1988-09-29

    A detailed phenomenological analysis of the lepton mass matrices and their implications in the low energy theory are discussed, within the recently proposed SU(5)xU(1) string model. The unification scale is highly constrained while the Yukawa couplings lie in a natural region. The flavour changing decays ..mu.. -> e..gamma.., ..mu.. -> 3e, ..mu.. -> e are highly suppressed while the depletion in the flux of muon neutrinos reported by the Kamiokande is explained through ..nu../sub ..mu../ reversible ..nu../sub tau/ oscillations.

  17. A minimal spontaneous CP violation model with small neutrino mass and SU(2) x U(1) x Z3 symmetry

    International Nuclear Information System (INIS)

    Geng, C.Q.; Ng, J.N.

    1988-04-01

    It is shown that spontaneous CP violation and natural flavor conservation can occur in the SU(2) L x U(1) Y model based on two Higgs doublet and one Higgs singlet fields with a Z 3 discrete symmetry. Physical CP nonconservation is purely due to scalar-pseudoscalar mixings. In order for this to be a major source of CP violation a light spin-O boson of mass less than 10 GeV is required. The see-saw mechanism can be implemented to generate small neutrino masses. The model implies a relatively large electric dipole moment for charged leptons and small value for ε'/ε

  18. Conflict between natural flavor conservation of Higgs couplings and Cabibbo mixing in SU(2)/sub L/ x U (1)

    International Nuclear Information System (INIS)

    Segre, G.; Arthur Weldon, H.

    1980-01-01

    The general problem of conservation of strangeness and other quark flavors by the exchange of several neutral Higgs mesons is investigated in SU (2)/sub L/ x U (1). We find that the horizontal symmetries necessary to enforce this conservation conflict with the known Cabibbo mixing. In particular, if the quarks form an irreducible representation of the horizontal symmetry, the mixing angles are all trivial (i.e. 0 or π/2); if they form a reducible representation, it is possible to have some nontrivial mixing angles, but only if there are several unmixed generations of quarks with exactly the same relative pattern of masses and mixings

  19. Extended SL(2,R)/U(1) characters, or modular properties of a simple non-rational conformal field theory

    International Nuclear Information System (INIS)

    Israel, D.; Pakman, A.; Troost, J.

    2004-01-01

    We define extended SL(2,R)/U(1) characters which include a sum over winding sectors. By embedding these characters into similarly extended characters of N=2 algebras, we show that they have nice modular transformation properties. We calculate the modular matrices of this simple but non-trivial non-rational conformal field theory explicitly. As a result, we show that discrete SL(2,R) representations mix with continuous SL(2,R) representations under modular transformations in the coset conformal field theory. We comment upon the significance of our results for a general theory of non-rational conformal field theories. (author)

  20. The moduli space of two U(1) instantons on noncommutative $R^4$ and $R^3\\times S^1$

    OpenAIRE

    Lee, Kimyeong; Tong, David; Yi, Sangheon

    2000-01-01

    We employ the ADHM method to derive the moduli space of two instantons in U(1) gauge theory on a noncommutative space. We show by an explicit hyperK\\"ahler quotient construction that the relative metric of the moduli space of two instantons on $R^4$ is the Eguchi-Hanson metric and find a unique threshold bound state. For two instantons on $R^3\\times S^1$, otherwise known as calorons, we give the asymptotic metric and conjecture a completion. We further discuss the relationship of caloron modu...

  1. On a phase transition of a Kosterlitz-thouless-type in the d=4, U(1)-lattice gauge theory

    International Nuclear Information System (INIS)

    Marchetti, D.H.U.; Perez, J.F.

    1986-12-01

    The d=4, U(1)-lattice gauge theory with the Villain action may be represented as a locally neutral gas of topological (plaquette) charges which interact via a logarithmically confining potential, is shown. Using this representation a renormalization group analysis to show the existence of a phase transition of the Kosterlitz-Thouless-type was performed. An improved hierarchical version of the model which displays (unlike the usual Migdal-Kadanoff approach) a stable line of gaussian fixed points at low temperatures, which should correspond to the usual deconfining region of these systems is presented. (Author) [pt

  2. Neutrinophilic two Higgs doublet model with dark matter under an alternative U(1)_{B-L} gauge symmetry

    Science.gov (United States)

    Nomura, Takaaki; Okada, Hiroshi

    2018-03-01

    We propose a Dirac type active neutrino with rank two mass matrix and a Majorana fermion dark matter candidate with an alternative local U(1)_{B-L} extension of neutrinophilic two Higgs doublet model. Our dark matter candidate can be stabilized due to charge assignment under the gauge symmetry without imposing extra discrete Z_2 symmetry and the relic density is obtained from an Z' boson exchanging process. Taking into account collider constraints on the Z' boson mass and coupling, we estimate the relic density.

  3. Pure classical SU(2) Yang-Mills theory with potentials invariant under a U(1) gauge subgroup

    International Nuclear Information System (INIS)

    Bacry, H.

    1978-07-01

    The present article is devoted to pure SU(2) classical Yang-Mills theories whose potentials are invariant under a U(1) gauge subgroup. Such potentials are shown to be associated with classical Maxwell-like fields with magnetic sources as 't Hooft's monopole is associated with the Dirac magnetic monopole. Conversely, the authors give Yang-Mills potentials corresponding to some Maxwell-like fields, in particular static magnetic fields with emphasis on those with cylindrical symmetry (including the dipole and other multipoles) and the ephemerons corresponding to an instantaneous magnetic multipole

  4. Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine Expression

    Directory of Open Access Journals (Sweden)

    Hai Van Le

    2016-06-01

    Full Text Available Toll-like receptor 10 (TLR10 is the only orphan receptor whose natural ligand and function are unknown among the 10 human TLRs. In this study, to test whether TLR10 recognizes some known TLR ligands, we established a stable TLR10 knockdown human monocytic cell line THP-1 using TLR10 short hairpin RNA lentiviral particle and puromycin selection. Among 60 TLR10 knockdown clones that were derived from each single transduced cell, six clones were randomly selected, and then one of those clones, named E7, was chosen for the functional study. E7 exhibited approximately 50% inhibition of TLR10 mRNA and protein expression. Of all the TLRs, only the expression of TLR10 changed significantly in this cell line. Additionally, phorbol 12-myristate 13-acetate-induced macrophage differentiation of TLR10 knockdown cells was not affected in the knockdown cells. When exposed to TLR ligands, such as synthetic diacylated lipoprotein (FSL-1, lipopolysaccharide (LPS, and flagellin, significant induction of proinflammatory cytokine gene expression including Interleukin-8 (IL-8, Interleukin-1 beta (IL-1β, Tumor necrosis factor-alpha (TNF-α and Chemokine (C–C Motif Ligand 20 (CCL20 expression, was found in the control THP-1 cells, whereas the TLR10 knockdown cells exhibited a significant reduction in the expression of IL-8, IL-1β, and CCL20. TNF-α was the only cytokine for which the expression did not decrease in the TLR10 knockdown cells from that measured in the control cells. Analysis of putative binding sites for transcription factors using a binding-site-prediction program revealed that the TNF-α promoter does not have putative binding sites for AP-1 or c-Jun, comprising a major transcription factor along with NF-κB for TLR signaling. Our results suggest that TLR10 is involved in the recognition of FSL-1, LPS, and flagellin and TLR-ligand-induced expression of TNF-α does not depend on TLR10.

  5. Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine Expression.

    Science.gov (United States)

    Le, Hai Van; Kim, Jae Young

    2016-06-01

    Toll-like receptor 10 (TLR10) is the only orphan receptor whose natural ligand and function are unknown among the 10 human TLRs. In this study, to test whether TLR10 recognizes some known TLR ligands, we established a stable TLR10 knockdown human monocytic cell line THP-1 using TLR10 short hairpin RNA lentiviral particle and puromycin selection. Among 60 TLR10 knockdown clones that were derived from each single transduced cell, six clones were randomly selected, and then one of those clones, named E7, was chosen for the functional study. E7 exhibited approximately 50% inhibition of TLR10 mRNA and protein expression. Of all the TLRs, only the expression of TLR10 changed significantly in this cell line. Additionally, phorbol 12-myristate 13-acetate-induced macrophage differentiation of TLR10 knockdown cells was not affected in the knockdown cells. When exposed to TLR ligands, such as synthetic diacylated lipoprotein (FSL-1), lipopolysaccharide (LPS), and flagellin, significant induction of proinflammatory cytokine gene expression including Interleukin-8 (IL-8), Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha (TNF-α) and Chemokine (C-C Motif) Ligand 20 (CCL20) expression, was found in the control THP-1 cells, whereas the TLR10 knockdown cells exhibited a significant reduction in the expression of IL-8, IL-1β, and CCL20. TNF-α was the only cytokine for which the expression did not decrease in the TLR10 knockdown cells from that measured in the control cells. Analysis of putative binding sites for transcription factors using a binding-site-prediction program revealed that the TNF-α promoter does not have putative binding sites for AP-1 or c-Jun, comprising a major transcription factor along with NF-κB for TLR signaling. Our results suggest that TLR10 is involved in the recognition of FSL-1, LPS, and flagellin and TLR-ligand-induced expression of TNF-α does not depend on TLR10.

  6. Depdc5 knockdown causes mTOR-dependent motor hyperactivity in zebrafish.

    Science.gov (United States)

    de Calbiac, Hortense; Dabacan, Adriana; Marsan, Elise; Tostivint, Hervé; Devienne, Gabrielle; Ishida, Saeko; Leguern, Eric; Baulac, Stéphanie; Muresan, Raul C; Kabashi, Edor; Ciura, Sorana

    2018-05-01

    DEPDC5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in a wide range of inherited forms of focal epilepsy, associated with malformation of cortical development in certain cases. Identification of frameshift, truncation, and deletion mutations implicates haploinsufficiency of DEPDC5 in the etiology of focal epilepsy. DEPDC5 is a component of the GATOR1 complex, acting as a negative regulator of mTOR signaling. Zebrafish represents a vertebrate model suitable for genetic analysis and drug screening in epilepsy-related disorders. In this study, we defined the expression of depdc5 during development and established an epilepsy model with reduced Depdc5 expression. Here we report a zebrafish model of Depdc5 loss-of-function that displays a measurable behavioral phenotype, including hyperkinesia, circular swimming, and increased neuronal activity. These phenotypic features persisted throughout embryonic development and were significantly reduced upon treatment with the mTORC1 inhibitor, rapamycin, as well as overexpression of human WT DEPDC5 transcript. No phenotypic rescue was obtained upon expression of epilepsy-associated DEPDC5 mutations (p.Arg487* and p.Arg485Gln), indicating that these mutations cause a loss of function of the protein. This study demonstrates that Depdc5 knockdown leads to early-onset phenotypic features related to motor and neuronal hyperactivity. Restoration of phenotypic features by WT but not epilepsy-associated Depdc5 mutants, as well as by mTORC1 inhibition confirm the role of Depdc5 in the mTORC1-dependent molecular cascades, defining this pathway as a potential therapeutic target for DEPDC5 -inherited forms of focal epilepsy.

  7. Knockdown of Progesterone Receptor (PGR) in Macaque Granulosa Cells Disrupts Ovulation and Progesterone Production.

    Science.gov (United States)

    Bishop, Cecily V; Hennebold, Jon D; Kahl, Christoph A; Stouffer, Richard L

    2016-05-01

    Adenoviral vectors (vectors) expressing short-hairpin RNAs complementary to macaque nuclear progesterone (P) receptor PGR mRNA (shPGR) or a nontargeting scrambled control (shScram) were used to determine the role PGR plays in ovulation/luteinization in rhesus monkeys. Nonluteinized granulosa cells collected from monkeys (n = 4) undergoing controlled ovarian stimulation protocols were exposed to either shPGR, shScram, or no virus for 24 h; human chorionic gonadotropin (hCG) was then added to half of the wells to induce luteinization (luteinized granulosa cells [LGCs]; n = 4-6 wells/treatment/monkey). Cells/media were collected 48, 72, and 120 h postvector for evaluation of PGR mRNA and P levels. Addition of hCG increased (P < 0.05) PGR mRNA and medium P levels in controls. However, a time-dependent decline (P < 0.05) in PGR mRNA and P occurred in shPGR vector groups. Injection of shPGR, but not shScram, vector into the preovulatory follicle 20 h before hCG administration during controlled ovulation protocols prevented follicle rupture in five of six monkeys as determined by laparoscopic evaluation, with a trapped oocyte confirmed in three of four follicles of excised ovaries. Injection of shPGR also prevented the rise in serum P levels following the hCG bolus compared to shScram (P < 0.05). Nuclear PGR immunostaining was undetectable in granulosa cells from shPGR-injected follicles, compared to intense staining in shScram controls. Thus, the nuclear PGR appears to mediate P action in the dominant follicle promoting ovulation in primates. In vitro and in vivo effects of PGR knockdown in LGCs also support the hypothesis that P enhances its own synthesis in the primate corpus luteum by promoting luteinization. © 2016 by the Society for the Study of Reproduction, Inc.

  8. PlGF gene knockdown in human retinal pigment epithelial cells.

    Science.gov (United States)

    Akrami, Hassan; Soheili, Zahra-Soheila; Sadeghizadeh, Majid; Ahmadieh, Hamid; Rezaeikanavi, Mozhgan; Samiei, Shahram; Khalooghi, Keynoush

    2011-04-01

    To evaluate the knockdown of placental growth factor (PlGF) gene expression in human retinal pigment epithelium (RPE) cells and its effect on cell proliferation, apoptosis and angiogenic potential of RPE cells. Human RPE cells were isolated by dispase I solution and cultured in DMEM/F12 supplemented with 10% fetal calf serum (FCS). A small interfering RNA (siRNA) corresponding to PlGF mRNA and a scrambled siRNA (scRNA) were introduced into the cells. Cell proliferation and cell death were examined by ELISA. PlGF mRNA and protein were quantified by real-time polymerase chain reaction (PCR) and western blot. The levels of gene expression for human retinal pigment epithelium-specific protein 65 kDa (RPE65), cellular retinaldehyde-binding protein (CRALBP) and tyrosinase were examined by real-time PCR. The angiogenic activity of RPE cell-derived conditioned media was assayed by a tube formation assay using human umbilical vein endothelial cells (HUVECs). At a final siRNA concentration of 20 pmol/ml, the transfection efficiency was about 80%. The amount of PlGF transcripts was reduced to 10% after 36 h of incubation, and the amount of PlGF protein in culture supernatant was significantly decreased. Suppression of PlGF gene had no effect on RPE cell proliferation and survival, and there were no notable changes in the transcript levels of RPE65, CRALBP or tyrosinase for the cultures treated by siRNA cognate to PlGF. Vascular tube formation was efficiently reduced in HUVECs. Our findings present PlGF as a key modulator of angiogenic potential in RPE cells of the human retina.

  9. Functional characterization of Pol III U6 promoters for gene knockdown and knockout in Plutella xylostella.

    Science.gov (United States)

    Huang, Yuping; Wang, Yajun; Zeng, Baosheng; Liu, Zhaoxia; Xu, Xuejiao; Meng, Qian; Huang, Yongping; Yang, Guang; Vasseur, Liette; Gurr, Geoff M; You, Minsheng

    2017-10-01

    RNA polymerase type III (Pol-III) promoters such as U6 are commonly used to express small RNAs, including short hairpin RNAs (shRNAs) and single guide RNAs (sgRNAs). Functional U6 promoters are widely used in CRISPR systems, and their characterization can facilitate genome editing of non-model organisms. In the present study, six U6 small nuclear RNA (snRNA) promoters containing two conserved elements of a proximal sequence element (PSEA) and a TATA box, were identified and characterized in the diamondback moth (Plutella xylostella) genome. Relative efficiency of the U6 promoters to express shRNA induced EGFP knockdown was tested in a P. xylostella cell line, revealing that the PxU6:3 promoter had the strongest expression effect. Further work with the PxU6:3 promoter showed its efficacy in EGFP knockout using CRISPR/Cas9 system in the cells. The expression plasmids with versatile Pxabd-A gene specific sgRNA driven by the PxU6:3 promoter, combined with Cas9 mRNA, could induce mutagenesis at specific genomic loci in vivo. The phenotypes induced by sgRNA expression plasmids were similar to those done in vitro transcription sgRNAs. A plasmid with two tandem arranged PxU6:3:sgRNA expression cassettes targeting Pxabd-A loci was generated, which caused a 28,856 bp fragment deletion, suggesting that the multi-sgRNA expression plasmid can be used for multi-targeting. Our work indicates that U6 snRNA promoters can be used for functional studies of genes with the approach of reverse genetics in P. xylostella. These essential promoters also provide valuable potential for CRISPR-derived gene drive as a tactic for population control in this globally significant pest. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Genetic architecture of a hormonal response to gene knockdown in honey bees.

    Science.gov (United States)

    Ihle, Kate E; Rueppell, Olav; Huang, Zachary Y; Wang, Ying; Fondrk, M Kim; Page, Robert E; Amdam, Gro V

    2015-01-01

    Variation in endocrine signaling is proposed to underlie the evolution and regulation of social life histories, but the genetic architecture of endocrine signaling is still poorly understood. An excellent example of a hormonally influenced set of social traits is found in the honey bee (Apis mellifera): a dynamic and mutually suppressive relationship between juvenile hormone (JH) and the yolk precursor protein vitellogenin (Vg) regulates behavioral maturation and foraging of workers. Several other traits cosegregate with these behavioral phenotypes, comprising the pollen hoarding syndrome (PHS) one of the best-described animal behavioral syndromes. Genotype differences in responsiveness of JH to Vg are a potential mechanistic basis for the PHS. Here, we reduced Vg expression via RNA interference in progeny from a backcross between 2 selected lines of honey bees that differ in JH responsiveness to Vg reduction and measured JH response and ovary size, which represents another key aspect of the PHS. Genetic mapping based on restriction site-associated DNA tag sequencing identified suggestive quantitative trait loci (QTL) for ovary size and JH responsiveness. We confirmed genetic effects on both traits near many QTL that had been identified previously for their effect on various PHS traits. Thus, our results support a role for endocrine control of complex traits at a genetic level. Furthermore, this first example of a genetic map of a hormonal response to gene knockdown in a social insect helps to refine the genetic understanding of complex behaviors and the physiology that may underlie behavioral control in general. © The American Genetic Association. 2015.

  11. Rip3 knockdown rescues photoreceptor cell death in blind pde6c zebrafish.

    Science.gov (United States)

    Viringipurampeer, I A; Shan, X; Gregory-Evans, K; Zhang, J P; Mohammadi, Z; Gregory-Evans, C Y

    2014-05-01

    Achromatopsia is a progressive autosomal recessive retinal disease characterized by early loss of cone photoreceptors and later rod photoreceptor loss. In most cases, mutations have been identified in CNGA3, CNGB3, GNAT2, PDE6C or PDE6H genes. Owing to this genetic heterogeneity, mutation-independent therapeutic schemes aimed at preventing cone cell death are very attractive treatment strategies. In pde6c(w59) mutant zebrafish, cone photoreceptors expressed high levels of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3) kinases, key regulators of necroptotic cell death. In contrast, rod photoreceptor cells were alternatively immunopositive for caspase-3 indicating activation of caspase-dependent apoptosis in these cells. Morpholino gene knockdown of rip3 in pde6c(w59) embryos rescued the dying cone photoreceptors by inhibiting the formation of reactive oxygen species and by inhibiting second-order neuron remodelling in the inner retina. In rip3 morphant larvae, visual function was restored in the cones by upregulation of the rod phosphodiesterase genes (pde6a and pde6b), compensating for the lack of cone pde6c suggesting that cones are able to adapt to their local environment. Furthermore, we demonstrated through pharmacological inhibition of RIP1 and RIP3 activity that cone cell death was also delayed. Collectively, these results demonstrate that the underlying mechanism of cone cell death in the pde6c(w59) mutant retina is through necroptosis, whereas rod photoreceptor bystander death occurs through a caspase-dependent mechanism. This suggests that targeting the RIP kinase signalling pathway could be an effective therapeutic intervention in retinal degeneration patients. As bystander cell death is an important feature of many retinal diseases, combinatorial approaches targeting different cell death pathways may evolve as an important general principle in treatment.

  12. Knockdown of IL-8 Provoked Premature Senescence of Placenta-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Li, Juan-Juan; Ma, Feng-Xia; Wang, You-Wei; Chen, Fang; Lu, Shi-Hong; Chi, Ying; Du, Wen-Jing; Song, Bao-Quan; Hu, Liang-Ding; Chen, Hu; Han, Zhong-Chao

    2017-06-15

    Mesenchymal stem cells (MSCs) have shown promise for use in cell therapy, and due to their tumor tropism can serve as vehicles for delivering therapeutic agents to tumor sites. Because interleukin-8 (IL-8) is known to mediate the protumor effect of MSCs, elimination of IL-8 secretion by MSCs may enhance their safety for use in cancer gene therapy. However, little is known concerning the effect of endogenously secreted IL-8 on MSCs. We performed studies using placenta-derived MSCs (PMSCs) to determine whether knockdown of IL-8 would influence their biological activity. We first verified that IL-8 and its membrane receptor CXCR2, but not CXCR1, were highly expressed in PMSCs. We then employed lentivirus-mediated small hairpin RNA interference to generate stable IL-8-silenced PMSCs, which displayed a variety of characteristic senescent phenotypes. We observed that at day 9 post-transfection, IL-8-silenced PMSCs had become larger and displayed a more flattened appearance when compared with their controls. Moreover, their proliferation, colony forming unit-fibroblast formation, adipogenic and osteogenic differentiation, and immunosuppressive potentials were significantly impaired. Enhanced senescence-associated β-galactosidase (SA-β-gal) activity and specific global gene expression profiles confirmed that IL-8 silencing evoked the senescence process in PMSCs. Increased levels of p-Akt and decreased levels of FOXO3a protein expression suggested that reactive oxygen species played a role in the initiation and maintenance of senescence in IL-8-silenced PMSCs. Notably, the majority of CXCR2 ligands were downregulated in presenescent IL-8-silenced PMSCs but upregulated in senescent cells, indicating an antagonistic pleiotropy of the IL-8/CXCR2 signaling pathway in PMSCs. This effect may promote the proliferation of young cells and accelerate senescence of old cells.

  13. [Knock-down of ZEB1 inhibits the proliferation, invasion and migration of gastric cancer cells].

    Science.gov (United States)

    Chen, Dengyu; Chu, Yifan; Zheng, Qingwei; Xu, Zhiben; Zhou, Ping; Li, Sheng

    2017-08-01

    Objective To down-regulate the expression of zinc-finger E-box binding homeobox 1 (ZEB1) gene by shRNA, and investigate its effect on invasion, migration and proliferation, as well as the related gene expressions of lncRNA HOTAIR and E-cadherin in human gastric cancer BGC823 cells. Methods RNA interfering (RNAi) was used to knock down ZEB1 in gastric cancer BGC823 cells. The recombinant plasmid shZEB1 was constructed and transfected into the gastric cancer BGC823 cells by Lipofectamine TM 2000, and the stably transfected cells were isolated by G418 selection and limited dilution. The expression of ZEB1 mRNA and protein was detected by real-time quantitative PCR and Western blot analysis. Cell proliferation was determined by MTT assay, and the invasion and migration abilities of BGC823 cells were monitored by Transwell TM invasion assay and wound healing assay, respectively. The expressions of lncRNA HOTAIR and E-cadherin mRNA were detected by real-time quantitative PCR. Results After ZEB1 expression was successfully down-regulated in BGC823 cells by siRNA, the proliferation, invasion and migration rates in shZEB1 transfection group were significantly lower than those in control group; meanwhile, the expression of lncRNA HOTAIR was reduced and E-cadherin expression was enhanced. Conclusion Knock-down of ZEB1 expression by RNA interference can decease lncRNA HOTAIR expression and restrain cell proliferation, invasion and migration in gastric cancer BGC823 cells.

  14. [Knockdown of ATG5 enhances the sensitivity of human renal carcinoma cells to sunitinib].

    Science.gov (United States)

    Li, Peng; Han, Qi; Tang, Ming; Zhang, Keqin

    2017-03-01

    Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown. Proliferation rate of A-498 cells in control group and ATG5 low expression group was determined by flow cytometry. Finally, the survival rate was detected by MTT assay after A-498 cells were treated with different concentrations of sunitinib. Results The expression levels of ATG5 and LC3 in renal clear cell carcinoma tissues were significantly higher than those in para-tumor tissues. The expression levels of ATG5 and LC3 were associated with classification, histological grade, TNM stage and survival rate, rather than gender, age, location, tumor size. Compared with the control group, the protein expressions of ATG5 and LC3 significantly decreased in A-498 cells with ATG5 low expression. The cell proliferation rate in ATG5 downregulation group was lower than that in the control group. Compared with control group, the survival rate in ATG5 low expression group were significantly reduced in a dose-dependent manner after sunitinib treatment. Conclusion Autophagy is active in renal clear cell carcinoma, and the drug sensitivity to sunitinib in renal cancer cells can be enhanced by the downregulation of ATG5.

  15. A small interfering RNA screen of genes involved in DNA repair identifies tumor-specific radiosensitization by POLQ knockdown

    DEFF Research Database (Denmark)

    Higgins, Geoff S; Prevo, Remko; Lee, Yin-Fai

    2010-01-01

    The effectiveness of radiotherapy treatment could be significantly improved if tumor cells could be rendered more sensitive to ionizing radiation (IR) without altering the sensitivity of normal tissues. However, many of the key therapeutically exploitable mechanisms that determine intrinsic tumor...... radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity. Parallel siRNA screens were conducted in irradiated and unirradiated tumor cells (SQ20B......) and irradiated normal tissue cells (MRC5). Using gammaH2AX foci at 24 hours after IR, we identified several genes, such as BRCA2, Lig IV, and XRCC5, whose knockdown is known to cause increased cell radiosensitivity, thereby validating the primary screening end point. In addition, we identified POLQ (DNA...

  16. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC

    DEFF Research Database (Denmark)

    Garbarino, J.; Pan, M. H.; Chin, H. F.

    2012-01-01

    small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT...... synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein...... membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well. -Garbarino, J., M. Pan, H.F. Chin, F.W. Lund, F.R. Maxfield, and J.L. Breslow. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma...

  17. Investigating knockdown resistance (kdr) mechanism against pyrethroids/DDT in the malaria vector Anopheles funestus across Africa.

    Science.gov (United States)

    Irving, Helen; Wondji, Charles S

    2017-08-09

    Understanding the molecular basis of insecticide resistance is key to improve the surveillance and monitoring of malaria vector populations under control. In the major malaria vector Anopheles funestus, little is currently known about the role of the knockdown resistance (kdr) mechanism. Here, we investigated the presence and contribution of knockdown resistance (kdr) to pyrethroids/DDT resistance observed in Anopheles funestus across Africa. Pyrosequencing genotyping and sequencing of the voltage gated sodium channel (VGSC) gene did not detect the common L1014F mutation in field collected An. funestus across Africa. Amplification and cloning of the full-length of the sodium channel gene in pyrethroid resistant mosquitoes revealed evidences of alternative splicing events with three transcripts of 2092, 2061 and 2117 amino acids (93% average similarity to An. gambiae). Several amino acid changes were detected close to the domain II of the protein such as L928R, F938 W, I939S, L802S and T1008 M. However, all these mutations are found at low frequency and their role in pyrethroid resistance could not be established. The presence of the exclusive alternative splicing at exon 19 was not associated with resistance phenotype. Analysis of patterns of genetic diversity of the VGSC gene revealed a high polymorphism level of this gene across Africa with no evidence of directional selection suggesting a limited role for knockdown resistance in pyrethroid resistance in An. funestus. Patterns of genetic differentiation correlate with previous observations of the existence of barriers to gene flow Africa-wide with southern population significantly differentiated from other regions. Despite an apparent limited role of knockdown resistance in An. funestus, it is necessary to continue to monitor the contribution of the mutations detected here as increasing selection from insecticide-based interventions may change the dynamic in field populations as previously observed in other

  18. Can RNAi-mediated hsp90α knockdown in combination with 17-AAG be a therapy for glioma?

    Science.gov (United States)

    Mehta, Adi; Shervington, Amal; Howl, John; Jones, Sarah; Shervington, Leroy

    2013-01-01

    Heat shock protein 90 promotes tumor progression and survival and has emerged as a vital therapeutic target. Previously we reported that the combinatorial treatment of 17AAG/sihsp90α significantly downregulated Hsp90α mRNA and protein levels in Glioblastoma Multiforme (GBM). Here we investigated the ability of cell penetrating peptide (Tat48-60 CPP)-mediated siRNA-induced hsp90α knockdown as a single agent and in combination with 17-allylamino-17-demethoxygeldanamycin (17-AAG) to induce tumor growth inhibition in GBM and whether it possessed therapeutic implications. GBM and non-tumorigenic cells exposed to siRNA and/or 17-AAG were subsequently assessed by qRT-PCR, immunofluorescence, FACS analysis, quantitative Akt, LDH leakage and cell viability assays. PAGE was performed for serum stability assessment. A combination of siRNA/17-AAG treatment significantly induced Hsp90α gene and protein knockdown by 95% and 98%, respectively, concomitant to 84% Akt kinase activity attenuation, induced cell cycle arrest and tumor-specific cytotoxicity by 88%. Efficient complex formation between CPP and siRNA exhibited improved serum stability of the siRNA with minimal intrinsic toxicity in vitro. The preliminary in vivo results showed that combination therapy induced hsp90α knockdown and attenuated Akt kinase activity in intracranial glioblastoma mouse models. The results imply that RNAi-mediated hsp90α knockdown increases 17-AAG treatment efficacy in GBM. In addition, the cytotoxic response observed was the consequence of downregulation of hsp90α gene expression, reduced Akt kinase activity and S-G2/M cell cycle arrest. These results are novel and highlight the ability of Tat to efficiently deliver siRNA in GBM and suggest that the dual inhibition of Hsp90 has therapeutic potentials.

  19. Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.

    Science.gov (United States)

    Ye, Xueting; Xie, Jing; Huang, Hang; Deng, Zhexian

    2018-01-01

    Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling. © 2018 The Author(s). Published by S. Karger AG, Basel.

  20. Acute Podocyte Vascular Endothelial Growth Factor (VEGF-A) Knockdown Disrupts alphaVbeta3 Integrin Signaling in the Glomerulus

    Science.gov (United States)

    Veron, Delma; Villegas, Guillermo; Aggarwal, Pardeep Kumar; Bertuccio, Claudia; Jimenez, Juan; Velazquez, Heino; Reidy, Kimberly; Abrahamson, Dale R.; Moeckel, Gilbert; Kashgarian, Michael; Tufro, Alda

    2012-01-01

    Podocyte or endothelial cell VEGF-A knockout causes thrombotic microangiopathy in adult mice. To study the mechanism involved in acute and local injury caused by low podocyte VEGF-A we developed an inducible, podocyte-specific VEGF-A knockdown mouse, and we generated an immortalized podocyte cell line (VEGFKD) that downregulates VEGF-A upon doxycycline exposure. Tet-O-siVEGF:podocin-rtTA mice express VEGF shRNA in podocytes in a doxycycline-regulated manner, decreasing VEGF-A mRNA and VEGF-A protein levels in isolated glomeruli to ∼20% of non-induced controls and urine VEGF-A to ∼30% of control values a week after doxycycline induction. Induced tet-O-siVEGF:podocin-rtTA mice developed acute renal failure and proteinuria, associated with mesangiolysis and microaneurisms. Glomerular ultrastructure revealed endothelial cell swelling, GBM lamination and podocyte effacement. VEGF knockdown decreased podocyte fibronectin and glomerular endothelial alphaVbeta3 integrin in vivo. VEGF receptor-2 (VEGFR2) interacts with beta3 integrin and neuropilin-1 in the kidney in vivo and in VEGFKD podocytes. Podocyte VEGF knockdown disrupts alphaVbeta3 integrin activation in glomeruli, detected by WOW1-Fab. VEGF silencing in cultured VEGFKD podocytes downregulates fibronectin and disrupts alphaVbeta3 integrin activation cell-autonomously. Collectively, these studies indicate that podocyte VEGF-A regulates alphaVbeta3 integrin signaling in the glomerulus, and that podocyte VEGF knockdown disrupts alphaVbeta3 integrin activity via decreased VEGFR2 signaling, thereby damaging the three layers of the glomerular filtration barrier, causing proteinuria and acute renal failure. PMID:22808199

  1. Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Arzt, Lisa; Halbwedl, Iris; Gogg-Kamerer, Margit; Popper, Helmut H

    2017-07-01

    Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail. A miRNA profiling was performed on 52 MPM tissue samples. Upregulated miRNAs (targeting SOCS1/3) were knocked-down using miRNA inhibitors. mRNA expression levels of STAT1/3, SOCS1/3 were detected in MPM cell lines. STAT1 has been knocked-down using siRNA and qPCR was used to detect mRNA expression levels of all JAK/STAT family members and genes that regulate them. An immunohistochemical staining was performed to detect the expression of caspases. STAT1 was upregulated and STAT3 was downregulated, SOCS1/3 protein was not detected but it was possible to detect SOCS1/3 mRNA in MPM cell lines. The upregulated miRNAs were successfully knocked-down, however the expected effect on SOCS1 expression was not detected. STAT1 knock-down had different effects on STAT3/5 expression. Caspase 3a and 8 expression was found to be increased after STAT1 knock-down. The physiologic regulation of STAT1 via SOCS1 is completely lost in MPM and it does not seem that the miRNAs identified by now, do inhibit the expression of SOCS1. MPM cell lines compensate STAT1 knock-down by increasing the expression of STAT3 or STAT5a, two genes which are generally considered to be oncogenes. And much more important, STAT1 knock-down induces apoptosis in MPM cell lines and STAT1 might therefore be a target for therapeutic intervention.

  2. Knockdown of UbcH10 Enhances the Chemosensitivity of Dual Drug Resistant Breast Cancer Cells to Epirubicin and Docetaxel

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    2015-03-01

    Full Text Available Breast cancer is one of the most common and lethal cancers in women. As a hub gene involved in a diversity of tumors, the ubiquitin-conjugating enzyme H10 (UbcH10, may also play some roles in the genesis and development of breast cancer. In the current study, we found that the expression of UbcH10 was up-regulated in some breast cancer tissues and five cell lines. We established a dual drug resistant cell line MCF-7/EPB (epirubicin/TXT (docetaxel and a lentiviral system expressing UbcH10 shRNA to investigate the effects of UbcH10 knockdown on the chemosensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel. The knockdown of UbcH10 inhibited the proliferation of both MCF-7 and MCF-7/EPB/TXT cells, due to the G1 phase arrest in cell cycle. Furthermore, UbcH10 knockdown increased the sensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel and promoted the apoptosis induced by these two drugs. Protein detection showed that, in addition to inhibiting the expression of Ki67 and cyclin D1, UbcH10 RNAi also impaired the increased BCL-2 and MDR-1 expression levels in MCF-7/EPB/TXT cells, which may contribute to abating the drug resistance in the breast cancer cells. Our research in the current study demonstrated that up-regulation of UbcH10 was involved in breast cancer and its knockdown can inhibit the growth of cancer cells and increase the chemosensitivity of the dual drug resistant breast cancer cells to epirubicin and docetaxel, suggesting that UbcH10 may be a promising target for the therapy of breast cancer.

  3. Knockdown of asporin affects transforming growth factor-β1-induced matrix synthesis in human intervertebral annulus cells

    Directory of Open Access Journals (Sweden)

    Xu Jiang

    2016-10-01

    Conclusion: Our results have verified a functional feedback loop between TGF-β1 and asporin in human intervertebral annulus cells indicating that TGF-β1-induced annulus matrix biosynthesis can be significantly upregulated by knockdown of asporin. Therefore, asporin could be a potential new therapeutic target and inhibition of asporin could be adopted to enhance the anabolic effect of TGF-β1 in human intervertebral annulus cells in degenerative IVD diseases.

  4. Sqstm1 knock-down causes a locomotor phenotype ameliorated by rapamycin in a zebrafish model of ALS/FTLD.

    Science.gov (United States)

    Lattante, Serena; de Calbiac, Hortense; Le Ber, Isabelle; Brice, Alexis; Ciura, Sorana; Kabashi, Edor

    2015-03-15

    Mutations in SQSTM1, encoding for the protein SQSTM1/p62, have been recently reported in 1-3.5% of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS/FTLD). Inclusions positive for SQSTM1/p62 have been detected in patients with neurodegenerative disorders, including ALS/FTLD. In order to investigate the pathogenic mechanisms induced by SQSTM1 mutations in ALS/FTLD, we developed a zebrafish model. Knock-down of the sqstm1 zebrafish ortholog, as well as impairment of its splicing, led to a specific phenotype, consisting of behavioral and axonal anomalies. Here, we report swimming deficits associated with shorter motor neuronal axons that could be rescued by the overexpression of wild-type human SQSTM1. Interestingly, no rescue of the loss-of-function phenotype was observed when overexpressing human SQSTM1 constructs carrying ALS/FTLD-related mutations. Consistent with its role in autophagy regulation, we found increased mTOR levels upon knock-down of sqstm1. Furthermore, treatment of zebrafish embryos with rapamycin, a known inhibitor of the mTOR pathway, yielded an amelioration of the locomotor phenotype in the sqstm1 knock-down model. Our results suggest that loss-of-function of SQSTM1 causes phenotypic features characterized by locomotor deficits and motor neuron axonal defects that are associated with a misregulation of autophagic processes. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing.

    Science.gov (United States)

    Xie, Zhongcong; Dong, Yuanlin; Maeda, Uta; Xia, Weiming; Tanzi, Rudolph E

    2012-03-22

    Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimer's disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided.

  6. RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing

    Directory of Open Access Journals (Sweden)

    Xie Zhongcong

    2012-03-01

    Full Text Available Abstract Amyloid-β-protein (Aβ, the key component of senile plaques in Alzheimer's disease (AD brain, is produced from amyloid precursor protein (APP by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB domains, including Dab (gene: DAB and Numb (gene: NUMB, can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells or APP-C99 (H4-APP-C99 cells increased levels of APP-C-terminal fragments (APP-CTFs and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided.

  7. RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing

    Science.gov (United States)

    2012-01-01

    Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimer's disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided. PMID:23211096

  8. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Directory of Open Access Journals (Sweden)

    L. Zhao

    2014-01-01

    Full Text Available Fanconi anemia complementation group F protein (FANCF is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  9. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    International Nuclear Information System (INIS)

    Zhao, L.; Li, N.; Yu, J.K.; Tang, H.T.; Li, Y.L.; He, M.; Yu, Z.J.; Bai, X.F.; Zheng, Z.H.; Wang, E.H.; Wei, M.J.

    2013-01-01

    Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer

  10. Keratin23 (KRT23 knockdown decreases proliferation and affects the DNA damage response of colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Karin Birkenkamp-Demtröder

    Full Text Available Keratin 23 (KRT23 is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed that KRT23 depletion affected molecules of the cell cycle and DNA replication, recombination and repair. In vitro analyses confirmed that KRT23 depletion significantly decreased the cellular proliferation of SW948 and LS1034 cells and markedly decreased the expression of genes involved in DNA damage response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced proliferation of the KRT23 depleted cells compared to irradiated control cells.

  11. A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets.

    Science.gov (United States)

    Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

    2014-12-05

    Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways.

  12. N-Myc knockdown and apigenin treatment controlled growth of malignant neuroblastoma cells having N-Myc amplification.

    Science.gov (United States)

    Hossain, Md Motarab; Banik, Naren L; Ray, Swapan K

    2013-10-15

    Malignant neuroblastomas mostly occur in children and are frequently associated with N-Myc amplification. Oncogene amplification, which is selective increase in copy number of the oncogene, provides survival advantages in solid tumors including malignant neuroblastoma. We have decreased expression of N-Myc oncogene using short hairpin RNA (shRNA) plasmid to increase anti-tumor efficacy of the isoflavonoid apigenin (APG) in human malignant neuroblastoma SK-N-DZ and SK-N-BE2 cell lines that harbor N-Myc amplification. N-Myc knockdown induced morphological and biochemical features of neuronal differentiation. Combination of N-Myc knockdown and APG most effectively induced morphological and biochemical features of apoptotic death. This combination therapy also prevented cell migration and decreased N-Myc driven survival, angiogenic, and invasive factors. Collectively, N-Myc knockdown and APG treatment is a promising strategy for controlling the growth of human malignant neuroblastoma cell lines that harbor N-Myc amplification. © 2013 Elsevier B.V. All rights reserved.

  13. RNAi-mediated knockdown of the voltage gated sodium ion channel TcNav causes mortality in Tribolium castaneum.

    Science.gov (United States)

    Abd El Halim, Hesham M; Alshukri, Baida M H; Ahmad, Munawar S; Nakasu, Erich Y T; Awwad, Mohammed H; Salama, Elham M; Gatehouse, Angharad M R; Edwards, Martin G

    2016-07-14

    The voltage-gated sodium ion channel (VGSC) belongs to the largest superfamily of ion channels. Since VGSCs play key roles in physiological processes they are major targets for effective insecticides. RNA interference (RNAi) is widely used to analyse gene function, but recently, it has shown potential to contribute to novel strategies for selectively controlling agricultural insect pests. The current study evaluates the delivery of dsRNA targeted to the sodium ion channel paralytic A (TcNav) gene in Tribolium castaneum as a viable means of controlling this insect pest. Delivery of TcNav dsRNA caused severe developmental arrest with larval mortalities up to 73% post injection of dsRNA. Injected larvae showed significant (p < 0.05) knockdown in gene expression between 30-60%. Expression was also significantly (p < 0.05) reduced in pupae following injection causing 30% and 42% knockdown for early and late pupal stages, respectively. Oral delivery of dsRNA caused dose-dependant mortalities of between 19 and 51.34%; this was accompanied by significant (p < 0.05) knockdown in gene expression following 3 days of continuous feeding. The majority of larvae injected with, or fed, dsRNA died during the final larval stage prior to pupation. This work provides evidence of a viable RNAi-based strategy for insect control.

  14. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.; Li, N.; Yu, J.K.; Tang, H.T.; Li, Y.L.; He, M.; Yu, Z.J.; Bai, X.F. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Zheng, Z.H.; Wang, E.H. [Institute of Pathology and Pathophysiology, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Wei, M.J. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China)

    2013-12-12

    Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  15. Synergistic effect of some essential oils on toxicity and knockdown effects, against mosquitos, cockroaches and housefly

    Directory of Open Access Journals (Sweden)

    Idin Zibaee

    2015-12-01

    Full Text Available The toxicity and knockdown effect of Eucalyptus globulus, Rosmarinus officinalis essential oils and their mixed formulation on Periplaneta Americana (L., Blattella germanica (L., Supella longipalpa, Culex pipiens, Anopheles stephensi and Musca domestica were evaluated in a series of laboratory experiments. In all bioassay five different doses (0.625, 1.25, 2.5, 5 and 10% were used by filter paper (cm2 and aerosol (cm3 bioassay methods, all essential oils was toxic to cockroaches, mosquitos and housefly species the lowest and the highest LC50 belong to mixed formulation on B. germanica (LC50 6.1 and E. globulus on P. americana (LC50 27.7 respectively. In continuous exposure experiments, Mortality (LT50 values for cockroaches ranged from 1403.3 min with 0.625% E. globulus (for P. americana to 2.2 min with 10% mixed formulation for A. stephensi. The KT50 values ranged from 0.1 to 1090.8 min for 10% and 0.625 for mixed formulation and R. officinalis respectively. The mortality after 24 h for mixed formulation was 100% but for single essential oils ranged from 81.5 to 98.3 for P. americana treated with R. officinalis and A. stephensi treated with E. globulus respectively. Studies on persistence of essential oils on impregnated paper revealed that it has more adulticidal activity for longer period at low storage temperature. Gas chromatographic-mass spectrometric analysis of essential oil showed 14 and 16 peaks for E. globules and R. officinalis respectively. α-Pinene (39.8%, 1, 8-Cineole (13.2%, Camphene (9.1% and Borneol (3.7% were present in major amounts for R. officinalis and 1,8-Cineole (31.4%, α-Pinene (15.3%, d-Limonene (9.7% and α-Terpinolen (5.3% were present in major amounts for E. globulus respectively. Our results showed that two surveyed essential oils has compatible with synergistic effect on various insect species, furthermore it is useful for applying as integrated pest management tool for studied insects management, especially in

  16. AAV-mediated knock-down of HRC exacerbates transverse aorta constriction-induced heart failure.

    Directory of Open Access Journals (Sweden)

    Chang Sik Park

    Full Text Available Histidine-rich calcium binding protein (HRC is located in the lumen of sarcoplasmic reticulum (SR that binds to both triadin (TRN and SERCA affecting Ca(2+ cycling in the SR. Chronic overexpression of HRC that may disrupt intracellular Ca(2+ homeostasis is implicated in pathogenesis of cardiac hypertrophy. Ablation of HRC showed relatively normal phenotypes under basal condition, but exhibited a significantly increased susceptibility to isoproterenol-induced cardiac hypertrophy. In the present study, we characterized the functions of HRC related to Ca(2+ cycling and pathogenesis of cardiac hypertrophy using the in vitro siRNA- and the in vivo adeno-associated virus (AAV-mediated HRC knock-down (KD systems, respectively.AAV-mediated HRC-KD system was used with or without C57BL/6 mouse model of transverse aortic constriction-induced failing heart (TAC-FH to examine whether HRC-KD could enhance cardiac function in failing heart (FH. Initially we expected that HRC-KD could elicit cardiac functional recovery in failing heart (FH, since predesigned siRNA-mediated HRC-KD enhanced Ca(2+ cycling and increased activities of RyR2 and SERCA2 without change in SR Ca(2+ load in neonatal rat ventricular cells (NRVCs and HL-1 cells. However, AAV9-mediated HRC-KD in TAC-FH was associated with decreased fractional shortening and increased cardiac fibrosis compared with control. We found that phospho-RyR2, phospho-CaMKII, phospho-p38 MAPK, and phospho-PLB were significantly upregulated by HRC-KD in TAC-FH. A significantly increased level of cleaved caspase-3, a cardiac cell death marker was also found, consistent with the result of TUNEL assay.Increased Ca(2+ leak and cytosolic Ca(2+ concentration due to a partial KD of HRC could enhance activity of CaMKII and phosphorylation of p38 MAPK, causing the mitochondrial death pathway observed in TAC-FH. Our results present evidence that down-regulation of HRC could deteriorate cardiac function in TAC-FH through

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

    Directory of Open Access Journals (Sweden)

    Andrea Addazi

    2016-08-01

    Full Text Available The extended electroweak SU(3c⊗SU(3L⊗U(1X 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 (unoriented 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.

  18. Study of electrical transport properties of (U 1- xY x)RuP 2Si 2

    Science.gov (United States)

    Radha, S.; Park, J.-G.; Roy, S. B.; Coles, B. R.; Nigam, A. K.; McEwen, K. A.

    1996-02-01

    Electrical resistivity and magnetoresistance ( {δϱ}/{ϱ}) measurements on a series of (U 1- xY x)Ru 2Si 2 (0 ⩽ x ⩽ 0.9) compounds in the temperature range 4.2-300 K and in magnetic fields up to 45 kOe are reported. The resistivity measurements do not show any signature of antiferromagnetism for x > 0.5. The compound URu 2Si 2 exhibits a large, positive ( {δϱ}/{ϱ}) presumably due to destruction of Kondo coherence as well as due to antiferromagnetism. The presence of even 5% Y at U-site weakens the Kondo coherence and reduces the magnetoresistance considerably.

  19. Novel SM-like Higgs decay into displaced heavy neutrino pairs in U(1){sup ′} models

    Energy Technology Data Exchange (ETDEWEB)

    Accomando, Elena [School of Physics and Astronomy, University of Southampton,Highfield, Southampton SO17 1BJ (United Kingdom); Rose, Luigi Delle; Moretti, Stefano [School of Physics and Astronomy, University of Southampton,Highfield, Southampton SO17 1BJ (United Kingdom); Particle Physics Department, Rutherford Appleton Laboratory,Chilton, Didcot, Oxon OX11 0QX (United Kingdom); Olaiya, Emmanuel; Shepherd-Themistocleous, Claire H. [Particle Physics Department, Rutherford Appleton Laboratory,Chilton, Didcot, Oxon OX11 0QX (United Kingdom)

    2017-04-13

    We examine the observability of heavy neutrino (ν{sub h}) signatures of a U(1){sup ′} enlarged Standard Model (SM) encompassing three heavy Majorana neutrinos alongside the known light neutrino states at the the Large Hadron Collider (LHC). We show that heavy neutrinos can be rather long-lived particles producing distinctive displaced vertices that can be accessed in the CERN LHC detectors. We concentrate here on the gluon fusion production mechanism gg→H{sub 1,2}→ν{sub h}ν{sub h}, where H{sub 1} is the discovered SM-like Higgs and H{sub 2} is a heavier state, yielding displaced leptons following ν{sub h} decays into weak gauge bosons. Using data collected by the end of the LHC Run 2, these signatures would prove to be accessible with negligibly small background.

  20. Search for OH 18 cm Radio Emission from 1I/2017 U1 with the Green Bank Telescope

    Science.gov (United States)

    Park, Ryan S.; Pisano, D. J.; Lazio, T. Joseph W.; Chodas, Paul W.; Naidu, Shantanu P.

    2018-05-01

    This paper reports the first OH 18 cm line observation of the first detected interstellar object 1I/2017 U1 (‘Oumuamua) using the Green Bank Telescope. We have observed the OH lines at 1665.402, 1667.359, and 1720.53 MHz frequencies with a spectral resolution of 357 Hz (approximately 0.06 km s‑1). At the time of the observation, ‘Oumuamua was at topocentric distance and velocity of 1.07 au and 63.4 km s‑1, respectively, or at heliocentric distance and velocity of 1.8 au and 39 km s‑1, respectively. Based on a detailed data reduction and an analogy-based inversion, our final results confirm the asteroidal origin of ‘Oumuamua with an upper bound OH production of Q[OH] < 0.17 × 1028 s‑1.

  1. Global analysis of general SU(2)xSU(2)xU(1) models with precision data

    International Nuclear Information System (INIS)

    Hsieh, Ken; Yu, Jiang-Hao; Yuan, C.-P.; Schmitz, Kai

    2010-01-01

    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 ' and W ' 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.

  2. Dimensional reduction of U(1) x SU(2) Chern-Simons bosonization: Application to the t - J model

    International Nuclear Information System (INIS)

    Marchetti, P.A.

    1996-09-01

    We perform a dimensional reduction of the U(1) x SU(2) Chern-Simons bosonization and apply it to the t - J model, relevant for high T c superconductors. This procedure yields a decomposition of the electron field into a product of two ''semionic'' fields, i.e. fields obeying Abelian braid statistics with statistics parameter θ = 1/4, one carrying the charge and the other the spin degrees of freedom. A mean field theory is then shown to reproduce correctly the large distance behaviour of the correlation functions of the 1D t - J model at >> J. This result shows that to capture the essential physical properties of the model one needs a specific ''semionic'' form of spin-charge separation. (author). 31 refs

  3. Charge commutation relation approach to composite vector bosons in SU(2)sub(L)xU(1)sub(Y)

    International Nuclear Information System (INIS)

    Yasue, Masaki; Oneda, Sadao.

    1984-09-01

    Under the assumption that the local SU(2)sub(L)xU(1)sub(Y) symmetry is a good symmetry for new resonances, we predict that msub(W)msub(W*)=costhetamsub(Z)msub(Z*) where theta represents the mixing angle between neutral gauge bosons and msub(W), msub(Z), msub(W*) and msub(Z*) are the masses of W, Z, W* and Z*, respectively. W* and Z* are the lowest lying spin one resonances, whose pure states belong to a triplet of SU(2)sub(L). Possible SU(2)sub(L)-singlet state is assumed to be much heavier than W* and Z*. Low energy phenomenology of weak interactions indicates msub(W)--costhetamsub(Z), suggesting msub(W*)--msub(Z*). (author)

  4. Palynology of the middle jurassic lower graben sand formation of the U-1 well, Danish Central Trough

    Energy Technology Data Exchange (ETDEWEB)

    Hoelstad, T.

    1986-01-01

    Twenty-one sidewall core samples from the lower 56 metres of the Lower Graben Sand Formation in the U-1 well are described with respect to their kerogen content and microflora in order to gain a better understanding of the depositional environment and the age relations. Based on e.g. the inconsistent dinoflagellate cyst occurrences, marginal marine conditions are concluded. The dinoglagellate cyst Pareodinia prolongata, Acanthaulax senta, Scriniodinium crystallinum, Energlynia acollaris, Wanaea thysanota and Hystrichogonyaulax cladophora and the recovered playnomorph assemblage in general permit an age determination as follows: 21 m Collovian undifferentiated, 7.9 latest Middle Callovian - earliest Late Callovian, 6.1 m latest Late Callovian and 21 m latest Late Callovian. - earliest Early Oxfordian.

  5. Phenomenology of the SU(3)cxSU(3)LxU(1)X model with exotic charged leptons

    International Nuclear Information System (INIS)

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

    2007-01-01

    A phenomenological analysis of the three-family model based on the local gauge group SU(3) c xSU(3) L xU(1) 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

  6. Phenomenology of the SU(3)c x SU(3)L x U(1)X model with right-handed neutrinos

    International Nuclear Information System (INIS)

    Gutierrez, D.A.; Ponce, W.A.; Sanchez, L.A.

    2006-01-01

    A phenomenological analysis of the three-family model based on the local gauge group SU(3) c x SU(3) L x U(1) X with right-handed neutrinos 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, produces a quark mass spectrum without hierarchies in the Yukawa coupling constants. We also embed the structure into a simple gauge group and show some conditions for achieving 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. (orig.)

  7. Progranulin modulates zebrafish motoneuron development in vivo and rescues truncation defects associated with knockdown of Survival motor neuron 1

    Directory of Open Access Journals (Sweden)

    Bateman Andrew

    2010-10-01

    Full Text Available Abstract Background Progranulin (PGRN encoded by the GRN gene, is a secreted glycoprotein growth factor that has been implicated in many physiological and pathophysiological processes. PGRN haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to progressive neuronal atrophy in the form of frontotemporal lobar degeneration (FTLD. This form of the disease is associated with neuronal inclusions that bear the ubiquitinated TAR DNA Binding Protein-43 (TDP-43 molecular signature (FTLD-U. The neurotrophic properties of PGRN in vitro have recently been reported but the role of PGRN in neurons is not well understood. Here we document the neuronal expression and functions of PGRN in spinal cord motoneuron (MN maturation and branching in vivo using zebrafish, a well established model of vertebrate embryonic development. Results Whole-mount in situ hybridization and immunohistochemical analyses of zebrafish embryos revealed that zfPGRN-A is expressed within the peripheral and central nervous systems including the caudal primary (CaP MNs within the spinal cord. Knockdown of zfPGRN-A mRNA translation mediated by antisense morpholino oligonucleotides disrupted normal CaP MN development resulting in both truncated MNs and inappropriate early branching. Ectopic over-expression of zfPGRN-A mRNA resulted in increased MN branching and rescued the truncation defects brought about by knockdown of zfPGRN-A expression. The ability of PGRN to interact with established MN developmental pathways was tested. PGRN over-expression was found to reverse the truncation defect resulting from knockdown of Survival of motor neuron 1 (smn1. This is involved in small ribonucleoprotein biogenesis RNA processing, mutations of which cause Spinal Muscular Atrophy (SMA in humans. It did not reverse the MN defects caused by interfering with the neuronal guidance pathway by knockdown of expression of NRP-1, a semaphorin co-receptor. Conclusions Expression of

  8. Mosquito knock-down and adulticidal activities of essential oils by vaporizer, impregnated filter paper and aerosol methods

    Directory of Open Access Journals (Sweden)

    M. Ramar

    2014-09-01

    Full Text Available Essential oils from 12 medicinal plants were evaluated by three different bioassay methods (Vaporizer, Filter paper and Aerosol for Knock-down and adulticidal efficacy on the filarial vector mosquito, Culex quinquefasciatus. Based on screening results the effective plants were selected for investigating Knock-down and adulticidal potential against adult female of the laboratory-reared mosquito species, Cx. quinquefasciatus. In vaporizer bioassay method four different doses (1.25, 2.5, 5 and 10% were used. Four different doses (0.625, 1.25, 2.5 and 10% were used both filter paper (cm2 and aerosol (cm3 bioassay methods. Five essential oils (calamus, camphor, citronella, clove and eucalyptus were identified as potential treatments in vaporizer bioassay. The result showed that the knock down time decreased with increased concentration in clove oil treatment; the Knock-down time (KT 50 = 46.1 ± 0.1, 38.5 ± 0.1, 30.7 ± 0.2, and 20.1 ± 0.1 minutes was recorded at 1.25, 2.5, 5 and 10% /cm3 respectively. In filter paper method nine essential oils were identified as potential treatments. After 1 hr exposure period clove oil recorded the lowest median Knock-down time (KT50 which was calculated as 9.15 ± 0.1min/cm2. Followed by citronella (KT50 =11.4 ± 0.1 min and eucalyptus (KT50 =11.4 ±0.1min oils since they recorded lower median Knock-down time. All the twelve essential oils were identified as potential treatments in aerosol activity. The lethal time decreased when the concentration increased. At 5 % concentration the median lethal time (LT50 for clove oil was calculated as (LT50=3.80 ± 0.1minutes. The Cinnamon oil was effective which recorded (LT50 = 1.99 mins as median lethal time. Camphor (LT50 =19.6± 0.1 min oil were found to be less toxic by aerosol method. These results suggest that clove oil and cinnamon oil have the potential to be used as a eco-friendly approach for the control of the major important filaria vector Cx. quinquefasciatus

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

    Science.gov (United States)

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

    2013-08-01

    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. 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. 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. 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%. 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.

  10. Phenomenology of U(1){sub F} extension of inert-doublet model with exotic scalars and leptons

    Energy Technology Data Exchange (ETDEWEB)

    Dhargyal, Lobsang [Harish-Chandra Research Institute, HBNI, Allahabad (India)

    2018-02-15

    In this work we will extend the inert-doublet model (IDM) by adding a new U(1){sub F} gauge symmetry to it, under which, a Z{sub 2} even scalar (φ{sub 2}) and Z{sub 2} odd right handed component of two exotic charged leptons (F{sub eR}, F{sub μR}), are charged. We also add one Z{sub 2} even real scalar (φ{sub 1}) and one complex scalar (φ), three neutral Majorana right handed fermions (N{sub 1}, N{sub 2}, N{sub 3}), two left handed components of the exotic charged leptons (F{sub eL}, F{sub μL}) as well as F{sub τ} are all odd under the Z{sub 2}, all of which are not charged under the U(1){sub F}. With these new particles added to the IDM, we have a model which can give two scalar DM candidates, together they can explain the present DM relic density as well as the muon (g-2) anomaly simultaneously. Also in this model the neutrino masses are generated at one loop level. One of the most peculiar feature of this model is that non-trivial solution to the axial gauge anomaly free conditions lead to the prediction of a stable very heavy partner to the electron (F{sub e}), whose present collider limit (13 TeV LHC) on its mass should be around m{sub F{sub e}} ≥ few TeV. (orig.)

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

    International Nuclear Information System (INIS)

    Nakayama, Yu

    2008-01-01

    We show a calculable example of stable supersymmetry (SUSY) breaking models with O(10) eV gravitino mass based on the combination of D-term gauge mediation and U(1)' mediation. A potential problem of the negative mass squared for the SUSY standard model (SSM) sfermions in the D-term gauge mediation is solved by the contribution from the U(1)' mediation. On the other hand, the splitting between the SSM gauginos and sfermions in the U(1)' mediation is circumvented by the contributions from the D-term gauge mediation. Since the U(1)' mediation does not introduce any new SUSY vacua, we achieve a completely stable model under thermal effects. Our model, therefore, has no cosmological difficulty

  12. Fascin-1 knock-down of human glioma cells reduces their microvilli/filopodia while improving their susceptibility to lymphocyte-mediated cytotoxicity

    Science.gov (United States)

    Hoa, Neil T; Ge, Lisheng; Erickson, Kate L; Kruse, Carol A; Cornforth, Andrew N; Kuznetsov, Yurii; McPherson, Alex; Martini, Filippo; Jadus, Martin R

    2015-01-01

    Cancer cells derived from Glioblastoma multiforme possess membranous protrusions allowing these cells to infiltrate surrounding tissue, while resisting lymphocyte cytotoxicity. Microvilli and filopodia are supported by actin filaments cross-linked by fascin. Fascin-1 was genetically silenced within human U251 glioma cells; these knock-down glioma cells lost their microvilli/filopodia. The doubling time of these fascin-1 knock-down cells was doubled that of shRNA control U251 cells. Fascin-1 knock-down cells lost their transmigratory ability responding to interleukin-6 or insulin-like growth factor-1. Fascin-1 silenced U251 cells were more easily killed by cytolytic lymphocytes. Fascin-1 knock-down provides unique opportunities to augment glioma immunotherapy by simultaneously targeting several key glioma functions: like cell transmigration, cell division and resisting immune responses. PMID:25901196

  13. Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats.

    Science.gov (United States)

    Mandal, Kamal; Sarkar, Rajesh K; Sen Sharma, Souvik; Jain, Ayushi; Majumdar, Subeer S

    2018-01-30

    Globally, there is an alarming decline in sperm count. Very often hormonal supplementation fails to restore normal sperm count. Sertoli cells (Sc) present within seminiferous tubules provide appropriate niche and factors required for the differentiation of germ cells (Gc) into mature sperm (spermatogenesis). Functionally compromised Sc may be one of the reasons for failure of hormones to facilitate normal spermatogenesis. Although role of secretory proteins and signaling molecules of Sc has been studied well, role of transcription factors regulating sperm count has not been addressed appropriately. Retinoic acid receptor-related orphan receptor (ROR)-alpha is one of such transcription factors reported in testis but its role in testicular function is not yet known. In a separate study, we found abundant ROR-alpha binding sites on promoter regions of several genes upregulated in pubertal rat Sc as compared to infant Sc. Immunostaining studies also revealed presence of ROR alpha in nucleus of pubertal Sc. We generated a transgenic knockdown rat model expressing shRNA targeted to ROR-alpha under Sc specific promoter, which is transcriptionally active only at and after puberty. ROR-alpha knockdown animals were found to have abnormal association of Sc and Gc, including Gc sloughing and restricted release of sperm. The knockdown animals displayed compromised spermatogenesis leading to significant reduction in sperm count. This is the first report describing the Sc specific role of ROR-alpha in maintaining quantitatively normal sperm output. Identification of various such molecules can generate avenues to limit or reverse an alarmingly declining sperm count witnessed globally in men. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Rajnikumar Sangani

    2014-03-01

    Full Text Available Bone marrow stromal cell (BMSC adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38 and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions.

  15. Targeted siRNA Delivery and mRNA Knockdown Mediated by Bispecific Digoxigenin-binding Antibodies

    Directory of Open Access Journals (Sweden)

    Britta Schneider

    2012-01-01

    Full Text Available Bispecific antibodies (bsAbs that bind to cell surface antigens and to digoxigenin (Dig were used for targeted small interfering RNA (siRNA delivery. They are derivatives of immunoglobulins G (IgGs that bind tumor antigens, such as Her2, IGF1-R, CD22, and LeY, with stabilized Dig-binding variable domains fused to the C-terminal ends of the heavy chains. siRNA that was digoxigeninylated at its 3′end was bound in a 2:1 ratio to the bsAbs. These bsAb–siRNA complexes delivered siRNAs specifically to cells that express the corresponding antigen as demonstrated by flow cytometry and confocal microscopy. The complexes internalized into endosomes and Dig-siRNAs separated from bsAbs, but Dig-siRNA was not released into the cytoplasm; bsAb-targeting alone was thus not sufficient for effective mRNA knockdown. This limitation was overcome by formulating the Dig-siRNA into nanoparticles consisting of dynamic polyconjugates (DPCs or into lipid-based nanoparticles (LNPs. The resulting complexes enabled bsAb-targeted siRNA-specific messenger RNA (mRNA knockdown with IC50 siRNA values in the low nanomolar range for a variety of bsAbs, siRNAs, and target cells. Furthermore, pilot studies in mice bearing tumor xenografts indicated mRNA knockdown in endothelial cells following systemic co-administration of bsAbs and siRNA formulated in LNPs that were targeted to the tumor vasculature.

  16. Knockdown of BAG3 sensitizes bladder cancer cells to treatment with the BH3 mimetic ABT-737.

    Science.gov (United States)

    Mani, Jens; Antonietti, Patrick; Rakel, Stefanie; Blaheta, Roman; Bartsch, Georg; Haferkamp, Axel; Kögel, Donat

    2016-02-01

    BAG3 is overexpressed in several malignancies and mediates a non-canonical, selective form of (macro)autophagy. By stabilizing pro-survival Bcl-2 proteins in complex with HSP70, BAG3 can also exert an apoptosis-antagonizing function. ABT-737 is a high affinity Bcl-2 inhibitor that fails to target Mcl-1. This failure may confer resistance in various cancers. Urothelial cancer cells were treated with the BH3 mimetics ABT-737 and (-)-gossypol, a pan-Bcl-2 inhibitor which inhibits also Mcl-1. To clarify the importance of the core autophagy regulator ATG5 and BAG3 in ABT-737 treatment, cell lines carrying a stable lentiviral knockdown of ATG5 and BAG3 were created. The synergistic effect of ABT-737 and pharmaceutical inhibition of BAG3 with the HSF1 inhibitor KRIBB11 or sorafenib was also evaluated. Total cell death and apoptosis were quantified by FACS analysis of propidium iodide, annexin. Target protein analysis was conducted by Western blotting. Knockdown of BAG3 significantly downregulated Mcl-1 protein levels and sensitized urothelial cancer cells to apoptotic cell death induced by ABT-737, while inhibition of bulk autophagy through depletion of ATG5 had no discernible effect on cell death. Similar to knockdown of BAG3, pharmacological targeting of the BAG3/Mcl-1 pathway with KRIBB11 was capable to sensitize both cell lines to treatment with ABT-737. Our results show that BAG3, but not bulk autophagy has a major role in the response of bladder cancer cells to BH3 mimetics. They also suggest that BAG3 is a suitable target for combined therapies aimed at synergistically inducing apoptosis in bladder cancer.

  17. HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its knockdown induces cell cycle arrest and apoptosis

    International Nuclear Information System (INIS)

    Chile, Thais; Bacchella, Telésforo; Giorgi, Ricardo Rodrigues; Fortes, Maria Angela Henriques Zanella; Corrêa-Giannella, Maria Lúcia Cardillo; Brentani, Helena Paula; Maria, Durvanei Augusto; Puga, Renato David; Paula, Vanessa de Jesus R de; Kubrusly, Marcia Saldanha; Novak, Estela Maria

    2013-01-01

    Human homeobox genes encode nuclear proteins that act as transcription factors involved in the control of differentiation and proliferation. Currently, the role of these genes in development and tumor progression has been extensively studied. Recently, increased expression of HOXB7 homeobox gene (HOXB7) in pancreatic ductal adenocarcinomas (PDAC) was shown to correlate with an invasive phenotype, lymph node metastasis and worse survival outcomes, but no influence on cell proliferation or viability was detected. In the present study, the effects arising from the knockdown of HOXB7 in PDAC cell lines was investigated. Real time quantitative PCR (qRT-PCR) (Taqman) was employed to assess HOXB7 mRNA expression in 29 PDAC, 6 metastatic tissues, 24 peritumoral tissues and two PDAC cell lines. siRNA was used to knockdown HOXB7 mRNA in the cell lines and its consequences on apoptosis rate and cell proliferation were measured by flow cytometry and MTT assay respectively. Overexpression of HOXB7 mRNA was observed in the tumoral tissues and in the cell lines MIA PaCa-2 and Capan-1. HOXB7 knockdown elicited (1) an increase in the expression of the pro-apoptotic proteins BAX and BAD in both cell lines; (2) a decrease in the expression of the anti-apoptotic protein BCL-2 and in cyclin D1 and an increase in the number of apoptotic cells in the MIA PaCa-2 cell line; (3) accumulation of cell in sub-G1 phase in both cell lines; (4) the modulation of several biological processes, especially in MIA PaCa-2, such as proteasomal ubiquitin-dependent catabolic process and cell cycle. The present study confirms the overexpression of HOXB7 mRNA expression in PDAC and demonstrates that decreasing its protein level by siRNA could significantly increase apoptosis and modulate several biological processes. HOXB7 might be a promising target for future therapies

  18. Knockdown of the fat mass and obesity gene disrupts cellular energy balance in a cell-type specific manner.

    Directory of Open Access Journals (Sweden)

    Ryan T Pitman

    Full Text Available Recent studies suggest that FTO variants strongly correlate with obesity and mainly influence energy intake with little effect on the basal metabolic rate. We suggest that FTO influences eating behavior by modulating intracellular energy levels and downstream signaling mechanisms which control energy intake and metabolism. Since FTO plays a particularly important role in adipocytes and in hypothalamic neurons, SH-SY5Y neuronal cells and 3T3-L1 adipocytes were used to understand how siRNA mediated knockdown of FTO expression alters cellular energy homeostasis. Cellular energy status was evaluated by measuring ATP levels using a luminescence assay and uptake of fluorescent glucose. FTO siRNA in SH-SY5Y cells mediated mRNA knockdown (-82%, increased ATP concentrations by up to 46% (P = 0.013 compared to controls, and decreased phosphorylation of AMPk and Akt in SH-SY5Y by -52% and -46% respectively as seen by immunoblotting. In contrast, FTO siRNA in 3T3-L1 cells decreased ATP concentration by -93% (p<0.0005, and increased AMPk and Akt phosphorylation by 204% and 70%, respectively suggesting that FTO mediates control of energy levels in a cell-type specific manner. Furthermore, glucose uptake was decreased in both SH-SY5Y (-51% p = 0.015 and 3T3-L1 cells (-30%, p = 0.0002. We also show that FTO knockdown decreases NPY mRNA expression in SH-SY5Y cells (-21% through upregulation of pSTAT3 (118%. These results provide important evidence that FTO-variant linked obesity may be associated with altered metabolic functions through activation of downstream metabolic mediators including AMPk.

  19. Upper bounds on Higgs and top quark masses in the flipped SU(5)xU(1) superstring model

    Energy Technology Data Exchange (ETDEWEB)

    Durand, L.; Lopez, J.L.

    1989-02-02

    In this letter, we use a simplified method to calculate high-energy unitarity constraints on grand unified broken supersymmetric models. We apply the method to the ''flipped'' SU(5)xU(1) superstring model, obtain the constraints at a grand unified mass scale M/sub G/=4x10/sup 16/ GeV, and then use the renormalization group equations to evolve the constraints to the low-energy mass scale M/sub W/. We find upper bounds on the low-energy superpotential parameters which in turn imply absolute upper bounds on the top quark mass, m/sub t/< or approx.200 GeV, and on the lightest neutral Higgs boson mass, Msub(H/sub 1//sup 0/)< or approx.155 GeV. We also obtain an upper bound on Msub(H/sub 1//sup 0/) as a function of m/sub t/ which shows that for favored values of the ratio of Higgs vacuum expectation values Msub(H/sub 1//sup 0/)< or approx.125 GeV.

  20. Black hole physics from two-dimensional dilaton gravity based on the SL(2,R)/U(1) coset model

    International Nuclear Information System (INIS)

    Nojiri, S.; Oda, I.

    1994-01-01

    We analyze the quantum two-dimensional dilaton gravity model, which is described by the SL(2,R)/U(1) gauged Wess-Zumino-Witten model deformed by a (1,1) operator. We show that the curvature singularity does not appear when the central charge c matter of the matter fields is given by 22 matter matter matter ∝δ(x + -x 0 + ), create a kind of wormholes, i.e., causally disconnected regions. Most of the quantum information in past null infinity is lost in future null infinity but the lost information would be carried by the wormholes. We also discuss the problem of defining the mass of quantum black holes. On the basis of the argument by Regge and Teitelboim, we show that the ADM mass measured by the observer who lives in one of the asymptotically flat regions is finite and does not vanish in general. On the other hand, the Bondi mass is ill defined in this model. Instead of the Bondi mass, we consider the mass measured by observers who live in an asymptotically flat region at first. A class of observers finds the mass of the black hole created by a shock wave changes as the observers' proper time goes by, i.e., they observe Hawking radiation. The measured mass vanishes after the infinite proper time and the black hole evaporates completely. Therefore the total Hawking radiation is positive even when N<24

  1. Dark Matter's secret liaisons: phenomenology of a dark U(1) sector with bound states

    Energy Technology Data Exchange (ETDEWEB)

    Cirelli, Marco; Petraki, Kalliopi; Sala, Filippo [Laboratoire de Physique Théorique et Hautes Energies (LPTHE), UMR 7589 CNRS and UPMC, 4 Place Jussieu, F-75252, Paris (France); Panci, Paolo [CERN Theoretical Physics Department, CERN, Case C01600, CH-1211 Genève (Switzerland); Taoso, Marco, E-mail: marco.cirelli@gmail.com, E-mail: paolo.panci@cern.ch, E-mail: kpetraki@lpthe.jussieu.fr, E-mail: filo.sala@gmail.com, E-mail: m.taoso@csic.es [Instituto de Física Teórica (IFT) UAM/CSIC, calle Nicolás Cabrera 13-15, 28049 Cantoblanco, Madrid (Spain)

    2017-05-01

    Dark matter (DM) charged under a dark U(1) force appears in many extensions of the Standard Model, and has been invoked to explain anomalies in cosmic-ray data, as well as a self-interacting DM candidate. In this paper, we perform a comprehensive phenomenological analysis of such a model, assuming that the DM abundance arises from the thermal freeze-out of the dark interactions. We include, for the first time, bound-state effects both in the DM production and in the indirect detection signals, and quantify their importance for FERMI, AMS-02, and CMB experiments. We find that DM in the mass range 1 GeV to 100 TeV, annihilating into dark photons of MeV to GeV mass, is in conflict with observations. Instead, DM annihilation into heavier dark photons is viable. We point out that the late decays of multi-GeV dark photons can produce significant entropy and thus dilute the DM density. This can lower considerably the dark coupling needed to obtain the DM abundance, and in turn relax the existing constraints.

  2. Neutrino mixing and R{sub K} anomaly in U(1){sub X} models: a bottom-up approach

    Energy Technology Data Exchange (ETDEWEB)

    Bhatia, Disha; Chakraborty, Sabyasachi; Dighe, Amol [Tata Institute of Fundamental Research,Mumbai 400005 (India)

    2017-03-22

    We identify a class of U(1){sub X} models which can explain the R{sub K} anomaly and the neutrino mixing pattern, by using a bottom-up approach. The different X-charges of lepton generations account for the lepton universality violation required to explain R{sub K}. In addition to the three right-handed neutrinos needed for the Type-I seesaw mechanism, these minimal models only introduce an additional doublet Higgs and a singlet scalar. While the former helps in reproducing the quark mixing structure, the latter gives masses to neutrinos and the new gauge boson Z{sup ′}. Our bottom-up approach determines the X-charges of all particles using theoretical consistency and experimental constraints. We find the parameter space allowed by the constraints from neutral meson mixing, rare b→s decays and direct collider searches for Z{sup ′}. Such a Z{sup ′} may be observable at the ongoing run of the Large Hadron Collider with a few hundred fb{sup −1} of integrated luminosity.

  3. An SU(3)xU(1) theory of weak-electromagnetic interactions with charged boson mixing

    International Nuclear Information System (INIS)

    Singer, M.

    1978-01-01

    An SU(3)xU(1) gauge theory of weak electromagnetic interactions is proposed in which the charged bosons mix with each other. The model naturally ensures e-μ and quark-lepton universality in couplings, and the charged boson mixing permits an equal number of leptons and quark flavours. There are no new stable leptons. All the fermions are placed in triplets and singlets and the theory is vector-like and hence free of anomalies. In addition one of the charged bosons can have a mass less than 43 GeV. Discrete symmetries and specific choices for Higgs fields are postulated to obtain the appropriate boson and fermion masses. Calculations for the decay of the tau particle, which is described as a heavy electron, are given. Multimuon events are discussed as are neutrino neutral currents. Calculations are also given for testing asymmetries in e-hadron scattering due to weak electron neutral currents along with other phenomenology of the model

  4. Spin Triplet Nematic Pairing Symmetry and Superconducting Double Transition in U1-xThxBe13

    Science.gov (United States)

    Machida, Kazushige

    2018-03-01

    Motivated by a recent experiment on U1-xThxBe13 with x = 3%, we develop a theory to narrow down the possible pair symmetry to consistently describe the double transition utilizing various theoretical tools, including group theory and Ginzburg-Landau theory. It is explained in terms of the two-dimensional representation Eu with spin triplet. Symmetry breaking causes the degenerate Tc to split into two. The low-temperature phase is identified as the cyclic p wave: d(k) = \\hat{x}kx + ɛ \\hat{y}ky + ɛ 2\\hat{z}kz with ɛ3 = 1, whereas the biaxial nematic phase: d(k) = √{3} (\\hat{x}kx - \\hat{y}ky) is the high-temperature one. This allows us to simultaneously identify the uniaxial nematic phase: d(k) = 2\\hat{z}kz - \\hat{x}kx - \\hat{y}ky for UBe13, which spontaneously breaks the cubic symmetry of the system. Those pair functions are fully consistent with this description and existing data. We comment on the accidental scenario in addition to this degeneracy scenario and the intriguing topological nature hidden in this long-known material.

  5. Explaining the DAMPE data with scalar dark matter and gauged U(1)_{L_e-L_μ } interaction

    Science.gov (United States)

    Cao, Junjie; Feng, Lei; Guo, Xiaofei; Shang, Liangliang; Wang, Fei; Wu, Peiwen; Zu, Lei

    2018-03-01

    Inspired by the peak structure observed by recent DAMPE experiment in e^+e^- cosmic-ray spectrum, we consider a scalar dark matter (DM) model with gauged U(1)_{L_e-L_μ } symmetry, which is the most economical anomaly-free theory to potentially explain the peak by DM annihilation in nearby subhalo. We utilize the process χ χ → Z^' Z^' → l \\bar{l} l^' \\bar{l}^' , where χ , Z^' , l^{(' )} denote the scalar DM, the new gauge boson and l^{(' )} =e, μ , respectively, to generate the e^+e^- spectrum. By fitting the predicted spectrum to the experimental data, we obtain the favored DM mass range m_χ ˜eq 3060^{+80}_{-100} GeV and Δ m ≡ m_χ - m_{Z^' } ≲ 14 GeV at 68% Confidence Level (C.L.). Furthermore, we determine the parameter space of the model which can explain the peak and meanwhile satisfy the constraints from DM relic abundance, DM direct detection and the collider bounds. We conclude that the model we consider can account for the peak, although there exists a tension with the constraints from the LEP-II bound on m_{Z^' } arising from the cross section measurement of e^+e^- → Z^' *} → e^+ e^-.

  6. RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2011-07-28

    We previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70\\/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered. In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours. Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.

  7. Human equilibrative nucleoside transporter-1 knockdown tunes cellular mechanics through epithelial-mesenchymal transition in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Yeonju Lee

    Full Text Available We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1, a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM and correlated to microfluidic platform. The hENT1 knockdown induced reduction of cellular stiffness in both of cells up to 70%. In addition, cellular phenotypic changes such as cell morphology, migration, and expression level of epithelial-mesenchymal transition (EMT markers were observed after hENT1 knockdown. Cells with suppressed hENT1 became elongated, migrated faster, and had reduced E-cadherin and elevated N-cadherin compared to parental cells which are consistent with epithelial-mesenchymal transition (EMT. Those cellular phenotypic changes closely correlated with changes in cellular stiffness. This study suggests that hENT1 expression level affects cellular phenotype and cell elastic behavior can be a physical biomarker for quantify hENT1 expression and detect phenotypic shift. Furthermore, cell mechanics can be a critical tool in detecting disease progression and response to therapy.

  8. Vitellogenin knockdown strongly affects cotton boll weevil egg viability but not the number of eggs laid by females.

    Science.gov (United States)

    Coelho, Roberta R; de Souza Júnior, José Dijair Antonino; Firmino, Alexandre A P; de Macedo, Leonardo L P; Fonseca, Fernando C A; Terra, Walter R; Engler, Gilbert; de Almeida Engler, Janice; da Silva, Maria Cristina M; Grossi-de-Sa, Maria Fatima

    2016-09-01

    Vitellogenin (Vg), a yolk protein precursor, is the primary egg nutrient source involved in insect reproduction and embryo development. The Cotton Boll weevil (CBW) Anthonomus grandis Boheman, the most important cotton pest in Americas, accumulates large amounts of Vg during reproduction. However, the precise role of this protein during embryo development in this insect remains unknown. Herein, we investigated the effects of vitellogenin (AgraVg) knockdown on the egg-laying and egg viability in A. grandis females, and also characterized morphologically the unviable eggs. AgraVg transcripts were found during all developmental stages of A. grandis, with highest abundance in females. Silencing of AgraVg culminated in a significant reduction in transcript amount, around 90%. Despite this transcriptional reduction, egg-laying was not affected in dsRNA-treated females but almost 100% of the eggs lost their viability. Eggs from dsRNA-treated females showed aberrant embryos phenotype suggesting interference at different stages of embryonic development. Unlike for other insects, the AgraVg knockdown did not affect the egg-laying ability of A. grandis, but hampered A. grandis reproduction by perturbing embryo development. We concluded that the Vg protein is essential for A. grandis reproduction and a good candidate to bio-engineer the resistance against this devastating cotton pest.

  9. Contrasting patterns of insecticide resistance and knockdown resistance (kdr) in the dengue vectors Aedes aegypti and Aedes albopictus from Malaysia.

    Science.gov (United States)

    Ishak, Intan H; Jaal, Zairi; Ranson, Hilary; Wondji, Charles S

    2015-03-25

    Knowledge on the extent, distribution and mechanisms of insecticide resistance is essential for successful insecticide-based dengue control interventions. Here, we report an extensive resistance profiling of the dengue vectors Aedes aegypti and Aedes albopictus across Malaysia and establish the contribution of knockdown resistance mechanism revealing significant contrast between both species. Aedes mosquitoes were collected from four states in Malaysia in 2010 using ovitraps and tested against six major insecticides using WHO bioassays. Knockdown resistance (kdr) was investigated in both species. A moderate resistance to temephos was detected from samples collected in 2010 in Penang, Kuala Lumpur, Johor Bharu and Kota Bharu (1.5 Malaysia but neither of these mutations were found in Ae. albopictus. Additionally, signatures of selection were detected on the Voltage-gated sodium channel gene in Ae. aegypti but not in Ae. albopictus. The presence of the 1534C allele was significantly associated with pyrethroid resistance and an additive effect to pyrethroid resistance was observed in individuals containing both kdr alleles. Findings from this study will help to design and implement successful insecticide-based interventions against Ae. aegypti and Ae. albopictus to improve dengue control across Malaysia.

  10. RNAi Knockdown of Hypoxia-Inducible Factor-1α Decreased the Proliferation, Migration, and Invasion of Hypoxic Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Chen, ChengShi; Liu, Rong; Wang, JianHua; Yan, ZhiPing; Qian, Sheng; Zhang, Wei

    2015-04-01

    The obstruction of hepatic arterial blood flow results in tumor tissue hypoxia and elevated expression of hypoxia-inducible factor-1alpha (HIF-1α). Our study evaluated whether lentivirus-mediated short interference RNA against HIF-1α inhibits proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells under hypoxia. RNA interference knockdown of HIF-1α was achieved by HIF-1α-directed lentiviral shRNA, in a rat HCC cell line cultured under hypoxia condition for varying length of times. The expression levels of HIF-1α and vascular endothelial growth factor were examined using reverse transcription polymerase chain reaction and western blot analyses. Cell proliferation, migration, and invasion were measured by cell viability, transwell migration, and invasion assays, respectively. Inhibition of HIF-1α expression by shRNA suppressed vascular endothelial growth factor mRNA and protein levels under both normoxia and hypoxia. It also suppressed cell migration and invasion, which were enhanced under hypoxic conditions. RNAi knockdown of HIF-1α further suppressed hypoxia-mediated inhibition of the cell proliferation. These data suggest that shRNA of HIF-1α could antagonize the hypoxia-mediated increase in hepatic cancer cell migration and invasion, and synergize with hypoxia to inhibit the cell proliferation in HCC cells.

  11. Stable SREBP-1a knockdown decreases the cell proliferation rate in human preadipocyte cells without inducing senescence

    International Nuclear Information System (INIS)

    Alvarez, María Soledad; Fernandez-Alvarez, Ana; Cucarella, Carme; Casado, Marta

    2014-01-01

    Highlights: • SGBS cells mostly expressed SREBP-1a variant. • SREBP-1a knockdown decreased the proliferation of SGBS cells without inducing senescence. • We have identified RBBP8 and CDKN3 genes as potential SREBP-1a targets. - Abstract: Sterol regulatory element binding proteins (SREBP), encoded by the Srebf1 and Srebf2 genes, are important regulators of genes involved in cholesterol and fatty acid metabolism. Whereas SREBP-2 controls the cholesterol synthesis, SREBP-1 proteins (-1a and -1c) function as the central hubs in lipid metabolism. Despite the key function of these transcription factors to promote adipocyte differentiation, the roles of SREBP-1 proteins during the preadipocyte state remain unknown. Here, we evaluate the role of SREBP-1 in preadipocyte proliferation using RNA interference technology. Knockdown of the SREBP-1a gene decreased the proliferation rate in human SGBS preadipocyte cell strain without inducing senescence. Furthermore, our data identified retinoblastoma binding protein 8 and cyclin-dependent kinase inhibitor 3 genes as new potential SREBP-1 targets, in addition to cyclin-dependent kinase inhibitor 1A which had already been described as a gene regulated by SREBP-1a. These data suggested a new role of SREBP-1 in adipogenesis via regulation of preadipocyte proliferation

  12. Design of 8-ft-Diameter Barrel Test Article Attachment Rings for Shell Buckling Knockdown Factor Project

    Science.gov (United States)

    Lovejoy, Andrew E.; Hilburger, Mark W.

    2010-01-01

    The Shell Buckling Knockdown Factor (SBKF) project includes the testing of sub-scale cylinders to validate new shell buckling knockdown factors for use in the design of the Ares-I and Ares-V launch vehicles. Test article cylinders represent various barrel segments of the Ares-I and Ares-V vehicles, and also include checkout test articles. Testing will be conducted at Marshall Space Flight Center (MSFC) for test articles having an eight-foot diameter outer mold line (OML) and having lengths that range from three to ten feet long. Both ends of the test articles will be connected to the test apparatus using attachment rings. Three multiple-piece and one single-piece design for the attachment rings were developed and analyzed. The single-piece design was chosen and will be fabricated from either steel or aluminum (Al) depending on the required safety factors (SF) for test hardware. This report summarizes the design and analysis of these attachment ring concepts.

  13. Strong morphological defects in conditional Arabidopsis abp1 knock-down mutants generated in absence of functional ABP1 protein.

    Science.gov (United States)

    Michalko, Jaroslav; Glanc, Matouš; Perrot-Rechenmann, Catherine; Friml, Jiří

    2016-01-01

    The Auxin Binding Protein 1 (ABP1) is one of the most studied proteins in plants. Since decades ago, it has been the prime receptor candidate for the plant hormone auxin with a plethora of described functions in auxin signaling and development. The developmental importance of ABP1 has recently been questioned by identification of Arabidopsis thaliana abp1 knock-out alleles that show no obvious phenotypes under normal growth conditions. In this study, we examined the contradiction between the normal growth and development of the abp1 knock-outs and the strong morphological defects observed in three different ethanol-inducible abp1 knock-down mutants ( abp1-AS, SS12K, SS12S). By analyzing segregating populations of abp1 knock-out vs. abp1 knock-down crosses we show that the strong morphological defects that were believed to be the result of conditional down-regulation of ABP1 can be reproduced also in the absence of the functional ABP1 protein. This data suggests that the phenotypes in  abp1 knock-down lines are due to the off-target effects and asks for further reflections on the biological function of ABP1 or alternative explanations for the missing phenotypic defects in the abp1 loss-of-function alleles.

  14. Stable SREBP-1a knockdown decreases the cell proliferation rate in human preadipocyte cells without inducing senescence

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, María Soledad [Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia (Spain); Fernandez-Alvarez, Ana [Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE (Argentina); Cucarella, Carme [Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia (Spain); Casado, Marta, E-mail: mcasado@ibv.csic.es [Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia (Spain)

    2014-04-25

    Highlights: • SGBS cells mostly expressed SREBP-1a variant. • SREBP-1a knockdown decreased the proliferation of SGBS cells without inducing senescence. • We have identified RBBP8 and CDKN3 genes as potential SREBP-1a targets. - Abstract: Sterol regulatory element binding proteins (SREBP), encoded by the Srebf1 and Srebf2 genes, are important regulators of genes involved in cholesterol and fatty acid metabolism. Whereas SREBP-2 controls the cholesterol synthesis, SREBP-1 proteins (-1a and -1c) function as the central hubs in lipid metabolism. Despite the key function of these transcription factors to promote adipocyte differentiation, the roles of SREBP-1 proteins during the preadipocyte state remain unknown. Here, we evaluate the role of SREBP-1 in preadipocyte proliferation using RNA interference technology. Knockdown of the SREBP-1a gene decreased the proliferation rate in human SGBS preadipocyte cell strain without inducing senescence. Furthermore, our data identified retinoblastoma binding protein 8 and cyclin-dependent kinase inhibitor 3 genes as new potential SREBP-1 targets, in addition to cyclin-dependent kinase inhibitor 1A which had already been described as a gene regulated by SREBP-1a. These data suggested a new role of SREBP-1 in adipogenesis via regulation of preadipocyte proliferation.

  15. Knockdown of XBP1 by RNAi in Mouse Granulosa Cells Promotes Apoptosis, Inhibits Cell Cycle, and Decreases Estradiol Synthesis

    Directory of Open Access Journals (Sweden)

    Nan Wang

    2017-05-01

    Full Text Available Granulosa cells are crucial for follicular growth, development, and follicular atresia. X-box binding protein 1 (XBP1, a basic region-leucine zipper protein, is widely involved in cell differentiation, proliferation, apoptosis, cellular stress response, and other signaling pathways. In this study, RNA interference, flow cytometry, western blot, real-time PCR, Cell Counting Kit (CCK8, and ELISA were used to investigate the effect of XBP1 on steroidogenesis, apoptosis, cell cycle, and proliferation of mouse granulosa cells. ELISA analysis showed that XBP1 depletion significantly decreased the concentrations of estradiol (E2. Additionally, the expression of estrogen synthesis enzyme Cyp19a1 was sharply downregulated. Moreover, flow cytometry showed that knockdown of XBP1 increased the apoptosis rate and arrests the cell cycle in S-phase in granulosa cells (GCs. Further study confirmed these results. The expression of CCAAT-enhancer-binding protein homologous protein (CHOP, cysteinyl aspartate specific proteases-3 (caspase-3, cleaved caspase-3, and Cyclin E was upregulated, while that of Bcl-2, Cyclin A1, and Cyclin B1 was downregulated. Simultaneously, CCK8 analysis indicated that XBP1 disruption inhibited cell proliferation. In addition, XBP1 knockdown also alters the expression of Has2 and Ptgs2, two essential genes for folliculogenesis. Collectively, these data reveal a novel critical role of XBP1 in folliculogenesis by regulating the cell cycle, apoptosis, and steroid synthesis of mouse granulosa cells.

  16. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

    Science.gov (United States)

    Nagarkar-Jaiswal, Sonal; Lee, Pei-Tseng; Campbell, Megan E; Chen, Kuchuan; Anguiano-Zarate, Stephanie; Cantu Gutierrez, Manuel; Busby, Theodore; Lin, Wen-Wen; He, Yuchun; Schulze, Karen L; Booth, Benjamin W; Evans-Holm, Martha; Venken, Koen JT; Levis, Robert W; Spradling, Allan C; Hoskins, Roger A; Bellen, Hugo J

    2015-01-01

    Here, we document a collection of ∼7434 MiMIC (Minos Mediated Integration Cassette) insertions of which 2854 are inserted in coding introns. They allowed us to create a library of 400 GFP-tagged genes. We show that 72% of internally tagged proteins are functional, and that more than 90% can be imaged in unfixed tissues. Moreover, the tagged mRNAs can be knocked down by RNAi against GFP (iGFPi), and the tagged proteins can be efficiently knocked down by deGradFP technology. The phenotypes associated with RNA and protein knockdown typically correspond to severe loss of function or null mutant phenotypes. Finally, we demonstrate reversible, spatial, and temporal knockdown of tagged proteins in larvae and adult flies. This new strategy and collection of strains allows unprecedented in vivo manipulations in flies for many genes. These strategies will likely extend to vertebrates. DOI: http://dx.doi.org/10.7554/eLife.05338.001 PMID:25824290

  17. Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Xie Li

    2009-02-01

    Full Text Available Abstract Background Astrocyte elevated gene-1 (AEG-1 was originally characterized as a HIV-1-inducible gene in primary human fetal astrocyte. Recent studies highlight a potential role of AEG-1 in promoting tumor progression and metastasis. The aim of this study was to investigate if AEG-1 serves as a potential therapeutic target of human neuroblastoma. Methods We employed RNA interference to reduce AEG-1 expression in human neuroblastoma cell lines and analyzed their phenotypic changes. Results We found that the knockdown of AEG-1 expression in human neuroblastoma cells significantly inhibited cell proliferation and apoptosis. The specific downregulation induced cell arrest in the G0/G1 phase of cell cycle. In the present study, we also observed a significant enhancement of chemo-sensitivity to cisplatin and doxorubicin by knockdown of AEG-1. Conclusion Our study suggests that overexpressed AEG-1 enhance the tumorogenic properties of neuroblastoma cells. The inhibition of AEG-1 expression could be a new adjuvant therapy for neuroblastoma.

  18. Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation

    Science.gov (United States)

    Meng, X; Kong, D-H; Li, N; Zong, Z-H; Liu, B-Q; Du, Z-X; Guan, Y; Cao, L; Wang, H-Q

    2014-01-01

    The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial–mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of β-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis. PMID:24577090

  19. Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer cells through ZEB1 activation.

    Science.gov (United States)

    Meng, X; Kong, D-H; Li, N; Zong, Z-H; Liu, B-Q; Du, Z-X; Guan, Y; Cao, L; Wang, H-Q

    2014-02-27

    The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial-mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of β-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis.

  20. Individual eigenvalue distributions of crossover chiral random matrices and low-energy constants of SU(2) × U(1) lattice gauge theory

    Science.gov (United States)

    Yamamoto, Takuya; Nishigaki, Shinsuke M.

    2018-02-01

    We compute individual distributions of low-lying eigenvalues of a chiral random matrix ensemble interpolating symplectic and unitary symmetry classes by the Nyström-type method of evaluating the Fredholm Pfaffian and resolvents of the quaternion kernel. The one-parameter family of these distributions is shown to fit excellently the Dirac spectra of SU(2) lattice gauge theory with a constant U(1) background or dynamically fluctuating U(1) gauge field, which weakly breaks the pseudoreality of the unperturbed SU(2) Dirac operator. The observed linear dependence of the crossover parameter with the strength of the U(1) perturbations leads to precise determination of the pseudo-scalar decay constant, as well as the chiral condensate in the effective chiral Lagrangian of the AI class.

  1. Classical local U(1 gauge invariance in Weyl 2-spinor lenguage and charge quantization from irreducible representations of the gauge group

    Directory of Open Access Journals (Sweden)

    J. Buitrago

    Full Text Available A new classical 2-spinor approach to U(1 gauge theory is presented in which the usual four-potential vector field is replaced by a symmetric second rank spinor. Following a lagrangian formulation, it is shown that the four-rank spinor representing the Maxwell field tensor has a U(1 local gauge invariance in terms of the electric and magnetic field strengths. When applied to the magnetic field of a monopole, this formulation, via the irreducible representation condition for the gauge group, leads to a quantization condition differing by a factor 2 of the one predicted by Dirac without relying on any kind of singular vector potentials. Finally, the U(1 invariant spinor equations, are applied to electron magnetic resonance which has many applications in the study of materials. Keywords: Weyl 2-spinor lenguage, Dirac equation, Gauge theories, Charge quantization

  2. Membrane-bound human orphan cytochrome P450 2U1: Sequence singularities, construction of a full 3D model, and substrate docking.

    Science.gov (United States)

    Ducassou, Lionel; Dhers, Laura; Jonasson, Gabriella; Pietrancosta, Nicolas; Boucher, Jean-Luc; Mansuy, Daniel; André, François

    2017-09-01

    Human cytochrome P450 2U1 (CYP2U1) is an orphan CYP that exhibits several distinctive characteristics among the 57 human CYPs with a highly conserved sequence in almost all living organisms. We compared its protein sequence with those of the 57 human CYPs and constructed a 3D structure of a full-length CYP2U1 model bound to a POPC membrane. We also performed docking experiments of arachidonic acid (AA) and N-arachidonoylserotonin (AS) in this model. The protein sequence of CYP2U1 displayed two unique characteristics when compared to those of the human CYPs, the presence of a longer N-terminal region upstream of the putative trans-membrane helix (TMH) containing 8 proline residues, and of an insert of about 20 amino acids containing 5 arginine residues between helices A' and A. Its N-terminal part upstream of TMH involved an additional short terminal helix, in a manner similar to what was reported in the crystal structure of Saccharomyces cerevisiae CYP51. Our model also showed a specific interaction between the charged residues of insert AA' and phosphate groups of lipid polar heads, suggesting a possible role of this insert in substrate recruitment. Docking of AA and AS in this model showed these substrates in channel 2ac, with the terminal alkyl chain of AA or the indole ring of AS close to the heme, in agreement with the reported CYP2U1-catalyzed AA and AS hydroxylation regioselectivities. This model should be useful to find new endogenous or exogenous CYP2U1 substrates and to interpret the regioselectivity of their hydroxylation. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  3. QCD sum rules of the Laplace transform type for the gluon component of the U(1)sub(A) meson mass

    International Nuclear Information System (INIS)

    Narison, S.

    1981-07-01

    We get upper bound of the gluon component of the U(1)sub(A) meson mass using QCD sum rules of the Laplace transform type to the two-point functions associated to the divergence of the U(1)sub(A) current in the chiral limit. For Λ is approximately equal to 70 is approximately 210 MeV and fsub(eta') is approximately equal to (0.5 is approximately 0.7) sqrt 3 fsub(π), we obtain Msub(G) is approximately smaller to (0.6 is approximately 0.85) GeV, which indicates an important gluon contribution to the eta' mass. (author)

  4. Spontaneous compactification of D=10 Maxwell-Einstein theory leads to SU(3) X SU(2) X U(1) gauge symmetry

    International Nuclear Information System (INIS)

    Watamura, S.

    1983-01-01

    Solutions of ten-dimensional Maxwell-Einstein theory and a bosonic part of N = 2, D = 10 supergravity theory are examined. It is shown that there is a solution for which six-dimensional internal space is compactified into CP 2 x S 2 . The gauge symmetry of the effective four-dimensional theory is SU(3) x SU(2) x U(1). The introduction of fermions is also considered. The requirement of consistency in introducing a spinsup(C) structure on CP 2 results in a U(1) charge quantization condition. (orig.)

  5. snRNP proteins in health and disease

    Czech Academy of Sciences Publication Activity Database

    Krausová, Michaela; Staněk, David

    S1084-9521, č. 17 (2017), s. 30150-30157 ISSN 1084-9521 R&D Projects: GA ČR GA15-00790S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : Congenital craniofacial disorders * Haematological malignancies * Mutations * Retinopathy * Spliceosome Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.614, year: 2016

  6. PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro

    Directory of Open Access Journals (Sweden)

    Cui W

    2017-04-01

    Full Text Available Wenli Cui,1–4,* Shutao Zheng,5,6,* Zebing Liu,1–3 Weige Wang,1–3 Ying Cai,1–3 Rui Bi,1–3 Bing Cao,1–3 Xiaoyan Zhou1–3 1Department of Pathology, Shanghai Cancer Center, Fudan University, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Institute of Pathology, Fudan University, Shanghai, 4Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, 5Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 6State Key Lab Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: PIK3CA has been extensively investigated from its molecular mechanism perspective and epidemiological association with its mutations in different types of cancers. However, little has been reported regarding the clinicopathological significance of PIK3CA expression in diffuse large B cell lymphoma (DLBCL. In the present study, we investigated the clinicopathological significance of PIK3CA in DLBCL by performing immunohistochemical evaluation of PIK3CA in tissue microarrays consisting of 199 cases of DLBCL. Kaplan–Meier survival analysis was performed to analyze the association between PIK3CA expression and overall prognosis. To further investigate the role of PIK3CA mediated in the proliferation, cell cycle and apoptosis of DLBCL cells, Cell Counting Kit-8 (CCK-8 and flow cytometry assays were carried out in DLBCL cell lines after successful, stable knockdown of PIK3CA using lentiviral short hairpin RNA inference. Our results indicated that although PIK3CA was shown to be extensively expressed in DLBCL, no significant association was observed between PIK3CA expression and clinical outcome or between PIK3CA expression and other clinicopathological parameters, except between performance state (PS

  7. PRX1 knockdown potentiates vitamin K3 toxicity in cancer cells: a potential new therapeutic perspective for an old drug.

    Science.gov (United States)

    He, Tiantian; Hatem, Elie; Vernis, Laurence; Lei, Ming; Huang, Meng-Er

    2015-12-21

    Many promising anticancer molecules are abandoned during the course from bench to bedside due to lack of clear-cut efficiency and/or severe side effects. Vitamin K3 (vitK3) is a synthetic naphthoquinone exhibiting significant in vitro and in vivo anticancer activity against multiple human cancers, and has therapeutic potential when combined with other anticancer molecules. The major mechanism for the anticancer activity of vitK3 is the generation of cytotoxic reactive oxygen species (ROS). We thus reasoned that a rational redox modulation of cancer cells could enhance vitK3 anticancer efficiency. Cancer cell lines with peroxiredoxin 1 (PRX1) gene transiently or stably knocked-down and corresponding controls were exposed to vitK3 as well as a set of anticancer molecules, including vinblastine, taxol, doxorubicin, daunorubicin, actinomycin D and 5-fluorouracil. Cytotoxic effects and cell death events were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based assay, cell clonogenic assay, measurement of mitochondrial membrane potential and annexin V/propidium iodide double staining. Global ROS accumulation and compartment-specific H2O2 generation were determined respectively by a redox-sensitive chemical probe and H2O2-sensitive sensor HyPer. Oxidation of endogenous antioxidant proteins including TRX1, TRX2 and PRX3 was monitored by redox western blot. We observed that the PRX1 knockdown in HeLa and A549 cells conferred enhanced sensitivity to vitK3, reducing substantially the necessary doses to kill cancer cells. The same conditions (combination of vitK3 and PRX1 knockdown) caused little cytotoxicity in non-cancerous cells, suggesting a cancer-cell-selective property. Increased ROS accumulation had a crucial role in vitK3-induced cell death in PRX1 knockdown cells. The use of H2O2-specific sensors HyPer revealed that vitK3 lead to immediate accumulation of H2O2 in the cytosol, nucleus, and mitochondrial matrix. PRX1 silencing

  8. [Knockdown of STAT3 inhibits proliferation and migration of HepG2 hepatoma cells induced by IFN1].

    Science.gov (United States)

    Li, Xiaofang; Wang, Yuqi; Yan, Ben; Fang, Peipei; Ma, Chao; Xu, Ning; Fu, Xiaoyan; Liang, Shujuan

    2018-02-01

    Objective To prepare lentiviruses expressing shRNA sequences targeting human signal transducer and activator of transcription 3 (STAT3) and detect the effect of STAT3 knockdown on type I interferon (IFN1)-induced proliferation and migration in HepG2 cells. Methods Four STAT3-targeting shRNA sequences (shRNA1-shRNA4) and one control sequence (Ctrl shRNA) were selected and cloned respectively into pLKO.1-sp6-pgk-GFP to construct shRNA-expressing vectors. Along with backbone psPAX2 and pMD2.G vectors, they were separately transfected into HEK293T cells to prepare lentiviruses. HepG2 cells were infected with the lentiviruses. Cytoplastic STAT3 level was detected by Western blotting to screen effective shRNA sequence(s) targeting STAT3. Proliferation and migration of HepG2 cells were analyzed by CCK-8 assay and Transwell TM migration and scratching assay, respectively. To detect the effect of IFN1 on cell proliferation and migration of HepG2 cells, the cells were treated with 2000 U/mL IFNα2b for indicated time and the activation of IFN-triggered STAT1 signal transduction was assayed by Western blotting. Results Two most effective STAT3-targeting shRNA sequences shRNA1 and shRNA2 were selected, and the expression of both STAT3 shRNA significantly decreased proliferation and migration of HepG2 cells. When treated with IFNα2b, 2000 U/mL of IFN1 showed more competent in attenuating growth and migration of HepG2 cells. Our data further proved that knockdown of STAT3 increased the phosphorylation of STAT1, and IFNα2b further enhanced the activation of STAT1 signaling in HepG2 cells. Conclusion Knockdown of STAT3 inhibits cell migration and growth, and rescues IFN response through up-regulating STAT1 signal transduction in HepG2 hepatoma cells.

  9. Self-interacting dark matter and Higgs bosons in the SU(3)C x SU(3)L x U(1)N model with right-handed neutrinos

    International Nuclear Information System (INIS)

    Hoang Ngoc Long; Nguyen Quynh Lan

    2003-05-01

    We show that the SU(3) C x SU(3) L x U(1) N (3-3-1) model with right-handed neutrinos can provide candidates for self-interacting dark matter, namely they are the CP-even and odd Higgs bosons. These dark matters are stable without imposing of new symmetry and should be weak-interacting. (author)

  10. Comparative performance of the protocol of plasma rich in growth factors - universal 1 (PRGF-U1 for obtaining platelet rich plasma.

    Directory of Open Access Journals (Sweden)

    Augusto Aguirre

    2017-01-01

    Full Text Available Objective: To compare the platelet concentration obtained after application of the protocol of plasma rich in growth factors - universal 1 (PRGF-U1 and the protocol of Anitua and Andia (PRP-A for obtaining platelet rich plasma. Material and Method: A descriptive, cross-sectional and comparative study was carried out with a simple random probabilistic sample consisting of 16 patients who attended the Periodontics service of the Unit of Second Specialization in Stomatology of the National University of Trujillo. Five blood samples were obtained from each patient, after applying a health questionnaire to rule out any disease or drug consumption, in order to obtain the baseline platelet concentration and that obtained after PRGF-U1 and PRP-A. To compare the platelet concentrations of the two protocols, Student’s t-test was used considering a significance level of p<0.05. RESULTS: The baseline platelet concentration was 371,250±68,203 platelets/μL, for PRGF-U1 it was 747,875±121,645 platelets/μL and for PRP-A it was 595,000±129,202 platelets/μL. A statistically significant difference (p<0.001 was found between both protocols. Conclusion: The PRGF-U1 protocol yielded a higher platelet concentration compared to the Anitúa and Andía protocol.

  11. Pre-Test Analysis Predictions for the Shell Buckling Knockdown Factor Checkout Tests - TA01 and TA02

    Science.gov (United States)

    Thornburgh, Robert P.; Hilburger, Mark W.

    2011-01-01

    This report summarizes the pre-test analysis predictions for the SBKF-P2-CYL-TA01 and SBKF-P2-CYL-TA02 shell buckling tests conducted at the Marshall Space Flight Center (MSFC) in support of the Shell Buckling Knockdown Factor (SBKF) Project, NASA Engineering and Safety Center (NESC) Assessment. The test article (TA) is an 8-foot-diameter aluminum-lithium (Al-Li) orthogrid cylindrical shell with similar design features as that of the proposed Ares-I and Ares-V barrel structures. In support of the testing effort, detailed structural analyses were conducted and the results were used to monitor the behavior of the TA during the testing. A summary of predicted results for each of the five load sequences is presented herein.

  12. Knock-down of ELMO1 in Paediatric Rhabdomyosarcoma Cells by Nanoparticle Mediated siRNA Delivery

    Directory of Open Access Journals (Sweden)

    Xinyue Huang

    2016-03-01

    Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue sarcoma that is found in children and has a poor outcome for those with metastatic disease. Two histological groups have been distinguished - embryonal (ERMS and alveolar (ARMS forms. The ARMS subtype has higher rates of metastasis, as well as higher levels of ELMO1, which is thought to be involved in cell migration. Therefore, the knock-down of ELMO1 by targeted siRNA could provide a mechanism to prevent the metastatic behaviour of ARMS cells. However, challenges still lie in the delivery of nucleotides to a tumour site. Herein, we have described the use of a variety of mesoporous silica nanoparticles as a delivery system for siRNA that is specific for ELMO1 and shown the effective reduction in cell invasive behaviour in these cells.

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

    International Nuclear Information System (INIS)

    Reddy, A.S.N.

    2008-01-01

    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

  14. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.

    Science.gov (United States)

    Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen

    2016-08-01

    Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments.

  15. Knockdown resistance, Rdl alleles, and the annual entomological Inoculation rate of wild mosquito populations from Lower Moshi, Northern Tanzania

    Directory of Open Access Journals (Sweden)

    Aneth M Mahande

    2012-01-01

    Full Text Available Aim: Understanding vector behavioral response due to ecological factors is important in the control of disease vectors. This study was conducted to determine the knockdown resistance (kdr alleles, dieldrin resistance alleles, and entomological inoculation rates (EIRs of malaria vectors in lower Moshi irrigation schemes for the mitigation of disease transmission. Materials and Methods: The study was longitudinal design conducted for 14 months. Mosquitoes were collected fortnightly by using a CDC miniature light trap in 20 houses. Mosquitoes were identified morphologically in the field, of which 10% of this population was identified to species level by using molecular techniques. Samples from this study population were taken for kdr and resistance to dieldrin (rdl genes detection. Results: A total of 6220 mosquitoes were collected by using a light trap, of which 86.0% (n=5350 were Anopheles gambiae sensu lato and 14.0% (n=870 were Culex quinquefasciatus. Ten percent of the An. gambiae s.l. (n=535 collected were taken for species identification, of which 99.8% (n=534 were identified as An. arabiensis while 0.2% (n=1 were An. gambiae sensu stricto. Of the selected mosquitoes, 3.5% (n=19 were sporozoite positive. None of the mosquitoes tested had the kdr gene. The rdl resistant allele was detected at a frequency of 0.48 throughout the year. EIR was determined to be 0.54 ib/trap/year. Conclusion: The findings of this study suggest that the homozygous and the heterozygous resistance present in rdl genes demonstrated the effect of pesticide residues on resistance selection pressure in mosquitoes. A better insecticide usage protocol needs to be developed for farmers to use in order to avoid excessive use of pesticides. Key words: An. arabiensis, EIR, Knockdown mutation, Moshi, rdl locus, Tanzania

  16. Peripheral-specific y2 receptor knockdown protects mice from high-fat diet-induced obesity.

    Science.gov (United States)

    Shi, Yan-Chuan; Lin, Shu; Castillo, Lesley; Aljanova, Aygul; Enriquez, Ronaldo F; Nguyen, Amy D; Baldock, Paul A; Zhang, Lei; Bijker, Martijn S; Macia, Laurence; Yulyaningsih, Ernie; Zhang, Hui; Lau, Jackie; Sainsbury, Amanda; Herzog, Herbert

    2011-11-01

    Y2 receptors, particularly those in the brain, have been implicated in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone mass. Recent evidence also indicates a role for Y2 receptors in peripheral tissues in this process by promoting adipose tissue accretion; however their effects on energy balance remain unclear. Here, we show that adult-onset conditional knockdown of Y2 receptors predominantly in peripheral tissues results in protection against diet-induced obesity accompanied by significantly reduced weight gain, marked reduction in adiposity and improvements in glucose tolerance without any adverse effect on lean mass or bone. These changes occur in association with significant increases in energy expenditure, respiratory exchange ratio, and physical activity and despite concurrent hyperphagia. On a chow diet, knockdown of peripheral Y2 receptors results in increased respiratory exchange ratio and physical activity with no effect on lean or bone mass, but decreases energy expenditure without effecting body weight or food intake. These results suggest that peripheral Y2 receptor signaling is critical in the regulation of oxidative fuel selection and physical activity and protects against the diet-induced obesity. The lack of effects on bone mass seen in this model further indicates that bone mass is primarily controlled by non-peripheral Y2 receptors. This study provides evidence that novel drugs that target peripheral rather than central Y2 receptors could provide benefits for the treatment of obesity and glucose intolerance without adverse effects on lean and bone mass, with the additional benefit of avoiding side effects often associated with pharmaceuticals that act on the central nervous system.

  17. Network Analysis for the Identification of Differentially Expressed Hub Genes Using Myogenin Knock-down Muscle Satellite Cells.

    Directory of Open Access Journals (Sweden)

    Adeel Malik

    Full Text Available Muscle, a multinucleate syncytium formed by the fusion of mononuclear myoblasts, arises from quiescent progenitors (satellite cells via activation of muscle-specific transcription factors (MyoD, Myf5, myogenin: MYOG, and MRF4. Subsequent to a decline in Pax7, induction in the expression of MYOG is a hallmark of myoblasts that have entered the differentiation phase following cell cycle withdrawal. It is evident that MYOG function cannot be compensated by any other myogenic regulatory factors (MRFs. Despite a plethora of information available regarding MYOG, the mechanism by which MYOG regulates muscle cell differentiation has not yet been identified. Using an RNA-Seq approach, analysis of MYOG knock-down muscle satellite cells (MSCs have shown that genes associated with cell cycle and division, DNA replication, and phosphate metabolism are differentially expressed. By constructing an interaction network of differentially expressed genes (DEGs using GeneMANIA, cadherin-associated protein (CTNNA2 was identified as the main hub gene in the network with highest node degree. Four functional clusters (modules or communities were identified in the network and the functional enrichment analysis revealed that genes included in these clusters significantly contribute to skeletal muscle development. To confirm this finding, in vitro studies revealed increased expression of CTNNA2 in MSCs on day 12 compared to day 10. Expression of CTNNA2 was decreased in MYOG knock-down cells. However, knocking down CTNNA2, which leads to increased expression of extracellular matrix (ECM genes (type I collagen α1 and type I collagen α2 along with myostatin (MSTN, was not found significantly affecting the expression of MYOG in C2C12 cells. We therefore propose that MYOG exerts its regulatory effects by acting upstream of CTNNA2, which in turn regulates the differentiation of C2C12 cells via interaction with ECM genes. Taken together, these findings highlight a new

  18. Amastin Knockdown in Leishmania braziliensis Affects Parasite-Macrophage Interaction and Results in Impaired Viability of Intracellular Amastigotes.

    Directory of Open Access Journals (Sweden)

    Rita Marcia Cardoso de Paiva

    2015-12-01

    Full Text Available Leishmaniasis, a human parasitic disease with manifestations ranging from cutaneous ulcerations to fatal visceral infection, is caused by several Leishmania species. These protozoan parasites replicate as extracellular, flagellated promastigotes in the gut of a sandfly vector and as amastigotes inside the parasitophorous vacuole of vertebrate host macrophages. Amastins are surface glycoproteins encoded by large gene families present in the genomes of several trypanosomatids and highly expressed in the intracellular amastigote stages of Trypanosoma cruzi and Leishmania spp. Here, we showed that the genome of L. braziliensis contains 52 amastin genes belonging to all four previously described amastin subfamilies and that the expression of members of all subfamilies is upregulated in L. braziliensis amastigotes. Although primary sequence alignments showed no homology to any known protein sequence, homology searches based on secondary structure predictions indicate that amastins are related to claudins, a group of proteins that are components of eukaryotic tight junction complexes. By knocking-down the expression of δ-amastins in L. braziliensis, their essential role during infection became evident. δ-amastin knockdown parasites showed impaired growth after in vitro infection of mouse macrophages and completely failed to produce infection when inoculated in BALB/c mice, an attenuated phenotype that was reverted by the re-expression of an RNAi-resistant amastin gene. Further highlighting their essential role in host-parasite interactions, electron microscopy analyses of macrophages infected with amastin knockdown parasites showed significant alterations in the tight contact that is normally observed between the surface of wild type amastigotes and the membrane of the parasitophorous vacuole.

  19. Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis

    Energy Technology Data Exchange (ETDEWEB)

    Doyen, Jérome [Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284, University of Nice Sophia-Antipolis,, Nice (France); Department of Radiation Oncology, Centre Antoine-Lacassagne, Nice (France); Parks, Scott K. [Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284, University of Nice Sophia-Antipolis,, Nice (France); Marcié, Serge [Department of Radiation Oncology, Centre Antoine-Lacassagne, Nice (France); Pouysségur, Jacques [Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284, University of Nice Sophia-Antipolis,, Nice (France); Centre Scientifique de Monaco (Monaco); Chiche, Johanna, E-mail: chiche@unice.fr [Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284, University of Nice Sophia-Antipolis,, Nice (France)

    2013-01-07

    The relationship between acidosis within the tumor microenvironment and radioresistance of hypoxic tumor cells remains unclear. Previously we reported that hypoxia-induced carbonic anhydrases (CA) IX and CAXII constitute a robust intracellular pH (pH{sub i})-regulating system that confers a survival advantage on hypoxic human colon carcinoma LS174Tr cells in acidic microenvironments. Here we investigate the role of acidosis, CAIX and CAXII knock-down in combination with ionizing radiation. Fibroblasts cells (-/+ CAIX) and LS174Tr cells (inducible knock-down for ca9/ca12) were analyzed for cell cycle phase distribution and survival after irradiation in extracellular pH{sub o} manipulations and hypoxia (1% O{sub 2}) exposure. Radiotherapy was used to target ca9/ca12-silenced LS174Tr tumors grown in nude mice. We found that diminishing the pH{sub i}-regulating capacity of fibroblasts through inhibition of Na{sup +}/H{sup +} exchanger 1 sensitize cells to radiation-induced cell death. Secondly, the pH{sub i}-regulating function of CAIX plays a key protective role in irradiated fibroblasts in an acidic environment as accompanied by a reduced number of cells in the radiosensitive phases of the cell cycle. Thirdly, we demonstrate that irradiation of LS174Tr spheroids, silenced for either ca9 or both ca9/ca12, showed a respective 50 and 75% increase in cell death as a result of a decrease in cell number in the radioresistant S phase and a disruption of CA-mediated pH{sub i} regulation. Finally, LS174Tr tumor progression was strongly decreased when ca9/ca12 silencing was combined with irradiation in vivo. These findings highlight the combinatory use of radiotherapy with targeting of the pH{sub i}-regulating CAs as an anti-cancer strategy.

  20. Effects of DCK knockdown on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells.

    Science.gov (United States)

    Shang, Q-Y; Wu, C-S; Gao, H-R

    2017-09-01

    The present study explored the effect that deoxycytidine kinase (DCK) knockdown had on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells. Human cervical cancer HeLa cells that had received no prior treatment were selected from the HeLa group. The HeLa-negative control (NC) group consisted of cells that had undergone an empty vector treatment, and finally the HeLa-short hairpin RNA (shRNA) group included cells that were treated by means of shRNA-DCK expression. DCK expressions were evaluated by quantitative real-time polymerase chain reaction in addition to western blotting assays. Cell proliferation was estimated using the Cell Counting Kit-8 (CCK-8) assay and cell cycle progression. Cell apoptosis was determined by flow cytometry. BALB/c nude mice (n=24) were selected to establish transplanted tumor models, with gross tumor volume measured every 3 days. The results in vitro were as follows: compared with the HeLa group, the HeLa-shRNA group exhibited downregulation of DCK expression and inhibition of cell proliferation at 48, 72 and 96 h. Additionally, more cells in the HeLa-shRNA group were arrested in G0/G1 stage and less in S and G2/M stages, as well as in promotion of cell apoptosis. In vivo results are as follows: when comparing the HeLa and HeLa-NC groups, the gross tumor volume of the transplanted tumor in nude mice in the HeLa-shRNA group was found to have decreased in 13, 16, 19 and 22 days. Based on these findings, our study suggests that DCK knockdown facilitates apoptosis while inhibiting proliferation and tumorigenicity in vivo of cervical cancer HeLa cells.

  1. Structural study of U1-xAmxO2±δ oxide microspheres dedicated to the production of americium bearing blankets

    International Nuclear Information System (INIS)

    Caisso, Marie

    2016-01-01

    One of the studied routes to reduce nuclear waste amount, is, after plutonium recycling, americium (Am) heterogeneous transmutation in fast neutron reactors, through the generation of short-lives and inert elements. Am irradiation requires the fabrication of U 1-x Am x O 2±δ pellets and the CRMP (Calcined Resin Microsphere Pelletization) process is currently considered as one the most promising candidate among other fabrication routes. It is based, before pellet sintering, on the compaction of U 1-x Am x O 2±δ oxide microspheres, synthesized through the thermal conversion of ion exchange resin microspheres, loaded with UO 2 2+ and Am 3+ cations. Compared to standard methods using powder metallurgy, CRMP process favours pressing step (easy microsphere flow) while limiting generation of highly radioactive Am-based fine particles. In this context, this PhD work was focused on the exhaustive characterization of CRMP process different steps, from a mechanistic and structural point of view. The cation molecular complex used in the resin was thus determined, highlighting carboxylic bidentate ligand binding around U and Am elements. Thermal conversion was also in-situ followed, and the structures of the different synthesized compounds evidenced and accurately characterized, i.e. (U 1-x Am x ) 3 O 8 et U 1-x Am x O 2±δ . Am substitution in each of them was explained, revealing related distortions around U and Am cations. Finally, sintering of U 1-x Am x O 2±δ microspheres shaped into pellets was studied, showing a two-step densification. This unusual behavior corresponds to multi-scale reorganization into the material during sintering thermal treatment, associated to the presence of nanoparticles in the green pellet that sinter at low temperature. (author) [fr

  2. Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Motoharu Ono

    Full Text Available We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

  3. RNAi-mediated knockdown of MTNR1B without disrupting the effects of melatonin on apoptosis and cell cycle in bovine granulose cells

    Directory of Open Access Journals (Sweden)

    Wenju Liu

    2018-04-01

    Full Text Available Melatonin is well known as a powerful free radical scavenger and exhibits the ability to prevent cell apoptosis. In the present study, we investigated the role of melatonin and its receptor MTNR1B in regulating the function of bovine granulosa cells (GCs and hypothesized the involvement of MTNR1B in mediating the effect of melatonin on GCs. Our results showed that MTNR1B knockdown significantly promoted GCs apoptosis but did not affect the cell cycle. These results were further verified by increasing the expression of pro-apoptosis genes (BAX and CASP3, decreasing expression of the anti-apoptosis genes (BCL2 and BCL-XL and anti-oxidant genes (SOD1 and GPX4 without affecting cell cycle factors (CCND1, CCNE1 and CDKN1A and TP53. In addition, MTNR1B knockdown did not disrupt the effects of melatonin in suppressing the GCs apoptosis or blocking the cell cycle. Moreover, MTNR1B knockdown did not affect the role of melatonin in increasing BCL2, BCL-XL, and CDKN1A expression, or decreasing BAX, CASP3, TP53, CCND1 and CCNE1 expression. The expression of MTNR1A was upregulated after MTNR1B knockdown, and melatonin promoted MTNR1A expression with or without MTNR1B knockdown. However, despite melatonin supplementation, the expression of SOD1 and GPX4 was still suppressed after MTNR1B knockdown. In conclusion, these findings indicate that melatonin and MTNR1B are involved in BCL2 family and CASP3-dependent apoptotic pathways in bovine GCs. MTNR1A and MTNR1B may coordinate the work of medicating the appropriate melatonin responses to GCs.

  4. Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

    Science.gov (United States)

    Ono, Motoharu; Yamada, Kayo; Avolio, Fabio; Afzal, Vackar; Bensaddek, Dalila; Lamond, Angus I

    2015-01-01

    We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

  5. RNAi-mediated knockdown of pituitary tumor-transforming gene-1 (PTTG1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells

    International Nuclear Information System (INIS)

    Huang, S.Q.; Liao, Q.J.; Wang, X.W.; Xin, D.Q.; Chen, S.X.; Wu, Q.J.; Ye, G.

    2012-01-01

    Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy

  6. A botanical containing freeze dried açai pulp promotes healthy aging and reduces oxidative damage in sod1 knockdown flies

    OpenAIRE

    Laslo, Mara; Sun, Xiaoping; Hsiao, Cheng-Te; Wu, Wells W.; Shen, Rong-Fong; Zou, Sige

    2012-01-01

    Superoxide dismutase 1 (SOD1), a critical enzyme against oxidative stress, is implicated in aging and degenerative diseases. We previously showed that a nutraceutical containing freeze-dried açai pulp promotes survival of flies fed a high-fat diet or sod1 knockdown flies fed a standard diet. Here, we investigated the effect of açai supplementation initiated at the early or late young adulthood on lifespan, physiological function, and oxidative damage in sod1 knockdown flies. We found that Aça...

  7. Cajal bodies and snRNPs friends with benefits

    Czech Academy of Sciences Publication Activity Database

    Staněk, David

    2017-01-01

    Roč. 14, č. 6 (2017), s. 671-679 ISSN 1547-6286 R&D Projects: GA ČR GA15-00790S Institutional support: RVO:68378050 Keywords : spinal muscular-atrophy * small nuclear-rna * u4/u6.u5 tri-snrnp * xenopus-laevis oocytes * u6 spliceosomal rna * coiled bodies * smn complex * u1 snrnp * u2 snrnp * in-vivo Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 3.900, year: 2016

  8. O(5) x U(1) electro weak gauge theory and the relevance of the Cabibbo angle in CP violation in K-decays

    International Nuclear Information System (INIS)

    Samiullah, M.

    1987-11-01

    Some of the relevant mathematics of O(5)xU(1) electro weak gauge theory is briefly sketched. The O(5)xU(1) model is presented. To facilitate the discussion of CP-violation in K-decays the relevant Lagrangian is given in several alternative forms. It is shown that in the CP-violating part of the Lagrangian, by a redefinition of quark phases, the coupling of the CP eigenstates K 1 and K 2 cannot be broken. However, if the Cabibbo angle were not present, the states K 1 and K 2 would decouple and the theory would become CP-invariant. Such a result was also reported by Deshpande et al. working with a different formalism. Relating the mixing parameters θ and φ to the parameters ε 1 and ε 2 it is shown that when ε 1 =ε 2 =ε, ε reduces to the usual CP-violating and CPT conserving parameter. (author). 14 refs

  9. ɛ '/ ɛ anomaly and neutron EDM in SU(2) L × SU(2) R × U(1) B- L model with charge symmetry

    Science.gov (United States)

    Haba, Naoyuki; Umeeda, Hiroyuki; Yamada, Toshifumi

    2018-05-01

    The Standard Model prediction for ɛ '/ ɛ based on recent lattice QCD results exhibits a tension with the experimental data. We solve this tension through W R + gauge boson exchange in the SU(2) L × SU(2) R × U(1) B- L model with `charge symmetry', whose theoretical motivation is to attribute the chiral structure of the Standard Model to the spontaneous breaking of SU(2) R × U(1) B- L gauge group and charge symmetry. We show that {M_W}{_R}study a correlation between ɛ ' /ɛ and the neutron EDM. We confirm that the model can solve the ɛ ' /ɛ anomaly without conflicting the current bound on the neutron EDM, and further reveal that almost all parameter regions in which the ɛ ' /ɛ anomaly is explained will be covered by future neutron EDM searches, which leads us to anticipate the discovery of the neutron EDM.

  10. Phenomenological analysis of supersymmetric σ-models on coset spaces SO(10)/U(5) and E6/[SO(10)xU(1)

    International Nuclear Information System (INIS)

    Nyawelo, T.S.

    2004-12-01

    We discuss some phenomenological aspects of gauged supersymmetric σ-models on homogeneous coset-spaces E 6 /[SO(10)xU(1)] and SO(10)/U(5) which are some of the most interesting for phenomenology. We investigate in detail the vacuum configurations of these models, and study the resulting consequences for supersymmetry breaking and breaking of the internal symmetry. Some supersymmetric minima for both models with gauged full isometry groups E 6 and SO(10) are physically problematic as the Kaehler metric becomes singular ad hence the kinetic terms of the Goldstone boson multiplets vanish. This leads us to introduce recently proposed soft supersymmetry-breaking mass terms which displace the minimum away from the singulax point. A non-singular Kaehler metric breaks the linear subgroup SO(10)xU(1) of the E 6 model spontaneously. The particle spectrum of all these different models is computed. (author)

  11. Liraglutide increases FGF-21 activity and insulin sensitivity in high fat diet and adiponectin knockdown induced insulin resistance.

    Directory of Open Access Journals (Sweden)

    Mengliu Yang

    Full Text Available BACKGROUND: Liraglutide is a glucagon-like peptide-1 analogue that stimulates insulin secretion and improves β-cell function. However, it is not clear whether liraglutide achieves its glucose lowering effect only by its known effects or whether other as yet unknown mechanisms are involved. The aim of this study was to examine the effects of liraglutide on Fibroblast growth factor-21 (FGF-21 activity in High-fat diet (HFD fed ApoE(-/- mice with adiponectin (Acrp30 knockdown. METHOD: HFD-fed ApoE(-/- mice were treated with adenovirus vectors expressing shAcrp30 to produce insulin resistance. Hyperinsulinemic-euglycemic clamp studies were performed to evaluate insulin sensitivity of the mouse model. QRT-PCR and Western blot were used to measure the mRNA and protein expression of the target genes. RESULTS: The combination of HFD, ApoE deficiency, and hypoadiponectinemia resulted in an additive effect on insulin resistance. FGF-21 mRNA expressions in both liver and adipose tissues were significantly increased while FGF-21 receptor 1 (FGFR-1 and β-Klotho mRNA levels in adipose tissue, as well as FGFR-1-3 and β-Klotho mRNA levels in liver were significantly decreased in this model. Liraglutide treatment markedly improved insulin resistance and increased FGF-21 expression in liver and FGFR-3 in adipose tissue, restored β-Klotho mRNA expression in adipose tissue as well as FGFR-1-3, β-Klotho levels and phosphorylation of FGFR1 up to the levels observed in control mice in liver. Liraglutide treatment also further increased FGF-21 proteins in liver and plasma. In addition, as shown by hyperinsulinemic-euglycemic clamp, liraglutide treatment also markedly improved glucose metabolism and insulin sensitivity in these animals. CONCLUSION: These findings demonstrate an additive effect of HFD, ApoE deficiency, and adiponectin knockdown on insulin resistance and unveil that the regulation of glucose metabolism and insulin sensitivity by liraglutide may be

  12. Neuronal markers are expressed in human gliomas and NSE knockdown sensitizes glioblastoma cells to radiotherapy and temozolomide

    International Nuclear Information System (INIS)

    Yan, Tao; Skaftnesmo, Kai Ove; Leiss, Lina; Sleire, Linda; Wang, Jian; Li, Xingang; Enger, Per Øyvind

    2011-01-01

    Expression of neuronal elements has been identified in various glial tumors, and glioblastomas (GBMs) with neuronal differentiation patterns have reportedly been associated with longer survival. However, the neuronal class III β-tubulin has been linked to increasing malignancy in astrocytomas. Thus, the significance of neuronal markers in gliomas is not established. The expressions of class III β-tubulin, neurofilament protein (NFP), microtubule-associated protein 2 (MAP2) and neuron-specific enolase (NSE) were investigated in five GBM cell lines and two GBM biopsies with immunocytochemistry and Western blot. Moreover, the expression levels were quantified by real-time qPCR under different culture conditions. Following NSE siRNA treatment we used Electric cell-substrate impedance sensing (ECIS) to monitor cell growth and migration and MTS assays to study viability after irradiation and temozolomide treatment. Finally, we quantitated NSE expression in a series of human glioma biopsies with immunohistochemistry using a morphometry software, and collected survival data for the corresponding patients. The biopsies were then grouped according to expression in two halves which were compared by survival analysis. Immunocytochemistry and Western blotting showed that all markers except NFP were expressed both in GBM cell lines and biopsies. Notably, qPCR demonstrated that NSE was upregulated in cellular stress conditions, such as serum-starvation and hypoxia, while we found no uniform pattern for the other markers. NSE knockdown reduced the migration of glioma cells, sensitized them to hypoxia, radio- and chemotherapy. Furthermore, we found that GBM patients in the group with the highest NSE expression lived significantly shorter than patients in the low-expression group. Neuronal markers are aberrantly expressed in human GBMs, and NSE is consistently upregulated in different cellular stress conditions. Knockdown of NSE reduces the migration of GBM cells and sensitizes

  13. Knockdown of long non-coding RNA Taurine Up-Regulated 1 inhibited doxorubicin resistance of bladder urothelial carcinoma via Wnt/β-catenin pathway.

    Science.gov (United States)

    Xie, Dalong; Zhang, Hui; Hu, Xuanhao; Shang, Chao

    2017-10-24

    In genitourinary system, bladder cancer (BC) is the most common and lethal malignant tumor, which most common type is bladder urothelial carcinoma (BUC). Long non-coding RNA (lncRNA) Taurine Up-Regulated 1 (TUG1) gene is high-expressed in several malignant tumors, including BC. In this study, over-expression of TUG1 was found in BUC tissues and cell line resistant to doxorubicin (Dox). Knockdown of TUG1 inhibited the Dox resistance and promoted the cytotoxicity induced by Dox in T24/Dox cells. TUG1 knockdown also depressed the Wnt/β-catenin pathway, and the activation the Wnt/β-catenin pathway partly reversed the inhibitory effects of TUG1 knockdown on Dox resistance in T24/Dox cells. In conclusion, up-regulation of lncRNA TUG1 was related with the poor response of BUC patients to Dox chemotherapy, knockdown of TUG1 inhibited the Dox resistance of BUC cells via Wnt/β-catenin pathway. These findings might assist in the discovery of novel potential diagnostic and therapeutic target for BUC, thereby improve the effects of clinical treatment in patients.

  14. Impact of Subolesin and Cystatin Knockdown by RNA Interference in Adult Female Haemaphysalis longicornis (Acari: Ixodidae on Blood Engorgement and Reproduction

    Directory of Open Access Journals (Sweden)

    Md. Khalesur Rahman

    2018-04-01

    Full Text Available Currently, multi-antigenic vaccine use is the method of choice for the strategic control of ticks. Therefore, determining the efficacy of combined antigens is a promising avenue of research in the development of anti-tick vaccines. The antigen responsible for blood intake and reproduction has proven suitable as a vaccine antigen. It has been shown to silence Haemaphysalis longicornis salivary cystatin (HlSC-1 and subolesin by RNA interference. Adult unfed female ticks were injected with double-stranded RNA of (A subolesin, (B cystatin, (C subolesin plus cystatin, and (D injection buffer, then fed alongside normal unfed males up to spontaneous drop-down. The percentage of knockdowns was determined by real-time polymerase chain reaction. Sixty-three percent and 53% knockdown rates were observed in subolesin and cystatin double-stranded RNA-injected ticks respectively, while 32 and 26% knockdown rates of subolesin and cystatin transcript were observed in subolesin plus cystatin double-stranded RNA-injected ticks. Subolesin and/or cystatin knockdown causes a significant (p < 0.05 reduction in tick engorgement, egg mass weight, and egg conversion ratio. Most importantly, combined silencing did not act synergistically, but caused a similarly significant (p < 0.05 reduction in tick engorgement, egg mass weight, and egg conversion ratio. Therefore, the elucidation of multiple antigens may be helpful in the future of vaccines.

  15. Partial Correction of Psoriasis upon Genetic Knock-Down of Human TNF-α by Lentivirus-Encoded shRNAs in a Xenograft Mouse Model

    DEFF Research Database (Denmark)

    Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia

    samples treated with irrelevant shRNAs, were selected and cloned into lentiviral vectors. The lentiviral vectors expressing TNF- shRNAs were used to transduce HEK-293 cells and verify vector-derived knock-down of stable TNF- expression in vitro. The most efficient TNF- -directed shRNA, which in cell lines...

  16. Salt Sensitive Tet-Off-Like Systems to Knockdown Primordial Germ Cell Genes for Repressible Transgenic Sterilization in Channel Catfish, Ictalurus punctatus.

    Science.gov (United States)

    Li, Hanbo; Su, Baofeng; Qin, Guyu; Ye, Zhi; Alsaqufi, Ahmed; Perera, Dayan A; Shang, Mei; Odin, Ramjie; Vo, Khoi; Drescher, David; Robinson, Dalton; Zhang, Dan; Abass, Nermeen; Dunham, Rex A

    2017-05-31

    Repressible knockdown approaches were investigated for transgenic sterilization in channel catfish, Ictalurus punctatus . Two primordial germ cell (PGC) marker genes, nanos and dead end , were targeted for knockdown, and an off-target gene, vasa , was monitored. Two potentially salt sensitive repressible promoters, zebrafish adenylosuccinate synthase 2 (ADSS) and zebrafish racemase (Rm), were each coupled with four knockdown strategies: ds-sh RNA targeting the 5' end (N1) or 3' end (N2) of channel catfish nanos , full-length cDNA sequence of channel catfish nanos for overexpression (cDNA) and ds-sh RNA targeting channel catfish dead end (DND). Each construct had an untreated group and treated group with sodium chloride as the repressor compound. Spawning rates of full-sibling P₁ fish exposed or not exposed to the constructs as treated and untreated embryos were 93% and 59%, respectively, indicating potential sterilization of fish and repression of the constructs. Although the mRNA expression data of PGC marker genes were inconsistent in P₁ fish, most F₁ individuals were able to downregulate the target genes in untreated groups and repress the knockdown process in treated groups. The results indicate that repressible transgenic sterilization is feasible for reproductive control of fish, but more data from F₂ or F₃ are needed for evaluation.

  17. Salt Sensitive Tet-Off-Like Systems to Knockdown Primordial Germ Cell Genes for Repressible Transgenic Sterilization in Channel Catfish, Ictalurus punctatus

    Directory of Open Access Journals (Sweden)

    Hanbo Li

    2017-05-01

    Full Text Available Repressible knockdown approaches were investigated for transgenic sterilization in channel catfish, Ictalurus punctatus. Two primordial germ cell (PGC marker genes, nanos and dead end, were targeted for knockdown, and an off-target gene, vasa, was monitored. Two potentially salt sensitive repressible promoters, zebrafish adenylosuccinate synthase 2 (ADSS and zebrafish racemase (Rm, were each coupled with four knockdown strategies: ds-sh RNA targeting the 5′ end (N1 or 3′ end (N2 of channel catfish nanos, full-length cDNA sequence of channel catfish nanos for overexpression (cDNA and ds-sh RNA targeting channel catfish dead end (DND. Each construct had an untreated group and treated group with sodium chloride as the repressor compound. Spawning rates of full-sibling P1 fish exposed or not exposed to the constructs as treated and untreated embryos were 93% and 59%, respectively, indicating potential sterilization of fish and repression of the constructs. Although the mRNA expression data of PGC marker genes were inconsistent in P1 fish, most F1 individuals were able to downregulate the target genes in untreated groups and repress the knockdown process in treated groups. The results indicate that repressible transgenic sterilization is feasible for reproductive control of fish, but more data from F2 or F3 are needed for evaluation.

  18. Sign of the neutron-proton mass difference in an SU(2)xU(1) supersymmetric toy model: A possible scenario for solving the old puzzle

    International Nuclear Information System (INIS)

    Desai, B.R.; Xu, G.

    1990-01-01

    Based on the idea that electromagnetism is responsible for mass differences within isotopic multiplets (e.g., pointlike neutron and proton or u and d quarks), we generalize an SU(2)xU(1) model in a toy field theory of vectors to a supersymmetric model and investigate the finite mass difference within the isotopic doublet. It is found that under soft-supersymmetry breaking, a positive n-p mass difference can be obtained under reasonable assumptions for the parameters involved

  19. The linked units of 5S rDNA and U1 snDNA of razor shells (Mollusca: Bivalvia: Pharidae).

    Science.gov (United States)

    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.

  20. Isotopic production cross-sections and recoil velocities of spallation-fission fragments in the reaction 238U(1A GeV)+e

    CERN Document Server

    Pereira, J; Wlazlo, W; Benlliure, J; Casarejos, E; Armbruster, P; Bernas, M; Enqvist, T; Legrain, R; Leray, S; Rejmund, F; Mustapha, B; Schmidt, K.-H; Stéphan, C; Taïeb, J; Tassan-Got, L; Volant, C; Boudard, A; Czajkowski, S; 10.1103/PhysRevC.75.014602

    2007-01-01

    Fission fragments of 1A GeV 238U nuclei interacting with a deuterium target have been investigatedwith the Fragment Separator (FRS) at GSI (Darmstadt) by measuring their isotopicproduction cross-sections and recoil velocities. The results, along with those obtained recently forspallation-evaporation fragments, provide a comprehensive analysis of the spallation nuclear productionsin the reaction 238U(1A GeV)+d. Details about experiment performance, data reductionand results will be presented.

  1. Monte Carlo analysis of the SU(2)xU(1) and U(2) lattice gauge theories at different space-time dimensionalities

    International Nuclear Information System (INIS)

    Baig, M.; Colet, J.

    1986-01-01

    Using Monte Carlo simulations the SU(2)xU(1) lattice gauge theory has been analyzed, which is equivalent for the Wilson action to a U(2) theory, at space-time dimensionalities from d=3 to 5. It has been shown that there exist first-order phase transitions for both d=4 and d=5. A monopole-condensation mechanism seems to be responsible for these phase transitions. At d=3 no phase transitions have been detected. (orig.)

  2. New approach to SU2LxU1 radiative corrections in e+e- annihilation processes near the Z0 resonance

    International Nuclear Information System (INIS)

    Jadach, S.; Ward, B.F.L.

    1988-08-01

    We show explicitly how to proceed in the Monte Carlo simulation of SU 2L xU 1 radiative corrections in order to include multiple soft photon emission on an event by event basis. The method is based on the rigorous theory of summing infrared contributions to the respective cross section by Yennie, Frautschi and Suura. Our method is illustrated on the example of initial state bremsstrahlung. (author). 10 refs, 2 figs

  3. O(5)sub(L)xO(5)sub(R)xU(1)sub(V) electro-weak gauge theory and the neutrino pairing mechanism

    International Nuclear Information System (INIS)

    Samiullah, M.; Mubarak, A.

    1981-08-01

    The possibility of using the group O(5)sub(L)xO(5)sub(R)xU(1)sub(V) for unifying the weak and electromagnetic interactions is studied. We are led to an anomaly free theory. Potentially the theory has the advantage of incorporating the previous results. For example, all the results of O(5)sub(L)xU(1) studies are, as a special case, obtainable at low energies. In the process of breaking the symmetry down to Weinberg-Salam theory at the level of SU(2)sub(L)xSU(2)sub(R)xU(1)sub(V), we have employed the neutrino proposed by Mannheim. We have been able to reproduce several of the conventional electroweak aspects such as the parity violation in both the lepton and charged quark sectors, Weinberg mixing pattern in the neutral current sector while keeping the left-handed neutrinos massless. All the salient features of low energy phenomenology are shown to follow. (author)

  4. Knockdown of long noncoding RNA linc-ITGB1 suppresses migration, invasion of hepatocellular carcinoma via regulating ZEB1.

    Science.gov (United States)

    Yu, W-W; Wang, K; Liao, G-J

    2017-11-01

    This research focuses on the influence of linc-ITGB1 on the metastasis of hepatocellular carcinoma and further explores its underlying mechanism. A total of 70 hepatocellular carcinoma patients were chosen for our study. RT-qPCR was used for detecting the expression level of linc-ITGB1 in their cancer tissues. Moreover, the expression level of linc-ITGB1 was also detected in hepatocellular carcinoma cell lines. Furthermore, whether linc-ITGB1 could affect the migrated and invaded ability of hepatocellular carcinoma cells was determined by wound healing assay and transwell assay. We further explored the potential mechanism by RT-qPCR and Western blot assay. Linc-ITGB1 expression level in hepatocellular carcinoma tissues was remarkably higher than that in adjacent tissues. Moreover, migrated and invaded ability of hepatocellular carcinoma cells was inhibited through knockdown of linc-ITGB1. Further study revealed that silenced linc-ITGB1 inhibited the expression of ZEB1 and then suppressed epithelial to mesenchymal transition (EMT), which was important during the metastasis of hepatocellular carcinoma. Moreover, the inhibition of cell invasion by silenced linc-ITGB1 could be rescued through overexpression of ZEB1 in hepatocellular carcinoma. The results indicate that linc-ITGB1, a novel oncogene in tumorigenesis, could promote the metastasis and EMT via ZEB1, which may offer a possible therapeutic target in hepatocellular carcinoma.

  5. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC.

    Science.gov (United States)

    Garbarino, Jeanne; Pan, Meihui; Chin, Harvey F; Lund, Frederik W; Maxfield, Frederick R; Breslow, Jan L

    2012-12-01

    STARD4, a member of the evolutionarily conserved START gene family, has been implicated in the nonvesicular intracellular transport of cholesterol. However, the direction of transport and the membranes with which this protein interacts are not clear. We present studies of STARD4 function using small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein receptor (LDLR) levels were increased and decreased, respectively. We also observed a decrease in NPC1 protein expression, suggesting the induction of compensatory pathways to maintain cholesterol balance. These data indicate a role for STARD4 in nonvesicular transport of cholesterol from the plasma membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well.

  6. Hypomorphic Smn knockdown C2C12 myoblasts reveal intrinsic defects in myoblast fusion and myotube morphology

    International Nuclear Information System (INIS)

    Shafey, Dina; Cote, Patrice D.; Kothary, Rashmi

    2005-01-01

    Dosage of the survival motor neuron (SMN) protein has been directly correlated with the severity of disease in patients diagnosed with spinal muscular atrophy (SMA). It is also clear that SMA is a neurodegenerative disorder characterized by the degeneration of the α-motor neurons in the anterior horn of the spinal cord and atrophy of the associated skeletal muscle. What is more controversial is whether it is neuronal and/or muscle-cell-autonomous defects that are responsible for the disease per se. Although motor neuron degeneration is generally accepted as the primary event in SMA, intrinsic muscle defects in this disease have not been ruled out. To gain a better understanding of the influence of SMN protein dosage in muscle, we have generated a hypomorphic series of myoblast (C2C12) stable cell lines with variable Smn knockdown. We show that depletion of Smn in these cells resulted in a decrease in the number of nuclear 'gems' (gemini of coiled bodies), reduced proliferation with no increase in cell death, defects in myoblast fusion, and malformed myotubes. Importantly, the severity of these abnormalities is directly correlated with the decrease in Smn dosage. Taken together, our work supports the view that there is an intrinsic defect in skeletal muscle cells of SMA patients and that this defect contributes to the overall pathogenesis in this devastating disease

  7. A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Yoav Ben-Simon

    2015-07-01

    Full Text Available Neurotransmitter release probability (Pr largely determines the dynamic properties of synapses. While much is known about the role of presynaptic proteins in transmitter release, their specific contribution to synaptic plasticity is unclear. One such protein, tomosyn, is believed to reduce Pr by interfering with the SNARE complex formation. Tomosyn is enriched at hippocampal mossy fiber-to-CA3 pyramidal cell synapses (MF-CA3, which characteristically exhibit low Pr, strong synaptic facilitation, and pre-synaptic protein kinase A (PKA-dependent long-term potentiation (LTP. To evaluate tomosyn’s role in MF-CA3 function, we used a combined knockdown (KD-optogenetic strategy whereby presynaptic neurons with reduced tomosyn levels were selectively activated by light. Using this approach in mouse hippocampal slices, we found that facilitation, LTP, and PKA-induced potentiation were significantly impaired at tomosyn-deficient synapses. These findings not only indicate that tomosyn is a key regulator of MF-CA3 plasticity but also highlight the power of a combined KD-optogenetic approach to determine the role of presynaptic proteins.

  8. CaMKII knockdown affects both early and late phases of olfactory long-term memory in the honeybee.

    Science.gov (United States)

    Scholl, Christina; Kübert, Natalie; Muenz, Thomas S; Rössler, Wolfgang

    2015-12-01

    Honeybees are able to solve complex learning tasks and memorize learned information for long time periods. The molecular mechanisms mediating long-term memory (LTM) in the honeybee Apis mellifera are, to a large part, still unknown. We approached this question by investigating the potential function of the calcium/calmodulin-dependent protein kinase II (CaMKII), an enzyme known as a 'molecular memory switch' in vertebrates. CaMKII is able to switch to a calcium-independent constitutively active state, providing a mechanism for a molecular memory and has further been shown to play an essential role in structural synaptic plasticity. Using a combination of knockdown by RNA interference and pharmacological manipulation, we disrupted the function of CaMKII during olfactory learning and memory formation. We found that learning, memory acquisition and mid-term memory were not affected, but all manipulations consistently resulted in an impaired LTM. Both early LTM (24 h after learning) and late LTM (72 h after learning) were significantly disrupted, indicating the necessity of CaMKII in two successive stages of LTM formation in the honeybee. © 2015. Published by The Company of Biologists Ltd.

  9. Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

    Science.gov (United States)

    Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

    2010-04-29

    Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

  10. The TetO rat as a new translational model for type 2 diabetic retinopathy by inducible insulin receptor knockdown.

    Science.gov (United States)

    Reichhart, Nadine; Crespo-Garcia, Sergio; Haase, Nadine; Golic, Michaela; Skosyrski, Sergej; Rübsam, Anne; Herrspiegel, Christina; Kociok, Norbert; Alenina, Natalia; Bader, Michael; Dechend, Ralf; Strauss, Olaf; Joussen, Antonia M

    2017-01-01

    Although the renin-angiotensin system plays an important role in the progression of diabetic retinopathy, its influence therein has not been systematically evaluated. Here we test the suitability of a new translational model of diabetic retinopathy, the TetO rat, for addressing the role of angiotensin-II receptor 1 (AT1) blockade in experimental diabetic retinopathy. Diabetes was induced by tetracycline-inducible small hairpin RNA (shRNA) knockdown of the insulin receptor in rats, generating TetO rats. Systemic treatment consisted of an AT1 blocker (ARB) at the onset of diabetes, following which, 4-5 weeks later the retina was analysed in vivo and ex vivo. Retinal function was assessed by Ganzfeld electroretinography (ERG). Retinal vessels in TetO rats showed differences in vessel calibre, together with gliosis. The total number and the proportion of activated mononuclear phagocytes was increased. TetO rats presented with loss of retinal ganglion cells (RGC) and ERG indicated photoreceptor malfunction. Both the inner and outer blood-retina barriers were affected. The ARB treated group showed reduced gliosis and an overall amelioration of retinal function, alongside RGC recovery, whilst no statistically significant differences in vascular and inflammatory features were detected. The TetO rat represents a promising translational model for the early neurovascular changes associated with type 2 diabetic retinopathy. ARB treatment had an effect on the neuronal component of the retina but not on the vasculature.

  11. Increased cell motility and invasion upon knockdown of lipolysis stimulated lipoprotein receptor (LSR in SW780 bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Ørntoft Torben F

    2008-07-01

    Full Text Available Abstract Background Mechanisms underlying the malignant development in bladder cancer are still not well understood. Lipolysis stimulated lipoprotein receptor (LSR has previously been found to be upregulated by P53. Furthermore, we have previously found LSR to be differentially expressed in bladder cancer. Here we investigated the role of LSR in bladder cancer. Methods A time course siRNA knock down experiment was performed to investigate the functional role of LSR in SW780 bladder cancer cells. Since LSR was previously shown to be regulated by P53, siRNA against TP53 was included in the experimental setup. We used Affymetrix GeneChips for measuring gene expression changes and we used Ingenuity Pathway Analysis to investigate the relationship among differentially expressed genes upon siRNA knockdown. Results By Ingenuity Pathway analysis of the microarray data from the different timepoints we identified six gene networks containing genes mainly related to the functional categories "cancer", "cell death", and "cellular movement". We determined that genes annotated to the functional category "cellular movement" including "invasion" and "cell motility" were highly significantly overrepresented. A matrigel assay showed that 24 h after transfection the invasion capacity was significantly increased 3-fold (p Conclusion We conclude that LSR may impair bladder cancer cells from gaining invasive properties.

  12. [Improvement and the mechanism of cardiac function by knockdown of ADAM10 in adriamycin-induced cardiomyopathy rats].

    Science.gov (United States)

    Li, Xiaoou; Xie, Lili; He, Bing; Huang, Wei

    2018-01-01

    Objective To study the role of a disintegrin and metalloproteinase10 (ADAM10) in shedding neural cadherin (N-cadherin) and develop an approach to interfere the process of ventricular remodeling in adriamycin-induced cardiomyopathy (ACM) rats. Methods In a rat model of ACM, the effects of intraperitoneal injection of the lentiviral RNAi vector of ADAM10 on the morphology of cardiomyocytes and contractile function were observed by HE staining and color Doppler echocardiography. The expressions of N-cadherin and C-terminal fragment 1 (CTF1) were detected by Western blotting and immunohistochemistry. Results In the in vivo experiment, a large amount of fluorescence was seen in the isolated primary cardiomyocytes, which indicated that the transfection in the rat model was successful. In the treatment group, the morphology of cardiomyocytes and function of the heart were evidently improved, N-cadherin protein expression was remarkably up-regulated and CTF1 protein was obviously down-regulated compared with the model group. Conclusion Knock-down of ADAM10 increases N-cadherin expression and decreases CTF1 expression, thus improves cardiac function in the rat model of ACM.

  13. [Knockdown of dopamine receptor D2 upregulates the expression of adiogenic genes in mouse primary mesencephalic neurons].

    Science.gov (United States)

    Ding, Jiaqi; Chen, Xiaoli; Lin, Jiaji; Zhu, Junling; Li, Zhuyi

    2018-01-01

    Objective To study the effects of dopamine receptor D2 (DRD2) on the adipogenesis genes in mouse primary mesencephalic neurons. Methods The lentiviral vectors which expressed specific shRNA targeting DRD2 were constructed to decrease DRD2 expression in mouse primary mesencephalic neurons. High throughput sequencing (HTS) analysis was used to investigate gene expression changes between the DRD2 knock-down group and the negative control group. Real-time quantitative PCR (qRT-PCR) and Western blot analysis were applied to verify the differently expressed genes. Fatty acids were measured by fatty acid detection kit. Results DRD2 expression was effectively down-regulated in mouse primary mesencephalic neurons by lentiviral vectors. HTS revealed adipogenesis genes were significantly up-regulated after DRD2 down-regulation, mainly including delta(14)-sterol reductase, acetyl-coenzyme A synthetase, insulin-induced gene 1 protein and especially stearoyl-coenzyme A desaturase 1 (SCD1, 4-fold upregulated). The qRT-PCR and Western blot analysis verified that SCD1 was upregulated 2.6 folds and 2 folds respectively by lentiviral DRD2-shRNA vectors. Moreover, the SCD1-related free fatty acids were significantly more increased than the negative control group. Conclusion DRD2 in primary mesencephalic neurons had a significant regulative effect on the adipogenesis genes. The up-regulation of SCD1 can accelerate the conversion of saturated fatty acids to monounsaturated fatty acids and prevent the damage of lipid toxicity to cells.

  14. Gene-knockdown in the honey bee mite Varroa destructor by a non-invasive approach: studies on a glutathione S-transferase

    Directory of Open Access Journals (Sweden)

    Campbell Ewan M

    2010-08-01

    Full Text Available Abstract Background The parasitic mite Varroa destructor is considered the major pest of the European honey bee (Apis mellifera and responsible for declines in honey bee populations worldwide. Exploiting the full potential of gene sequences becoming available for V. destructor requires adaptation of modern molecular biology approaches to this non-model organism. Using a mu-class glutathione S-transferase (VdGST-mu1 as a candidate gene we investigated the feasibility of gene knockdown in V. destructor by double-stranded RNA-interference (dsRNAi. Results Intra-haemocoelic injection of dsRNA-VdGST-mu1 resulted in 97% reduction in VdGST-mu1 transcript levels 48 h post-injection compared to mites injected with a bolus of irrelevant dsRNA (LacZ. This gene suppression was maintained to, at least, 72 h. Total GST catalytic activity was reduced by 54% in VdGST-mu1 gene knockdown mites demonstrating the knockdown was effective at the translation step as well as the transcription steps. Although near total gene knockdown was achieved by intra-haemocoelic injection, only half of such treated mites survived this traumatic method of dsRNA administration and less invasive methods were assessed. V. destructor immersed overnight in 0.9% NaCl solution containing dsRNA exhibited excellent reduction in VdGST-mu1 transcript levels (87% compared to mites immersed in dsRNA-LacZ. Importantly, mites undergoing the immersion approach had greatly improved survival (75-80% over 72 h, approaching that of mites not undergoing any treatment. Conclusions Our findings on V. destructor are the first report of gene knockdown in any mite species and demonstrate that the small size of such organisms is not a major impediment to applying gene knockdown approaches to the study of such parasitic pests. The immersion in dsRNA solution method provides an easy, inexpensive, relatively high throughput method of gene silencing suitable for studies in V. destructor, other small mites and

  15. Knock-down and speed of kill of a combination of fipronil and permethrin for the prevention of Ctenocephalides felis flea infestation in dogs.

    Science.gov (United States)

    Halos, Lénaïg; Fourie, Josephus J; Fankhauser, Becky; Beugnet, Frederic

    2016-02-02

    A topical combination of fipronil + permethrin (Frontline Tri-Act/Frontect, Merial) has recently been developed to control fleas, ticks, mosquitoes, sandflies and stable flies on dogs. Two studies were conducted to assess its speed of kill and knock-down effect on Ctenocephalides felis fleas. The combination was compared to either fipronil alone or to a combination of permethrin, dinotefuran, and pyriproxyfen, In each study, 18 dogs were randomly allocated to one of three groups: (Group 1: untreated dog; Group 2: treated once on D0 with the combination of fipronil and permethrin; Group 3: treated once on D0 either with fipronil alone (study 1) or with a combination of permethrin, dinetofuran and pyriproxyfen (study 2)). Each dog was infested with 100 unfed adult C. felis fleas on Days 2 (study 2), 7, 14, 21 and 28. Fleas were collected from dogs at 1 h and 12 h post- infestations (PI) (study 1) or at 2 h and 6 h PI (study 2) to assess efficacy and from collection pans underneath cages 1 h (study 1) or 5 min (study 2) PI to assess knock-down effect. All treated dogs had significantly (p ≤ 0.01) lower flea counts than untreated dogs at every time point in both studies. For a whole month, a significant knock-down effect against infesting fleas is obtained in five minutes PI with the combination of permethrin and fipronil. Complete efficacy (>95%) was achieved in 1 h (study 1) or 2 h (study 2) PI for 14 days and by 6 h PI for all challenges conducted throughout the month. Efficacy remains >85% at 2 h PI for the whole month. A significantly higher efficacy of the fipronil + permethrin combination compared to other treatments was demonstrated at the earliest time points for the month (1 h knock-down effect and insecticidal efficacy compared to fipronil alone; 5 min knock-down effect compared to the combination of permethrin + dinetofuran + pyriproxyfen). The rapid flea knock-down effect and speed of kill demonstrated by the spot on combination of

  16. Parthenogenetic embryonic stem cells with H19 siRNA-mediated knockdown as a potential resource for cell therapy.

    Science.gov (United States)

    Kwak, Minhye; Hong, Su; Yu, Seong-Lan; Sim, Bo-Woong; Seo, Jeong-Sun; Kang, Jaeku

    2012-02-01

    Embryonic stem (ES) cells are used in cell therapy and tissue engineering due to their ability to produce different cells types. However, studies of ES cells that are derived from fertilized embryos have raised concerns about the limitations imposed by ethical and political considerations. Therefore, many studies of stem cells use the stem cells that are derived from unfertilized oocytes and adult tissue. Although parthenogenetic embryonic stem (ESP) cells also avoid ethical and political dilemmas and can be used in cell-based therapy, the ESP cells exhibit growth retardation problems. Therefore, to investigate the potential for muscle growth from genetically modified ESP cells, we established four ES cell types, including normal embryonic stem (ESN) cells, ESP cells, ESP cells that overexpress the insulin-like growth factor 2 (Igf2) gene (ESI) and ESP cells with down-regulated H19 gene expression (ESH). Using these cells, we examined the expression profiles of genes that were related to imprinting and muscle using microarrays. The gene expression patterns of ESI and ESH cells were similar and were more closely related to the ESN pattern than that of the ESP cells. Differentiated ESH cells exhibited increased expression of bone morphologic protein 4 (BMP4), which is a mesoderm marker, compared with the differentiated ESI cells. We showed that Igf2 expression was induced by H19 silencing in the ESP cells via hypermethylation of the H19 imprinting control region 1 (ICR1). Moreover, the proportion of ESH-derived chimera was slightly higher than those produced from the ESP cells. In addition, we detected increased cell proliferation in the MEF cells following H19 knock-down. These results indicate that the ESH cells may be a source of cell-based therapy for conditions such as muscular atrophy.

  17. γ-Catenin at Adherens Junctions: Mechanism and Biologic Implications in Hepatocellular Cancer after β-Catenin Knockdown

    Directory of Open Access Journals (Sweden)

    Emily Diane Wickline

    2013-04-01

    Full Text Available β-Catenin is important in liver homeostasis as a part of Wnt signaling and adherens junctions (AJs, while its aberrant activation is observed in hepatocellular carcinoma (HCC. We have reported hepatocyte-specific β-catenin knockout (KO mice to lack adhesive defects as γ-catenin compensated at AJ. Because γ-catenin is a desmosomal protein, we asked if its increase in KO might deregulate desmosomes. No changes in desmosomal proteins or ultrastructure other than increased plakophilin-3 were observed. To further elucidate the role and regulation of γ-catenin, we contemplate an in vitro model and show γ-catenin increase in HCC cells upon β-catenin knockdown (KD. Here, γ-catenin is unable to rescue β-catenin/T cell factor (TCF reporter activity; however, it sufficiently compensates at AJs as assessed by scratch wound assay, centrifugal assay for cell adhesion (CAFCA, and hanging drop assays. γ-Catenin increase is observed only after β-catenin protein decrease and not after blockade of its transactivation. γ-Catenin increase is associated with enhanced serine/threonine phosphorylation and abrogated by protein kinase A (PKA inhibition. In fact, several PKA-binding sites were detected in γ-catenin by in silico analysis. Intriguingly γ-catenin KD led to increased β-catenin levels and transactivation. Thus, γ-catenin compensates for β-catenin loss at AJ without affecting desmosomes but is unable to fulfill functions in Wnt signaling. γ-Catenin stabilization after β-catenin loss is brought about by PKA. Catenin-sensing mechanism may depend on absolute β-catenin levels and not its activity. Anti-β-catenin therapies for HCC affecting total β-catenin may target aberrant Wnt signaling without negatively impacting intercellular adhesion, provided mechanisms leading to γ-catenin stabilization are spared.

  18. Knockdown of TC-1 enhances radiosensitivity of non-small cell lung cancer via the Wnt/β-catenin pathway.

    Science.gov (United States)

    Wu, Dapeng; Li, Lei; Yan, Wei

    2016-04-15

    Thyroid cancer 1 (TC-1, C8ofr4) is widely expressed in vertebrates and associated with many kinds of tumors. Previous studies indicated that TC-1 functions as a positive regulator in the Wnt/β-catenin signaling pathway in non-small cell lung cancer (NSCLC). However, its exact role and regulation mechanism in radiosensitivity of NSCLC are still unclear. The expression level of TC-1 was measured by qRT-PCR and western blot in NSCLC cell lines. Proliferation and apoptosis of NSCLC cells in response to TC-1 knockdown or/and radiation were determined by MTT assay and flow cytometry, respectively. The activation of the Wnt/β-catenin signaling pathway was further examined by western blotin vitroandin vivo Compared to TC-1 siRNA or radiotherapy alone, TC-1 silencing combined with radiation inhibited cell proliferation and induced apoptosis in NSCLC cell lines by inactivating of the Wnt/β-catenin signaling pathway. Furthermore, inhibition of the Wnt/β-catenin signaling pathway by XAV939, a Wnt/β-catenin signaling inhibitor, contributed to proliferation inhibition and apoptosis induction in NSCLC A549 cells. Combinative treatment of A549 xenografts with TC-1 siRNA and radiation caused significant tumor regression and inactivation of the Wnt/β-catenin signaling pathway relative to TC-1 siRNA or radiotherapy alone. The results fromin vitroandin vivostudies indicated that TC-1 silencing sensitized NSCLC cell lines to radiotherapy through the Wnt/β-catenin signaling pathway. © 2016. Published by The Company of Biologists Ltd.

  19. Knock-down of miR-221 and miR-222 in the radiosensitization of breast cancer cells

    International Nuclear Information System (INIS)

    Zhang Chunzhi; Kang Chunsheng; Cao Yongzhen; Pu Peiyu; Lu Zhonghong; Du Yue

    2009-01-01

    Objective: To investigate the radiosensitizing effect of knock-down of miR-221 miR-222 on MCF-7 human breast cancer cells and explore the possible mechanism. Methods: Antisense oligonucleotides of miR-221 and miR-222 (AS-miR-221 and AS-miR-222), mediated by lipofectamine, were transfected to MCF-7 cells to knock down miR-221 and miR-222, Northern blotting was conducted to detect the expression of miR-221 and miR-222 in transfected cells. The cell apoptosis was detected by flow cytometry and Caspase-3 and Caspase-7 activity assay. Clonogenic assay was used to measure the sensitizing enhancement ratio. Target genes of miR-221 and miR-222 relevant to radio-sensitivity were searched using bioinformatics analysis. The targeted protein expression was determined by Western blot analysis. Results: The expression of miR-221 and miR-222 in the AS-miR-221/222 cells determined by Northern blotting was significantly reduced. Compared with the control group, the cell apoptosis and mitotic cell death after the radiation were significantly higher in AS-miR-221/222 cells. The sensitizing enhancement ratio was 1.87. Based on bioinformatics analysis, PTEN was a target gene of miR-221 and miR-222 which could enhance the radiosensitivity of MCF-7 cells. In AS-miR-221/222 cells, the expression of PTEN was up-regulated while pAkt down-regulated. Conclusions: AS-miR-221 and AS-miR-222 may enhance the radiosensitivity of MCF-7 breast cancer cells by up-regulating the expression of PTEN. (authors)

  20. RNAi-mediated knockdown of serine protease inhibitor genes increases the mortality of Plutella xylostella challenged by destruxin A.

    Science.gov (United States)

    Han, Pengfei; Fan, Jiqiao; Liu, Yu; Cuthbertson, Andrew G S; Yan, Shaoqiao; Qiu, Bao-Li; Ren, Shunxiang

    2014-01-01

    Destruxin A is a mycotoxin that is secreted by entomopathogenic fungi which has a broad-spectrum insecticidal effect. Previous transcript and protein profiling analysis showed that destruxin A has significant effects on the expression of serine protease inhibitor genes (serpin-2, 4, 5) in the larvae of Plutella xylostella. In the current study, we aimed to understand the role of serpins under application of destruxin A. We obtained two full-length cDNA sequences of P. xylostella serpins, named serpin-4 and serpin-5, and cloned the serpin-2 gene whose full-length has already been published. Phylogenetic analysis indicated that these two serpin genes were highly clustered with other serpins associated with the immune response in other insects. The temporal and spatial expression of serpin-2, serpin-4 and serpin-5 were determined to be the highest in the fat body and hemolymph of 4th larval stage using qRT-PCR and western blot detection techniques. RNA interference (RNAi) mediated knockdown of P. xylostella serpin genes was carried out by microinjection of double-stranded RNA (dsRNA). The expression levels of serpins decreased significantly after RNAi. Results showed that the depletion of serpins induced cecropins expression, increased phenoloxidase (PO) activity, body melanization and mortality in the larvae of P. xylostella under the same lethal concentration of destruxin A. The superimposed effects of serpins RNAi were similar with the destruxin A treatment upon mortality of P. xylostella larvae. We discovered for the first time that serpins play indispensable role in P. xylostella when challenged by destruxin A and deduced the possible function mechanism of destruxin A. Our findings are conducive to fully understanding the potential insecticidal mechanism of destruxin A and constitute a well-defined potential molecular target for novel insecticides.