WorldWideScience

Sample records for gene loops function

  1. Regulation of gene expression by Goodwin's loop with many genes

    Science.gov (United States)

    Sielewiesiuk, Jan; Łopaciuk, Agata

    2012-01-01

    The paper presents a simple analysis of a long Goodwin's loop containing many genes. The genes form a closed series. The rate of transcription of any gene is up or down regulated by theprotein product of the preceding gene. We describe the loop with a system of ordinary differential equations of order s. Oscillatory solutions of the system are possible at the odd number of repressions and any number of inductions if the product of all Hill's coefficients, related to both repressions and inductions, is larger than:

  2. Identifying Novel Helix-Loop-Helix Genes in "Caenorhabditis elegans" through a Classroom Demonstration of Functional Genomics

    Science.gov (United States)

    Griffin, Vernetta; McMiller, Tracee; Jones, Erika; Johnson, Casonya M.

    2003-01-01

    A 14-week, undergraduate-level Genetics and Population Biology course at Morgan State University was modified to include a demonstration of functional genomics in the research laboratory. Students performed a rudimentary sequence analysis of the "Caenorhabditis elegans" genome and further characterized three sequences that were predicted to encode…

  3. Hexagon functions and the three-loop remainder function

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Lance J.; Drummond, James M.; von Hippel, Matt; Pennington, Jeffrey

    2013-12-01

    We present the three-loop remainder function, which describes the scattering of six gluons in the maximally-helicity-violating configuration in planar NN = 4 super-Yang-Mills theory, as a function of the three dual conformal cross ratios. The result can be expressed in terms of multiple Goncharov polylogarithms. We also employ a more restricted class of hexagon functions which have the correct branch cuts and certain other restrictions on their symbols. We classify all the hexagon functions through transcendental weight five, using the coproduct for their Hopf algebra iteratively, which amounts to a set of first-order differential equations. The three-loop remainder function is a particular weight-six hexagon function, whose symbol was determined previously. The differential equations can be integrated numerically for generic values of the cross ratios, or analytically in certain kinematic limits, including the near-collinear and multi-Regge limits. These limits allow us to impose constraints from the operator product expansion and multi-Regge factorization directly at the function level, and thereby to fix uniquely a set of Riemann ζ valued constants that could not be fixed at the level of the symbol. The near-collinear limits agree precisely with recent predictions by Basso, Sever and Vieira based on integrability. The multi-Regge limits agree with the factorization formula of Fadin and Lipatov, and determine three constants entering the impact factor at this order. We plot the three-loop remainder function for various slices of the Euclidean region of positive cross ratios, and compare it to the two-loop one. For large ranges of the cross ratios, the ratio of the three-loop to the two-loop remainder function is relatively constant, and close to -7.

  4. LOOL: Mathematica package for evaluating leading order one loop functions

    OpenAIRE

    Ilakovac, Amon; Popov, Luka

    2014-01-01

    One-loop functions with loop masses larger than external masses and momenta can always be expanded in terms of external masses and momenta. The precision requested for observables determines the number of the expansion terms retained in the evaluation. The evaluation of these expansion terms turns out to be much simpler than the exact evaluation of the corresponding one-loop function. Here we present the program which evaluates those expansion terms. This Mathematica package provides two subr...

  5. BPS Wilson loops and Bremsstrahlung function in ABJ(M): a two loop analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Marco S. [Institut für Physik, Humboldt-Universität zu Berlin,Newtonstraße 15, 12489 Berlin (Germany); Griguolo, Luca [Dipartimento di Fisica e Scienze della Terra, Università di Parmaand INFN Gruppo Collegato di Parma,Viale G.P. Usberti 7/A, 43100 Parma (Italy); Leoni, Matias [Physics Department, FCEyN-UBA & IFIBA-CONICETCiudad Universitaria, Pabellón I, 1428, Buenos Aires (Argentina); Penati, Silvia [Dipartimento di Fisica, Università di Milano-Bicoccaand INFN, Sezione di Milano-Bicocca,Piazza della Scienza 3, I-20126 Milano (Italy); Seminara, Domenico [Dipartimento di Fisica, Università di Firenzeand INFN Sezione di Firenze,via G. Sansone 1, 50019 Sesto Fiorentino (Italy)

    2014-06-19

    We study a family of circular BPS Wilson loops in N=6 super Chern-Simons-matter theories, generalizing the usual 1/2-BPS circle. The scalar and fermionic couplings depend on two deformation parameters and these operators can be considered as the ABJ(M) counterpart of the DGRT latitudes defined in N=4 SYM. We perform a complete two-loop analysis of their vacuum expectation value, discuss the appearance of framing-like phases and propose a general relation with cohomologically equivalent bosonic operators. We make an all-loop proposal for computing the Bremsstrahlung function associated to the 1/2-BPS cusp in terms of these generalized Wilson loops. When applied to our two-loop result it reproduces the known expression. Finally, we comment on the generalization of this proposal to the bosonic 1/6-BPS case.

  6. Reactivation of developmentally silenced globin genes by forced chromatin looping.

    Science.gov (United States)

    Deng, Wulan; Rupon, Jeremy W; Krivega, Ivan; Breda, Laura; Motta, Irene; Jahn, Kristen S; Reik, Andreas; Gregory, Philip D; Rivella, Stefano; Dean, Ann; Blobel, Gerd A

    2014-08-14

    Distal enhancers commonly contact target promoters via chromatin looping. In erythroid cells, the locus control region (LCR) contacts β-type globin genes in a developmental stage-specific manner to stimulate transcription. Previously, we induced LCR-promoter looping by tethering the self-association domain (SA) of Ldb1 to the β-globin promoter via artificial zinc fingers. Here, we show that targeting the SA to a developmentally silenced embryonic globin gene in adult murine erythroblasts triggers its transcriptional reactivation. This activity depends on the LCR, consistent with an LCR-promoter looping mechanism. Strikingly, targeting the SA to the fetal γ-globin promoter in primary adult human erythroblasts increases γ-globin promoter-LCR contacts, stimulating transcription to approximately 85% of total β-globin synthesis, with a reciprocal reduction in adult β-globin expression. Our findings demonstrate that forced chromatin looping can override a stringent developmental gene expression program and suggest a novel approach to control the balance of globin gene transcription for therapeutic applications.

  7. R Loops in the Regulation of Antibody Gene Diversification.

    Science.gov (United States)

    Pavri, Rushad

    2017-06-02

    For nearly three decades, R loops have been closely linked with class switch recombination (CSR), the process that generates antibody isotypes and that occurs via a complex cascade initiated by transcription-coupled mutagenesis in switch recombination sequences. R loops form during transcription of switch recombination sequences in vitro and in vivo, and there is solid evidence that R loops are required for efficient class switching. The classical model of R loops posits that they boost mutation rates by generating stable and long tracts of single-stranded DNA that serve as the substrate for activation induced deaminase (AID), the enzyme that initiates the CSR reaction cascade by co-transcriptionally mutating ssDNA in switch recombination sequences. Though logical and compelling, this model has not been supported by in vivo evidence. Indeed, several reports suggest that R loops may not be involved in recruiting AID activity to switch regions, meaning that R loops probably serve other unanticipated roles in CSR. Here, I review the key findings in this field to date and propose hypotheses that could help towards elucidating the precise function of R loops in CSR.

  8. LOOL: Mathematica package for evaluating leading order one loop functions

    CERN Document Server

    Ilakovac, Amon

    2014-01-01

    One-loop functions with loop masses larger than external masses and momenta can always be expanded in terms of external masses and momenta. The precision requested for observables determines the number of the expansion terms retained in the evaluation. The evaluation of these expansion terms turns out to be much simpler than the exact evaluation of the corresponding one-loop function. Here we present the program which evaluates those expansion terms. This Mathematica package provides two subroutines. First one performs analytical evaluation of basic one loop integrals. The second one is used to construct composite functions out of those integrals. Composite functions thus obtained are ready for numerical evaluation with literary no time consumption.

  9. One-loop Partition Functions of 3D Gravity

    CERN Document Server

    Giombi, Simone; Yin, Xi

    2008-01-01

    We consider the one-loop partition function of free quantum field theory in locally Anti-de Sitter space-times. In three dimensions, the one loop determinants for scalar, gauge and graviton excitations are computed explicitly using heat kernel techniques. We obtain precisely the result anticipated by Brown and Henneaux: the partition function includes a sum over "boundary excitations" of AdS3, which are the Virasoro descendants of empty Anti-de Sitter space. This result also allows us to compute the one-loop corrections to the Euclidean action of the BTZ black hole as well its higher genus generalizations.

  10. Functional Loop Dynamics of the Streptavidin-Biotin Complex

    Science.gov (United States)

    Song, Jianing; Li, Yongle; Ji, Changge; Zhang, John Z. H.

    2015-01-01

    Accelerated molecular dynamics (aMD) simulation is employed to study the functional dynamics of the flexible loop3-4 in the strong-binding streptavidin-biotin complex system. Conventional molecular (cMD) simulation is also performed for comparison. The present study reveals the following important properties of the loop dynamics: (1) The transition of loop3-4 from open to closed state is observed in 200 ns aMD simulation. (2) In the absence of biotin binding, the open-state streptavidin is more stable, which is consistent with experimental evidences. The free energy (ΔG) difference is about 5 kcal/mol between two states. But with biotin binding, the closed state is more stable due to electrostatic and hydrophobic interactions between the loop3-4 and biotin. (3) The closure of loop3-4 is concerted to the stable binding of biotin to streptavidin. When the loop3-4 is in its open-state, biotin moves out of the binding pocket, indicating that the interactions between the loop3-4 and biotin are essential in trapping biotin in the binding pocket. (4) In the tetrameric streptavidin system, the conformational change of the loop3-4 in each monomer is independent of each other. That is, there is no cooperative binding for biotin bound to the four subunits of the tetramer.

  11. The autoregulatory loop: A common mechanism of regulation of key sex determining genes in insects

    Indian Academy of Sciences (India)

    Suresh Kumar Kumar; Gajula Gopinath; Nagraj Sambrani; Kallare P Arunkumar

    2016-06-01

    Sex determination in most insects is structured as a gene cascade, wherein a primary signal is passed through a series of sex-determining genes, culminating in a downstream double-switch known as doublesex that decides the sexual fate of the embryo. From the literature available on sex determination cascades, it becomes apparent that sex determination mechanisms have evolved rapidly. The primary signal that provides the cue to determine the sex of the embryo varies remarkably, not only among taxa, but also within taxa. Furthermore, the upstream key gene in the cascade also varies between species and even among closely related species. The order Insecta alone provides examples of astoundingly complex diversity of upstream key genes in sex determination mechanisms. Besides, unlike key upstream genes, the downstream double-switch gene is alternatively spliced to form functional sex-specific isoforms. This sex-specific splicing is conserved across insect taxa. The genes involved in the sex determination cascade such as Sex-lethal (Sxl) in Drosophila melanogaster, transformer (tra) in many other dipterans, coleopterans and hymenopterans, Feminizer (fem) in Apis mellifera, and IGF-II mRNA-binding protein (Bmimp) in Bombyx mori are reported to be regulated by an autoregulatory positive feedback loop. In this review, by taking examples from various insects, we propose the hypothesis that autoregulatory loop mechanisms of sex determination might be a general strategy. We also discuss the possible reasons for the evolution of autoregulatory loops in sex determination cascades and their impact on binary developmental choices.

  12. The autoregulatory loop: A common mechanism of regulation of key sex determining genes in insects.

    Science.gov (United States)

    Sawanth, Suresh Kumar; Gopinath, Gajula; Sambrani, Nagraj; Arunkumar, Kallare P

    2016-06-01

    Sex determination in most insects is structured as a gene cascade, wherein a primary signal is passed through a series of sex-determining genes, culminating in a downstream double-switch known as doublesex that decides the sexual fate of the embryo. From the literature available on sex determination cascades, it becomes apparent that sex determination mechanisms have evolved rapidly. The primary signal that provides the cue to determine the sex of the embryo varies remarkably, not only among taxa, but also within taxa. Furthermore, the upstream key gene in the cascade also varies between species and even among closely related species. The order Insecta alone provides examples of astoundingly complex diversity of upstream key genes in sex determination mechanisms. Besides, unlike key upstream genes, the downstream double-switch gene is alternatively spliced to form functional sex-specific isoforms. This sex-specific splicing is conserved across insect taxa. The genes involved in the sex determination cascade such as Sex-lethal (Sxl) in Drosophila melanogaster, transformer (tra) in many other dipterans, coleopterans and hymenopterans, Feminizer (fem) in Apis mellifera, and IGF-II mRNA-binding protein (Bmimp) in Bombyx mori are reported to be regulated by an autoregulatory positive feedback loop. In this review, by taking examples from various insects, we propose the hypothesis that autoregulatory loop mechanisms of sex determination might be a general strategy. We also discuss the possible reasons for the evolution of autoregulatory loops in sex determination cascades and their impact on binary developmental choices.

  13. Functional Erythropoietin Autocrine Loop in Melanoma

    OpenAIRE

    Kumar, Suresh M; Acs, Geza; Fang, Dong; Herlyn, Meenhard; Elder, David E.; Xu, Xiaowei

    2005-01-01

    Although erythropoietin (Epo) is a known stimulator of erythropoiesis, recent evidence suggests that its biological functions are not confined to hematopoietic cells. To elucidate the role of Epo and erythropoietin receptor (EpoR) in melanoma, we examined the expression and function of these proteins in melanocytes and melanoma cells. We found increased expression of Epo in melanoma cells compared to melanocyte in vitro. EpoR was also strongly expressed in all of the melanoma cell lines and t...

  14. Semiclassical correlation functions of Wilson loops and local vertex operators

    CERN Document Server

    Hernandez, Rafael

    2012-01-01

    We analyze correlation functions of Wilson loop observables and local vertex operators within the strong-coupling regime of the AdS/CFT correspondence. When the local operator corresponds to a light string state with finite conserved charges the correlation function can be evaluated in the semiclassical approximation of large string tension, where the contribution from the light vertex can be neglected. We consider the cases where the Wilson loops are described by two concentric surfaces and the local vertices are the superconformal chiral primary scalar or a singlet massive scalar operator.

  15. Two-loop beta functions for supersymmetric gauge theories

    Energy Technology Data Exchange (ETDEWEB)

    Jack, I. (Imperial Coll. of Science and Technology, London (UK). Blackett Lab.)

    1984-11-15

    The two-loop ..beta.. functions in the dimensional regularisation framework for a general gauge theory coupled to scalar and spinor fields are presented and by means of a finite transformation of the couplings are converted into a form which vanishes for special cases corresponding to supersymmetric gauge theories.

  16. Electromagnetism and multiple-valued loop-dependent wave functionals

    CERN Document Server

    Leal, Lorenzo

    2009-01-01

    We quantize the Maxwell theory in the presence of a electric charge in a "dual" Loop Representation, i.e. a geometric representation of magnetic Faraday's lines. It is found that the theory can be seen as a theory without sources, except by the fact that the wave functional becomes multivalued. This can be seen as the dual counterpart of what occurs in Maxwell theory with a magnetic pole, when it is quantized in the ordinary Loop Representation. The multivaluedness can be seen as a result of the multiply-connectedness of the configuration space of the quantum theory.

  17. Illuminating the structure and function of Cys-loop receptors

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Lynch, Joseph W

    2008-01-01

    transitional and steady state conformations and serves as a real time correlate of the channel structure and its function. Voltage-clamp fluorometry experiments on Cys-loop receptors have yielded a large body of data concerning the mechanisms by which agonists, antagonists and modulators act on these receptors......Cys-loop receptors are an important class of ligand-gated ion channels. They mediate fast synaptic neurotransmission, are implicated in various 'channelopathies' and are important pharmacological targets. Recent progress in X-ray crystallography and electron microscopy has provided a considerable...... insight into the structure of Cys-loop receptors. However, data from these experiments only provide 'snapshots' of the proteins under investigation. They cannot provide information about the various conformations the protein adopts during transition from the closed to the open and desensitized states...

  18. Stem loop sequences specific to transposable element IS605 are found linked to lipoprotein genes in Borrelia plasmids.

    Directory of Open Access Journals (Sweden)

    Nicholas Delihas

    Full Text Available BACKGROUND: Plasmids of Borrelia species are dynamic structures that contain a large number of repetitive genes, gene fragments, and gene fusions. In addition, the transposable element IS605/200 family, as well as degenerate forms of this IS element, are prevalent. In Helicobacter pylori, flanking regions of the IS605 transposase gene contain sequences that fold into identical small stem loops. These function in transposition at the single-stranded DNA level. METHODOLOGY/PRINCIPAL FINDINGS: In work reported here, bioinformatics techniques were used to scan Borrelia plasmid genomes for IS605 transposable element specific stem loop sequences. Two variant stem loop motifs are found in the left and right flanking regions of the transposase gene. Both motifs appear to have dispersed in plasmid genomes and are found "free-standing" and phylogenetically conserved without the associated IS605 transposase gene or the adjacent flanking sequence. Importantly, IS605 specific stem loop sequences are also found at the 3' ends of lipoprotein genes (PFam12 and PFam60, however the left and right sequences appear to develop their own evolutionary patterns. The lipoprotein gene-linked left stem loop sequences maintain the IS605 stem loop motif in orthologs but only at the RNA level. These show mutations whereby variants fold into phylogenetically conserved RNA-type stem loops that contain the wobble non-Watson-Crick G-U base-pairing. The right flanking sequence is associated with the family lipoprotein-1 genes. A comparison of homologs shows that the IS605 stem loop motif rapidly dissipates, but a more elaborate secondary structure appears to develop in its place. CONCLUSIONS/SIGNIFICANCE: Stem loop sequences specific to the transposable element IS605 are present in plasmid regions devoid of a transposase gene and significantly, are found linked to lipoprotein genes in Borrelia plasmids. These sequences are evolutionarily conserved and/or structurally developed in

  19. Chromatin looping and eRNA transcription precede the transcriptional activation of gene in the β-globin locus.

    Science.gov (United States)

    Kim, Yea Woon; Lee, Sungkung; Yun, Jangmi; Kim, AeRi

    2015-03-18

    Enhancers are closely positioned with actively transcribed target genes by chromatin looping. Non-coding RNAs are often transcribed on active enhancers, referred to as eRNAs (enhancer RNAs). To explore the kinetics of enhancer-promoter looping and eRNA transcription during transcriptional activation, we induced the β-globin locus by chemical treatment and analysed cross-linking frequency between the β-globin gene and locus control region (LCR) and the amount of eRNAs transcribed on the LCR in a time course manner. The cross-linking frequency was increased after chemical induction but before the transcriptional activation of gene in the β-globin locus. Transcription of eRNAs was increased in concomitant with the increase in cross-linking frequency. These results show that chromatin looping and eRNA transcription precedes the transcriptional activation of gene. Concomitant occurrence of the two events suggests functional relationship between them.

  20. The partition function of a ferromagnet up to three loops

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, C P, E-mail: christoph@ucol.mx [Facultad de Ciencias, Universidad de Colima, Bernal Diaz del Castillo 340, Colima, Colima 28045 (Mexico)

    2011-04-01

    The low-temperature behavior of ferromagnets with a spontaneously broken symmetry O(3) {yields} O(2) is analyzed within the perspective of effective Lagrangians. The leading coefficients of the low-temperature expansion for the partition function are calculated up to three loops and the manifestation of the spin-wave interaction in this series is discussed. The effective field theory method has the virtue of being completely systematic and model-independent.

  1. The four-loop six-gluon NMHV ratio function

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Lance J. [SLAC National Accelerator Lab., Stanford, CA (United States); California Inst. of Technology (CalTech), Pasadena, CA (United States); von Hippel, Matt [Perimeter Inst. for Theoretical Physics, Waterloo, ON (Canada); McLeod, Andrew J. [SLAC National Accelerator Lab., Stanford, CA (United States)

    2016-01-11

    We use the hexagon function bootstrap to compute the ratio function which characterizes the next-to-maximally-helicity-violating (NMHV) six-point amplitude in planar N = 4 super-Yang-Mills theory at four loops. A powerful constraint comes from dual superconformal invariance, in the form of a Q- differential equation, which heavily constrains the first derivatives of the transcendental functions entering the ratio function. At four loops, it leaves only a 34-parameter space of functions. Constraints from the collinear limits, and from the multi-Regge limit at the leading-logarithmic (LL) and next-to-leading-logarithmic (NLL) order, suffice to fix these parameters and obtain a unique result. We test the result against multi- Regge predictions at NNLL and N3LL, and against predictions from the operator product expansion involving one and two flux-tube excitations; all cross-checks are satisfied. We also study the analytical and numerical behavior of the parity-even and parity-odd parts on various lines and surfaces traversing the three-dimensional space of cross ratios. As part of this program, we characterize all irreducible hexagon functions through weight eight in terms of their coproduct. Furthermore, we provide representations of the ratio function in particular kinematic regions in terms of multiple polylogarithms.

  2. The one loop gluon emission light cone wave function

    CERN Document Server

    Lappi, Tuomas

    2016-01-01

    Light cone perturbation theory has become an essential tool to calculate cross sections for various small-$x$ dilute-dense processes such as deep inelastic scattering and forward proton-proton and proton-nucleus collisions. Here we set out to do one loop calculations in an explicit helicity basis in the four dimensional helicity scheme. As a first process we calculate light cone wave function for one gluon emission to one-loop order in Hamiltonian perturbation theory on the light front. We regulate ultraviolet divergences with transverse dimensional regularization and soft divergences with using a cut-off on longitudinal momentum. We show that when all the renormalization constants are combined, the ultraviolet divergences can be absorbed into the standard QCD running coupling constant, and give an explicit expression for the remaining finite part.

  3. The four-loop six-gluon NMHV ratio function

    CERN Document Server

    Dixon, Lance J; McLeod, Andrew J

    2015-01-01

    We use the hexagon function bootstrap to compute the ratio function which characterizes the next-to-maximally-helicity-violating (NMHV) six-point amplitude in planar $\\mathcal{N} = 4$ super-Yang-Mills theory at four loops. A powerful constraint comes from dual superconformal invariance, in the form of a $\\bar{Q}$ differential equation, which heavily constrains the first derivatives of the transcendental functions entering the ratio function. At four loops, it leaves only a 34-parameter space of functions. Constraints from the collinear limits, and from the multi-Regge limit at the leading-logarithmic (LL) and next-to-leading-logarithmic (NLL) order, suffice to fix these parameters and obtain a unique result. We test the result against multi-Regge predictions at NNLL and N$^3$LL, and against predictions from the operator product expansion involving one and two flux-tube excitations; all cross-checks are satisfied. We study the analytical and numerical behavior of the parity-even and parity-odd parts on various...

  4. Functional characteristics of a double positive feedback loop coupled with autorepression

    Science.gov (United States)

    Banerjee, Subhasis; Bose, Indrani

    2008-12-01

    We study the functional characteristics of a two-gene motif consisting of a double positive feedback loop and an autoregulatory negative feedback loop. The motif appears in the gene regulatory network controlling the functional activity of pancreatic β-cells. The model exhibits bistability and hysteresis in appropriate parameter regions. The two stable steady states correspond to low (OFF state) and high (ON state) protein levels, respectively. Using a deterministic approach, we show that the region of bistability increases in extent when the copy number of one of the genes is reduced from 2 to 1. The negative feedback loop has the effect of reducing the size of the bistable region. Loss of a gene copy, brought about by mutations, hampers the normal functioning of the β-cells giving rise to the genetic disorder, maturity-onset diabetes of the young (MODY). The diabetic phenotype makes its appearance when a sizable fraction of the β-cells is in the OFF state. Using stochastic simulation techniques we show that, on reduction of the gene copy number, there is a transition from the monostable ON to the ON state in the bistable region of the parameter space. Fluctuations in the protein levels, arising due to the stochastic nature of gene expression, can give rise to transitions between the ON and OFF states. We show that as the strength of autorepression increases, the ON → OFF state transitions become less probable whereas the reverse transitions are more probable. The implications of the results in the context of the occurrence of MODY are pointed out.

  5. Correlation Function of Circular Wilson Loops at Strong Coupling

    CERN Document Server

    Dekel, Amit

    2013-01-01

    We study the correlation function of two circular Wilson loops at strong coupling in N=4 super Yang-Mills theory. Using the AdS/CFT correspondence, the problem maps to finding the minimal surface between two circles defined on the boundary of AdS, and the fluctuations around the classical solution in AdS_5 x S^5. At the classical level, we derive the string solution in H_3 x S^1 explicitly, and focus on properties such as stability and phase transition. Furthermore, a computation of the associated algebraic curve is given. At the quantum level, the one-loop partition function is constructed by introducing quadratic bosonic and fermionic fluctuations around the classical solution, embedded in AdS_5 x S^5. We find an analytic, formal expression for the partition function in terms of an infinite product by employing the Gel'fand-Yaglom method and supersymmetric regularization. We regulate the expression and evaluate the partition function numerically.

  6. Rapidity renormalized TMD soft and beam functions at two loops

    Energy Technology Data Exchange (ETDEWEB)

    Luebbert, Thomas [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Oredsson, Joel [DESY, Hamburg (Germany). Theory Group; Lund Univ. (Sweden). Dept. of Astronomy and Theoretical Physics; Stahlhofen, Maximilian [DESY, Hamburg (Germany). Theory Group; Mainz Univ. (Germany). PRISMA Cluster of Excellence

    2016-03-15

    We compute the transverse momentum dependent (TMD) soft function for the production of a color-neutral final state at the LHC within the rapidity renormalization group (RRG) framework to next-to-next-to-leading order (NNLO). We use this result to extract the universal renormalized TMD beam functions (aka TMDPDFs) in the same scheme and at the same order from known results in another scheme. We derive recurrence relations for the logarithmic structure of the soft and beam functions, which we use to cross check our calculation. We also explicitly confirm the non-Abelian exponentiation of the TMD soft function in the RRG framework at two loops. Our results provide the ingredients for resummed predictions of p {sub perpendicular} {sub to} -differential cross sections at NNLL' in the RRG formalism. The RRG provides a systematic framework to resum large (rapidity) logarithms through (R)RG evolution and assess the associated perturbative uncertainties.

  7. Heavy-quark QCD vacuum polarisation function. Analytical results at four loops

    Energy Technology Data Exchange (ETDEWEB)

    Kniehl, B.A.; Kotikov, A.V. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2006-07-15

    The first two moments of the heavy-quark vacuum polarisation function at four loops in quantum chromo-dynamics are found in fully analytical form by evaluating the missing massive four-loop tadpole master integrals. (orig.)

  8. Multi-loop zeta function regularization and spectral cutoff in curved spacetime

    Energy Technology Data Exchange (ETDEWEB)

    Bilal, Adel, E-mail: adel.bilal@lpt.ens.fr [Centre National de la Recherche Scientifique, Laboratoire de Physique Théorique de l' École Normale Supérieure, 24 rue Lhomond, F-75231 Paris Cedex 05 (France); Ferrari, Frank, E-mail: frank.ferrari@ulb.ac.be [Service de Physique Théorique et Mathématique, Université Libre de Bruxelles and International Solvay Institutes, Campus de la Plaine, CP 231, B-1050 Bruxelles (Belgium)

    2013-12-21

    We emphasize the close relationship between zeta function methods and arbitrary spectral cutoff regularizations in curved spacetime. This yields, on the one hand, a physically sound and mathematically rigorous justification of the standard zeta function regularization at one loop and, on the other hand, a natural generalization of this method to higher loops. In particular, to any Feynman diagram is associated a generalized meromorphic zeta function. For the one-loop vacuum diagram, it is directly related to the usual spectral zeta function. To any loop order, the renormalized amplitudes can be read off from the pole structure of the generalized zeta functions. We focus on scalar field theories and illustrate the general formalism by explicit calculations at one-loop and two-loop orders, including a two-loop evaluation of the conformal anomaly.

  9. Effect of Interaction between Chromatin Loops on Cell-to-Cell Variability in Gene Expression.

    Directory of Open Access Journals (Sweden)

    Tuoqi Liu

    2016-05-01

    Full Text Available According to recent experimental evidence, the interaction between chromatin loops, which can be characterized by three factors-connection pattern, distance between regulatory elements, and communication form, play an important role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effect that addresses the question of how changes in these factors affect variability at the expression level in a systematic rather than case-by-case fashion. Here we make such an effort, based on a mechanic model that maps three fundamental patterns for two interacting DNA loops into a 4-state model of stochastic transcription. We first show that in contrast to side-by-side loops, nested loops enhance mRNA expression and reduce expression noise whereas alternating loops have just opposite effects. Then, we compare effects of facilitated tracking and direct looping on gene expression. We find that the former performs better than the latter in controlling mean expression and in tuning expression noise, but this control or tuning is distance-dependent, remarkable for moderate loop lengths, and there is a limit loop length such that the difference in effect between two communication forms almost disappears. Our analysis and results justify the facilitated chromatin-looping hypothesis.

  10. Two-point functions in (loop) quantum cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Calcagni, Gianluca; Gielen, Steffen; Oriti, Daniele, E-mail: calcagni@aei.mpg.de, E-mail: gielen@aei.mpg.de, E-mail: doriti@aei.mpg.de [Max Planck Institute for Gravitational Physics (Albert Einstein Institute), Am Muehlenberg 1, D-14476 Golm (Germany)

    2011-06-21

    The path-integral formulation of quantum cosmology with a massless scalar field as a sum-over-histories of volume transitions is discussed, with particular but non-exclusive reference to loop quantum cosmology. Exploiting the analogy with the relativistic particle, we give a complete overview of the possible two-point functions, pointing out the choices involved in their definitions, deriving their vertex expansions and the composition laws they satisfy. We clarify the origin and relations of different quantities previously defined in the literature, in particular the tie between definitions using a group averaging procedure and those in a deparametrized framework. Finally, we draw some conclusions about the physics of a single quantum universe (where there exist superselection rules on positive- and negative-frequency sectors and different choices of inner product are physically equivalent) and multiverse field theories where the role of these sectors and the inner product are reinterpreted.

  11. Two-point functions in (loop) quantum cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Calcagni, Gianluca; Oriti, Daniele [Max-Planck-Institute for Gravitational Physics (Albert Einstein Institute), Am Muehlenberg 1, D-14476 Golm (Germany); Gielen, Steffen [Max-Planck-Institute for Gravitational Physics (Albert Einstein Institute), Am Muehlenberg 1, D-14476 Golm (Germany); DAMTP, Centre for Mathematical Sciences, Wilberforce Road, Cambridge CB3 0WA (United Kingdom)

    2011-07-01

    We discuss the path-integral formulation of quantum cosmology with a massless scalar field as a sum-over-histories of volume transitions, with particular but non-exclusive reference to loop quantum cosmology (LQC). Exploiting the analogy with the relativistic particle, we give a complete overview of the possible two-point functions, pointing out the choices involved in their definitions, deriving their vertex expansions and the composition laws they satisfy. We clarify the origin and relations of different quantities previously defined in the literature, in particular the tie between definitions using a group averaging procedure and those in a deparametrized framework. Finally, we draw some conclusions about the physics of a single quantum universe (where there exist superselection rules on positive- and negative-frequency sectors and different choices of inner product are physically equivalent) and multiverse field theories where the role of these sectors and the inner product are reinterpreted.

  12. R-loop induced stress response by second (p)ppGpp synthetase in Mycobacterium smegmatis: functional and domain interdependence.

    Science.gov (United States)

    Krishnan, Sushma; Petchiappan, Anushya; Singh, Albel; Bhatt, Apoorva; Chatterji, Dipankar

    2016-10-01

    Persistent R-loops lead to replicative stress due to RNA polymerase stalling and DNA damage. RNase H enzymes facilitate the organisms to survive in the hostile condition by removing these R-loops. MS_RHII-RSD was previously identified to be the second (p)ppGpp synthetase in Mycobacterium smegmatis. The unique presence of an additional RNase HII domain raises an important question regarding the significance of this bifunctional protein. In this report, we demonstrate its ability to hydrolyze R-loops in Escherichia coli exposed to UV stress. MS_RHII-RSD gene expression was upregulated under UV stress, and this gene deleted strain showed increased R-loop accumulation as compared to the wild type. The domains in isolation are known to be inactive, and the full length protein is required for its function. Domain interdependence studies using active site mutants reveal the necessity of a hexamer form with high alpha helical content. In previous studies, bacterial RNase type HI has been mainly implicated in R-loop hydrolysis, but in this study, the RNase HII domain containing protein showed the activity. The prospective of this differential RNase HII activity is discussed. This is the first report to implicate a (p)ppGpp synthetase protein in R-loop-induced stress response.

  13. Including Functional Annotations and Extending the Collection of Structural Classifications of Protein Loops (ArchDB

    Directory of Open Access Journals (Sweden)

    Antoni Hermoso

    2007-01-01

    Full Text Available Loops represent an important part of protein structures. The study of loop is critical for two main reasons: First, loops are often involved in protein function, stability and folding. Second, despite improvements in experimental and computational structure prediction methods, modeling the conformation of loops remains problematic. Here, we present a structural classification of loops, ArchDB, a mine of information with application in both mentioned fields: loop structure prediction and function prediction. ArchDB (http://sbi.imim.es/archdb is a database of classified protein loop motifs. The current database provides four different classification sets tailored for different purposes. ArchDB-40, a loop classification derived from SCOP40, well suited for modeling common loop motifs. Since features relevant to loop structure or function can be more easily determined on well-populated clusters, we have developed ArchDB-95, a loop classification derived from SCOP95. This new classification set shows a ∼40% increase in the number of subclasses, and a large 7-fold increase in the number of putative structure/function-related subclasses. We also present ArchDB-EC, a classification of loop motifs from enzymes, and ArchDB-KI, a manually annotated classification of loop motifs from kinases. Information about ligand contacts and PDB sites has been included in all classification sets. Improvements in our classification scheme are described, as well as several new database features, such as the ability to query by conserved annotations, sequence similarity, or uploading 3D coordinates of a protein. The lengths of classified loops range between 0 and 36 residues long. ArchDB offers an exhaustive sampling of loop structures. Functional information about loops and links with related biological databases are also provided. All this information and the possibility to browse/query the database through a web-server outline an useful tool with application in the

  14. The visual corticostriatal loop through the tail of the caudate: Circuitry and function

    Directory of Open Access Journals (Sweden)

    Carol A Seger

    2013-12-01

    Full Text Available Although high level visual cortex projects to a specific region of the striatum, the tail of the caudate, and participates in corticostriatal loops, the function of this visual corticostriatal system is not well understood. This article first reviews what is known about the anatomy of the visual corticostriatal loop across mammals, including rodents, cats, monkeys, and humans. Like other corticostriatal systems, the visual corticostriatal system includes both closed loop components (recurrent projections that return to the originating cortical location and open loop components (projections that terminate in other neural regions. The article then reviews what previous empircal research has shown about the function of the tail of the caudate. The article finally addresses the possible functions of the closed and open loop connections of the visual loop in the context of theories and computational models of corticostriatal function.

  15. A negative regulatory loop between microRNA and Hox gene controls posterior identities in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Zhongying Zhao

    2010-09-01

    Full Text Available MicroRNAs (miRNAs have been found to regulate gene expression across eukaryotic species, but the function of most miRNA genes remains unknown. Here we describe how the analysis of the expression patterns of a well-conserved miRNA gene, mir-57, at cellular resolution for every minute during early development of Caenorhabditis elegans provided key insights in understanding its function. Remarkably, mir-57 expression shows strong positional bias but little tissue specificity, a pattern reminiscent of Hox gene function. Despite the minor defects produced by a loss of function mutation, overexpression of mir-57 causes dramatic posterior defects, which also mimic the phenotypes of mutant alleles of a posterior Hox gene, nob-1, an Abd homolog. More importantly, nob-1 expression is found in the same two posterior AB sublineages as those expressing mir-57 but with an earlier onset. Intriguingly, nob-1 functions as an activator for mir-57 expression; it is also a direct target of mir-57. In agreement with this, loss of mir-57 function partially rescues the nob-1 allele defects, indicating a negative feedback regulatory loop between the miRNA and Hox gene to provide positional cues. Given the conservation of the miRNA and Hox gene, the regulatory mechanism might be broadly used across species. The strategy used here to explore mir-57 function provides a path to dissect the regulatory relationship between genes.

  16. Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes.

    Science.gov (United States)

    Hu, Jiazhi; Zhang, Yu; Zhao, Lijuan; Frock, Richard L; Du, Zhou; Meyers, Robin M; Meng, Fei-long; Schatz, David G; Alt, Frederick W

    2015-11-05

    RAG initiates antibody V(D)J recombination in developing lymphocytes by generating "on-target" DNA breaks at matched pairs of bona fide recombination signal sequences (RSSs). We employ bait RAG-generated breaks in endogenous or ectopically inserted RSS pairs to identify huge numbers of RAG "off-target" breaks. Such breaks occur at the simple CAC motif that defines the RSS cleavage site and are largely confined within convergent CTCF-binding element (CBE)-flanked loop domains containing bait RSS pairs. Marked orientation dependence of RAG off-target activity within loops spanning up to 2 megabases implies involvement of linear tracking. In this regard, major RAG off-targets in chromosomal translocations occur as convergent RSS pairs at enhancers within a loop. Finally, deletion of a CBE-based IgH locus element disrupts V(D)J recombination domains and, correspondingly, alters RAG on- and off-target distributions within IgH. Our findings reveal how RAG activity is developmentally focused and implicate mechanisms by which chromatin domains harness biological processes within them. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. CTCF-mediated chromatin loops enclose inducible gene regulatory domains

    NARCIS (Netherlands)

    Oti, M.O.; Falck, J.; Huynen, M.A.; Zhou, Huiqing

    2016-01-01

    BACKGROUND: The CCTC-binding factor (CTCF) protein is involved in genome organization, including mediating three-dimensional chromatin interactions. Human patient lymphocytes with mutations in a single copy of the CTCF gene have reduced expression of enhancer-associated genes involved in response to

  18. Structure and function in bacteriorhodopsin: the role of the interhelical loops in the folding and stability of bacteriorhodopsin.

    Science.gov (United States)

    Kim, J M; Booth, P J; Allen, S J; Khorana, H G

    2001-04-27

    Bacteriorhodopsin functions as a light-driven proton pump in Halobacterium salinarium. The functional protein consists of an apoprotein, bacterioopsin, with seven transmembrane alpha helices together with a covalently bound all-trans retinal chromophore. In order to study the role of the interhelical loop conformations in the structure and function of bacteriorhodopsin, we have constructed bacterioopsin genes where each loop is replaced, one at a time, by a peptide linker consisting of Gly-Gly-Ser- repeat sequences, which are believed to have flexible conformations. These mutant proteins have been expressed in Escherichia coli, purified and reconstituted with all-trans retinal in l-alpha-1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/3-(3-cholamidopropyl)dimethylammonio-1-propane sulfonate (CHAPS)/SDS and l-alpha-1,2-dihexanoylphosphatidylcholine (DHPC)/DMPC/SDS micelles. Wild-type-like chromophore formation was observed in all the mutants containing single loop replacements. In the BC and FG mutants, an additional chromophore band with an absorption band at about 480 nm was observed, which was in equilibrium with the 550 nm, wild-type band. The position of the equilibrium depended on temperature, SDS and relative DMPC concentration. The proton pumping activity of all of the mutants was comparable to that of wild-type bR except for the BC and FG mutants, which had lower activity. All of the loop mutants were more sensitive to denaturation by SDS than the wild-type protein, except the mutant where the DE loop was replaced. These results suggest that a specific conformation of all the loops of bR, except the DE loop, contributes to bR stability and is required for the correct folding and function of the protein. An increase in the relative proportion of DHPC in DHPC/DMPC micelles, which reduces the micelle rigidity and alters the micelle shape, resulted in lower folding yields of all loop mutants except the BC and DE mutants. This effect of micelle rigidity on

  19. The Y-located gonadoblastoma gene TSPY amplifies its own expression through a positive feedback loop in prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kido, Tatsuo; Lau, Yun-Fai Chris, E-mail: Chris.Lau@UCSF.edu

    2014-03-28

    Highlights: • Y-encoded proto-oncoprotein TSPY amplifies its expression level via a positive feedback loop. • TSPY binds to the chromatin/DNA at exon 1 of TSPY gene. • TSPY enhances the gene expression in a TSPY exon 1 sequence dependent manner. • The conserved SET/NAP-domain is essential for TSPY transactivation. • Insights on probable mechanisms on TSPY exacerbation on cancer development in men. - Abstract: The testis-specific protein Y-encoded (TSPY) is a repetitive gene located on the gonadoblastoma region of the Y chromosome, and has been considered to be the putative gene for this oncogenic locus on the male-only chromosome. It is expressed in spermatogonial cells and spermatocytes in normal human testis, but abundantly in gonadoblastoma, testicular germ cell tumors and a variety of somatic cancers, including melanoma, hepatocellular carcinoma and prostate cancer. Various studies suggest that TSPY accelerates cell proliferation and growth, and promotes tumorigenesis. In this report, we show that TSPY could bind directly to the chromatin/DNA at exon 1 of its own gene, and greatly enhance the transcriptional activities of the endogenous gene in the LNCaP prostate cancer cells. Domain mapping analyses of TSPY have localized the critical and sufficient domain to the SET/NAP-domain. These results suggest that TSPY could efficiently amplify its expression and oncogenic functions through a positive feedback loop, and contribute to the overall tumorigenic processes when it is expressed in various human cancers.

  20. Relations between the loop transposition of DNA G-quadruplex and the catalytic function of DNAzyme.

    Science.gov (United States)

    Cheng, Mingpan; Zhou, Jun; Jia, Guoqing; Ai, Xuanjun; Mergny, Jean-Louis; Li, Can

    2017-08-01

    The structures of DNA G-quadruplexes are essential for their functions in vivo and in vitro. Our present study revealed that sequential order of the three G-quadruplex loops, that is, loop transposition, could be a critical factor to determinate the G-quadruplex conformation and consequently improved the catalytic function of G-quadruplex based DNAzyme. In the presence of 100mM K(+), loop transposition induced one of the G-quadruplex isomers which shared identical loops but differed in the sequential order of loops into a hybrid topology while the others into predominately parallel topologies. (1)D NMR spectroscopy and mutation analysis suggested that the hydrogen bonding from loops residues with nucleotides in flanking sequences may be responsible for the stabilization of the different conformations. A well-known DNAzyme consisting of G-quadruplex and hemin (Ferriprotoporphyrin IX chloride) was chosen to test the catalytic function. We found that the loop transposition could enhance the reaction rate obviously by increasing the hemin binding affinity to G-quadruplex. These findings disclose the relations between the loop transposition, G-quadruplex conformation and catalytic function of DNAzyme. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Functional characterization of antibodies against Neisseria gonorrhoeae opacity protein loops.

    Directory of Open Access Journals (Sweden)

    Jessica G Cole

    Full Text Available BACKGROUND: The development of a gonorrhea vaccine is challenged by the lack of correlates of protection. The antigenically variable neisserial opacity (Opa proteins are expressed during infection and have a semivariable (SV and highly conserved (4L loop that could be targeted in a vaccine. Here we compared antibodies to linear (Ab(linear and cyclic (Ab(cyclic peptides that correspond to the SV and 4L loops and selected hypervariable (HV(2 loops for surface-binding and protective activity in vitro and in vivo. METHODS/FINDINGS: Ab(SV cyclic bound a greater number of different Opa variants than Ab(SV linear, including variants that differed by seven amino acids. Antibodies to the 4L peptide did not bind Opa-expressing bacteria. Ab(SV (cyclic and Ab(HV2 (cyclic, but not Ab(SV (linear or Ab(HV2 linear agglutinated homologous Opa variants, and Ab(HV2BD (cyclic but not Ab(HV2BD (linear blocked the association of OpaB variants with human endocervical cells. Only Ab(HV2BD (linear were bactericidal against the serum resistant parent strain. Consistent with host restrictions in the complement cascade, the bactericidal activity of Ab(HV2BD (linear was increased 8-fold when rabbit complement was used. None of the antibodies was protective when administered vaginally to mice. Antibody duration in the vagina was short-lived, however, with <50% of the antibodies recovered 3 hrs post-administration. CONCLUSIONS: We conclude that an SV loop-specific cyclic peptide can be used to induce antibodies that recognize a broad spectrum of antigenically distinct Opa variants and have agglutination abilities. HV(2 loop-specific cyclic peptides elicited antibodies with agglutination and adherence blocking abilities. The use of human complement when testing the bactericidal activity of vaccine-induced antibodies against serum resistant gonococci is also important.

  2. The cys-loop ligand-gated ion channel gene superfamily of the red flour beetle, Tribolium castaneum

    Directory of Open Access Journals (Sweden)

    Sattelle David B

    2007-09-01

    Full Text Available Abstract Background Members of the cys-loop ligand-gated ion channel (cys-loop LGIC superfamily mediate chemical neurotransmission and are studied extensively as potential targets of drugs used to treat neurological disorders such as Alzheimer's disease. Insect cys-loop LGICs are also of interest as they are targets of highly successful insecticides. The red flour beetle, Tribolium castaneum, is a major pest of stored agricultural products and is also an important model organism for studying development. Results As part of the T. castaneum genome sequencing effort, we have characterized the beetle cys-loop LGIC superfamily which is the third insect superfamily to be described after those of Drosophila melanogaster and Apis mellifera, and also the largest consisting of 24 genes. As with Drosophila and Apis, Tribolium possesses ion channels gated by acetylcholine, γ-amino butyric acid (GABA, glutamate and histamine as well as orthologs of the Drosophila pH-sensitive chloride channel subunit (pHCl, CG8916 and CG12344. Similar to Drosophila and Apis, Tribolium cys-loop LGIC diversity is broadened by alternative splicing although the beetle orthologs of RDL and GluCl possess more variants of exon 3. Also, RNA A-to-I editing was observed in two Tribolium nicotinic acetylcholine receptor subunits, Tcasα6 and Tcasβ1. Editing in Tcasα6 is evolutionarily conserved with D. melanogaster, A. mellifera and Heliothis virescens, whereas Tcasβ1 is edited at a site so far only observed in the beetle. Conclusion Our findings reveal that in diverse insect species the cys-loop LGIC superfamily has remained compact with only minor changes in gene numbers. However, alternative splicing, RNA editing and the presence of divergent subunits broadens the cys-loop LGIC proteome and generates species-specific receptor isoforms. These findings on Tribolium castaneum enhance our understanding of cys-loop LGIC functional genomics and provide a useful basis for the

  3. THUMB-LOOPS UP FOR CATALYSIS: A STRUCTURE/FUNCTION INVESTIGATION OF A FUNCTIONAL LOOP MOVEMENT IN A GH11 XYLANASE

    Directory of Open Access Journals (Sweden)

    Gabriel Paës

    2012-07-01

    Full Text Available Dynamics is a key feature of enzyme catalysis. Unfortunately, current experimental and computational techniques do not yet provide a comprehensive understanding and description of functional macromolecular motions. In this work, we have extended a novel computational technique, which combines molecular modeling methods and robotics algorithms, to investigate functional motions of protein loops. This new approach has been applied to study the functional importance of the so-called thumb-loop in the glycoside hydrolase family 11 xylanase from Thermobacillus xylanilyticus (Tx-xyl. The results obtained provide new insight into the role of the loop in the glycosylation/deglycosylation catalytic cycle, and underline the key importance of the nature of the residue located at the tip of the thumb-loop. The effect of mutations predicted in silico has been validated by in vitro site-directed mutagenesis experiments. Overall, we propose a comprehensive model of Tx-xyl catalysis in terms of substrate and product dynamics by identifying the action of the thumb-loop motion during catalysis.

  4. Chaperonin function depends on structure and disorder in co-chaperonin mobile loops.

    Science.gov (United States)

    Landry, S J; Steede, N K; Garaudy, A M; Maskos, K; Viitanen, P V

    1999-01-01

    Co-chaperonins from diverse organisms exhibit mobile loops which fold into a beta hairpin conformation upon binding to the chaperonin. GroES, Gp31, and human Hsp10 mobile loops exhibit a preference for the beta hairpin conformation in the free co-chaperonins, and the conformational dynamics of the human Hsp10 mobile loop appear to be restricted by nascent hairpin formation. Backbone conformational entropy must weigh against binding of co-chaperonins to chaperonins, and thus the conformational preferences of the loops may strongly influence chaperonin-binding affinity. Indeed, subtle mutations in the loops change GroEL-binding affinity and cause defects in chaperonin function, and these defects can be suppressed by mutations in GroEL which compensate for the changes in affinity. The fact that high-affinity co-chaperonin binding impairs chaperonin function has implications for the mechanism of chaperonin-assisted protein folding.

  5. HP1a/KDM4A is involved in the autoregulatory loop of the oncogene gene c-Jun.

    Science.gov (United States)

    Liu, Yan; Zhang, Daoyong

    2015-01-01

    The proto-oncogene c-Jun plays crucial roles in tumorigenesis, and its aberrant expression has been implicated in many cancers. Previous studies have shown that the c-Jun gene is positively autoregulated by its product. Notably, it has also been reported that c-Jun proteins are enriched in its gene body region. However, the role of c-Jun proteins in its gene body region has yet to be uncovered. HP1a is an evolutionarily conserved heterochromatin-associated protein, which plays an essential role in heterochromatin-mediated gene silencing. Interestingly, accumulating evidence shows that HP1a is also localized to euchromatic regions to positively regulate gene transcription. However, the underlying mechanism has not been defined. In this study, we demonstrate that HP1a is involved in the positive autoregulatory loop of the Jra gene, the c-Jun homolog in Drosophila. Jra recruits the HP1a/KDM4A complex to its gene body region upon osmotic stress to reduce H3K36 methylation levels and disrupt H3K36 methylation-dependent histone deacetylation, resulting in high levels of histone acetylation in the Jra gene body region, thus promoting gene transcription. These results not only expand our knowledge toward the mechanism of c-Jun regulation, but also reveal the mechanism by which HP1a exerts its positive regulatory function in gene expression.

  6. Gauge Coupling Beta Functions in the Standard Model to Three Loops

    CERN Document Server

    Mihaila, Luminita N; Steinhauser, Matthias

    2012-01-01

    In this paper we compute the three-loop corrections to the beta functions of the three gauge couplings in the Standard Model of particle physics using the minimal subtraction scheme and taking into account Yukawa and Higgs self couplings.

  7. On the Green's function and iterative solutions of Loop Quantum Cosmology

    OpenAIRE

    Shojai, F.; Shojai, A.

    2006-01-01

    Here we shall find the Green’s function of the difference equation of loop quantum cosmology. To illustrate how to use it, we shall obtain an iterative solution for closed model and evaluate its corresponding Bohmian trajectory.

  8. PROAPOPTOTIC FUNCTION OF FHIT GENE

    Institute of Scientific and Technical Information of China (English)

    QIU Zhe-fu; HAN De-min; ZHANG Luo; ZHANG Wei

    2006-01-01

    Tumor suppressor gene plays an important role in maintaining the homeostasis between cell loss and growth. Fragile in maintaining the homeostasis between cell loss and growth. Fragile histidine triad (FHIT) gene found recently was studied in a deep going way; it becomes the focus as a result of its roleof ep going way; it becomes the focus as a result of its roleof anti-tumor in human various type of tissue. Due to the high efficiency of FHIT gene benefiting the anti-tumor, it is proposed gh efficiency of FHIT gene benefiting the anti-tumor, it is proposed as a candidate of tumor suppressor gene though there are several opposite opinions.several opposite opinions. We stress the summary of some properties of FHIT gene on proapoptosis according to the published data which showed gene on proapoptosis according to the published data which showed the stronger proapoptotic function of FHIT gene; the apoptosis induced by FHIT depends on the expression level and status of ene; the apoptosis induced by FHIT depends on the expression level and status of FHIT; and FHIT gene can alternate the cell cycling properties and reduce the tumorigenic potential; the apoptotic process e can alternate the cell cycling properties and reduce the tumorigenic potential; the apoptotic process induced by FHIT has no relation to p53 gene. In a ward, in consideration of its multiple functions against malignancies, FHIT in consideration of its multiple functions against malignancies, FHIT gene deserves attention and exploration as a selective target for searching the mechanism of tumorigenesis and clinical et for searching the mechanism of tumorigenesis and clinical therapeutic applications in further.le histidine triad (FHIT) gene; Apoptosis; Tumorigenesis; Tumor suppressor gene deserves attention and exploration as a selective target for searching the mechanism of tumorigenesis and clinical therapeutic applications in further.

  9. On the four-loop strong coupling beta-function in the SM

    CERN Document Server

    Bednyakov, A V

    2016-01-01

    In the talk the leading four-loop contribution to the beta-function of the strong coupling in the SM is discussed. Some details of calculation techniques are provided. Special attention is paid to the ambiguity due to utilized $\\gamma_5$ treatment and a particular prescription with anticommuting $\\gamma_5$ is advocated. As a by-product of our computation the four-loop beta-function in QCD with "gluino" is also obtained.

  10. Mutations in the catalytic loop HRD motif alter the activity and function of Drosophila Src64.

    Directory of Open Access Journals (Sweden)

    Taylor C Strong

    Full Text Available The catalytic loop HRD motif is found in most protein kinases and these amino acids are predicted to perform functions in catalysis, transition to, and stabilization of the active conformation of the kinase domain. We have identified mutations in a Drosophila src gene, src64, that alter the three HRD amino acids. We have analyzed the mutants for both biochemical activity and biological function during development. Mutation of the aspartate to asparagine eliminates biological function in cytoskeletal processes and severely reduces fertility, supporting the amino acid's critical role in enzymatic activity. The arginine to cysteine mutation has little to no effect on kinase activity or cytoskeletal reorganization, suggesting that the HRD arginine may not be critical for coordinating phosphotyrosine in the active conformation. The histidine to leucine mutant retains some kinase activity and biological function, suggesting that this amino acid may have a biochemical function in the active kinase that is independent of its side chain hydrogen bonding interactions in the active site. We also describe the phenotypic effects of other mutations in the SH2 and tyrosine kinase domains of src64, and we compare them to the phenotypic effects of the src64 null allele.

  11. Function analysis of unknown genes

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, A.

    2002-01-01

      This thesis entitled "Function analysis of unknown genes" presents the use of proteome analysis for the characterisation of yeast (Saccharomyces cerevisiae) genes and their products (proteins especially those of unknown function). This study illustrates that proteome analysis can be used...... to describe different aspects of molecular biology of the cell, to study changes that occur in the cell due to overexpression or deletion of a gene and to identify various protein modifications. The biological questions and the results of the described studies show the diversity of the information that can...... genes and proteins. It reports the first global proteome database collecting 36 yeast single gene deletion mutants and selecting over 650 differences between analysed mutants and the wild type strain. The obtained results show that two-dimensional gel electrophoresis and mass spectrometry based proteome...

  12. Loop structures in the 5' untranslated region and antisense RNA mediate pilE gene expression in Neisseria gonorrhoeae.

    Science.gov (United States)

    Masters, Thao L; Wachter, Jenny; Hill, Stuart A

    2016-11-01

    Regulation of the Neisseria gonorrhoeae pilE gene is ill-defined. In this study, post-transcriptional effects on expression were assessed. In silico analysis predicts the formation of three putative stable stem-loop structures with favourable free energies within the 5' untranslated region of the pilE message. Using quantitative reverse transcriptase PCR analyses, we show that each loop structure forms, with introduced destabilizing stem-loop mutations diminishing loop stability. Utilizing a series of pilE translational fusions, deletion of either loop 1 or loop 2 caused a significant reduction of pilE mRNA resulting in reduced expression of the reporter gene. Consequently, the formation of the loops apparently protects the pilE transcript from degradation. Putative loop 3 contains the pilE ribosomal binding site. Consequently, its formation may influence translation. Analysis of a small RNA transcriptome revealed an antisense RNA being produced upstream of the pilE promoter that is predicted to hybridize across the 5' untranslated region loops. Insertional mutants were created where the antisense RNA is not transcribed. In these mutants, pilE transcript levels are greatly diminished, with any residual message apparently not being translated. Complementation of these insertion mutants in trans with the antisense RNA gene facilitates pilE translation yielding a pilus + phenotype. Overall, this study demonstrates a complex relationship between loop-dependent transcript protection and antisense RNA in modulating pilE expression levels.

  13. Hexagon remainder function in the limit of self-crossing up to three loops

    CERN Document Server

    Dorn, Harald

    2011-01-01

    We consider Wilson loops in planar N=4 SYM for null polygons in the limit of two crossing edges. The analysis is based on a renormalisation group technique. We show that the previously obtained result for the leading and next-leading divergent term of the two loop hexagon remainder is in full agreement with the appropriate continuation of the exact analytic formula for this quantity. Furthermore, we determine the coefficients of the leading and next-leading singularity for the three loop remainder function for null n-gons with n >= 6.

  14. Appell functions and the scalar one-loop three-point integrals in Feynman diagrams

    Energy Technology Data Exchange (ETDEWEB)

    Cabral-Rosetti, L G [Departamento de Posgrado, Centro Interdisciplinario de Investigacion y Docencia en Educacion Tecnica (CIIDET), Av. Universidad 282 Pte., Col. Centro, A. Postal 752, C.P. 76000, Santiago de Queretaro, Qro. (Mexico); Sanchis-Lozano, M A [Departamento de Fisica Teorica and IFIC, Centro Mixto Universidad de Valencia-CSIC, 46100 Burjassot, Valencia (Spain)

    2006-05-15

    The scalar three-point function appearing in one-loop Feynman diagrams is compactly expressed in terms of a generalized hypergeometric function of two variables. Use is made of the connection between such Appell function and dilogarithms coming from a previous investigation. Special cases are obtained for particular values of internal masses and external momenta.

  15. Appell Functions and the Scalar One-Loop Three-point Integrals in Feynman Diagrams

    CERN Document Server

    Cabral-Rosetti, L G; Cabral-Rosetti, Luis G.; Sanchis-Lozano, Miguel A.

    2006-01-01

    The scalar three-point function appearing in one-loop Feynman diagrams is compactly expressed in terms of a generalized hypergeometric function of two variables. Use is made of the connection between such Appell function and dilogarithms coming from a previous investigation. Special cases are obtained for particular values of internal masses and external momenta.

  16. Two-loop RG functions of the massive φ4 field theory in general dimensions

    Directory of Open Access Journals (Sweden)

    M.A. Shpot

    2010-01-01

    Full Text Available Two-loop Feynman integrals of the massive φ4d field theory are explicitly obtained for generic space dimensions d. Corresponding renormalization-group functions are expressed in a compact form in terms of Gauss hypergeometric functions. A number of interesting and useful relations are given for these integrals as well as for several special mathematical functions and constants.

  17. Symmetric point four-point functions at one loop in QCD

    Science.gov (United States)

    Gracey, J. A.

    2017-03-01

    We evaluate the quartic ghost and quark Green's functions as well as the gluon-ghost, gluon-quark and ghost-quark four-point functions of quantum chromodynamics at one loop at the fully symmetric point in a linear covariant gauge. Similar expressions for the analogous Green's functions in quantum electrodynamics are also provided.

  18. A systematic classification of Plasmodium falciparum P-loop NTPases: structural and functional correlation

    Directory of Open Access Journals (Sweden)

    Chauhan Virander S

    2009-04-01

    Full Text Available Abstract Background The P-loop NTPases constitute one of the largest groups of globular protein domains that play highly diverse functional roles in most of the organisms. Even with the availability of nearly 300 different Hidden Markov Models representing the P-loop NTPase superfamily, not many P-loop NTPases are known in Plasmodium falciparum. A number of characteristic attributes of the genome have resulted into the lack of knowledge about this functionally diverse, but important class of proteins. Method In the study, protein sequences with characteristic motifs of NTPase domain (Walker A and Walker B are computationally extracted from the P. falciparum database. A detailed secondary structure analysis, functional classification, phylogenetic and orthology studies of the NTPase domain of repertoire of 97 P. falciparum P-loop NTPases is carried out. Results Based upon distinct sequence features and secondary structure profile of the P-loop domain of obtained sequences, a cladistic classification is also conceded: nucleotide kinases and GTPases, ABC and SMC family, SF1/2 helicases, AAA+ and AAA protein families. Attempts are made to identify any ortholog(s for each of these proteins in other Plasmodium sp. as well as its vertebrate host, Homo sapiens. A number of P. falciparum P-loop NTPases that have no homologue in the host, as well as those annotated as hypothetical proteins and lack any characteristic functional domain are identified. Conclusion The study suggests a strong correlation between sequence and secondary structure profile of P-loop domains and functional roles of these proteins and thus provides an opportunity to speculate the role of many hypothetical proteins. The study provides a methodical framework for the characterization of biologically diverse NTPases in the P. falciparum genome. The efforts made in the analysis are first of its kind; and the results augment to explore the functional role of many of these proteins from

  19. The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops.

    Science.gov (United States)

    Pokhilko, Alexandra; Fernández, Aurora Piñas; Edwards, Kieron D; Southern, Megan M; Halliday, Karen J; Millar, Andrew J

    2012-03-06

    Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene Pseudo-Response Regulator 9 was repressed by an evening gene, previously identified with Timing Of CAB Expression1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes Late Elongated Hypocotyl and Circadian Clock Associated1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure.

  20. One-loop $\\mathbf{\\beta}$-function of noncommutative scalar $QED_{4}$

    CERN Document Server

    Ghasemkhani, M; Rahmanpour, V; Nouri, E

    2016-01-01

    In this paper we consider the $\\beta$-function at one-loop approximation for noncommutative scalar QED. The renormalization of the full theory, including the basic vertices, and the renormalization group equation are fully established. Next, the complete set of the one-loop diagrams corresponding to the first-order radiative corrections to the basic functions is considered: gauge, charged scalar and ghost fields self-energies, three- and four-point vertex functions $\\left$ and $\\left$, respectively. We pay special attention to the noncommutative contributions to the renormalization constants. To conclude, the one-loop $\\beta$-function of noncommutative scalar QED is then computed and comparison to known results is presented.

  1. Loop expansion of the average effective action in the functional renormalization group approach

    Science.gov (United States)

    Lavrov, Peter M.; Merzlikin, Boris S.

    2015-10-01

    We formulate a perturbation expansion for the effective action in a new approach to the functional renormalization group method based on the concept of composite fields for regulator functions being their most essential ingredients. We demonstrate explicitly the principal difference between the properties of effective actions in these two approaches existing already on the one-loop level in a simple gauge model.

  2. Loop expansion of average effective action in functional renormalization group approach

    CERN Document Server

    Lavrov, Peter M

    2015-01-01

    We formulate a perturbation expansion for the effective action in new approach to the functional renormalization group (FRG) method based on concept of composite fields for regulator functions being therein most essential ingredients. We demonstrate explicitly the principal difference between properties of effective actions in these two approaches existing already on the one-loop level in a simple gauge model.

  3. Evolution of double positive autoregulatory feedback loops in CYCLOIDEA2 clade genes is associated with the origin of floral zygomorphy.

    Science.gov (United States)

    Yang, Xia; Pang, Hong-Bo; Liu, Bo-Ling; Qiu, Zhi-Jing; Gao, Qiu; Wei, Lai; Dong, Yang; Wang, Yin-Zheng

    2012-05-01

    Members of the CYCLOIDEA2 (CYC2) clade of the TEOSINTE BRANCHED1, CYCLOIDEA, and PCF transcription factor genes are widely involved in controlling floral zygomorphy, a key innovation in angiosperm evolution, depending on their persistently asymmetric expression in the corresponding floral domains. However, it is unclear how this asymmetric expression is maintained throughout floral development. Selecting Primulina heterotricha as a model, we examined the expression and function of two CYC2 genes, CYC1C and CYC1D. We analyzed the role of their promoters in protein-DNA interactions and transcription activation using electrophoresis mobility shift assays, chromatin immunoprecipitation, and transient gene expression assays. We find that CYC1C and CYC1D positively autoregulate themselves and cross-regulate each other. Our results reveal a double positive autoregulatory feedback loop, evolved for a pair of CYC2 genes to maintain their expression in developing flowers. Further comparative genome analyses, together with the available expression and function data of CYC2 genes in the core eudicots, suggest that this mechanism might have led to the independent origins of floral zygomorphy, which are associated with plant-insect coevolution and the adaptive radiation of angiosperms.

  4. Loop A Is Critical for the Functional Interaction of Two Beta vulgaris PIP Aquaporins

    Science.gov (United States)

    Jozefkowicz, Cintia; Rosi, Pablo; Sigaut, Lorena; Soto, Gabriela; Pietrasanta, Lía Isabel; Amodeo, Gabriela; Alleva, Karina

    2013-01-01

    Research done in the last years strongly support the hypothesis that PIP aquaporin can form heterooligomeric assemblies, specially combining PIP2 monomers with PIP1 monomers. Nevertheless, the structural elements involved in the ruling of homo versus heterooligomeric organization are not completely elucidated. In this work we unveil some features of monomer-monomer interaction in Beta vulgaris PIP aquaporins. Our results show that while BvPIP2;2 is able to interact with BvPIP1;1, BvPIP2;1 shows no functional interaction. The lack of functional interaction between BvPIP2;1 and BvPIP1;1 was further corroborated by dose-response curves of water permeability due to aquaporin activity exposed to different acidic conditions. We also found that BvPIP2;1 is unable to translocate BvPIP1;1-ECFP from an intracellular position to the plasma membrane when co-expressed, as BvPIP2;2 does. Moreover we postulate that the first extracellular loop (loop A) of BvPIP2;1, could be relevant for the functional interaction with BvPIP1;1. Thus, we investigate BvPIP2;1 loop A at an atomic level by Molecular Dynamics Simulation (MDS) and by direct mutagenesis. We found that, within the tetramer, each loop A presents a dissimilar behavior. Besides, BvPIP2;1 loop A mutants restore functional interaction with BvPIP1;1. This work is a contribution to unravel how PIP2 and PIP1 interact to form functional heterooligomeric assemblies. We postulate that BvPIP2;1 loop A is relevant for the lack of functional interaction with BvPIP1;1 and that the monomer composition of PIP assemblies determines their functional properties. PMID:23483963

  5. Semiclassical partition function for strings dual to Wilson loops with small cusps in ABJM

    Science.gov (United States)

    Aguilera-Damia, Jeremías; Correa, Diego H.; Silva, Guillermo A.

    2015-03-01

    We compute the 1-loop partition function for strings in , whose worldsheets end along a line with small cusp angles in the boundary of AdS. We obtain these 1-loop results in terms of the vacuum energy for on-shell modes. Our results verify the proposal by Lewkowycz and Maldacena in arXiv:1312.5682 for the exact Bremsstrahlung function up to the next to leading order in the strong coupling expansion. The agreement is observed for cusps distorting either the 1/2 BPS or the 1/6 BPS Wilson line.

  6. Semiclassical partition function for strings dual to Wilson loops with small cusps in ABJM

    CERN Document Server

    Aguilera-Damia, Jeremias; Silva, Guillermo A

    2014-01-01

    We compute the 1-loop partition function for strings in $AdS_4\\times\\mathbb{CP}^3$, whose worldsheets end along a line with small cusp angles in the boundary of AdS. We obtain these 1-loop results in terms of the vacuum energy for on-shell modes. Our results verify the proposal by Lewkowycz and Maldacena in arXiv:1312.5682 for the exact Bremsstrahlung function up to the next to leading order in the strong coupling expansion. The agreement is observed for cusps distorting either the 1/2 BPS or the 1/6 BPS Wilson line.

  7. SATB1 packages densely-looped, transciptionally-active chromatinfor coordinated expression of cytokine genes

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Shutao; Lee, Charles C.; Kohwi-Shigematsu, Terumi

    2006-05-23

    SATB1 is an important regulator of nuclear architecture that anchors specialized DNA sequences onto its cage-like network and recruits chromatin remodeling/modifying factors to control gene transcription. We studied the role of SATB1 in regulating the coordinated expression of Il5, Il4, and Il13 from the 200kb cytokine gene cluster region of mouse chromosome 11 during T-helper 2 (Th2)-cell activation. We show that upon cell activation, SATB1 is rapidly induced to form a unique transcriptionally-active chromatin structure that includes the cytokine gene region. Chromatin is folded into numerous small loops all anchored by SATB1, is histone H3 acetylated at lysine 9/14, and associated with Th2-specific factors, GATA3, STAT6, c-Maf, the chromatin-remodeling enzyme Brg-1, and RNA polymerase II across the 200kb region. Before activation, the chromatin displays some of these features, such as association with GATA3 and STAT6, but these were insufficient for cytokine gene expression. Using RNA interference (RNAi), we show that upon cell activation, SATB1 is not only required for chromatin folding into dense loops, but also for c-Maf induction and subsequently for Il4, Il5, and Il13 transcription. Our results show that SATB1 is an important determinant for chromatin architecture that constitutes a novel higher-order, transcriptionally-active chromatin structure upon Th2-cell activation.

  8. Study of the Six-Loop Beta Function of the $\\lambda\\phi^4_4$ Theory

    OpenAIRE

    Shrock, Robert

    2016-01-01

    We investigate whether the six-loop beta function of the $\\lambda \\phi^4_4$ theory exhibits evidence for an ultraviolet zero. As part of our analysis, we calculate and analyze Pad\\'e approximants to this beta function. Extending our earlier results at the five-loop level, we find that in the range of $\\lambda$ where the perturbative calculation of the six-loop beta function is reliable, the theory does not exhibit robust evidence for an ultraviolet zero.

  9. Study of the Six-Loop Beta Function of the $\\lambda\\phi^4_4$ Theory

    CERN Document Server

    Shrock, Robert

    2016-01-01

    We investigate whether the six-loop beta function of the $\\lambda \\phi^4_4$ theory exhibits evidence for an ultraviolet zero. As part of our analysis, we calculate and analyze Pad\\'e approximants to this beta function. Extending our earlier results at the five-loop level, we find that in the range of $\\lambda$ where the perturbative calculation of the six-loop beta function is reliable, the theory does not exhibit robust evidence for an ultraviolet zero.

  10. Supersymmetric Localization for BPS Black Hole Entropy: 1-loop Partition Function from Vector Multiplets

    CERN Document Server

    Gupta, Rajesh Kumar; Jeon, Imtak

    2015-01-01

    We use the techniques of supersymmetric localization to compute the BPS black hole entropy in N=2 supergravity. We focus on the n_v+1 vector multiplets on the black hole near horizon background which is AdS_2 x S^2 space. We find the localizing saddle point of the vector multiplets by solving the localization equations, and compute the exact one loop partition function on the saddle point. Furthermore, we propose the appropriate functional integration measure. Through this measure, the one loop determinant is written in terms of the radius of the physical metric, which depends on the localizing saddle point value of the vector multiplets. The result for the one loop determinant is consistent with the logarithmic corrections to the BPS black hole entropy from vector multiplets.

  11. The dynamic mechanism of presenilin-function: Sensitive gate dynamics and loop unplugging control protein access

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2016-01-01

    molecular dynamics in an explicit membrane with particular account of the as yet unexplored loop dynamics. We find that mature PSEN1 contains multiple distinct conformational states whereas non-mature PSEN1 is a typical one-state protein. We confirm a previously suggested gating mechanism, and find......There is no molecular explanation for the many presenilin 1 (PSEN1) mutations causing Alzheimer's disease, but both gain of function relating to amyloid production and loss of isolated PSEN1 function have been implied. We report here the first detailed dynamic all-atom model of mature PSEN1 from...... that the 106-131 loop acts as a "hinge" for the TM2 and TM6 "doors". More importantly, we identify an unplugging mechanism of the Exon 9 loop associated only with mature PSEN1. Proper opening of both the "gate" and "plug" in the membrane produces channel-like morphologies and access to the catalytic aspartates...

  12. A work-loop method for characterizing leg function during sagittal plane movements.

    Science.gov (United States)

    Maykranz, Daniel; Grimmer, Sten; Seyfarth, Andre

    2013-10-01

    The work-loop method is frequently used to determine the mechanical work performed by a system, for instance, when analyzing muscles or describing the work balance at the joint level. While for these examples usually only one-dimensional movements are investigated, for two- or three-dimensional movements, such as leg function during walking and running, the work-loop has to be adapted. In this paper, we present an analytical derivation that extends the work-loop method to two-dimensional sagittal plane movements. Three effects contribute to the mechanical work of the leg: (1) forces directed along the leg axis, (2) forces acting perpendicular to the leg axis, and (3) a shift of the center of pressure (COP) during stance. These three contributors to the mechanical work performed can be interpreted as three general tasks of the leg. To demonstrate the new work-loop method, we analyzed experimental data on hopping, running and walking. The results indicate that the proposed new generalized work-loop concept is suitable for describing the overall mechanical work performed on the COM during stance with energy consistent net work balances. Depending on the type of gait, specific contributions of each work term were found that characterize leg function during locomotion.

  13. Correlating Expression Data with Gene Function Using Gene Ontology

    Institute of Scientific and Technical Information of China (English)

    LIU,Qi; DENG,Yong; WANG,Chuan; SHI,Tie-Liu; LI,Yi-Xue

    2006-01-01

    Clustering is perhaps one of the most widely used tools for microarray data analysis. Proposed roles for genes of unknown function are inferred from clusters of genes similarity expressed across many biological conditions.However, whether function annotation by similarity metrics is reliable or not and to what extent the similarity in gene expression patterns is useful for annotation of gene functions, has not been evaluated. This paper made a comprehensive research on the correlation between the similarity of expression data and of gene functions using Gene Ontology. It has been found that although the similarity in expression patterns and the similarity in gene functions are significantly dependent on each other, this association is rather weak. In addition, among the three categories of Gene Ontology, the similarity of expression data is more useful for cellular component annotation than for biological process and molecular function. The results presented are interesting for the gene functions prediction research area.

  14. [Structural and functional findings in experimental blind loop syndrome].

    Science.gov (United States)

    Riecken, E O

    1984-01-01

    Proximal and distal the blindsack a villus and crypt prolongation connected with a decreasing absorption of octanoate could be pointed out. The structural changes are very likely a hyperplasia of the mucosa. Within the blindsack a hyperplasia in connection with an accelerated proliferation of cells and an almost three and a halffold enlargement of the surface of the villi could be found. Simultaneously, the mucosa was damaged. An artificial bile duct as well as a neomycin therapy caused a decrease of the structural and functional changes but did not prevent the mucosal hyperplasia. These results are explained with adaptive processes of the small intestinal mucosa in a sense of hyperregeneration alterations of sprue typus.

  15. Phylogeny, Functional Annotation, and Protein Interaction Network Analyses of the Xenopus tropicalis Basic Helix-Loop-Helix Transcription Factors

    Directory of Open Access Journals (Sweden)

    Wuyi Liu

    2013-01-01

    Full Text Available The previous survey identified 70 basic helix-loop-helix (bHLH proteins, but it was proved to be incomplete, and the functional information and regulatory networks of frog bHLH transcription factors were not fully known. Therefore, we conducted an updated genome-wide survey in the Xenopus tropicalis genome project databases and identified 105 bHLH sequences. Among the retrieved 105 sequences, phylogenetic analyses revealed that 103 bHLH proteins belonged to 43 families or subfamilies with 46, 26, 11, 3, 15, and 4 members in the corresponding supergroups. Next, gene ontology (GO enrichment analyses showed 65 significant GO annotations of biological processes and molecular functions and KEGG pathways counted in frequency. To explore the functional pathways, regulatory gene networks, and/or related gene groups coding for Xenopus tropicalis bHLH proteins, the identified bHLH genes were put into the databases KOBAS and STRING to get the signaling information of pathways and protein interaction networks according to available public databases and known protein interactions. From the genome annotation and pathway analysis using KOBAS, we identified 16 pathways in the Xenopus tropicalis genome. From the STRING interaction analysis, 68 hub proteins were identified, and many hub proteins created a tight network or a functional module within the protein families.

  16. Towards the five-loop beta function for a general gauge group

    Energy Technology Data Exchange (ETDEWEB)

    Luthe, Thomas [Karlsruher Institut fuer Technologie (Germany). Inst. fuer Theoretische Teilchenphysik; Maier, Andreas [Durham Univ. (United Kingdom). Inst. for Particle Physics Phenomenology; Marquard, Peter [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Schroeder, York [Univ. del Bio-Bio, Chillan (Chile). Grupo de Fisica de Altas Energias

    2016-06-15

    We present analytical results for the N{sup 4}{sub f} and N{sup 3}{sub f} terms of the five-loop beta function, for a general gauge group. While the former term agrees with results available from large-N{sub f} studies, the latter is new and extends the value known for SU(3) from an independent calculation.

  17. Towards the five-loop Beta function for a general gauge group

    CERN Document Server

    Luthe, Thomas; Marquard, Peter; Schroder, York

    2016-01-01

    We present analytical results for the $N_f^4$ and $N_f^3$ terms of the five-loop Beta function, for a general gauge group. While the former term agrees with results available from large-$N_f$ studies, the latter is new and extends the value known for SU(3) from an independent calculation.

  18. Wilson loop remainder function for null polygons in the limit of self-crossing

    CERN Document Server

    Dorn, Harald

    2011-01-01

    The remainder function of Wilson loops for null polygons becomes divergent if two vertices approach each other. We apply RG techniques to the limiting configuration of a contour with self-intersection. As a result for the two loop remainder we find a quadratic divergence in the logarithm of the distance between the two approaching vertices. The divergence is multiplied by a factor, which is given by a pure number plus the product of two logarithms of cross-ratios characterising the conformal geometry of the self-crossing.

  19. Surprises in the AdS algebraic curve constructions - Wilson loops and correlation functions

    Energy Technology Data Exchange (ETDEWEB)

    Janik, Romuald A., E-mail: romuald@th.if.uj.edu.pl [Institute of Physics, Jagiellonian University, ul. Reymonta 4, 30-059 Krakow (Poland); Institute for Advanced Studies, The Hebrew University of Jerusalem, Givat Ram Campus, 91904 Jerusalem (Israel); Laskos-Grabowski, Pawel, E-mail: plg@th.if.uj.edu.pl [Institute of Physics, Jagiellonian University, ul. Reymonta 4, 30-059 Krakow (Poland); Institute for Theoretical Physics, University of Wroclaw, pl. Maxa Borna 9, 50-204 Wroclaw (Poland)

    2012-08-21

    The algebraic curve (finite-gap) classification of rotating string solutions was very important in the development of integrability through comparison with analogous structures at weak coupling. The classification was based on the analysis of monodromy around the closed string cylinder. In this paper we show that certain classical Wilson loop minimal surfaces corresponding to the null cusp and qq{sup Macron} potential with trivial monodromy can, nevertheless, be described by appropriate algebraic curves. We also show how a correlation function of a circular Wilson loop with a local operator fits into this framework. The latter solution has identical monodromy to the pointlike BMN string and yet is significantly different.

  20. Detection of Clostridium perfringens alpha toxin gene in lambs by loop mediated isothermal amplification

    Directory of Open Access Journals (Sweden)

    B. Radhika

    2016-01-01

    Full Text Available Aim: The loop mediated isothermal amplification (LAMP was standardized for rapid detection of Clostridium perfringens. Materials and Methods: A total of 120 fecal samples were collected from enterotoxemia suspected lambs were used for screening of C. perfringens cpa gene by LAMP. The specificity of the LAMP amplified products was tested by digesting with restriction enzyme XmnI for alpha toxin gene. Results: Out of 120 samples screened 112 (93.3% samples were positive by both LAMP and polymerase chain reaction (PCR for detection of cpa gene which indicated the equal sensitivity of both the tests. The enzyme produced single cut in 162 base pair amplified product of alpha toxin gene at 81 base pair resulting in a single band in gel electrophoresis. Conclusion: Both LAMP and PCR for detection of cpa gene indicated the equal sensitivity of both the tests. Standardization of LAMP reaction for amplification of epsilon and beta toxin genes will help to identify the C. perfringens toxin types from the clinical samples. The test could be a suitable alternative to the PCR in detection of toxin types without the help of sophisticated machinery like thermal cycler. Considering its simplicity in operation and high sensitivity, there is the potential use of this technique in clinical diagnosis and surveillance of infectious diseases.

  1. Three-loop SM beta-functions for matrix Yukawa couplings

    Directory of Open Access Journals (Sweden)

    A.V. Bednyakov

    2014-10-01

    Full Text Available We present the extension of our previous results for three-loop Yukawa coupling beta-functions to the case of complex Yukawa matrices describing the flavour structure of the SM. The calculation is carried out in the context of unbroken phase of the SM with the help of the MINCER program in a general linear gauge and cross-checked by means of MATAD/BAMBA codes. In addition, ambiguities in Yukawa matrix beta-functions are studied.

  2. Loop mediated isothermal amplification: An innovative gene amplification technique for animal diseases

    Directory of Open Access Journals (Sweden)

    Pravas Ranjan Sahoo

    2016-05-01

    Full Text Available India being a developing country mainly depends on livestock sector for its economy. However, nowadays, there is emergence and reemergence of more transboundary animal diseases. The existing diagnostic techniques are not so quick and with less specificity. To reduce the economy loss, there should be a development of rapid, reliable, robust diagnostic technique, which can work with high degree of sensitivity and specificity. Loop mediated isothermal amplification assay is a rapid gene amplification technique that amplifies nucleic acid under an isothermal condition with a set of designed primers spanning eight distinct sequences of the target. This assay can be used as an emerging powerful, innovative gene amplification diagnostic tool against various pathogens of livestock diseases. This review is to highlight the basic concept and methodology of this assay in livestock disease.

  3. Loop mediated isothermal amplification: An innovative gene amplification technique for animal diseases.

    Science.gov (United States)

    Sahoo, Pravas Ranjan; Sethy, Kamadev; Mohapatra, Swagat; Panda, Debasis

    2016-05-01

    India being a developing country mainly depends on livestock sector for its economy. However, nowadays, there is emergence and reemergence of more transboundary animal diseases. The existing diagnostic techniques are not so quick and with less specificity. To reduce the economy loss, there should be a development of rapid, reliable, robust diagnostic technique, which can work with high degree of sensitivity and specificity. Loop mediated isothermal amplification assay is a rapid gene amplification technique that amplifies nucleic acid under an isothermal condition with a set of designed primers spanning eight distinct sequences of the target. This assay can be used as an emerging powerful, innovative gene amplification diagnostic tool against various pathogens of livestock diseases. This review is to highlight the basic concept and methodology of this assay in livestock disease.

  4. Regularization independent analysis of the origin of two loop contributions to N=1 Super Yang-Mills beta function

    Energy Technology Data Exchange (ETDEWEB)

    Fargnoli, H.G.; Sampaio, Marcos; Nemes, M.C. [Federal University of Minas Gerais, ICEx, Physics Department, P.O. Box 702, Belo Horizonte, MG (Brazil); Hiller, B. [Coimbra University, Faculty of Science and Technology, Physics Department, Center of Computational Physics, Coimbra (Portugal); Baeta Scarpelli, A.P. [Setor Tecnico-Cientifico, Departamento de Policia Federal, Lapa, Sao Paulo (Brazil)

    2011-05-15

    We present both an ultraviolet and an infrared regularization independent analysis in a symmetry preserving framework for the N=1 Super Yang-Mills beta function to two loop order. We show explicitly that off-shell infrared divergences as well as the overall two loop ultraviolet divergence cancel out, whilst the beta function receives contributions of infrared modes. (orig.)

  5. Three-point functions in ${\\cal N}=4$ SYM: the hexagon proposal at three loops

    CERN Document Server

    Eden, Burkhard

    2015-01-01

    Basso, Komatsu and Vieira recently proposed an all-loop framework for the computation of three-point functions of single-trace operators of ${\\cal N}=4$ super-Yang-Mills, the "hexagon program". This proposal results in several remarkable predictions, including the three-point function of two protected operators with an unprotected one in the $SU(2)$ and $SL(2)$ sectors. Such predictions consist of an "asymptotic" part---similar in spirit to the asymptotic Bethe Ansatz of Beisert and Staudacher for two-point functions---as well as additional finite-size "wrapping" L\\"uscher-like corrections. The focus of this paper is on such wrapping corrections, which we compute at three-loops in the $SL(2)$ sector. The resulting structure constants perfectly match the ones obtained in the literature from four-point correlators of protected operators.

  6. Protein loop modeling using a new hybrid energy function and its application to modeling in inaccurate structural environments.

    Directory of Open Access Journals (Sweden)

    Hahnbeom Park

    Full Text Available Protein loop modeling is a tool for predicting protein local structures of particular interest, providing opportunities for applications involving protein structure prediction and de novo protein design. Until recently, the majority of loop modeling methods have been developed and tested by reconstructing loops in frameworks of experimentally resolved structures. In many practical applications, however, the protein loops to be modeled are located in inaccurate structural environments. These include loops in model structures, low-resolution experimental structures, or experimental structures of different functional forms. Accordingly, discrepancies in the accuracy of the structural environment assumed in development of the method and that in practical applications present additional challenges to modern loop modeling methods. This study demonstrates a new strategy for employing a hybrid energy function combining physics-based and knowledge-based components to help tackle this challenge. The hybrid energy function is designed to combine the strengths of each energy component, simultaneously maintaining accurate loop structure prediction in a high-resolution framework structure and tolerating minor environmental errors in low-resolution structures. A loop modeling method based on global optimization of this new energy function is tested on loop targets situated in different levels of environmental errors, ranging from experimental structures to structures perturbed in backbone as well as side chains and template-based model structures. The new method performs comparably to force field-based approaches in loop reconstruction in crystal structures and better in loop prediction in inaccurate framework structures. This result suggests that higher-accuracy predictions would be possible for a broader range of applications. The web server for this method is available at http://galaxy.seoklab.org/loop with the PS2 option for the scoring function.

  7. Cost benefit theory and optimal design of gene regulation functions

    Science.gov (United States)

    Kalisky, Tomer; Dekel, Erez; Alon, Uri

    2007-12-01

    Cells respond to the environment by regulating the expression of genes according to environmental signals. The relation between the input signal level and the expression of the gene is called the gene regulation function. It is of interest to understand the shape of a gene regulation function in terms of the environment in which it has evolved and the basic constraints of biological systems. Here we address this by presenting a cost-benefit theory for gene regulation functions that takes into account temporally varying inputs in the environment and stochastic noise in the biological components. We apply this theory to the well-studied lac operon of E. coli. The present theory explains the shape of this regulation function in terms of temporal variation of the input signals, and of minimizing the deleterious effect of cell-cell variability in regulatory protein levels. We also apply the theory to understand the evolutionary tradeoffs in setting the number of regulatory proteins and for selection of feed-forward loops in genetic circuits. The present cost-benefit theory can be used to understand the shape of other gene regulatory functions in terms of environment and noise constraints.

  8. Gene functional similarity search tool (GFSST

    Directory of Open Access Journals (Sweden)

    Russo James J

    2006-03-01

    Full Text Available Abstract Background With the completion of the genome sequences of human, mouse, and other species and the advent of high throughput functional genomic research technologies such as biomicroarray chips, more and more genes and their products have been discovered and their functions have begun to be understood. Increasing amounts of data about genes, gene products and their functions have been stored in databases. To facilitate selection of candidate genes for gene-disease research, genetic association studies, biomarker and drug target selection, and animal models of human diseases, it is essential to have search engines that can retrieve genes by their functions from proteome databases. In recent years, the development of Gene Ontology (GO has established structured, controlled vocabularies describing gene functions, which makes it possible to develop novel tools to search genes by functional similarity. Results By using a statistical model to measure the functional similarity of genes based on the Gene Ontology directed acyclic graph, we developed a novel Gene Functional Similarity Search Tool (GFSST to identify genes with related functions from annotated proteome databases. This search engine lets users design their search targets by gene functions. Conclusion An implementation of GFSST which works on the UniProt (Universal Protein Resource for the human and mouse proteomes is available at GFSST Web Server. GFSST provides functions not only for similar gene retrieval but also for gene search by one or more GO terms. This represents a powerful new approach for selecting similar genes and gene products from proteome databases according to their functions.

  9. Variants of the yeast MAPK Mpk1 are fully functional independently of activation loop phosphorylation

    Science.gov (United States)

    Goshen-Lago, Tal; Goldberg-Carp, Anat; Melamed, Dganit; Darlyuk-Saadon, Ilona; Bai, Chen; Ahn, Natalie G.; Admon, Arie; Engelberg, David

    2016-01-01

    MAP kinases of the ERK family are conserved from yeast to humans. Their catalytic activity is dependent on dual phosphorylation of their activation loop’s TEY motif, catalyzed by MAPK kinases (MEKs). Here we studied variants of Mpk1, a yeast orthologue of Erk, which is essential for cell wall integrity. Cells lacking MPK1, or the genes encoding the relevant MEKs, MKK1 and MKK2, do not proliferate under cell wall stress, imposed, for example, by caffeine. Mutants of Mpk1, Mpk1(Y268C) and Mpk1(Y268A), function independently of Mkk1 and Mkk2. We show that these variants are phosphorylated at their activation loop in mkk1∆mkk2∆ and mkk1∆mkk2∆pbs2∆ste7∆ cells, suggesting that they autophosphorylate. However, strikingly, when Y268C/A mutations were combined with the kinase-dead mutation, K54R, or mutations at the TEY motif, T190A+Y192F, the resulting proteins still allowed mkk1∆mkk2∆ cells to proliferate under caffeine stress. Mutating the equivalent residue, Tyr-280/Tyr-261, in Erk1/Erk2 significantly impaired Erk1/2’s catalytic activity. This study describes the first case in which a MAPK, Erk/Mpk1, imposes a phenotype via a mechanism that is independent of TEY phosphorylation and an unusual case in which an equivalent mutation in a highly conserved domain of yeast and mammalian Erks causes an opposite effect. PMID:27413009

  10. The Basic/Helix-Loop-Helix Protein Family in Gossypium: Reference Genes and Their Evolution during Tetraploidization.

    Directory of Open Access Journals (Sweden)

    Qian Yan

    Full Text Available Basic/helix-loop-helix (bHLH proteins comprise one of the largest transcription factor families and play important roles in diverse cellular and molecular processes. Comprehensive analyses of the composition and evolution of the bHLH family in cotton are essential to elucidate their functions and the molecular basis of cotton development. By searching bHLH homologous genes in sequenced diploid cotton genomes (Gossypium raimondii and G. arboreum, a set of cotton bHLH reference genes containing 289 paralogs were identified and named as GobHLH001-289. Based on their phylogenetic relationships, these cotton bHLH proteins were clustered into 27 subfamilies. Compared to those in Arabidopsis and cacao, cotton bHLH proteins generally increased in number, but unevenly in different subfamilies. To further uncover evolutionary changes of bHLH genes during tetraploidization of cotton, all genes of S5a and S5b subfamilies in upland cotton and its diploid progenitors were cloned and compared, and their transcript profiles were determined in upland cotton. A total of 10 genes of S5a and S5b subfamilies (doubled from A- and D-genome progenitors maintained in tetraploid cottons. The major sequence changes in upland cotton included a 15-bp in-frame deletion in GhbHLH130D and a long terminal repeat retrotransposon inserted in GhbHLH062A, which eliminated GhbHLH062A expression in various tissues. The S5a and S5b bHLH genes of A and D genomes (except GobHLH062 showed similar transcription patterns in various tissues including roots, stems, leaves, petals, ovules, and fibers, while the A- and D-genome genes of GobHLH110 and GobHLH130 displayed clearly different transcript profiles during fiber development. In total, this study represented a genome-wide analysis of cotton bHLH family, and revealed significant changes in sequence and expression of these genes in tetraploid cottons, which paved the way for further functional analyses of bHLH genes in the cotton genus.

  11. Three-Point Functions of Twist-Two Operators in N=4 SYM at One Loop

    CERN Document Server

    Plefka, Jan

    2012-01-01

    We calculate three-point functions of two protected operators and one twist-two operator with arbitrary even spin j in N=4 SYM theory to one-loop order. In order to carry out the calculations we project the indices of the spin j operator to the light-cone and evaluate the correlator in a soft-limit where the momentum coming in at the spin j operator becomes zero. This limit largely simplifies the perturbative calculation, since all three-point diagrams effectively reduce to two-point diagrams and the dependence on the one-loop mixing matrix drops out completely. The results of our direct calculation are in agreement with the structure constants obtained by F.A. Dolan and H. Osborn from the operator product expansion of four-point functions of half-BPS operators.

  12. The Callan-Symanzik equation of the electroweak Standard Model and its 1-loop functions

    CERN Document Server

    Kraus, E; Kraus, Elisabeth; Weiglein, Georg

    1999-01-01

    We derive the Callan-Symanzik equation of the electroweak Standard Model in the QED-like on-shell parameterization. The various coefficient functions, the the most general linear gauge compatible with rigid symmetry. In this way the basic elements for a systematic investigation of higher-order leading logarithmic contributions in the Standard Model are provided. The one-loop mass ratios and it is QED-like in this sense. Besides the QED-contributions of fermions it contains non-abelian contributions from vectors and ghosts with negative sign, which overcompensate the contributions of the fermions if one restricts the latter to one fermion generation. We also compare our results with the symmetric theory and give relations between the $\\beta$-functions of the spontaneously broken and the symmetric theory valid in one-loop order.

  13. One-Loop Partition Functions in Deformed $\\mathcal{N}=4$ SYM Theory

    CERN Document Server

    Fokken, Jan

    2014-01-01

    We study the thermodynamic behaviour of the real $\\beta$- and $\\gamma_i$-deformation of $\\mathcal{N}=4$ Super Yang-Mills theory on $\\mathbb{R}\\times S^3$ in the planar limit. These theories were shown to be the most general asymptotically integrable supersymmetric and non-supersymmetric field-theory deformations of $\\mathcal{N}=4$ Super Yang-Mills theory, respectively. We calculate the first loop correction to their partition functions using an extension of the dilatation-operator and P\\'{o}lya-counting approach. In particular, we account for the one-loop finite-size effects which occur for operators of length one and two. Remarkably, we find that the $\\mathcal{O}(\\lambda)$ correction to the Hagedorn temperature is independent of the deformation parameters, although the partition function depends on them in a non-trivial way.

  14. Function Projective Synchronization of Fractional-Order Hyperchaotic System Based on Open-Plus-Closed-Looping

    Institute of Scientific and Technical Information of China (English)

    WANG Xing-Yuan; LIU Rong; ZHANG Na

    2011-01-01

    The purpose of this paper is to analyze the dynamic behavior of fractional-order four-order hyperchaotic Lii system, and use the Open-Plus-Closed-Looping (OPCL) coupling method to construct the system's corresponding response system, and then implement function projective synchronization (FPS) of fractional-order drive-response system with system parameters perturbation or not. Finally, the numerical simulations verify the effectiveness and robustness of this scheme.

  15. Study of Wilson loop functionals in 2D Yang-Mills theories

    CERN Document Server

    Aroca, J M; Kubyshin, Yu.A.

    1998-01-01

    The derivation of the explicit formula for the vacuum expectation value of the Wilson loop functional for an arbitrary gauge group on an arbitrary orientable two-dimensional manifold is considered both in the continuum case and on the lattice. A contribution to this quantity, coming from the space of invariant connections, is also analyzed and is shown to be similar to the contribution of the monopoles.

  16. Towards three-loop QCD corrections to the time-like splitting functions

    CERN Document Server

    Gituliar, Oleksandr

    2015-01-01

    We report on the status of a direct computation of the time-like splitting functions at next-to-next-to-leading order in QCD. Time-like splitting functions govern the collinear kinematics of inclusive hadron production and the evolution of the parton fragmentation distributions. Current knowledge about them at three loops has been inferred by means of crossing symmetry from their related space-like counterparts, which has left certain parts of the off-diagonal quark-gluon splitting function undetermined. This motivates an independent calculation from first principles. We review the tools and methods which are applied to attack the problem.

  17. Top-level dynamics and the regulated gene response of feed-forward loop transcriptional motifs

    Science.gov (United States)

    Mayo, Michael; Abdelzaher, Ahmed; Perkins, Edward J.; Ghosh, Preetam

    2014-09-01

    Feed-forward loops are hierarchical three-node transcriptional subnetworks, wherein a top-level protein regulates the activity of a target gene via two paths: a direct-regulatory path, and an indirect route, whereby the top-level proteins act implicitly through an intermediate transcription factor. Using a transcriptional network of the model bacterium Escherichia coli, we confirmed that nearly all types of feed-forward loop were significantly overrepresented in the bacterial network. We then used mathematical modeling to study their dynamics by manipulating the rise times of the top-level protein concentration, termed the induction time, through alteration of the protein destruction rates. Rise times of the regulated proteins exhibited two qualitatively different regimes, depending on whether top-level inductions were "fast" or "slow." In the fast regime, rise times were nearly independent of rapid top-level inductions, indicative of biological robustness, and occurred when RNA production rate-limits the protein yield. Alternatively, the protein rise times were dependent upon slower top-level inductions, greater than approximately one bacterial cell cycle. An equation is given for this crossover, which depends upon three parameters of the direct-regulatory path: transcriptional cooperation at the DNA-binding site, a protein-DNA dissociation constant, and the relative magnitude of the top-level protien concentration.

  18. One-Loop One-Point Functions in Gauge-Gravity Dualities with Defects

    Science.gov (United States)

    Buhl-Mortensen, Isak; de Leeuw, Marius; Ipsen, Asger C.; Kristjansen, Charlotte; Wilhelm, Matthias

    2016-12-01

    We initiate the calculation of loop corrections to correlation functions in 4D defect conformal field theories (dCFTs). More precisely, we consider N =4 SYM theory with a codimension-one defect separating two regions of space, x3>0 and x30 . The holographic dual is the D 3 - D 5 probe brane system where the D 5 -brane geometry is AdS4×S2 and a background gauge field has k units of flux through the S2 . We diagonalize the mass matrix of the dCFT making use of fuzzy-sphere coordinates and we handle the x3 dependence of the mass terms in the 4D Minkowski space propagators by reformulating these as standard massive AdS4 propagators. Furthermore, we show that only two Feynman diagrams contribute to the one-loop correction to the one-point function of any single-trace operator and we explicitly calculate this correction in the planar limit for the simplest chiral primary. The result of this calculation is compared to an earlier string-theory computation in a certain double scaling limit and perfect agreement is found. Finally, we discuss how to generalize our calculation to any single-trace operator, to finite N , and to other types of observables such as Wilson loops.

  19. QCD with overlap fermions: Running coupling and the 3-loop beta-function

    CERN Document Server

    Constantinou, M

    2007-01-01

    We calculate the relation between the bare coupling constant g_0 and the MSbar-renormalized coupling g_MS: g_0 = Z_g(g_0,a \\mu) g_MS, to 2 loops in perturbation theory. We employ the standard Wilson action for gluons and the overlap action for fermions. For convenience, we have worked with the background field technique, which only requires evaluation of 2-point Green's function for the problem at hand. Our results depend explicitly on the number of fermion flavors (N_f) and colors (N). Since the dependence of Z_g on the overlap parameter rho cannot be extracted analytically, we tabulate our results for different values in the allowed range of rho (0 < rho < 2), focusing on values which are being used most frequently in simulations. Knowledge of Z_g allows us to derive the 3-loop coefficient of the bare beta-function (beta_L(g_0)) which, unlike the 1- and 2-loop coefficients, is regularization-dependent. The nontrivial dependence of Z_g and of beta_L(g_0) on rho is plotted for various choices of N, N_f.

  20. On the impact of kinetic mixing in beta functions at two-loop

    CERN Document Server

    Lyonnet, Florian

    2016-01-01

    Kinetic mixing is a fundamental property of models with a gauge symmetry involving several $\\mathrm{U}(1)$ group factors. In this paper, we perform a numerical study of the impact of kinetic mixing on beta functions at two-loop. To do so, we use the recently published PyR@TE 2 software to derive the complete set of RGEs of the SM B-L model at two-loop including kinetic mixing. We show that it is important to properly account for kinetic mixing as the evolution of the parameters with the energy scale can change drastically. In some cases, these modifications can even lead to a different conclusion regarding the stability of the scalar potential.

  1. A calculation of the three-loop helicity-dependent splitting functions in QCD

    CERN Document Server

    Vogt, A; Vermaseren, J A M

    2014-01-01

    We have calculated the complete matrix of three-loop helicity-difference (`polarized') splitting functions Delta P_ik^(2), i,k = q,g, in massless perturbative QCD. In this note we briefly discuss some properties of the polarized splitting functions and our non-standard determination of the hitherto missing lower-row quantities Delta P_gq^(2) and Delta P_gg^(2). The resulting next-to-next-to-leading order (NNLO) corrections to the evolution of polarized parton distributions are illustrated and found to be small even at rather large values of the strong coupling constant alpha_s.

  2. Renormalization group functions of $\\phi^4$ theory in the MS-scheme to six loops

    CERN Document Server

    Kompaniets, Mikhail

    2016-01-01

    Subdivergences constitute a major obstacle to the evaluation of Feynman integrals and an expression in terms of finite quantities can be a considerable advantage for both analytic and numeric calculations. We report on our implementation of the suggestion by F. Brown and D. Kreimer, who proposed to use a modified BPHZ scheme where all counterterms are single-scale integrals. Paired with parametric integration via hyperlogarithms, this method is particularly well suited for the computation of renormalization group functions and easily automated. As an application of this approach we compute the 6-loop beta function and anomalous dimensions of the $\\phi^4$ model.

  3. Development of a Loop-Mediated Isothermal Amplification Assay Targeting the mpb64 Gene for Diagnosis of Intraocular Tuberculosis

    Science.gov (United States)

    Balne, Praveen Kumar; Barik, Manas Ranjan; Sharma, Savitri

    2013-01-01

    A loop-mediated isothermal amplification (LAMP) assay targeting the mpb64 gene for the diagnosis of intraocular tuberculosis was highly specific (100%), sensitive (85.7%), rapid, and easy to perform. The LAMP assay can be an alternative to conventional PCR for the diagnosis of ocular tuberculosis in resource-limited settings. PMID:23966513

  4. FunGene: the Functional Gene Pipeline and Repository

    Directory of Open Access Journals (Sweden)

    Jordan A. Fish

    2013-10-01

    Full Text Available Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer.While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/ offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.

  5. Three-Loop Yang-Mills $\\beta$-Function via the Covariant Background Field Method

    CERN Document Server

    Boernsen, J P; Ven, Anton E. M. van de

    2003-01-01

    We demonstrate the effectivity of the covariant background field method by means of an explicit calculation of the 3-loop beta-function for a pure Yang-Mills theory. To maintain manifest background invariance throughout our calculation, we stay in coordinate space and treat the background field non-perturbatively. In this way the presence of a background field does not increase the number of vertices and leads to a relatively small number of vacuum graphs in the effective action. Restricting to a covariantly constant background field in Fock-Schwinger gauge permits explicit expansion of all quantum field propagators in powers of the field strength only. Hence, Feynman graphs are at most logarithmically divergent. At 2-loop order only a single Feynman graph without subdivergences needs to be calculated. At 3-loop order 24 graphs remain. Insisting on manifest background gauge invariance at all stages of a calculation is thus shown to be a major labor saving device. All calculations were performed with Mathemati...

  6. Genes2FANs: connecting genes through functional association networks

    Directory of Open Access Journals (Sweden)

    Dannenfelser Ruth

    2012-07-01

    Full Text Available Abstract Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs, researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our

  7. Hartree Approximation to the One Loop Quantum Gravitational Correction to the Graviton Mode Function on de Sitter

    CERN Document Server

    Mora, P J; Woodard, R P

    2013-01-01

    We use the Hartree approximation to the Einstein equation on de Sitter background to solve for the one loop correction to the graviton mode function. This should give a reasonable approximation to how the ensemble of inflationary gravitons affects a single external graviton. At late times we find that the one loop correction to the plane wave mode function $u(\\eta,k)$ goes like $G H^2 \\ln(a)/a^2$, where $a$ is the inflationary scale factor. One consequence is that the one loop corrections to the "electric" components of the linearized Weyl tensor grow compared to the tree order result.

  8. Cys-loop ligand-gated ion channel gene discovery in the Locusta migratoria manilensis through the neuron transcriptome.

    Science.gov (United States)

    Wang, Xin; Meng, Xiangkun; Liu, Chuanjun; Gao, Hongli; Zhang, Yixi; Liu, Zewen

    2015-05-01

    As an ideal model, Locusta migratoria manilensis (Meyen) has been widely used in the study of endocrinological and neurobiological processes. Here we created a large transcriptome of the locust neurons, which enriched ion channels whose potential for functional genetic experiments is currently limited. With high-throughput Illumina sequencing technology, we obtained more than 50 million raw reads, which were assembled into 61,056 unique sequences with average size of 737bp. Among the unigenes, a total 24,884 sequences had significant similarities with proteins in the five public databases (NR, SwissProt, GO, COG and KEGG) with a cut-off E-value of 10(-5) using BLASTx. Moreover, the number of potential genes of the cys-loop ligand-gated ion channels (LGICs) was manually curated, including 39 putative nicotinic acetylcholine receptors (nAChRs), 6 putative γ-aminobutyric acid (GABA) gated anion channels, 21 putative glutamate-gated chloride channels (GluCls) and 1 histamine-gated chloride channels (HisCls). In addition, the full-length of 11 nAChRs subunits (9 alpha and 2 beta) were obtained by RACE technique that would be helpful to further studies on nAChR neurochemistry and pharmacological aspects. To our knowledge, this is the first study to characterize the locust neuron transcriptome, which will provide a useful resource especially for future studies on the neuro-function and behavior of the locust.

  9. Two $\\Lambda(1405)$ states in a chiral unitary approach with a fully-calculated loop function

    CERN Document Server

    Dong, Fang-Yong; Pang, Jing-Long

    2016-01-01

    The Bethe-Salpeter equation is solved in the framework of unitary coupled-channel approximation by using the pseudoscalar meson-baryon octet interaction. The loop function of the intermediate meson and baryon is deduced accurately in a fully dimensional regularization scheme, where the off-shell correction is supplemented. Two $\\Lambda(1405)$ states are generated dynamically in the strangeness $S=-1$ and isospin $I=0$ sector, and their masses, decay widths and couplings to the meson and the baryon are similar to those values obtained in the on-shell factorization. However, the scattering amplitudes at these two poles become weaker than the cases in the on-shell factorization.

  10. A Platform for Closing the Open Data Feedback Loop Based on Web2.0 Functionality

    Directory of Open Access Journals (Sweden)

    Charalampos Alexopoulos

    2014-11-01

    Full Text Available One essential element of open data ecosystems concerns their development through feedback loops, discussions and dynamic supplier and user interactions. These user-centric features communicate the users’ needs to the open data community as well to the public sector bodies responsible for data publication. Addressing these needs by the corresponding public sector bodies or even by utilising the power of the community as ENGAGE supports will actually accelerate innovation. However, these elements appear barely to be part of existing open data practices. We conducted a survey which showed that most professional open data users did not know at least one open data infrastructure that enabled five specific types of discussion and feedback mechanisms. The survey showed that much can still be done to improve feedback and discussion on open data infrastructures. In this paper we discuss an open data platform which has started to contribute to filling this gap and present a usage scenario explaining the sequence of the underlined functionality. The discussed ENGAGE open data infrastructure combines functionalities to close the feedback loop and to return information to public authorities for better open data use and publication as well as establishing communication channels between stakeholders. This may effectively lead to the stimulation and facilitation of value generation from open data, as such functionality position the user at the centre of the open data publication process.

  11. Closed-loop control of spinal cord stimulation to restore hand function after paralysis

    Directory of Open Access Journals (Sweden)

    Jonas B Zimmermann

    2014-05-01

    Full Text Available As yet, no cure exists for upper-limb paralysis resulting from the damage to motor pathways after spinal cord injury or stroke. Recently, neural activity from the motor cortex of paralyzed individuals has been used to control the movements of a robot arm but restoring function to patients’ actual limbs remains a considerable challenge. Previously we have shown that electrical stimulation of the cervical spinal cord in anesthetized monkeys can elicit functional upper-limb movements like reaching and grasping. Here we show that stimulation can be controlled using cortical activity in awake animals to bypass disruption of the corticospinal system, restoring their ability to perform a simple upper-limb task. Monkeys were trained to grasp and pull a spring-loaded handle. After temporary paralysis of the hand was induced by reversible inactivation of primary motor cortex using muscimol, grasp-related single-unit activity from the ventral premotor cortex was converted into stimulation patterns delivered in real-time to the cervical spinal grey matter. During periods of closed-loop stimulation, task-modulated electromyogram, movement amplitude and task success rate were improved relative to interleaved control periods without stimulation. In some sessions, single motor unit activity from weakly active muscles was also used successfully to control stimulation. These results are the first use of a neural prosthesis to improve the hand function of primates after motor cortex disruption, and demonstrate the potential for closed-loop cortical control of spinal cord stimulation to reanimate paralyzed limbs.

  12. Two different modes of oscillation in a gene transcription regulatory network with interlinked positive and negative feedback loops

    Science.gov (United States)

    Karmakar, Rajesh

    2016-12-01

    We study the oscillatory behavior of a gene regulatory network with interlinked positive and negative feedback loop. The frequency and amplitude are two important properties of oscillation. The studied network produces two different modes of oscillation. In one mode (mode-I), frequency of oscillation remains constant over a wide range of amplitude and in the other mode (mode-II) the amplitude of oscillation remains constant over a wide range of frequency. Our study reproduces both features of oscillations in a single gene regulatory network and shows that the negative plus positive feedback loops in gene regulatory network offer additional advantage. We identified the key parameters/variables responsible for different modes of oscillation. The network is flexible in switching between different modes by choosing appropriately the required parameters/variables.

  13. Stable and enhanced gene expression in Clostridium acetobutylicum using synthetic untranslated regions with a stem-loop.

    Science.gov (United States)

    Lee, Joungmin; Jang, Yu-Sin; Papoutsakis, Eleftherios T; Lee, Sang Yup

    2016-07-20

    Gene overexpression is one of the most basic strategies in metabolic engineering, but the factors determining gene expression levels have been poorly studied in Clostridium species. In this study, we found that a short single-stranded 5' untranslated region (UTR) sequence led to decreased gene expression in Clostridium acetobutylicum. Using an in vitro enzyme assay and reverse transcription-quantitative PCR, we found that addition of a small stem-loop at the 5' end of mRNA increased mRNA levels and thereby protein expression levels up to 4.6-fold, possibly protecting mRNA from exonuclease attack. Gene-expression levels were apparently independent of the stability of the added stem-loop; the existence of a stem-loop itself appears to be more important. Our results indicate that efficient expression cassettes can be designed by taking the 5' UTR into consideration, as the expression levels can vary even though the same promoter and RBS are used. These findings will be useful for developing a more reliable gene expression system for metabolic engineering of Clostridium strains. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. 2D Quantum Gravity on Compact Riemann Surfaces and Two-Loop Partition Function: Circumventing the c=1 Barrier?

    CERN Document Server

    Bilal, Adel

    2014-01-01

    We study two-dimensional quantum gravity on arbitrary genus Riemann surfaces in the Kaehler formalism where the basic quantum field is the (Laplacian of the) Kaehler potential. We do a careful first-principles computation of the fixed-area partition function $Z[A]$ up to and including all two-loop contributions. This includes genuine two-loop diagrams as determined by the Liouville action, one-loop diagrams resulting from the non-trivial measure on the space of metrics, as well as one-loop diagrams involving various counterterm vertices. Contrary to what is often believed, several such counterterms, in addition to the usual cosmological constant, do and must occur. We consistently determine the relevant counterterms from a one-loop computation of the full two-point Green's function of the Kaehler field. Throughout this paper we use the general spectral cutoff regularization developed recently and which is well-suited for multi-loop computations on curved manifolds. At two loops, while all "unwanted" contribut...

  15. Goldstone bosons in a finite volume the partition function to three loops

    CERN Document Server

    Bietenholz, W

    1994-01-01

    A system of Goldstone bosons - stemming from a symmetry breaking $O(N) \\to O(N-1)$ - in a finite volume at finite temperature is considered. In the framework of dimensional regularization, the partition function is calculated to 3 loops for 3 and 4 dimensions, where Polyakov's measure for the functional integration is applied. Although the underlying theory is the non-linear $\\sigma $ model, the 3 loop result turns out to be renormalizable in the sense that all the singularities can be absorbed by the couplings occuring so far. In finite volume, this property is highly non trivial and confirms the method for the measure. We also show that the result coincides with the one obtained using the Faddeev- Popov measure. This is also true for the maximal generalization of Polyakov's measure: none of the additional invariant terms that can be added contributes to the dimensionally regularized system. Our phenomenological Lagrangian describes e.g. 2 flavor chiral QCD as well as the classical Heisenberg model, but ther...

  16. One-loop one-point functions in AdS/dCFT

    CERN Document Server

    Buhl-Mortensen, Isak; Ipsen, Asger C; Kristjansen, Charlotte; Wilhelm, Matthias

    2016-01-01

    We initiate the calculation of loop corrections to correlation functions in 4D defect CFTs. More precisely, we consider N=4 SYM with a codimension-one defect separating two regions of space, x_3>0 and x_30. The holographic dual is the D3-D5 probe brane system where the D5 brane geometry is AdS_4 x S^2 and a background gauge field has k units of flux through the S^2. We diagonalise the mass matrix of the defect CFT making use of fuzzy-sphere coordinates and we handle the x_3-dependence of the mass terms in the 4D Minkowski space propagators by reformulating these as standard massive AdS_4 propagators. Furthermore, we show that only two Feynman diagrams contribute to the one-loop correction to the one-point function of any single-trace operator and we explicitly calculate this correction in the planar limit for the simplest chiral primary. The result of this calculation is compared to an earlier string-theory computation. Finally, we discuss how to generalise our calculation to any single-trace operator, to fin...

  17. Central auditory function of deafness genes.

    Science.gov (United States)

    Willaredt, Marc A; Ebbers, Lena; Nothwang, Hans Gerd

    2014-06-01

    The highly variable benefit of hearing devices is a serious challenge in auditory rehabilitation. Various factors contribute to this phenomenon such as the diversity in ear defects, the different extent of auditory nerve hypoplasia, the age of intervention, and cognitive abilities. Recent analyses indicate that, in addition, central auditory functions of deafness genes have to be considered in this context. Since reduced neuronal activity acts as the common denominator in deafness, it is widely assumed that peripheral deafness influences development and function of the central auditory system in a stereotypical manner. However, functional characterization of transgenic mice with mutated deafness genes demonstrated gene-specific abnormalities in the central auditory system as well. A frequent function of deafness genes in the central auditory system is supported by a genome-wide expression study that revealed significant enrichment of these genes in the transcriptome of the auditory brainstem compared to the entire brain. Here, we will summarize current knowledge of the diverse central auditory functions of deafness genes. We furthermore propose the intimately interwoven gene regulatory networks governing development of the otic placode and the hindbrain as a mechanistic explanation for the widespread expression of these genes beyond the cochlea. We conclude that better knowledge of central auditory dysfunction caused by genetic alterations in deafness genes is required. In combination with improved genetic diagnostics becoming currently available through novel sequencing technologies, this information will likely contribute to better outcome prediction of hearing devices.

  18. Gene transfer strategies for augmenting cardiac function.

    Science.gov (United States)

    Peppel, K; Koch, W J; Lefkowitz, R J

    1997-07-01

    Recent transgenic as well as gene-targeted animal models have greatly increased our understanding of the molecular mechanisms of normal and compromised heart function. These studies have raised the possibility of using somatic gene transfer as a means for improving cardiac function. DNA transfer to a significant portion of the myocardium has thus far been difficult to accomplish. This review describes current efforts to achieve myocardial gene transfer in several model systems, with particular emphasis placed on adenovirus-mediated gene delivery, its possibilities, and current limitations. (Trend Cardiovasc Med 1997;7:145-150). © 1997, Elsevier Science Inc.

  19. Large-nf Contributions to the Four-Loop Splitting Functions in QCD

    CERN Document Server

    Davies, J; Ruijl, B; Ueda, T; Vermaseren, J A M

    2016-01-01

    We have computed the fourth-order nf^2 contributions to all three non-singlet quark-quark splitting functions and their four nf^3 flavour-singlet counterparts for the evolution of the parton distributions of hadrons in perturbative QCD with nf effectively massless quark flavours. The analytic form of these functions is presented in both Mellin N-space and momentum-fraction x-space; the large-x and small-x limits are discussed. Our results agree with all available predictions derived from lower-order information. The large-x limit of the quark-quark cases provides the complete nf^2 part of the four-loop cusp anomalous dimension which agrees with two recent partial computations.

  20. Large-nf contributions to the four-loop splitting functions in QCD

    Science.gov (United States)

    Davies, J.; Vogt, A.; Ruijl, B.; Ueda, T.; Vermaseren, J. A. M.

    2017-02-01

    We have computed the fourth-order nf2 contributions to all three non-singlet quark-quark splitting functions and their four nf3 flavour-singlet counterparts for the evolution of the parton distributions of hadrons in perturbative QCD with nf effectively massless quark flavours. The analytic form of these functions is presented in both Mellin N-space and momentum-fraction x-space; the large-x and small-x limits are discussed. Our results agree with all available predictions derived from lower-order information. The large-x limit of the quark-quark cases provides the complete nf2 part of the four-loop cusp anomalous dimension which agrees with two recent partial computations.

  1. Pattern Genes Suggest Functional Connectivity of Organs

    Science.gov (United States)

    Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

    2016-05-01

    Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose & gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets.

  2. Structural and Functional Studies on the Marburg Virus GP2 Fusion Loop.

    Science.gov (United States)

    Liu, Nina; Tao, Yisong; Brenowitz, Michael D; Girvin, Mark E; Lai, Jonathan R

    2015-10-01

    Marburg virus (MARV) and the ebolaviruses belong to the family Filoviridae (the members of which are filoviruses) that cause severe hemorrhagic fever. Infection requires fusion of the host and viral membranes, a process that occurs in the host cell endosomal compartment and is facilitated by the envelope glycoprotein fusion subunit, GP2. The N-terminal fusion loop (FL) of GP2 is a hydrophobic disulfide-bonded loop that is postulated to insert and disrupt the host endosomal membrane during fusion. Here, we describe the first structural and functional studies of a protein corresponding to the MARV GP2 FL. We found that this protein undergoes a pH-dependent conformational change, as monitored by circular dichroism and nuclear magnetic resonance. Furthermore, we report that, under low pH conditions, the MARV GP2 FL can induce content leakage from liposomes. The general aspects of this pH-dependent structure and lipid-perturbing behavior are consistent with previous reports on Ebola virus GP2 FL. However, nuclear magnetic resonance studies in lipid bicelles and mutational analysis indicate differences in structure exist between MARV and Ebola virus GP2 FL. These results provide new insight into the mechanism of MARV GP2-mediated cell entry.

  3. The functional landscape of mouse gene expression

    Directory of Open Access Journals (Sweden)

    Zhang Wen

    2004-12-01

    Full Text Available Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

  4. Integrative identification of deregulated miRNA/TF-mediated gene regulatory loops and networks in prostate cancer.

    Science.gov (United States)

    Afshar, Ali Sobhi; Xu, Joseph; Goutsias, John

    2014-01-01

    MicroRNAs (miRNAs) have attracted a great deal of attention in biology and medicine. It has been hypothesized that miRNAs interact with transcription factors (TFs) in a coordinated fashion to play key roles in regulating signaling and transcriptional pathways and in achieving robust gene regulation. Here, we propose a novel integrative computational method to infer certain types of deregulated miRNA-mediated regulatory circuits at the transcriptional, post-transcriptional and signaling levels. To reliably predict miRNA-target interactions from mRNA/miRNA expression data, our method collectively utilizes sequence-based miRNA-target predictions obtained from several algorithms, known information about mRNA and miRNA targets of TFs available in existing databases, certain molecular structures identified to be statistically over-represented in gene regulatory networks, available molecular subtyping information, and state-of-the-art statistical techniques to appropriately constrain the underlying analysis. In this way, the method exploits almost every aspect of extractable information in the expression data. We apply our procedure on mRNA/miRNA expression data from prostate tumor and normal samples and detect numerous known and novel miRNA-mediated deregulated loops and networks in prostate cancer. We also demonstrate instances of the results in a number of distinct biological settings, which are known to play crucial roles in prostate and other types of cancer. Our findings show that the proposed computational method can be used to effectively achieve notable insights into the poorly understood molecular mechanisms of miRNA-mediated interactions and dissect their functional roles in cancer in an effort to pave the way for miRNA-based therapeutics in clinical settings.

  5. Integrating Gene Ontology and Blast to predict gene functions

    Institute of Scientific and Technical Information of China (English)

    WANG Cheng-gang; MO Zhi-hong

    2007-01-01

    A GoBlast system was built to predict gene function by integrating Blast search and Gene Ontology (GO) annotations together. The operation system was based on Debian Linux 3.1, with Apache as the web server and Mysql database as the data storage system. FASTA files with GO annotations were taken as the sequence source for blast alignment, which were formatted by wu-formatdb program. The GoBlast system includes three Bioperl modules in Perl: a data input module, a data process module and a data output module. A GoBlast query starts with an amino acid or nucleotide sequence. It ends with an output in an html page, presenting high scoring gene products which are of a high homology to the queried sequence and listing associated GO terms beside respective gene poducts. A simple click on a GO term leads to the detailed explanation of the specific gene function. This avails gene function prediction by Blast. GoBlast can be a very useful tool for functional genome research and is available for free at http://bioq.org/goblast.

  6. Phase space quantization and loop quantum cosmology: a Wigner function for the Bohr-compactified real line

    Energy Technology Data Exchange (ETDEWEB)

    Fewster, Christopher J [Department of Mathematics, University of York, Heslington, York YO10 5DD (United Kingdom); Sahlmann, Hanno [Spinoza Institute, Universiteit Utrecht (Netherlands)

    2008-11-21

    We give a definition for the Wigner function for quantum mechanics on the Bohr compactification of the real line and prove a number of simple consequences of this definition. We then discuss how this formalism can be applied to loop quantum cosmology. As an example, we use the Wigner function to give a new quantization of an important building block of the Hamiltonian constraint.

  7. Phase space quantization and Loop Quantum Cosmology: a Wigner function for the Bohr-compactified real line

    NARCIS (Netherlands)

    Fewster, C.J.; Sahlmann, H.

    2008-01-01

    We give a definition for the Wigner function for quantum mechanics on the Bohr compactification of the real line and prove a number of simple consequences of this definition. We then discuss how this formalism can be applied to loop quantum cosmology. As an example, we use the Wigner function to giv

  8. Density functional theory studies of MTSL nitroxide side chain conformations attached to an activation loop

    CERN Document Server

    Concilio, Maria Grazia; Bayliss, Richard; Burgess, Selena G

    2016-01-01

    A quantum-mechanical (QM) method rooted on density functional theory (DFT) has been employed to determine conformations of the methane-thiosulfonate spin label (MTSL) attached to a fragment extracted from the activation loop of Aurora-A kinase. The features of the calculated energy surface revealed low energy barriers between isoenergetic minima and the system could be described in a population of 76 rotamers that can be also considered for other systems since it was found that the X3, X4 and X5 do not depend on the previous two dihedral angles. Conformational states obtained were seen to comparable to those obtained in the {\\alpha}-helix systems studied previously, indicating that the protein backbone does not affect the torsional profiles significantly and suggesting the possibility to use determined conformations for other protein systems for further modelling studies.

  9. Gene, environment and cognitive function

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Sun, Jianping; Duan, Haiping

    2015-01-01

    population living under distinct environmental condition as the Western populations. OBJECTIVE: this study aims to explore the genetic and environmental impact on normal cognitive ageing in the Chinese twins. DESIGN/SETTING: cognitive function was measured on 384 complete twin pairs with median age of 50...... factors accounting for 23-33% of the total variances. In contrast, all cognitive performances showed moderate to high influences by the unique environmental factors. CONCLUSIONS: genetic factor and common family environment have a limited contribution to cognitive function in the Chinese adults......BACKGROUND: the genetic and environmental contributions to cognitive function in the old people have been well addressed for the Western populations using twin modelling showing moderate to high heritability. No similar study has been conducted in the world largest and rapidly ageing Chinese...

  10. Silica nanowire conjugated with loop-shaped oligonucleotides: A new structure to silence cysteine proteinase gene in Leishmania tropica.

    Science.gov (United States)

    Bafghi, Ali Fatahi; Jebali, Ali; Daliri, Karim

    2015-12-01

    The main aim of this study was to evaluate the capability of silica nanowire conjugated with loop-shaped oligonucleotides (SNWCLSOs) to silence cysteine proteinase b (Cpb) gene in Leishmania (L) tropica. On the other hand, its toxicity on amastigotes and mouse peritoneal macrophages was evaluated by 5-diphenyl-tetrazolium bromide (MTT) assay. For control, two loop-shaped oligonucleotides (LSO) were considered. LSO1 and LSO2 were 5'-NH2-cccccaaaaaaaaaaaaaaaaaaaaaaaaaggggg-COOH-3' and LSO2: 5'-NH2-cccccttttttttttttttttttttttttttttttttttttttggggg-COOH-3', respectively. After 72 h incubation at 37 °C, AMSNW, LSO1, and LSO2 had no remarkable toxicity on L. tropica amastigote (2 × 10(5)/mL) and mouse peritoneal macrophages (2 × 10(5)/mL). In case of SNWCLSOs, they had high toxicity on L. tropica amastigote, but they had no effect on mouse peritoneal macrophages. At concentrations of 1, 10, and 25 μg/mL, AMSNW, LSO1 and LSO2 had no effect on the gene expression. But, at concentration of 50 and 100 μg/mL, decrease of gene expression was observed. In case of SNWCLSOs, they could dramatically decrease the gene expression. It could be concluded that since SNWCLSOs could silence Cpb gene with no remarkable toxicity, they are good choice for treat cutaneous leishmaniasis in future. As a new agent, it must be checked in vivo.

  11. Nicotinic acetylcholine receptor α7 subunits with a C2 cytoplasmic loop yellow fluorescent protein insertion form functional receptors

    Institute of Scientific and Technical Information of China (English)

    Teresa A MURRAY; Qiang LIU; Paul WHITEAKER; Jie WU; Ronald J LUKAS

    2009-01-01

    Aim: Several nicotinic acetylcholine receptor (nAChR) subunits have been engineered as fluorescent protein (FP) fusions and exploited to illuminate features of nAChRs. The aim of this work was to create a FP fusion in the nAChR a.7 subunit without compromising formation of functional receptors.Methods: A gene construct was generated to introduce yellow fluorescent protein (YFP), in frame, into the otherwise unaltered, large, second cytoplamsic loop between the third and fourth transmembrane domains of the mouse nAChR al sub-unit (a7Y). SH-EP1 cells were transfected with mouse nAChR wild type a.7 subunits (a.7) or with a7Y subunits, alone or with the chaperone protein, hRJC-3. Receptor function was assessed using whole-cell current recording. Receptor expression was measured with 125I-labeled a-bungarotoxin (I-Bgt) binding, laser scanning confocal microscopy, and total internal reflectance fluorescence (TIRF) microscopy.Results: Whole-cell currents revealed that a7Y nAChRs and al nAChRs were functional with comparable EC50 values for the a7 nAChR-selective agonist, choline, and IC50 values for the a.7 nAChR-selective antagonist, methyllycaconitine. I-Bgt binding was detected only after co-expression with hRIC-3. Confocal microscopy revealed that a7Y had primarily intracel-lular rather than surface expression. TIRF microscopy confirmed that little a7Y localized to the plasma membrane, typical of a7 nAChRs.Conclusion: nAChRs composed as homooligomers of a7Y subunits containing cytoplasmic loop YFP have functional, ligand binding, and trafficking characteristics similar to those of a.7 nAChRs. a7Y nAChRs may be used to elucidate properties of a.7 nAChRs and to identify and develop novel probes for these receptors, perhaps in high-throughput fashion.

  12. Evolution of Double Positive Autoregulatory Feedback Loops in CYCLOIDEA2 Clade Genes Is Associated with the Origin of Floral Zygomorphy[W

    Science.gov (United States)

    Yang, Xia; Pang, Hong-Bo; Liu, Bo-Ling; Qiu, Zhi-Jing; Gao, Qiu; Wei, Lai; Dong, Yang; Wang, Yin-Zheng

    2012-01-01

    Members of the CYCLOIDEA2 (CYC2) clade of the TEOSINTE BRANCHED1, CYCLOIDEA, and PCF transcription factor genes are widely involved in controlling floral zygomorphy, a key innovation in angiosperm evolution, depending on their persistently asymmetric expression in the corresponding floral domains. However, it is unclear how this asymmetric expression is maintained throughout floral development. Selecting Primulina heterotricha as a model, we examined the expression and function of two CYC2 genes, CYC1C and CYC1D. We analyzed the role of their promoters in protein–DNA interactions and transcription activation using electrophoresis mobility shift assays, chromatin immunoprecipitation, and transient gene expression assays. We find that CYC1C and CYC1D positively autoregulate themselves and cross-regulate each other. Our results reveal a double positive autoregulatory feedback loop, evolved for a pair of CYC2 genes to maintain their expression in developing flowers. Further comparative genome analyses, together with the available expression and function data of CYC2 genes in the core eudicots, suggest that this mechanism might have led to the independent origins of floral zygomorphy, which are associated with plant–insect coevolution and the adaptive radiation of angiosperms. PMID:22649271

  13. Photocontrol of mitotic kinesin Eg5 facilitated by thiol-reactive photochromic molecules incorporated into the loop L5 functional loop.

    Science.gov (United States)

    Ishikawa, Kumiko; Tamura, Yuhki; Maruta, Shinsaku

    2014-03-01

    Kinesin Eg5 is a plus-end-directed microtubule-based motor that is essential for bipolar spindle formation during eukaryotic cell division. Loop L5 of mitotic kinesin Eg5 is a key region determining ATPase activity and motor function. Photochromic molecules undergo reversible isomerization in response to ultraviolet and visible light irradiation. We introduced three kinds of photochromic molecules, 4-phenylazomaleinanil (PAM), 4-(N-(2-iodoacetyl)amino)-4'-(N-(2-(N-(triphenylmethyl)amino)acetyl)amino)azobenzene (IATAB) and 3,3-dimethyl-1-(2-(2-iodoacetoxy)ethyl)-3H-1,2-dihydroindole-2-spiro-2'-(2H)-6'-nitrochromene (IASP) into L5 to control the Eg5 ATPase activity using light irradiation. We prepared five kinesin Eg5 motor domain mutants, E116C, E118C, Y125C, W127C and D130C, which contained a single reactive cysteine residue in loop L5. The ability of S-trityl-l-cysteine (STLC), a specific Eg5 inhibitor, to inhibit E116C, W127C and D130C was significantly reduced. The photochromic molecules were stoichiometrically incorporated into the cysteine residues in L5 of mutants. W127C and D130C modified with IASP exhibited reversible ATPase activity alterations when subjected to light irradiation-induced photoisomerization. The two IASP modified mutants also demonstrated photocontrolled alterations following treatment with STLC. Additionally, the ATPase activity of the mutant D130C modified with PAM could be photocontrolled. Our findings demonstrate that incorporation of photochromic molecules into the key region of loop L5 facilitates the photocontrol of the function of kinesin Eg5.

  14. The activation loop of PIP5K functions as a membrane sensor essential for lipid substrate processing

    Science.gov (United States)

    Liu, Aizhuo; Sui, Dexin; Wu, Dianqing; Hu, Jian

    2016-01-01

    Phosphatidylinositol 4-phosphate 5-kinase (PIP5K), a representative member of the phosphatidylinositol phosphate kinase (PIPK) family, is a major enzyme that biosynthesizes the signaling molecule PI(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) in eukaryotic cells. The stringent specificity toward lipid substrates and the high sensitivity to the membrane environment strongly suggest a membrane-sensing mechanism, but the underlying structural basis is still largely unknown. We present a nuclear magnetic resonance (NMR) study on a peptide commensurate with a PIP5K’s activation loop, which has been reported to be a determinant of lipid substrate specificity and subcellular localization of PIP5K. Although the activation loop is severely disordered in the crystal structure of PIP5K, the NMR experiments showed that the largely unstructured peptide folded into an amphipathic helix upon its association with the 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) micellar surface. Systematic mutagenesis and functional assays further demonstrated the crucial roles of the amphipathic helix and its hydrophobic surface in kinase activity and membrane-sensing function, supporting a working model in which the activation loop is a critical structural module conferring a membrane-sensing mechanism on PIP5K. The activation loop, surprisingly functioning as a membrane sensor, represents a new paradigm of kinase regulation by the activation loop through protein-membrane interaction, which also lays a foundation on the regulation of PIP5K (and other PIPKs) by membrane lipids for future studies. PMID:28138522

  15. Stable One-Dimensional Integral Representations of One-Loop N-Point Functions in the General Massive Case: I - Three Point Functions

    CERN Document Server

    Guillet, J Ph; Rodgers, M; Zidi, M S

    2013-01-01

    In this article we provide representations for the one-loop three point functions in 4 and 6 dimensions in the general case with complex masses. The latter are part of the GOLEM library used for the computation of one-loop multileg amplitudes. These representations are one-dimensional integrals designed to be free of instabilites induced by inverse powers of Gram determinants, therefore suitable for stable numerical implementations.

  16. The nutritive effect of glucose on teh structure and function of jejunal self-emptying blind loops in the rat.

    Science.gov (United States)

    Menge, H; Werner, H; Lorenz-Meyer, H; Riecken, E O

    1975-01-01

    In an attempt to obtain further information on the influence of the intestinal contents on the development of mucosal structure and function, self-emptying blind loops of rat jejunum were constructed, and the oral end was exteriorized with a stoma to permit infusion of different solutions into the loop. Ringer solution or media containing glucose or galactose was instilled into the loops three times daily for 27 days before functional and structural examination of the loops. The body weight and food intake of the animals did not differ significantly from one group to another. Treatment with glucose, but not with galactose or Ringer solution alone, induced a significant increase in the villus height. Disaccharidase but not dipeptidase activity was concomitantly increased. Infusion of glucose or galactose both led to an increase in the transport capacity of the loop, as determined by glucose absorption in vivo. These results indicate that glucose has a nutritive effect, probably due to its intracellular metabolism, which is responsible for the structural alterations observed. On the other hand, the increase in transport capacity may be attributed to substrate-induced stimulation of the specific monosaccharide transport system in the epithelial cell. PMID:1150116

  17. Sugarcane genes related to mitochondrial function

    Directory of Open Access Journals (Sweden)

    Fonseca Ghislaine V.

    2001-01-01

    Full Text Available Mitochondria function as metabolic powerhouses by generating energy through oxidative phosphorylation and have become the focus of renewed interest due to progress in understanding the subtleties of their biogenesis and the discovery of the important roles which these organelles play in senescence, cell death and the assembly of iron-sulfur (Fe/S centers. Using proteins from the yeast Saccharomyces cerevisiae, Homo sapiens and Arabidopsis thaliana we searched the sugarcane expressed sequence tag (SUCEST database for the presence of expressed sequence tags (ESTs with similarity to nuclear genes related to mitochondrial functions. Starting with 869 protein sequences, we searched for sugarcane EST counterparts to these proteins using the basic local alignment search tool TBLASTN similarity searching program run against 260,781 sugarcane ESTs contained in 81,223 clusters. We were able to recover 367 clusters likely to represent sugarcane orthologues of the corresponding genes from S. cerevisiae, H. sapiens and A. thaliana with E-value <= 10-10. Gene products belonging to all functional categories related to mitochondrial functions were found and this allowed us to produce an overview of the nuclear genes required for sugarcane mitochondrial biogenesis and function as well as providing a starting point for detailed analysis of sugarcane gene structure and physiology.

  18. Two-Loop Beam and Soft Functions for Rapidity-Dependent Jet Vetoes

    CERN Document Server

    Gangal, Shireen; Stahlhofen, Maximilian; Tackmann, Frank J

    2016-01-01

    Jet vetoes play an important role in many analyses at the LHC. Traditionally, jet vetoes have been imposed using a restriction on the transverse momentum $p_{Tj}$ of jets. Alternatively, one can also consider jet observables for which $p_{Tj}$ is weighted by a smooth function of the jet rapidity $y_j$ that vanishes as $|y_j| \\to \\infty$. Such observables are useful as they provide a natural way to impose a tight veto on central jets but a looser one at forward rapidities. We consider two such rapidity-dependent jet veto observables, $\\mathcal{T}_{Bj}$ and $\\mathcal{T}_{Cj}$, and compute the required beam and dijet soft functions for the jet-vetoed color-singlet production cross section at two loops. At this order, clustering effects from the jet algorithm become important. The dominant contributions are computed fully analytically while corrections that are subleading in the limit of small jet radii are expressed in terms of finite numerical integrals. Our results enable the full NNLL' resummation and are an ...

  19. Studying Functions of All Yeast Genes Simultaneously

    Science.gov (United States)

    Stolc, Viktor; Eason, Robert G.; Poumand, Nader; Herman, Zelek S.; Davis, Ronald W.; Anthony Kevin; Jejelowo, Olufisayo

    2006-01-01

    A method of studying the functions of all the genes of a given species of microorganism simultaneously has been developed in experiments on Saccharomyces cerevisiae (commonly known as baker's or brewer's yeast). It is already known that many yeast genes perform functions similar to those of corresponding human genes; therefore, by facilitating understanding of yeast genes, the method may ultimately also contribute to the knowledge needed to treat some diseases in humans. Because of the complexity of the method and the highly specialized nature of the underlying knowledge, it is possible to give only a brief and sketchy summary here. The method involves the use of unique synthetic deoxyribonucleic acid (DNA) sequences that are denoted as DNA bar codes because of their utility as molecular labels. The method also involves the disruption of gene functions through deletion of genes. Saccharomyces cerevisiae is a particularly powerful experimental system in that multiple deletion strains easily can be pooled for parallel growth assays. Individual deletion strains recently have been created for 5,918 open reading frames, representing nearly all of the estimated 6,000 genetic loci of Saccharomyces cerevisiae. Tagging of each deletion strain with one or two unique 20-nucleotide sequences enables identification of genes affected by specific growth conditions, without prior knowledge of gene functions. Hybridization of bar-code DNA to oligonucleotide arrays can be used to measure the growth rate of each strain over several cell-division generations. The growth rate thus measured serves as an index of the fitness of the strain.

  20. Effect of Sildenafil on Pressure–Volume Loop Measures of Ventricular Function in Fontan Patients

    Science.gov (United States)

    Butts, Ryan J.; Chowdhury, Shahryar M.; Baker, George H.; Bandisode, Varsha; Savage, Andrew J.; Atz, Andrew M.

    2016-01-01

    Sildenafil has been reported to improve exercise capacity in Fontan patients, but the physiologic mechanisms behind these findings are not completely understood. The objective of this study was to study the acute effect of sildenafil on pressure–volume loop (PVL) measures of ventricular function in Fontan patients. Patients after Fontan operation who were presenting for a clinically indicated catheterization were enrolled. Patients were randomized in a double-blinded fashion to receive placebo (n = 9) or sildenafil (n = 10) 30–90 min prior to catheterization. PVLs were recorded using microconductance catheters at baseline and after infusion of dobutamine (10 mcg/kg/min). The primary outcome was change in ventriculoarterial (VA) coupling. For the entire cohort, VA coupling trended toward improvement with dobutamine (1.4 ± 0.4 to 1.8 ± 0.9, p = 0.07). End-systolic elastance showed improvement (2.6 ± 0.9 to 3.8 ± 1.4 mmHg m2/ml, p sildenafil cohort trended toward having less of an improvement in VA coupling with dobutamine stress (p = 0.06). There were no differences between PVL measures of systolic or diastolic function between treatment groups, both at baseline and after dobutamine infusion. Patients with Fontan circulation had improved contractility and trended toward improvement in VA coupling with dobutamine stress. Acute sildenafil administration was not associated with improved PVL measurements of ventricular function in this population. These results suggest that clinical improvements seen with administration of sildenafil in Fontan patients are not associated with an acute improvement in ventricular function. PMID:26409473

  1. Gene function prediction based on the Gene Ontology hierarchical structure.

    Science.gov (United States)

    Cheng, Liangxi; Lin, Hongfei; Hu, Yuncui; Wang, Jian; Yang, Zhihao

    2014-01-01

    The information of the Gene Ontology annotation is helpful in the explanation of life science phenomena, and can provide great support for the research of the biomedical field. The use of the Gene Ontology is gradually affecting the way people store and understand bioinformatic data. To facilitate the prediction of gene functions with the aid of text mining methods and existing resources, we transform it into a multi-label top-down classification problem and develop a method that uses the hierarchical relationships in the Gene Ontology structure to relieve the quantitative imbalance of positive and negative training samples. Meanwhile the method enhances the discriminating ability of classifiers by retaining and highlighting the key training samples. Additionally, the top-down classifier based on a tree structure takes the relationship of target classes into consideration and thus solves the incompatibility between the classification results and the Gene Ontology structure. Our experiment on the Gene Ontology annotation corpus achieves an F-value performance of 50.7% (precision: 52.7% recall: 48.9%). The experimental results demonstrate that when the size of training set is small, it can be expanded via topological propagation of associated documents between the parent and child nodes in the tree structure. The top-down classification model applies to the set of texts in an ontology structure or with a hierarchical relationship.

  2. Identifying Functional Requirements for Flexible Airspace Management Concept Using Human-In-The-Loop Simulations

    Science.gov (United States)

    Lee, Paul U.; Bender, Kim; Pagan, Danielle

    2011-01-01

    Flexible Airspace Management (FAM) is a mid- term Next Generation Air Transportation System (NextGen) concept that allows dynamic changes to airspace configurations to meet the changes in the traffic demand. A series of human-in-the-loop (HITL) studies have identified procedures and decision support requirements needed to implement FAM. This paper outlines a suggested FAM procedure and associated decision support functionality based on these HITL studies. A description of both the tools used to support the HITLs and the planned NextGen technologies available in the mid-term are presented and compared. The mid-term implementation of several NextGen capabilities, specifically, upgrades to the Traffic Management Unit (TMU), the initial release of an en route automation system, the deployment of a digital data communication system, a more flexible voice communications network, and the introduction of a tool envisioned to manage and coordinate networked ground systems can support the implementation of the FAM concept. Because of the variability in the overall deployment schedule of the mid-term NextGen capabilities, the dependency of the individual NextGen capabilities are examined to determine their impact on a mid-term implementation of FAM. A cursory review of the different technologies suggests that new functionality slated for the new en route automation system is a critical enabling technology for FAM, as well as the functionality to manage and coordinate networked ground systems. Upgrades to the TMU are less critical but important nonetheless for FAM to be fully realized. Flexible voice communications network and digital data communication system could allow more flexible FAM operations but they are not as essential.

  3. Constraints and Adaptation of Closed-Loop Neuroprosthetics for Functional Restoration

    Science.gov (United States)

    Bauer, Robert; Gharabaghi, Alireza

    2017-01-01

    Closed-loop neuroprosthetics aim to compensate for lost function, e.g., by controlling external devices such as prostheses or wheelchairs. Such assistive approaches seek to maximize speed and classification accuracy for high-dimensional control. More recent approaches use similar technology, but aim to restore lost motor function in the long term. To achieve this goal, restorative neuroprosthetics attempt to facilitate motor re-learning and to strengthen damaged and/or alternative neural connections on the basis of neurofeedback training within rehabilitative environments. Such a restorative approach requires reinforcement learning of self-modulated brain activity which is considered to be beneficial for functional rehabilitation, e.g., improvement of β-power modulation over sensorimotor areas for post-stroke movement restoration. Patients with motor impairments, however, may also have a compromised ability for motor task-related regulation of the targeted brain activity. This would affect the estimation of feature weights and hence the classification accuracy of the feedback device. This, in turn, can frustrate the patients and compromise their motor learning. Furthermore, the feedback training may even become erroneous when unconstrained classifier adaptation—which is often used in assistive approaches—is also applied in this rehabilitation context. In conclusion, the conceptual switch from assistance toward restoration necessitates a methodological paradigm shift from classification accuracy toward instructional efficiency. Furthermore, a constrained feature space, a priori regularized feature weights, and difficulty adaptation present key elements of restorative brain interfaces. These factors need, therefore, to be addressed within a therapeutic framework to facilitate reinforcement learning of brain self-regulation for restorative purposes. PMID:28348511

  4. Structure, expression and functions of MTA genes.

    Science.gov (United States)

    Kumar, Rakesh; Wang, Rui-An

    2016-05-15

    Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA. However, MTA proteins interact with a variety of chromatin remodeling factors and complexes with enzymatic activities for modulating the plasticity of nucleosomes, leading to the repression or derepression of target genes or other extra-nuclear and nucleosome remodeling and histone deacetylase (NuRD)-complex independent activities. The functions of MTA family members are driven by the steady state levels and subcellular localization of MTA proteins, the dynamic nature of modifying signals and enzymes, the structural features and post-translational modification of protein domains, interactions with binding proteins, and the nature of the engaged and resulting features of nucleosomes in the proximity of target genes. In general, MTA1 and MTA2 are the most upregulated genes in human cancer and correlate well with aggressive phenotypes, therapeutic resistance, poor prognosis and ultimately, unfavorable survival of cancer patients. Here we will discuss the structure, expression and functions of the MTA family of genes in the context of cancer cells.

  5. Cliff-wall surgery and vanishing of basic phase function for contractible topological Hamiltonian loop

    CERN Document Server

    Oh, Yong-Geun

    2012-01-01

    The main purpose of this note is to rectify the incomplete proof given in arXiv:1111.5992 of the following result, when $\\dim M = 2$. High dimensional cases will be treated elsewhere: For any \\emph{contractible topological Hamiltonian loop} $\\phi_F$, $$ f_{\\underline{\\mathbb F}} \\equiv 0, \\quad \\mathbb F(t,x,y) := F(t,x) $$ where $f_{\\underline{\\mathbb F}} := \\lim_{i \\to \\infty} f_{\\underline{\\mathbb F_i}}$ for an approximating sequence $F_i$ of $F$. Here $f_{\\underline{\\mathbb F_i}}$ is the basic phase function of the Lagrangian submanifold $\\phi_{\\mathbb F_i}^1(o_\\Delta) = \\Graph \\phi_{F_i}^1$ which is the graph selector previously constructed by Lagrangian Floer theory. A complete revision of the paper "Homotopy invariance of spectral invariants of topological Hamiltonian flows and its Lagrangian analog" in dimension 2, which combines Part I of arXiv:1111.5992(v5) and this note, is available in the author's homepage (http://www.math.wisc.edu/~oh/preprints.html).

  6. The Response Clamp: Functional characterization of neural systems using closed-loop control

    Directory of Open Access Journals (Sweden)

    Avner eWallach

    2013-01-01

    Full Text Available The voltage clamp method, pioneered by Hodgkin, Huxley and Katz, laid the foundations to neurophysiological research. Its core rationale is the use of closed-loop control as a tool for system characterization. A recently introduced method, the response clamp, extends the voltage clamp rationale to the functional, phenomenological level. The method consists of on-line estimation of a response variable of interest (e.g. the probability of response or its latency and a simple feedback control mechanism designed to tightly converge this variable towards a desired trajectory. In the present contribution I offer a perspective on this novel method and its applications in the broader context of system identification and characterization. First, I demonstrate how internal state variables are exposed using the method, and how the use of several controllers may allow for a detailed, multi-variable characterization of the system. Second, I discuss three different categories of applications of the method: (i exploration of intrinsically generated dynamics, (ii exploration of extrinsically generated dynamics and (iii generation of input-output trajectories. The relation of these categories to similar uses in the voltage clamp and other techniques is also discussed. Finally, I discuss the method’s limitations, as well as its possible synthesis with existing complementary approaches.

  7. Three-Point Functions in c≤1 Liouville Theory and Conformal Loop Ensembles.

    Science.gov (United States)

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

    2016-04-01

    The possibility of extending the Liouville conformal field theory from values of the central charge c≥25 to c≤1 has been debated for many years in condensed matter physics as well as in string theory. It was only recently proven that such an extension-involving a real spectrum of critical exponents as well as an analytic continuation of the Dorn-Otto-Zamolodchikov-Zamolodchikov formula for three-point couplings-does give rise to a consistent theory. We show in this Letter that this theory can be interpreted in terms of microscopic loop models. We introduce in particular a family of geometrical operators, and, using an efficient algorithm to compute three-point functions from the lattice, we show that their operator algebra corresponds exactly to that of vertex operators V_{α[over ^]} in c≤1 Liouville theory. We interpret geometrically the limit α[over ^]→0 of V_{α[over ^]} and explain why it is not the identity operator (despite having conformal weight Δ=0).

  8. C-edge loops of arrestin function as a membrane anchor

    Science.gov (United States)

    Lally, Ciara C M.; Bauer, Brian; Selent, Jana; Sommer, Martha E

    2017-01-01

    G-protein-coupled receptors are membrane proteins that are regulated by a small family of arrestin proteins. During formation of the arrestin–receptor complex, arrestin first interacts with the phosphorylated receptor C terminus in a pre-complex, which activates arrestin for tight receptor binding. Currently, little is known about the structure of the pre-complex and its transition to a high-affinity complex. Here we present molecular dynamics simulations and site-directed fluorescence experiments on arrestin-1 interactions with rhodopsin, showing that loops within the C-edge of arrestin function as a membrane anchor. Activation of arrestin by receptor-attached phosphates is necessary for C-edge engagement of the membrane, and we show that these interactions are distinct in the pre-complex and high-affinity complex in regard to their conformation and orientation. Our results expand current knowledge of C-edge structure and further illuminate the conformational transitions that occur in arrestin along the pathway to tight receptor binding. PMID:28220785

  9. Three-Point Functions in c ≤1 Liouville Theory and Conformal Loop Ensembles

    Science.gov (United States)

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

    2016-04-01

    The possibility of extending the Liouville conformal field theory from values of the central charge c ≥25 to c ≤1 has been debated for many years in condensed matter physics as well as in string theory. It was only recently proven that such an extension—involving a real spectrum of critical exponents as well as an analytic continuation of the Dorn-Otto-Zamolodchikov-Zamolodchikov formula for three-point couplings—does give rise to a consistent theory. We show in this Letter that this theory can be interpreted in terms of microscopic loop models. We introduce in particular a family of geometrical operators, and, using an efficient algorithm to compute three-point functions from the lattice, we show that their operator algebra corresponds exactly to that of vertex operators Vα ^ in c ≤1 Liouville theory. We interpret geometrically the limit α ^→0 of Vα ^ and explain why it is not the identity operator (despite having conformal weight Δ =0 ).

  10. Functional analysis of plastid-encoded genes

    OpenAIRE

    Swiatek, Magdalena

    2002-01-01

    Plastid chromosomes from the variety of plant species contain several conserved open reading frames of unknown function, which most probably represent functional genes. The primary aim of this thesis was the analysis of the role of two such ORFs, designated ycfs or hypothetical chloroplast reading frames, namely ycf9 (ORF62) and ycf10 (ORF229, cemA). Both were analyzed in Nicotiana tabacum (tobacco) via their inactivation using biolistic plastid transformation. A new experiment...

  11. The five-loop beta function of Yang-Mills theory with fermions

    Science.gov (United States)

    Herzog, F.; Ruijl, B.; Ueda, T.; Vermaseren, J. A. M.; Vogt, A.

    2017-02-01

    We have computed the five-loop corrections to the scale dependence of the renormalized coupling constant for Quantum Chromodynamics (QCD), its generalization to non-Abelian gauge theories with a simple compact Lie group, and for Quantum Electrodynamics (QED). Our analytical result, obtained using the background field method, infrared rearrangement via a new diagram-by-diagram implementation of the R* operation and the Forcer program for massless four-loop propagators, confirms the QCD and QED results obtained by only one group before. The numerical size of the five-loop corrections is briefly discussed in the standard overline{MS} scheme for QCD with n f flavours and for pure SU( N) Yang-Mills theory. Their effect in QCD is much smaller than the four-loop contributions, even at rather low scales.

  12. Effect of a Radiation Cooling and Heating Function on Standing Longitudinal Oscillations in Coronal Loops

    Science.gov (United States)

    Kumar, S.; Nakariakov, V. M.; Moon, Y.-J.

    2016-06-01

    Standing long-period (with periods longer than several minutes) oscillations in large, hot (with a temperature higher than 3 MK) coronal loops have been observed as the quasi-periodic modulation of the EUV and microwave intensity emission and the Doppler shift of coronal emission lines, and they have been interpreted as standing slow magnetoacoustic (longitudinal) oscillations. Quasi-periodic pulsations of shorter periods, detected in thermal and non-thermal emissions in solar flares could be produced by a similar mechanism. We present theoretical modeling of the standing slow magnetoacoustic mode, showing that this mode of oscillation is highly sensitive to peculiarities of the radiative cooling and heating function. We generalized the theoretical model of standing slow magnetoacoustic oscillations in a hot plasma, including the effects of the radiative losses and accounting for plasma heating. The heating mechanism is not specified and taken empirically to compensate the cooling by radiation and thermal conduction. It is shown that the evolution of the oscillations is described by a generalized Burgers equation. The numerical solution of an initial value problem for the evolutionary equation demonstrates that different dependences of the radiative cooling and plasma heating on the temperature lead to different regimes of the oscillations, including growing, quasi-stationary, and rapidly decaying. Our findings provide a theoretical foundation for probing the coronal heating function and may explain the observations of decayless long-period, quasi-periodic pulsations in flares. The hydrodynamic approach employed in this study should be considered with caution in the modeling of non-thermal emission associated with flares, because it misses potentially important non-hydrodynamic effects.

  13. The three-loop $\\beta$-function of SU(N) lattice gauge theories with overlap fermions

    CERN Document Server

    Constantinou, M

    2007-01-01

    We briefly report our calculation of the 2-loop coefficient of the coupling constant renormalization function Z_g in lattice perturbation theory. The quantity under study is defined through g_0 = Z_g g, where g_0 (g) is the bare (renormalized) coupling constant. The 2-loop expression for Z_g can be directly related to the 3-loop bare beta-function beta_L(g_0). Our calculation is performed using overlap fermions and Wilson gluons, and the background field technique has been chosen for convenience. Our results depend explicitly on the number of fermion flavors (N_f) and colors (N). Since the dependence of Z_g on the overlap parameter rho cannot be extracted analytically, we tabulate our results for different values of rho in the allowed range (0loop results for Z_g versus rho exhibit a nontrivial dependence on the overlap parameter. A longer write-up of this work may be found in 0709.4368.

  14. Limited gene flow and partial isolation phylogeography of Himalayan snowcock Tetraogallus himalayensis based on part mitochondrial D-loop sequences

    Institute of Scientific and Technical Information of China (English)

    Xiaoli WANG; Jiangyong QU; Naifa LIU; Xinkang BAO; Sen SONG

    2011-01-01

    Himalayan snowcock Tetraogallus himalayensis are distributed in alpine and subalpine areas in China.We used mitochondrial DNA control-region data to investigate the origin and past demographic change in sixty-seven Himalayan snowcock T.himalayensis.The fragments of 1155 nucleotides from the control region of mitochondrial DNA were sequenced,and 57 polymorphic positions defined 37 haplotypes.A high level of genetic diversity was detected in all populations sampled and may be associated isolation of the mountains and habitat fragmentation and deterioration from Quaternary glaciations.In the phylogenetic tree,all haplotypes grouped into four groups:clade A (Kunlun Mountains clade),clade B (Northern Qinghai-Tibetan Plateau clade),clade C (Tianshan Mountains clade) and clade D (Kalakunlun Mountains clade).We found a low level of gene flow and significant genetic differentiation among all populations.Based on divergence time we suggest that the divergence of Himalayan snowcock occurred in the middle Pleistocene inter-glaciation,and expansion occurred in the glaciation.Analysis of mtDNA D-loop sequences confirmed demographic population expansion,as did our non-significant mismatch distribution analysis.In conclusion,limited gene flow and a pattern of partial isolation phylogeographic was found in geographic populations of T.himalayansis based on the analysis on mtDNA D-loop sequences [Current Zoology 57 (6):758-767,2011 ].

  15. Clock genes, pancreatic function, and diabetes.

    Science.gov (United States)

    Vieira, Elaine; Burris, Thomas P; Quesada, Ivan

    2014-12-01

    Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic β cells, glucose homeostasis, and diabetes.

  16. Functional importance of GGXG sequence motifs in putative reentrant loops of 2HCT and ESS transport proteins.

    Science.gov (United States)

    Dobrowolski, Adam; Lolkema, Juke S

    2009-08-11

    The 2HCT and ESS families are two families of secondary transporters. Members of the two families are unrelated in amino acid sequence but share similar hydropathy profiles, which suggest a similar folding of the proteins in membranes. Structural models show two homologous domains containing five transmembrane segments (TMSs) each, with a reentrant or pore loop between the fourth and fifth TMSs in each domain. Here we show that GGXG sequence motifs present in the putative reentrant loops are important for the activity of the transporters. Mutation of the conserved Gly residues to Cys in the motifs of the Na(+)-citrate transporter CitS in the 2HCT family and the Na(+)-glutamate transporter GltS in the ESS family resulted in strongly reduced transport activity. Similarly, mutation of the variable residue "X" to Cys in the N-terminal half of GltS essentially inactivated the transporter. The corresponding mutations in the N- and C-terminal halves of CitS reduced transport activity to 60 and 25% of that of the wild type, respectively. Residual activity of any of the mutants could be further reduced by treatment with the membrane permeable thiol reagent N-ethylmaleimide (NEM). The X to Cys mutation (S405C) in the cytoplasmic loop in the C-terminal half of CitS rendered the protein sensitive to the bulky, membrane impermeable thiol reagent 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid (AmdiS) added at the periplasmic side of the membrane, providing further evidence that this part of the loop is positioned between the transmembrane segments. The putative reentrant loop in the C-terminal half of the ESS family does not contain the GGXG motif, but a conserved stretch rich in Gly residues. Cysteine-scanning mutagenesis of a stretch of 18 residues in the GltS protein revealed two residues important for function. Mutant N356C was completely inactivated by treatment with NEM, and mutant P351C appeared to be the counterpart of mutant S405C of CitS; the mutant was

  17. Understanding looping kinetics of a long polymer molecule in solution. Exact solution for delta function sink model

    Science.gov (United States)

    Ganguly, Moumita; Chakraborty, Aniruddha

    2017-10-01

    A diffusion theory for intramolecular reactions of polymer chain in dilute solution is formulated. We give a detailed analytical expression for calculation of rate of polymer looping in solution. The physical problem of looping can be modeled mathematically with the use of a Smoluchowski-like equation with a Dirac delta function sink of finite strength. The solution of this equation is expressed in terms of Laplace Transform of the Green's function for end-to-end motion of the polymer in absence of the sink. We have defined two different rate constants, the long term rate constant and the average rate constant. The average rate constant and long term rate constant varies with several parameters such as length of the polymer (N), bond length (b) and the relaxation time τR. The long term rate constant is independent of the initial probability distribution.

  18. Outage Key Safety Functions Configuration risk assessment for a three loops Westinghouse PWR

    Energy Technology Data Exchange (ETDEWEB)

    Cid, M.M.; Dies, J., E-mail: javier.Dies@Upc.Edu; Tapia, C., E-mail: carlos.Tapia@Upc.Edu; Diaz, P., E-mail: pedro.diaz.bayona@upc.edu

    2015-09-15

    Highlights: • The paper evaluates the use of PSA on the Outage configuration risk management. • A method is proposed based on Risk Criteria to evaluate the OKSFs’ Configurations. • The methodology allows to identify which of the OKSFs can be analyzed using PSA. • The method has been applied to a Pilot real case. The OKSFs procedure is evaluated. - Abstract: The methodology developed provides guidance on the use of Probabilistic Safety Assessment (PSA) for the risk-informed evaluation of Guides which ensure the compliment of Outage Key Safety Functions (OKSFs) in Nuclear Power Plants. The methodology has been applied to the 3rd and 13th Plant Operational States (POSs) as a pilot experience. These POSs are within the Operating Mode 4 (Hot Shutdown) of a three loops Westinghouse Pressurized Water Reactor. The addressed Guide requires the operability of just one charge pump as boric acid supply source. PSA gives a Core Damage Frequency increase (ΔCDF) of 1.19 × 10{sup −6} year{sup −1} for the unavailability of the charge pump in standby, consequently, the maximum exposure time (time for the Increase of Core Damage Probability of the configuration to reach 1.0E−06) for this situation is T = 53.6 h. Given an average time for the POSs of 40 h, it is concluded that the charge pumps requirement is correct. However, it could be improved with the inclusion of an additional inventory replacement function. This would limit the effect on risk of the charge pump unavailability. Furthermore, the need for the external electrical sources to be available during Mode 4 is ratified. The procedure requires the operability of both supply sources during the POSs. The unavailability of one of supply sources them involves a ΔCDF equal to 1.64 × 10{sup −5} year{sup −1} and a maximum exposure time of T = 3.89 h. This requirement is considered appropriate from the risk-informed regulation point of view.

  19. Loop-mediated isothermal amplification assay for 16S rRNA methylase genes in Gram-negative bacteria.

    Science.gov (United States)

    Nagasawa, Mitsuaki; Kaku, Mitsuo; Kamachi, Kazunari; Shibayama, Keigo; Arakawa, Yoshichika; Yamaguchi, Keizo; Ishii, Yoshikazu

    2014-10-01

    Using the loop-mediated isothermal amplification (LAMP) method, we developed a rapid assay for detection of 16S rRNA methylase genes (rmtA, rmtB, and armA), and investigated 16S rRNA methylase-producing strains among clinical isolates. Primer Explorer V3 software was used to design the LAMP primers. LAMP primers were prepared for each gene, including two outer primers (F3 and B3), two inner primers (FIP and BIP), and two loop primers (LF and LB). Detection was performed with the Loopamp DNA amplification kit. For all three genes (rmtA, rmtB, and armA), 10(2) copies/tube could be detected with a reaction time of 60 min. When nine bacterial species (65 strains saved in National Institute of Infectious Diseases) were tested, which had been confirmed to possess rmtA, rmtB, or armA by PCR and DNA sequencing, the genes were detected correctly in these bacteria with no false negative or false positive results. Among 8447 clinical isolates isolated at 36 medical institutions, the LAMP method was conducted for 191 strains that were resistant to aminoglycosides based on the results of antimicrobial susceptibility tests. Eight strains were found to produce 16S rRNA methylase (0.09%), with rmtB being identified in three strains (0.06%) of 4929 isolates of Enterobacteriaceae, rmtA in three strains (0.10%) of 3284 isolates of Pseudomonas aeruginosa, and armA in two strains (0.85%) of 234 isolates of Acinetobacter spp. At present, the incidence of strains possessing 16S rRNA methylase genes is very low in Japan. However, when Gram-negative bacteria showing high resistance to aminoglycosides are isolated by clinical laboratories, it seems very important to investigate the status of 16S rRNA methylase gene-harboring bacilli and monitor their trends among Japanese clinical settings.

  20. Evolution and function of de novo originated genes.

    Science.gov (United States)

    Wu, Dong-Dong; Zhang, Ya-Ping

    2013-05-01

    De novo origination has recently been appreciated to be an important mechanism contributing to the origin of genes. Evidence indicates that de novo originated genes can evolve important and even essential functions rapidly. We present an "adaptation following neutrality" process to explain the evolution of essential function of new genes. How new de novo originated genes become involved in pathways and interact with other old genes, and the exact functions of these new genes, however, remains largely undocumented. Examinations of the function of de novo origin and the function of noncoding RNA genes should become more frequent and appreciated in the future studies.

  1. Yeast expression and DNA immunization of hepatitis B virus S gene with second-loop deletion of α determinant region

    Institute of Scientific and Technical Information of China (English)

    Hui Hu; Xiao-Mou Peng; Yang-Su Huang; Lin Gu; Qi-Feng Xie; Zhi-Liang Gao

    2004-01-01

    AIM: Immune escape mutations of HBV often occur in the dominant epitope, the second-loop of the a determinant of hepatitis B surface antigen (HBsAg). To let the hosts respond to the subdominant epitopes in HBsAg may be an effective way to decrease the prevalence of immune escape mutants. For this reason, a man-made clone of HBV S gene with the second-loop deletion was constructed. Its antigenicity was evaluated by yeast expression analysis and DNA immunization in mice.METHODS: HBV S gene with deleted second-loop, amino acids from 139 to 145, was generated using splicing by overlap extension. HBV deleted S gene was then cloned into the yeast expression vector pPIC9 and the mammalian expression vector pcDNA3 to generate pHB-SDY and pHB-SD,respectively. The complete S gene was cloned into the same vectors as controls. The deleted recombinant HBsAg expressed in yeasts was detected using Abbott IMx HBsAg test kits, enzyme-linked immunoadsorbent assay (ELISA)and immune dot blotting to evaluate its antigenicity in vitro.The anti-HBs responses to DNA immunization in BALB/c mice were detected using Abbott IMx AUSAB test kits to evaluate the antigenicity of that recombinant protein in vivo.RESULTS: Both deleted and complete HBsAg were successfully expressed in yeasts. They were intracellular expressions. The deleted HBsAg could not be detected by ELISA, in which the monoclonal anti-HBs against the α determinant was used, but could be detected by Abbott IMx and immune dot blotting, in which multiple monoclonal antiHBs and polyclonal anti-HBs were used, respectively. The activity of the deleted HBsAg detected by Abbott IMx was much lower than that of complete HBsAg (the ratio of sample value/cut off value, 106±26.7 vs1 814.4±776.3, P<0.01,t = 5.02). The anti-HBs response of pHB-SD to DNA immunization was lower than that of complete HBV S gene vector pHB (the positive rate 2/10 vs6/10, 4.56±3.52 mIU/mL vs27.60±17.3 mIU/mL, P= 0.02, t= 2.7).CONCLUSIONS: HBsAg with deleted

  2. GO-based Functional Dissimilarity of Gene Sets

    Directory of Open Access Journals (Sweden)

    Aguilar-Ruiz Jesús S

    2011-09-01

    Full Text Available Abstract Background The Gene Ontology (GO provides a controlled vocabulary for describing the functions of genes and can be used to evaluate the functional coherence of gene sets. Many functional coherence measures consider each pair of gene functions in a set and produce an output based on all pairwise distances. A single gene can encode multiple proteins that may differ in function. For each functionality, other proteins that exhibit the same activity may also participate. Therefore, an identification of the most common function for all of the genes involved in a biological process is important in evaluating the functional similarity of groups of genes and a quantification of functional coherence can helps to clarify the role of a group of genes working together. Results To implement this approach to functional assessment, we present GFD (GO-based Functional Dissimilarity, a novel dissimilarity measure for evaluating groups of genes based on the most relevant functions of the whole set. The measure assigns a numerical value to the gene set for each of the three GO sub-ontologies. Conclusions Results show that GFD performs robustly when applied to gene set of known functionality (extracted from KEGG. It performs particularly well on randomly generated gene sets. An ROC analysis reveals that the performance of GFD in evaluating the functional dissimilarity of gene sets is very satisfactory. A comparative analysis against other functional measures, such as GS2 and those presented by Resnik and Wang, also demonstrates the robustness of GFD.

  3. Structure-Function Model for Kissing Loop Interactions That Initiate Dimerization of Ty1 RNA

    Directory of Open Access Journals (Sweden)

    Eric R. Gamache

    2017-04-01

    Full Text Available The genomic RNA of the retrotransposon Ty1 is packaged as a dimer into virus-like particles. The 5′ terminus of Ty1 RNA harbors cis-acting sequences required for translation initiation, packaging and initiation of reverse transcription (TIPIRT. To identify RNA motifs involved in dimerization and packaging, a structural model of the TIPIRT domain in vitro was developed from single-nucleotide resolution RNA structural data. In general agreement with previous models, the first 326 nucleotides of Ty1 RNA form a pseudoknot with a 7-bp stem (S1, a 1-nucleotide interhelical loop and an 8-bp stem (S2 that delineate two long, structured loops. Nucleotide substitutions that disrupt either pseudoknot stem greatly reduced helper-Ty1-mediated retrotransposition of a mini-Ty1, but only mutations in S2 destabilized mini-Ty1 RNA in cis and helper-Ty1 RNA in trans. Nested in different loops of the pseudoknot are two hairpins with complementary 7-nucleotide motifs at their apices. Nucleotide substitutions in either motif also reduced retrotransposition and destabilized mini- and helper-Ty1 RNA. Compensatory mutations that restore base-pairing in the S2 stem or between the hairpins rescued retrotransposition and RNA stability in cis and trans. These data inform a model whereby a Ty1 RNA kissing complex with two intermolecular kissing-loop interactions initiates dimerization and packaging.

  4. Structure-Function Model for Kissing Loop Interactions That Initiate Dimerization of Ty1 RNA.

    Science.gov (United States)

    Gamache, Eric R; Doh, Jung H; Ritz, Justin; Laederach, Alain; Bellaousov, Stanislav; Mathews, David H; Curcio, M Joan

    2017-04-26

    The genomic RNA of the retrotransposon Ty1 is packaged as a dimer into virus-like particles. The 5' terminus of Ty1 RNA harbors cis-acting sequences required for translation initiation, packaging and initiation of reverse transcription (TIPIRT). To identify RNA motifs involved in dimerization and packaging, a structural model of the TIPIRT domain in vitro was developed from single-nucleotide resolution RNA structural data. In general agreement with previous models, the first 326 nucleotides of Ty1 RNA form a pseudoknot with a 7-bp stem (S1), a 1-nucleotide interhelical loop and an 8-bp stem (S2) that delineate two long, structured loops. Nucleotide substitutions that disrupt either pseudoknot stem greatly reduced helper-Ty1-mediated retrotransposition of a mini-Ty1, but only mutations in S2 destabilized mini-Ty1 RNA in cis and helper-Ty1 RNA in trans. Nested in different loops of the pseudoknot are two hairpins with complementary 7-nucleotide motifs at their apices. Nucleotide substitutions in either motif also reduced retrotransposition and destabilized mini- and helper-Ty1 RNA. Compensatory mutations that restore base-pairing in the S2 stem or between the hairpins rescued retrotransposition and RNA stability in cis and trans. These data inform a model whereby a Ty1 RNA kissing complex with two intermolecular kissing-loop interactions initiates dimerization and packaging.

  5. Functional properties of the basal ganglia's re-entrant loop architecture: selection and reinforcement.

    Science.gov (United States)

    Redgrave, P; Vautrelle, N; Reynolds, J N J

    2011-12-15

    Multifunctional agents with limited motor resources must decide what actions will best ensure their survival. Moreover, given that in an unpredictable world things don't always work out, considerable advantage is to be gained by learning from experience - instrumental behaviour that maximises reward and minimises punishment. In this review we will argue that the re-entrant looped architecture of the basal ganglia represents biological solutions to these fundamental behavioural problems of selection and reinforcement. A potential solution to the selection problem is provided for by selective disinhibition within the parallel loop architecture that connects the basal ganglia with external neural structures. The relay points within these loops permit the signals of a particular channel to be modified by external influences. In part, these influences have the capacity to modify overall selections so that the probability of re-selecting reinforced behaviours in the future is altered. This is the basic process of instrumental learning, which we suggest decomposes into two sub-problems for the agent: (i) learning which external events it causes to happen and learning precisely what it is doing that is causal; and (ii) having determined agency and discovered novel action-outcome routines, how best to exploit this knowledge to maximise future reward acquisitions. Considerations of connectional architecture and signal timing suggest that the short-latency, sensory-evoked dopamine response, which can modulate the re-entrant loop structure within the basal ganglia, is ideally suited to reinforce the determination of agency and the discovery of novel actions. Alternatively, recent studies showing that presence or absence of reward can selectively modulate the magnitude of signals in structures providing input signals to the basal ganglia, offer an alternative mechanism for biasing selection within the re-entrant loop architecture. We suggest that this mechanism may be better

  6. Closed-loop spontaneous baroreflex transfer function is inappropriate for system identification of neural arc but partly accurate for peripheral arc: predictability analysis.

    Science.gov (United States)

    Kamiya, Atsunori; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

    2011-04-01

    Although the dynamic characteristics of the baroreflex system have been described by baroreflex transfer functions obtained from open-loop analysis, the predictability of time-series output dynamics from input signals, which should confirm the accuracy of system identification, remains to be elucidated. Moreover, despite theoretical concerns over closed-loop system identification, the accuracy and the predictability of the closed-loop spontaneous baroreflex transfer function have not been evaluated compared with the open-loop transfer function. Using urethane and α-chloralose anaesthetized, vagotomized and aortic-denervated rabbits (n = 10), we identified open-loop baroreflex transfer functions by recording renal sympathetic nerve activity (SNA) while varying the vascularly isolated intracarotid sinus pressure (CSP) according to a binary random (white-noise) sequence (operating pressure ± 20 mmHg), and using a simplified equation to calculate closed-loop-spontaneous baroreflex transfer function while matching CSP with systemic arterial pressure (AP). Our results showed that the open-loop baroreflex transfer functions for the neural and peripheral arcs predicted the time-series SNA and AP outputs from measured CSP and SNA inputs, with r2 of 0.8 ± 0.1 and 0.8 ± 0.1, respectively. In contrast, the closed-loop-spontaneous baroreflex transfer function for the neural arc was markedly different from the open-loop transfer function (enhanced gain increase and a phase lead), and did not predict the time-series SNA dynamics (r2; 0.1 ± 0.1). However, the closed-loop-spontaneous baroreflex transfer function of the peripheral arc partially matched the open-loop transfer function in gain and phase functions, and had limited but reasonable predictability of the time-series AP dynamics (r2, 0.7 ± 0.1). A numerical simulation suggested that a noise predominantly in the neural arc under resting conditions might be a possible mechanism responsible for our findings. Furthermore

  7. Variations of mitochondrial D-loop region plus downstream gene 12S rRNA-tRNAphe and gastric carcinomas

    Institute of Scientific and Technical Information of China (English)

    Cheng-Bo Han; Fan Li; Yu-Jie Zhao; Jia-Ming Ma; Dong-Ying Wu; Yu-Kui Zhang; Yan Xin

    2003-01-01

    AIM: To explore the instabilities, polymorphisms and other variations of mitochondrial D-loop region and downstream gene 12S rRNA-tRNAPhe in gastric cancers, and to study their relationship with gastric cancer.METHODS: Three adjacent regions (D-loop, tRNAphe and 12S rRNA) were detected for instabilities, polymorphisms and other variations via PCR amplification followed by direct DNA sequencing in 22 matched gastric cancerous tissues and para-cancerous normal tissues.RESULTS: PolyC or (CA)n instabilities were detected in 13/22(59.1%) gastric cancers and 9/22(40.9 %) in the control (P>0.05). There existed 2/12(16.7%) and 6/10(60%)alterations of 12S rR NA-tRNAphe in well differentiated gastric cancers and poorly differentiated ones, respectively(P0.05).Some new variations were found, among which np 318 and np 321 C-T transitions in D-loop region were two of the five bases for H-strand replication primer. Np 523 AC-deletion and np 527 C-T transition occurred at mtTF1 binding site (mtTFBS), which were associated with the transcription of downstream mitochondrial genome. Seven samples showed the np 16 182 polyC instabilities, five of which simultaneously showed np 16 189 T-C transitions.CONCLUSION: There is no statistic significance of instabilities and polymorphisms in mitochondrial D-loop region between gastric cancerous and para-cancerous normal tissues, which suggests that the instability might relate to heredity or be dependent on aging. There is asignificant correlation between differentiation degree of gastric cancer and variant frequencies of 12S rRNA-tRNAphe. The poorly differentiated gastric cancers are more prone to 12S rRNAtRNAphe variations, or gastric cancers with 12S rRNA-tRNAphe variations are more likely to be poorly differentiated, np 16189 T-C transition may be one of the important reasons for polyC instability in gastric cancer.

  8. Oscillatory Gene Expression by the microRAN Mediating Delayed Negative Feedback Loop

    Institute of Scientific and Technical Information of China (English)

    ZHANG Feng-pan; LU Jin-rui; LIU Zhi-guang

    2013-01-01

    More and more experiments show that microRNAs can regulate gene expression by stimulating degradation of mRNA or repression of translation of mRNA.In this paper,we incorporate the microRNA into a previous mathematical model of gene expression through forming a microRNA-induced silencing complex(RISC).Our findings demonstrate the dynamical behavior of the constructed system.By Hopf theories,we derive the theoretical results of globally asymptotical stability and provide the sufficient conditions for the oscillation of the simple gene regulatory system,and by numerical simulation further demonstrate how the amplitudes against the change of delay in the gene regulatory network.

  9. Periodic solutions of piecewise affine gene network models with non uniform decay rates: the case of a negative feedback loop.

    Science.gov (United States)

    Farcot, Etienne; Gouzé, Jean-Luc

    2009-12-01

    This paper concerns periodic solutions of a class of equations that model gene regulatory networks. Unlike the vast majority of previous studies, it is not assumed that all decay rates are identical. To handle this more general situation, we rely on monotonicity properties of these systems. Under an alternative assumption, it is shown that a classical fixed point theorem for monotone, concave operators can be applied to these systems. The required assumption is expressed in geometrical terms as an alignment condition on so-called focal points. As an application, we show the existence and uniqueness of a stable periodic orbit for negative feedback loop systems in dimension 3 or more, and of a unique stable equilibrium point in dimension 2. This extends a theorem of Snoussi, which showed the existence of these orbits only.

  10. Loop-Mediated Isothermal Amplification Assay Targeting the MOMP Gene for Rapid Detection of Chlamydia psittaci Abortus Strain

    Directory of Open Access Journals (Sweden)

    Guo-Zhen Lin, Fu-Ying Zheng, Ji-Zhang Zhou, Guang-Hua Wang, Xiao-An Cao, Xiao-Wei Gong and Chang-Qing Qiu*

    2012-05-01

    Full Text Available For rapid detection of the Chlamydia psittaci abortus strain, a loop-mediated isothermal amplification (LAMP assay was developed and evaluated in this study. The primers for the LAMP assay were designed on the basis of the main outer membrane protein (MOMP gene sequence of C. psittaci. Analysis showed that the assay could detect the abortus strain of C. psittaci with adequate specificity. The sensitivity of the test was the same as that of the nested-conventional PCR and higher than that of chick embryo isolation. Testing of 153 samples indicated that the LAMP assay could detect the genome of the C. psittaci abortus strain effectively in clinical samples. This assay is a useful tool for rapid diagnosis of C. psittaci infection in sheep, swine and cattle.

  11. Plant STAND P-loop NTPases: a current perspective of genome distribution, evolution, and function : Plant STAND P-loop NTPases: genomic organization, evolution, and molecular mechanism models contribute broadly to plant pathogen defense.

    Science.gov (United States)

    Arya, Preeti; Acharya, Vishal

    2017-09-12

    STAND P-loop NTPase is the common weapon used by plant and other organisms from all three kingdoms of life to defend themselves against pathogen invasion. The purpose of this study is to review comprehensively the latest finding of plant STAND P-loop NTPase related to their genomic distribution, evolution, and their mechanism of action. Earlier, the plant STAND P-loop NTPase known to be comprised of only NBS-LRRs/AP-ATPase/NB-ARC ATPase. However, recent finding suggests that genome of early green plants comprised of two types of STAND P-loop NTPases: (1) mammalian NACHT NTPases and (2) NBS-LRRs. Moreover, YchF (unconventional G protein and members of P-loop NTPase) subfamily has been reported to be exceptionally involved in biotic stress (in case of Oryza sativa), thereby a novel member of STAND P-loop NTPase in green plants. The lineage-specific expansion and genome duplication events are responsible for abundance of plant STAND P-loop NTPases; where "moderate tandem and low segmental duplication" trajectory followed in majority of plant species with few exception (equal contribution of tandem and segmental duplication). Since the past decades, systematic research is being investigated into NBS-LRR function supported the direct recognition of pathogen or pathogen effectors by the latest models proposed via 'integrated decoy' or 'sensor domains' model. Here, we integrate the recently published findings together with the previous literature on the genomic distribution, evolution, and distinct models proposed for functional molecular mechanism of plant STAND P-loop NTPases.

  12. Gauge theories with overlap fermions in an arbitrary representation: Evaluation of the 3-loop beta-function

    CERN Document Server

    Constantinou, M

    2007-01-01

    This work presents the calculation of the relation between the bare coupling constant g_0 and the MSbar-renormalized coupling g_MS, g_0 = Z_g(g_0,a\\mu) g_MS, to 2 loops in perturbation theory, with fermions in an arbitrary representation of the gauge group SU(N). Our calculation is performed using overlap fermions and Wilson gluons, and the background field technique has been chosen for convenience. The corresponding results in the fundamental representation appear in our longer publication [arXiv:0709.4368]. The 3-loop coefficient of the bare beta-function, b_2^L, is extracted using the 2-loop expression for Z_g, and it is presented as a function of the overlap parameter rho, the number of fermion flavors (N_f) and the number of colors (N). We also provide the expression for the ratio Lambda_L/Lambda_MS, in an arbitrary representation. A plot of Lambda_L/Lambda_MS is given in the adjoint representation.

  13. Renormalization constants and beta functions for the gauge couplings of the Standard Model to three-loop order

    CERN Document Server

    Mihaila, Luminita N; Steinhauser, Matthias

    2012-01-01

    We compute the beta functions for the three gauge couplings of the Standard Model in the minimal subtraction scheme to three loops. We take into account contributions from all sectors of the Standard Model. The calculation is performed using both Lorenz gauge in the unbroken phase of the Standard Model and background field gauge in the spontaneously broken phase. Furthermore, we describe in detail the treatment of $\\gamma_5$ and present the automated setup which we use for the calculation of the Feynman diagrams. It starts with the generation of the Feynman rules and leads to the bare result for the Green's function of a given process.

  14. Structure of three-loop contributions to the β-function of N = 1 supersymmetric QED with N f flavors regularized by the dimensional reduction

    Science.gov (United States)

    Aleshin, S. S.; Kataev, A. L.; Stepanyantz, K. V.

    2016-01-01

    In the case of using the higher derivative regularization for N = 1 supersymmetric quantum electrodynamics (SQED) with N f flavors, the loop integrals giving the β-function are integrals of double total derivatives in themomentum space. This feature allows reducing one of the loop integrals to an integral of the δ-function and deriving the Novikov-Shifman-Vainshtein-Zakharov relation for the renormalization group functions defined in terms of the bare coupling constant. We consider N = 1 SQED with N f flavors regularized by the dimensional reduction in the overline {DR} -scheme. Evaluating the scheme-dependent three-loop contribution to the β-function proportional to ( N f)2 we find the structures analogous to integrals of the δ-singularities. After adding the schemeindependent terms proportional to ( N f)1, we obtain the known result for the three-loop β-function.

  15. Rapid detection of the Klebsiella pneumoniae carbapenemase (KPC) gene by loop-mediated isothermal amplification (LAMP).

    Science.gov (United States)

    Nakano, Ryuichi; Nakano, Akiyo; Ishii, Yoshikazu; Ubagai, Tsuneyuki; Kikuchi-Ueda, Takane; Kikuchi, Hirotoshi; Tansho-Nagakawa, Shigeru; Kamoshida, Go; Mu, Xiaoqin; Ono, Yasuo

    2015-03-01

    Klebsiella pneumoniae carbapenemases (KPC), which are associated with resistance to carbapenem, have recently spread worldwide and have become a global concern. It is necessary to detect KPC-producing organisms in clinical settings to be able to control the spread of this resistance. We have developed a loop-mediated isothermal amplification (LAMP) method for rapid detection of KPC producers. LAMP primer sets were designed to recognize the homologous regions of blaKPC-2 to blaKPC-17 and could amplify blaKPC rapidly. The specificity and sensitivity of the primers in the LAMP reactions for blaKPC detection were determined. This LAMP assay was able to specifically detect KPC producers at 68 °C, and no cross-reactivity was observed for other types of β-lactamase (class A, B, C, or D) producers. The detection limit for this assay was found to be 10(0) CFU per tube, in 25 min, which was 10-fold more sensitive than a PCR assay for blaKPC detection. Then, the sensitivity of the LAMP reactions for blaKPC detection in human specimens (sputum samples, urine samples, fecal samples and blood samples) was analyzed; it was observed that the LAMP assay had almost the same sensitivity in these samples as when using purified DNA. The LAMP assay is easy to perform and rapid. It may therefore be routinely applied for detection of KPC producers in the clinical laboratory.

  16. A novel R-loop in mouse mitochondrial DNA

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Mammalian mitochondrial D-loop L-strand RNA (DL-RNA) is thought functionally not important because no obvious function has been found so far. In this study, we detected a novel D-loop L-strand RNA (DL-RNA) in mouse mitochondrion by RT-PCR. The L-strand RNA spans the whole D-loop region of mouse mtDNA, and is resistant to RNase A and RNase T1 but not RNase H digestion. After binding of the L-strand RNA to D-loop, the DL-RNA complex can protect the D-loop from digestion by restriction endonuclease HaeⅢ. These results indicate that a novel RNA-DNA triplex hybrid (R-loop) can be formed in mouse mtDNA D-loop region, and that the DL-RNA structure is capable of protecting the D-loop from certain microbial restriction enzyme digestion. And the similar R-loop structure can not be found in Cyt.b gene in control experiment which confirmed this R-loop is not the fleeting structure in RNA transcription. Considering the D-loop represents the control region of mtDNA, the novel triplex DNA-RNA complex may play an important role in mtDNA replication and transcription.

  17. Tumor-promoting function of apoptotic caspases by an amplification loop involving ROS, macrophages and JNK in Drosophila.

    Science.gov (United States)

    Pérez, Ernesto; Lindblad, Jillian L; Bergmann, Andreas

    2017-08-30

    Apoptosis and its molecular mediators, the caspases, have long been regarded as tumor suppressors and one hallmark of cancer is 'Evading Apoptosis'. However, recent work has suggested that apoptotic caspases can also promote proliferation and tumor growth under certain conditions. How caspases promote proliferation and how cells are protected from the potentially harmful action of apoptotic caspases is largely unknown. Here, we show that although caspases are activated in a well-studied neoplastic tumor model in Drosophila, oncogenic mutations of the proto-oncogene Ras (Ras(V12)) maintain tumorous cells in an 'undead'-like condition and transform caspases from tumor suppressors into tumor promotors. Instead of killing cells, caspases now promote the generation of intra- and extracellular reactive oxygen species (ROS). One function of the ROS is the recruitment and activation of macrophage-like immune cells which in turn signal back to tumorous epithelial cells to activate oncogenic JNK signaling. JNK further promotes and amplifies caspase activity, thereby constituting a feedback amplification loop. Interfering with the amplification loop strongly reduces the neoplastic behavior of these cells and significantly improves organismal survival. In conclusion, Ras(V12)-modified caspases initiate a feedback amplification loop involving tumorous epithelial cells and macrophage-like immune cells that is necessary for uncontrolled tumor growth and invasive behavior.

  18. Functional analysis of fungal polyketide biosynthesis genes.

    Science.gov (United States)

    Fujii, Isao

    2010-05-01

    Fungal polyketides have huge structural diversity from simple aromatics to highly modified complex reduced-type compounds. Despite such diversty, single modular iterative type I polyketide synthases (iPKSs) are responsible for their carbon skeleton construction. Using heterologous expression systems, we have studied on ATX, a 6-methylsalicylic acid synthase from Aspergillus terreus as a model iPKS. In addition, iPKS functions involved in fungal spore pigment biosynthesis were analyzed together with polyketide-shortening enzymes that convert products of PKSs to shorter ketides by hydrolytic C-C bond cleavage. In our studies on reducing-type iPKSs, we cloned and expressed PKS genes, pksN, pksF, pksK and sol1 from Alternaria solani. The sol gene cluster was found to be involved in solanapyrone biosynthesis and sol5 was identified to encode solanapyrone synthase, a Diels-Alder enzyme. Our fungal PKS studies were further extended to identify the function of PKS-nonribosomal peptide synthase involved in cyclopiazonic acid biosynthesis.

  19. Kissing loops hide premature termination codons in pre-mRNAof selenoprotein genes and in genes containing programmedribosomal frameshifts

    DEFF Research Database (Denmark)

    Knudsen, Steen; Brunak, Søren

    1997-01-01

    A novel RNA secondary structure that places the selenocysteine codon UGA in one hairpin and a donor splice site in another, has been discovered in selenoprotein genes. The presence of the structure resolves the discrepancy that the selenocysteine triplet, UGA, should block splicing. Without a spe...

  20. Rapid and specific detection of the thermostable direct hemolysin gene in Vibrio parahaemolyticus by loop-mediated isothermal amplification.

    Science.gov (United States)

    Nemoto, Jiro; Sugawara, Chiyo; Akahane, Kenji; Hashimoto, Keiji; Kojima, Tadashi; Ikedo, Masanari; Konuma, Hirotaka; Hara-Kudo, Yukiko

    2009-04-01

    Several investigators have reported that thermostable direct hemolysin (TDH) and TDH-related hemolysin are important virulence factors of Vibrio parahaemolyticus, but it has been difficult to detect these factors rapidly in seafood and other environmental samples. A novel nucleic acid amplification method, termed the loop-mediated isothermal amplification (LAMP), which amplifies DNA with high specificity and rapidity under isothermal conditions, was applied. In this study, we designed tdh gene-specific LAMP primers for detection of TDH-producing V. parahaemolyticus. The specificity of this assay was evaluated with 32 strains of TDH-producing V. parahaemolyticus, one strain of TDH-producing Grimontia hollisae, 10 strains of TDH-nonproducing V. parahaemolyticus, and 94 strains of TDH-nonproducing bacteria, and the sensitivity was high enough to detect one cell per test. Moreover, to investigate the detection of TDH-producing V. parahaemolyticus in oysters, the LAMP assay was performed with enrichment culture in alkaline peptone water of oyster samples inoculated with TDH-producing V. parahaemolyticus and TDH-nonproducing V. parahaemolyticus and V. alginolyticus after enrichment in alkaline peptone water. These results suggest that the LAMP assay targeting tdh gene has high sensitivity and specificity and is useful to detect TDH-producing V. parahaemolyticus in oyster after enrichment.

  1. Rapid and sensitive detection of Listeria ivanovii by loop-mediated isothermal amplification of the smcL gene.

    Directory of Open Access Journals (Sweden)

    Yi Wang

    Full Text Available A loop-mediated isothermal amplification (LAMP assay for rapid and sensitive detection of the L. ivanovii strains had been developed and evaluated in this study. Oligonucleotide primers specific for L. ivanovii species were designed corresponding to smcL gene sequences. The primers set comprise six primers targeting eight regions on the species-specific gene smcL. The LAMP assay could be completed within 1 h at 64°C in a water bath. Amplification products were directly observed by the Loopamp Fluorescent Detection Reagent (FD or detected by agarose gel electrophoresis. Moreover, the LAMP reactions were also detected by real-time measurement of turbidity. The exclusivity of 77 non-L. ivanovii and the inclusivity of 17 L. ivanovii were both 100% in the assay. Sensitivity of the LAMP assay was 250 fg DNA and 16 CFU per reaction for detection of L. ivanovii in pure cultures and simulated human stool. The LAMP assay was 10 and 100-fold more sensitive than quantitative PCR (qPCR and conventional PCR assays,respectively. When applied to human stool samples spiked with low level (8 CFU/0.5 g of L. ivanovii strains, the new LAMP assay described here achieved positive detection after 6 hours enrichment. In conclusion, the new LAMP assay in this study can be used as a valuable, rapid and sensitive detection tool for the detection of L. ivanovii in field, medical and veterinary laboratories.

  2. Loop-mediated amplification of the Clavibacter michiganensis subsp. michiganensis micA gene is highly specific.

    Science.gov (United States)

    Yasuhara-Bell, Jarred; Kubota, Ryo; Jenkins, Daniel M; Alvarez, Anne M

    2013-12-01

    Loop-mediated amplification (LAMP) was used to specifically identify Clavibacter michiganensis subsp. michiganensis, causal agent of bacterial canker of tomato. LAMP primers were developed to detect micA, a chromosomally stable gene that encodes a type II lantibiotic, michiganin A, which inhibits growth of other C. michiganensis subspecies. In all, 409 bacterial strains (351 C. michiganensis subsp. michiganensis and 58 non-C. michiganensis subsp. michiganensis) from a worldwide collection were tested with LAMP to determine its specificity. LAMP results were compared with genetic profiles established using polymerase chain reaction (PCR) amplification of seven genes (dnaA, ppaJ, pat-1, chpC, tomA, ppaA, and ppaC). C. michiganensis subsp. michiganensis strains produced eight distinct profiles. The LAMP reaction identified all C. michiganensis subsp. michiganensis strains and discriminated them from other C. michiganensis subspecies and non-Clavibacter bacteria. LAMP has advantages over immunodiagnostic and other molecular detection methods because of its specificity and isothermal nature, which allows for easy field application. The LAMP reaction is also not affected by as many inhibitors as PCR. This diagnostic tool has potential to provide an easy, one-step test for rapid identification of C. michiganensis subsp. michiganensis.

  3. Development of a rapid and specific loop-mediated isothermal amplification detection method that targets Marek's disease virus meq gene.

    Science.gov (United States)

    Wei, Xiuying; Shi, Xingming; Zhao, Yan; Zhang, Jing; Wang, Mei; Liu, Changjun; Cui, Hongyu; Hu, Shunlei; Quan, Yanming; Chen, Hongyan; Wang, Yunfeng

    2012-08-01

    A rapid, sensitive and specific loop-mediated isothermal amplification (LAMP) method was developed and evaluated for the detection of Marek's disease virus (MDV) by amplification of conserved MDV meq gene sequences. LAMP is an innovative technique that allows the rapid detection of targeted nucleic acid sequences under isothermal conditions without the need for complex instrumentation. In this study, meq gene sequences were amplified successfully from different MDV strains by LAMP within 60min and no cross-reactivity was observed in a panel of related viruses that were associated with diseases of chickens. The detection limit of LAMP was 3.2 copies/million cells compared with 320 copies/million cells required for conventional PCR. Positive detection rates were assessed using either LAMP or PCR by examination of feather follicles that were collected from chickens infected experimentally with either strain J-1 (n=20) or strain Md5 (n=17), In addition to these samples, three isolates that were suspected to have been infected in the clinic were also tested. Results showed that the positive detection rate for LAMP was 95% (38/40), compared with 87.5% (35/40) and 90% (38/40) for strains J-1 and Md5 by PCR, respectively. These results indicated that the LAMP assay was more sensitive, rapid and specific than conventional PCR for the detection of MDV. This easy-to-perform technique will be useful for the detection of MDV and will aid in the establishment of disease control protocols.

  4. Loop-mediated isothermal amplification of specific endoglucanase gene sequence for detection of the bacterial wilt pathogen Ralstonia solanacearum.

    Directory of Open Access Journals (Sweden)

    Rok Lenarčič

    Full Text Available The increased globalization of crops production and processing industries also promotes the side-effects of more rapid and efficient spread of plant pathogens. To prevent the associated economic losses, and particularly those related to bacterial diseases where their management relies on removal of the infected material from production, simple, easy-to-perform, rapid and cost-effective tests are needed. Loop-mediated isothermal amplification (LAMP assays that target 16S rRNA, fliC and egl genes were compared and evaluated as on-site applications. The assay with the best performance was that targeted to the egl gene, which shows high analytical specificity for diverse strains of the betaproteobacterium Ralstonia solanacearum, including its non-European and non-race 3 biovar 2 strains. The additional melting curve analysis provides confirmation of the test results. According to our extensive assessment, the egl LAMP assay requires minimum sample preparation (a few minutes of boiling for the identification of pure cultures and ooze from symptomatic material, and it can also be used in a high-throughput format in the laboratory. This provides sensitive and reliable detection of R. solanacearum strains of different phylotypes.

  5. A solution for tensor reduction of one-loop N-point functions with N{>=}6

    Energy Technology Data Exchange (ETDEWEB)

    Fleischer, J. [Bielefeld Univ. (Germany). Fakultaet fuer Physik; Riemann, T. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany)

    2011-11-15

    Collisions at the LHC produce many-particle final states, and for precise predictions the one-loop N-point corrections are needed. We study here the tensor reduction for Feynman integrals with N{>=}6. A general, recursive solution by Binoth et al. expresses N-point Feynman integrals of rank R in terms of (N-1)-point Feynman integrals of rank (R-1) (for N{>=}6). We show that the coefficients can be obtained analytically from suitable representations of the metric tensor. Contractions of the tensor integrals with external momenta can be efficiently expressed as well. We consider our approach particularly well suited for automatization. (orig.)

  6. A flexible loop as a functional element in the catalytic mechanism of nucleoside hydrolase from Trypanosoma vivax.

    Science.gov (United States)

    Vandemeulebroucke, An; De Vos, Stefan; Van Holsbeke, Els; Steyaert, Jan; Versées, Wim

    2008-08-08

    The nucleoside hydrolase of Trypanosoma vivax hydrolyzes the N-glycosidic bond of purine nucleosides. Structural and kinetic studies on this enzyme have suggested a catalytic role for a flexible loop in the vicinity of the active sites. Here we present the analysis of the role of this flexible loop via the combination of a proline scan of the loop, loop deletion mutagenesis, steady state and pre-steady state analysis, and x-ray crystallography. Our analysis reveals that this loop has an important role in leaving group activation and product release. The catalytic role involves the entire loop and could only be perturbed by deletion of the entire loop and not by single site mutagenesis. We present evidence that the loop closes over the active site during catalysis, thereby ordering a water channel that is involved in leaving group activation. Once chemistry has taken place, the loop dynamics determine the rate of product release.

  7. The cold-induced basic helix-loop-helix transcription factor gene MdCIbHLH1 encodes an ICE-like protein in apple

    Science.gov (United States)

    2012-01-01

    Background Plant growth is greatly affected by low temperatures, and the expression of a number of genes is induced by cold stress. Although many genes in the cold signaling pathway have been identified in Arabidopsis, little is known about the transcription factors involved in the cold stress response in apple. Results Here, we show that the apple bHLH (basic helix-loop-helix) gene MdCIbHLH1 (Cold-Induced bHLH1), which encodes an ICE-like protein, was noticeably induced in response to cold stress. The MdCIbHLH1 protein specifically bound to the MYC recognition sequences in the AtCBF3 promoter, and MdCIbHLH1 overexpression enhanced cold tolerance in transgenic Arabidopsis. In addition, the MdCIbHLH1 protein bound to the promoters of MdCBF2 and favorably contributed to cold tolerance in transgenic apple plants by upregulating the expression of MdCBF2 through the CBF (C-repeat-binding factor) pathway. Our findings indicate that MdCIbHLH1 functions in stress tolerance in different species. For example, ectopic MdCIbHLH1 expression conferred enhanced chilling tolerance in transgenic tobacco. Finally, we observed that cold induces the degradation of the MdCIbHLH1 protein in apple and that this degradation was potentially mediated by ubiquitination and sumoylation. Conclusions Based on these findings, MdCIbHLH1 encodes a transcription factor that is important for the cold tolerance response in apple. PMID:22336381

  8. The poplar basic helix-loop-helix transcription factor BEE3 – Like gene affects biomass production by enhancing proliferation of xylem cells in poplar

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Seol Ah, E-mail: s6022029@korea.ac.kr; Choi, Young-Im, E-mail: yichoi99@forest.go.kr; Cho, Jin-Seong, E-mail: jinsung3932@gmail.com; Lee, Hyoshin, E-mail: hslee@forest.go.kr

    2015-06-19

    Brassinosteroids (BRs) play important roles in many aspects of plant growth and development, including regulation of vascular cambium activities and cell elongation. BR-induced BEE3 (brassinosteroid enhanced expression 3) is required for a proper BR response. Here, we identified a poplar (Populus alba × Populus glandulosa) BEE3-like gene, PagBEE3L, encoding a putative basic helix-loop-helix (bHLH)-type transcription factor. Expression of PagBEE3L was induced by brassinolide (BL). Transcripts of PagBEE3L were mainly detected in stems, with the internode having a low level of transcription and the node having a relatively higher level. The function of the PagBEE3L gene was investigated through phenotypic analyses with PagBEE3L-overexpressing (ox) transgenic lines. This work particularly focused on a potential role of PagBEE3L in stem growth and development of polar. The PagBEE3L-ox poplar showed thicker and longer stems than wild-type plants. The xylem cells from the stems of PagBEE3L-ox plants revealed remarkably enhanced proliferation, resulting in an earlier thickening growth than wild-type plants. Therefore, this work suggests that xylem development of poplar is accelerated in PagBEE3L-ox plants and PagBEE3L plays a role in stem growth by increasing the proliferation of xylem cells to promote the initial thickening growth of poplar stems. - Highlights: • We identify the BEE3-like gene form hybrid poplar (Populus alba × Populus glandulosa). • We examine effects of overexpression of PagBEE3L on growth in poplar. • We found that 35S:BEE3L transgenic plants showed more rapid growth than wild-type plants. • BEE3L protein plays an important role in the development of plant stem.

  9. Single amino acid insertions in extracellular loop 2 of Bombyx mori ABCC2 disrupt its receptor function for Bacillus thuringiensis Cry1Ab and Cry1Ac but not Cry1Aa toxins.

    Science.gov (United States)

    Tanaka, Shiho; Miyamoto, Kazuhisa; Noda, Hiroaki; Endo, Haruka; Kikuta, Shingo; Sato, Ryoichi

    2016-04-01

    In a previous report, seven Cry1Ab-resistant strains were identified in the silkworm, Bombyx mori; these strains were shown to have a tyrosine insertion at position 234 in extracellular loop 2 of the ABC transporter C2 (BmABCC2). This insertion was confirmed to destroy the receptor function of BmABCC2 and confer the strains resistance against Cry1Ab and Cry1Ac. However, these strains were susceptible to Cry1Aa. In this report, we examined the mechanisms of the loss of receptor function of the transporter by expressing mutations in Sf9 cells. After replacement of one or two of the five amino acid residues in loop 2 of the susceptible BmABCC2 gene [BmABCC2_S] with alanine, cells still showed susceptibility, retaining the receptor function. Five mutants with single amino acid insertions at position 234 in BmABCC2 were also generated, resulting in loop 2 having six amino acids, which corresponds to replacing the tyrosine insertion in the resistant BmABCC2 gene [BmABCC2_R(+(234)Y)] with another amino acid. All five mutants exhibited loss of function against Cry1Ab and Cry1Ac. These results suggest that the amino acid sequence in loop 2 is less important than the loop size (five vs. six amino acids) or loop structure for Cry1Ab and Cry1Ac activity. Several domain-swapped mutant toxins were then generated among Cry1Aa, Cry1Ab, and Cry1Ac, which are composed of three domains. Swapped mutants containing domain II of Cry1Ab or Cry1Ac did not kill Sf9 cells expressing BmABCC2_R(+(234)Y), suggesting that domain II of the Cry toxin is related to the interaction with the receptor function of BmABCC2. This also suggests that different reactions against Bt-toxins in some B. mori strains, that is, Cry1Ab resistance or Cry1Aa susceptibility, are attributable to structural differences in domain II of Cry1A toxins.

  10. Genetic Programming with Simple Loops

    Institute of Scientific and Technical Information of China (English)

    QI Yuesheng; WANG Baozhong; KANG Lishan

    1999-01-01

    A kind of loop function LoopN inGenetic Programming (GP) is proposed.Different from other forms of loopfunction, such as While-Do and Repeat-Until, LoopNtakes only oneargument as its loop body and makes its loop body simply run N times,soinfinite loops will never happen. The problem of how to avoid too manylayers ofloops in Genetic Programming is also solved. The advantage ofLoopN in GP is shown bythe computational results in solving the mowerproblem.

  11. Collective estimation of multiple bivariate density functions with application to angular-sampling-based protein loop modeling

    KAUST Repository

    Maadooliat, Mehdi

    2015-10-21

    This paper develops a method for simultaneous estimation of density functions for a collection of populations of protein backbone angle pairs using a data-driven, shared basis that is constructed by bivariate spline functions defined on a triangulation of the bivariate domain. The circular nature of angular data is taken into account by imposing appropriate smoothness constraints across boundaries of the triangles. Maximum penalized likelihood is used to fit the model and an alternating blockwise Newton-type algorithm is developed for computation. A simulation study shows that the collective estimation approach is statistically more efficient than estimating the densities individually. The proposed method was used to estimate neighbor-dependent distributions of protein backbone dihedral angles (i.e., Ramachandran distributions). The estimated distributions were applied to protein loop modeling, one of the most challenging open problems in protein structure prediction, by feeding them into an angular-sampling-based loop structure prediction framework. Our estimated distributions compared favorably to the Ramachandran distributions estimated by fitting a hierarchical Dirichlet process model; and in particular, our distributions showed significant improvements on the hard cases where existing methods do not work well.

  12. Anticipating regime shifts in gene expression: The case of an autoactivating positive feedback loop

    Science.gov (United States)

    Sharma, Yogita; Dutta, Partha Sharathi; Gupta, A. K.

    2016-03-01

    Considerable evidence suggests that anticipating sudden shifts from one state to another in bistable dynamical systems is a challenging task; examples include ecosystems, financial markets, and complex diseases. In this paper, we investigate the effects of additive, multiplicative, and cross-correlated stochastic perturbations on determining the regime shifts in a bistable gene regulatory system, which gives rise to two distinct states of low and high concentrations of protein. We obtain the stationary probability density and mean first-passage time of the system. We show that increasing the additive (multiplicative) noise intensity induces a regime shift from a low (high) to a high (low) protein concentration state. However, an increase in the cross-correlation intensity always induces regime shifts from a high to a low protein concentration state. For both bifurcation-induced (often called the tipping point) and noise-induced (called stochastic switching) regime shifts, we further explore the robustness of recently developed critical-down-based early warning signal (EWS) indicators (e.g., rising variance and lag-1 autocorrelation) on our simulated time-series data. We identify that using EWS indicators, prediction of an impending bifurcation-induced regime shift is relatively easier than that of a noise-induced regime shift in the considered system. Moreover, the success of EWS indicators also strongly depends upon the nature of the noise.

  13. Rapid and sensitive detection of Plesiomonas shigelloides by loop-mediated isothermal amplification of the hugA gene.

    Directory of Open Access Journals (Sweden)

    Shuang Meng

    Full Text Available Plesiomonas shigelloides is one of the causative agents of human gastroenteritis, with increasing number of reports describing such infections in recent years. In this study, the hugA gene was chosen as the target to design loop-mediated isothermal amplification (LAMP assays for the rapid, specific, and sensitive detection of P. shigelloides. The performance of the assay with reference plasmids and spiked human stools as samples was evaluated and compared with those of quantitative PCR (qPCR. No false-positive results were observed for the 32 non-P. shigelloides strains used to evaluate assay specificity. The limit of detection for P. shigelloides was approximately 20 copies per reaction in reference plasmids and 5×10(3 CFU per gram in spiked human stool, which were more sensitive than the results of qPCR. When applied in human stool samples spiked with 2 low levels of P. shigelloides, the LAMP assays achieved accurate detection after 6-h enrichment. In conclusion, the LAMP assay developed in this study is a valuable method for rapid, cost-effective, and simple detection of P. shigelloides in basic clinical and field laboratories in the rural areas of China.

  14. Advanced Photovoltaic Inverter Functionality using 500 kW Power Hardware-in-Loop Complete System Laboratory Testing: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Mather, B. A.; Kromer, M. A.; Casey, L.

    2013-01-01

    With the increasing penetration of distribution connected photovoltaic (PV) systems, more and more PV developers and utilities are interested in easing future PV interconnection concerns by mitigating some of the impacts of PV integration using advanced PV inverter controls and functions. This paper describes the testing of a 500 kW PV inverter using Power Hardware-in-Loop (PHIL) testing techniques. The test setup is described and the results from testing the inverter in advanced functionality modes, not commonly used in currently interconnected PV systems, are presented. PV inverter operation under PHIL evaluation that emulated both the DC PV array connection and the AC distribution level grid connection are shown for constant power factor (PF) and constant reactive power (VAr) control modes. The evaluation of these modes was completed under varying degrees of modeled PV variability.

  15. A fuzzy cost-benefit function to select economical products for processing in a closed-loop supply chain

    Science.gov (United States)

    Pochampally, Kishore K.; Gupta, Surendra M.; Cullinane, Thomas P.

    2004-02-01

    The cost-benefit analysis of data associated with re-processing of used products often involves the uncertainty feature of cash-flow modeling. The data is not objective because of uncertainties in supply, quality and disassembly times of used products. Hence, decision-makers must rely on "fuzzy" data for analysis. The same parties that are involved in the forward supply chain often carry out the collection and re-processing of used products. It is therefore important that the cost-benefit analysis takes the data of both new products and used products into account. In this paper, a fuzzy cost-benefit function is proposed that is used to perform a multi-criteria economic analysis to select the most economical products to process in a closed-loop supply chain. Application of the function is detailed through an illustrative example.

  16. What Controls DNA Looping?

    Directory of Open Access Journals (Sweden)

    Pamela J. Perez

    2014-08-01

    Full Text Available The looping of DNA provides a means of communication between sequentially distant genomic sites that operate in tandem to express, copy, and repair the information encoded in the DNA base sequence. The short loops implicated in the expression of bacterial genes suggest that molecular factors other than the naturally stiff double helix are involved in bringing the interacting sites into close spatial proximity. New computational techniques that take direct account of the three-dimensional structures and fluctuations of protein and DNA allow us to examine the likely means of enhancing such communication. Here, we describe the application of these approaches to the looping of a 92 base-pair DNA segment between the headpieces of the tetrameric Escherichia coli Lac repressor protein. The distortions of the double helix induced by a second protein—the nonspecific nucleoid protein HU—increase the computed likelihood of looping by several orders of magnitude over that of DNA alone. Large-scale deformations of the repressor, sequence-dependent features in the DNA loop, and deformability of the DNA operators also enhance looping, although to lesser degrees. The correspondence between the predicted looping propensities and the ease of looping derived from gene-expression and single-molecule measurements lends credence to the derived structural picture.

  17. The four-loop remainder function and multi-Regge behavior at NNLLA in planar N=4 super-Yang-Mills theory

    CERN Document Server

    Dixon, Lance J.; Duhr, Claude; Pennington, Jeffrey

    2014-01-01

    We present the four-loop remainder function for six-gluon scattering with maximal helicity violation in planar N=4 super-Yang-Mills theory, as an analytic function of three dual-conformal cross ratios. The function is constructed entirely from its analytic properties, without ever inspecting any multi-loop integrand. We employ the same approach used at three loops, writing an ansatz in terms of hexagon functions, and fixing coefficients in the ansatz using the multi-Regge limit and the operator product expansion in the near-collinear limit. We express the result in terms of multiple polylogarithms, and in terms of the coproduct for the associated Hopf algebra. From the remainder function, we extract the BFKL eigenvalue at next-to-next-to-leading logarithmic accuracy (NNLLA), and the impact factor at NNNLLA. We plot the remainder function along various lines and on one surface, studying ratios of successive loop orders. As seen previously through three loops, these ratios are surprisingly constant over large r...

  18. The four-loop remainder function and multi-Regge behavior at NNLLA in planar $ \\mathcal{N} $ = 4 super-Yang-Mills theory

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2014-06-19

    We present the four-loop remainder function for six-gluon scattering with maximal helicity violation in planar NN = 4 super-Yang-Mills theory, as an analytic function of three dual-conformal cross ratios. The function is constructed entirely from its analytic properties, without ever inspecting any multi-loop integrand. We employ the same approach used at three loops, writing an ansatz in terms of hexagon functions, and fixing coefficients in the ansatz using the multi-Regge limit and the operator product expansion in the near-collinear limit. We express the result in terms of multiple polylogarithms, and in terms of the coproduct for the associated Hopf algebra. From the remainder function, we extract the BFKL eigenvalue at next-to-next-to-leading logarithmic accuracy (NNLLA), and the impact factor at N3LLA. We plot the remainder function along various lines and on one surface, studying ratios of successive loop orders. As seen previously through three loops, these ratios are surprisingly constant over large regions in the space of cross ratios, and they are not far from the value expected at asymptotically large orders of perturbation theory.

  19. DNA methylation and not H3K4 trimethylation dictates the expression status of miR-152 gene which inhibits migration of breast cancer cells via DNMT1/CDH1 loop.

    Science.gov (United States)

    Sengupta, Dipta; Deb, Moonmoon; Rath, Sandip Kumar; Kar, Swayamsiddha; Parbin, Sabnam; Pradhan, Nibedita; Patra, Samir Kumar

    2016-08-15

    MicroRNAs (miRNA) are small non-coding RNAs which targets most protein-coding transcripts (mRNA) and destroy them. Thus miRNA controls the abundance of those specific proteins and impact on developmental, physiological and pathological processes. Dysregulation of miRNA function thus may lead to various clinicopathological complications, including breast cancer. Silencing of miR-152 gene due to promoter DNA methylation alter the expression pattern of several other genes. E-cadherin (CDH1) forms the core of adherent junctions between surrounding epithelial cells, link with actin cytoskeleton and affects cell signaling. CDH1 gene is down regulated by promoter DNA methylation during cancer progression. In this investigation, we attempt to elucidate the correlation of miR-152 and CDH1 function, as it is well known that the loss of CDH1 function is one of the major reasons for cancer metastasis and aggressiveness of spreading. For the first time we have shown that loss of CDH1 expression is directly proportional to the loss of miR-152 function in breast cancer cells. mRNA and protein expression profile of DNMT1 implicate that miR-152 targets DNMT1 mRNA and inhibits its protein expression. Tracing the molecular marks on DNA and histone 3 for understanding the mechanism of gene regulation by ChIP analyses leads to a paradoxical result that shows DNA methylation adjacent to active histone marking (enrichment of H3K4me3) silence miR-152 gene. Further experiments revealed that DNMT1 plays crucial role for regulation of miR-152 gene. When DNMT1 protein function is blocked miR-152 expression prevails and destroys the mRNA of DNMT1; this molecular regulatory mechanism is creating a cyclic feedback loop, which is now focused as DNMT1/miR-152 switch for on/off of DNMT1 target genes. We discovered modulation of CDH1 gene expression by DNMT1/miR-152 switches. We have demonstrated further that DNMT1 down regulation mediated upregulation of CDH1 (hereafter, DNMT1/CDH1 loop) in

  20. Bioinformatic prediction and functional characterization of human KIAA0100 gene

    OpenAIRE

    He Cui; Xi Lan; Shemin Lu; Fujun Zhang; Wanggang Zhang

    2017-01-01

    Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells...

  1. Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome.

    Science.gov (United States)

    El Ghouzzi, V; Lajeunie, E; Le Merrer, M; Cormier-Daire, V; Renier, D; Munnich, A; Bonaventure, J

    1999-01-01

    Saethre-Chotzen syndrome (ACS III) is an autosomal dominant craniosynostosis syndrome recently ascribed to mutations in the TWIST gene, a basic helix-loop-helix (b-HLH) transcription factor regulating head mesenchyme cell development during cranial neural tube formation in mouse. Studying a series of 22 unrelated ACS III patients, we have found TWIST mutations in 16/22 cases. Interestingly, these mutations consistently involved the b-HLH domain of the protein. Indeed, mutant genotypes included frameshift deletions/insertions, nonsense and missense mutations, either truncating or disrupting the b-HLH motif of the protein. This observation gives additional support to the view that most ACS III cases result from loss-of-function mutations at the TWIST locus. The P250R recurrent FGFR 3 mutation was found in 2/22 cases presenting mild clinical manifestations of the disease but 4/22 cases failed to harbour TWIST or FGFR 3 mutations. Clinical re-examination of patients carrying TWIST mutations failed to reveal correlations between the mutant genotype and severity of the phenotype. Finally, since no TWIST mutations were detected in 40 cases of isolated coronal craniosynostosis, the present study suggests that TWIST mutations are specific to Saethre-Chotzen syndrome.

  2. Identifying cancer genes from cancer mutation profiles by cancer functions

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    It is of great importance to identify new cancer genes from the data of large scale genome screenings of gene mutations in cancers. Considering the alternations of some essential functions are indispensable for oncogenesis, we define them as cancer functions and select, as their approximations, a group of detailed functions in GO (Gene Ontology) highly enriched with known cancer genes. To evaluate the efficiency of using cancer functions as features to identify cancer genes, we define, in the screened genes, the known protein kinase cancer genes as gold standard positives and the other kinase genes as gold standard negatives. The results show that cancer associated functions are more efficient in identifying cancer genes than the selection pressure feature. Furthermore, combining cancer functions with the number of non-silent mutations can generate more reliable positive predictions. Finally, with precision 0.42, we suggest a list of 46 kinase genes as candidate cancer genes which are annotated to cancer functions and carry at least 3 non-silent mutations.

  3. The relation between the QED charge renormalized in MS{sup Macron} and on-shell schemes at four loops, the QED on-shell {beta}-function at five loops and asymptotic contributions to the muon anomaly at five and six loops

    Energy Technology Data Exchange (ETDEWEB)

    Baikov, P.A. [Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University, 1(2), Leninskie gory, Moscow 119234 (Russian Federation); Chetyrkin, K.G.; Kuehn, J.H. [Institut fuer Theoretische Teilchenphysik, Universitaet Karlsruhe, D-76128 Karlsruhe (Germany); Sturm, C., E-mail: sturm@mpp.mpg.de [Max-Planck-Institut fuer Physik (Werner-Heisenberg-Institut), Foehringer Ring 6, D-80805 Muenchen (Germany)

    2013-02-11

    In this paper we compute the four-loop corrections to the QED photon self-energy {Pi}(Q{sup 2}) in the two limits of q=0 and Q{sup 2}{yields}{infinity}. These results are used to explicitly construct the conversion relations between the QED charge renormalized in on-shell (OS) and MS{sup Macron} scheme. Using these relations and results of Baikov et al. [1] we construct the momentum dependent part of {Pi}(Q{sup 2},m,{alpha}) at large Q{sup 2} at five loops in both MS{sup Macron} and OS schemes. As a direct consequence we arrive at the full result for the QED {beta}-function in the OS scheme at five loops. These results are applied, in turn, to analytically evaluate a class of asymptotic contributions to the muon anomaly at five and six loops.

  4. Gene coexpression network analysis as a source of functional annotation for rice genes.

    Directory of Open Access Journals (Sweden)

    Kevin L Childs

    Full Text Available With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional

  5. Rapid, simple and sensitive detection of Q fever by loop-mediated isothermal amplification of the htpAB gene.

    Directory of Open Access Journals (Sweden)

    Lei Pan

    Full Text Available BACKGROUND: Q fever is the most widespread zoonosis, and domestic animals are the most common sources of transmission. It is not only difficult to distinguish from other febrile diseases because of the lack of specific clinical manifestations in humans, but it is also difficult to identify the disease in C. burnetii-carrying animals because of the lack of identifiable features. Conventional serodiagnosis requires sera from the acute and convalescent stages of infection, which are unavailable at early diagnosis. Nested PCR and real-time PCR require equipment. In this study, we developed a Loop-Mediated Isothermal Amplification (LAMP assay to identify C. burnetii rapidly and sensitively. METHODS: A universal LAMP primer set was designed to detect the repeated sequence IS1111a of the htpAB gene of C. burnetii using PrimerExplorer V4 software. The sensitivity of the LAMP assay was evaluated using known quantities of recombined reference plasmids containing the targeted genes. The specificity of the developed LAMP assay was determined using 26 members of order Rickettsiae and 18 other common pathogens. The utility of the LAMP assay was further compared with real time PCR by the examination 24 blood samples including 6 confirmed and 18 probable Q fever cases, which diagnosed by IFA serological assessment and real time PCR. In addition, 126 animal samples from 4 provinces including 97 goats, 7 cattle, 18 horses, 3 marmots and 1 deer were compared by these two methods. RESULTS: The limits of detection of the LAMP assay for the htpAB gene were 1 copy per reaction. The specificity of the LAMP assay was 100%, and no cross-reaction was observed among the bacteria used in the study. The positive rate of unknown febrile patients was 33.3%(95%CI 30.2%-36.4% for the LAMP assay and 8.3%(95%CI 7.4%-9.2% for the real time PCR(P<0.05. Similarly, the total positive rate of animals was 7.9%(95%CI 7.1%-8.7% for the LAMP assay and 0.8%(95%CI 0.7%-0.9%for the real time

  6. The Effect of Bevacizumab on Human Malignant Melanoma Cells with Functional VEGF/VEGFR2 Autocrine and Intracrine Signaling Loops

    Directory of Open Access Journals (Sweden)

    Una Adamcic

    2012-07-01

    Full Text Available Receptors for the angiogenic factor VEGF are expressed by tumor cancer cells including melanoma, although their functionality remains unclear. Paired human melanoma cell lines WM115 and WM239 were used to investigate differences in expression and functionality of VEGF and VEGFR2 in vitro and in vivo with the anti-VEGF antibody bevacizumab. Both WM115 and WM239 cells expressed VEGF and VEGFR2, the levels of which were modulated by hypoxia. Detection of native and phosphorylated VEGFR2 in subcellular fractions under serum-free conditions showed the presence of a functional autocrine as well as intracrine VEGF/VEGFR2 signaling loops. Interestingly, treatment of WM115 and WM239 cells with increasing doses of bevacizumab (0–300 µg/ml in vitro did not show any significant inhibition of VEGFR2 phosphorylation. Small-molecule tyrosine kinase inhibitor, sunitinib, caused an inhibition of VEGFR2 phosphorylation in WM239 but not in WM115 cells. An increase in cell proliferation was observed in WM115 cells treated with bevacizumab, whereas sunitinib inhibited proliferation. When xenografted to immune-deficient mice, we found bevacizumab to be an effective antiangiogenic but not antitumorigenic agent for both cell lines. Because bevacizumab is unable to neutralize murine VEGF, this supports a paracrine angiogenic response. We propose that the failure of bevacizumab to generate an antitumorigenic effect may be related to its generation of enhanced autocrine/intracrine signaling in the cancer cells themselves. Collectively, these results suggest that, for cancers with intracrine VEGF/ VEGFR2 signaling loops, small-molecule inhibitors of VEGFR2 may be more effective than neutralizing antibodies at disease control.

  7. Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5' exon usage and splicing.

    Directory of Open Access Journals (Sweden)

    Mari Sepp

    Full Text Available BACKGROUND: Transcription factor 4 (TCF4 alias ITF2, E2-2, ME2 or SEF2 is a ubiquitous class A basic helix-loop-helix protein that binds to E-box DNA sequences (CANNTG. While involved in the development and functioning of many different cell types, recent studies point to important roles for TCF4 in the nervous system. Specifically, human TCF4 gene is implicated in susceptibility to schizophrenia and TCF4 haploinsufficiency is the cause of the Pitt-Hopkins mental retardation syndrome. However, the structure, expression and coding potential of the human TCF4 gene have not been described in detail. PRINCIPAL FINDINGS: In the present study we used human tissue samples to characterize human TCF4 gene structure and TCF4 expression at mRNA and protein level. We report that although widely expressed, human TCF4 mRNA expression is particularly high in the brain. We demonstrate that usage of numerous 5' exons of the human TCF4 gene potentially yields in TCF4 protein isoforms with 18 different N-termini. In addition, the diversity of isoforms is increased by alternative splicing of several internal exons. For functional characterization of TCF4 isoforms, we overexpressed individual isoforms in cultured human cells. Our analysis revealed that subcellular distribution of TCF4 isoforms is differentially regulated: Some isoforms contain a bipartite nuclear localization signal and are exclusively nuclear, whereas distribution of other isoforms relies on heterodimerization partners. Furthermore, the ability of different TCF4 isoforms to regulate E-box controlled reporter gene transcription is varied depending on whether one or both of the two TCF4 transcription activation domains are present in the protein. Both TCF4 activation domains are able to activate transcription independently, but act synergistically in combination. CONCLUSIONS: Altogether, in this study we have described the inter-tissue variability of TCF4 expression in human and provided evidence

  8. Heat-inducible RNAi for gene functional analysis in plants.

    Science.gov (United States)

    Masclaux, Frédéric; Galaud, Jean-Philippe

    2011-01-01

    Controlling gene expression during plant development is an efficient method to explore gene function and RNA interference (RNAi) is now considered as a powerful technology for gene functional analysis. However, constitutive gene silencing cannot be used with genes involved in fundamental processes such as embryo viability or plant growth and alternative silencing strategies avoiding these limitations should be preferred. Tissue-specific and inducible promoters, able to control gene expression at spatial and/or temporal level, can be used to circumvent viability problems. In this chapter, after a rapid overview of the inducible promoters currently used for transgenic approaches in plants, we describe a method we have developed to study gene function by heat-inducible RNAi. This system is easy to use and complementary to those based on chemical gene inducer treatments and might be useful for both research and biotechnological applications.

  9. Semantic particularity measure for functional characterization of gene sets using gene ontology.

    Science.gov (United States)

    Bettembourg, Charles; Diot, Christian; Dameron, Olivier

    2014-01-01

    Genetic and genomic data analyses are outputting large sets of genes. Functional comparison of these gene sets is a key part of the analysis, as it identifies their shared functions, and the functions that distinguish each set. The Gene Ontology (GO) initiative provides a unified reference for analyzing the genes molecular functions, biological processes and cellular components. Numerous semantic similarity measures have been developed to systematically quantify the weight of the GO terms shared by two genes. We studied how gene set comparisons can be improved by considering gene set particularity in addition to gene set similarity. We propose a new approach to compute gene set particularities based on the information conveyed by GO terms. A GO term informativeness can be computed using either its information content based on the term frequency in a corpus, or a function of the term's distance to the root. We defined the semantic particularity of a set of GO terms Sg1 compared to another set of GO terms Sg2. We combined our particularity measure with a similarity measure to compare gene sets. We demonstrated that the combination of semantic similarity and semantic particularity measures was able to identify genes with particular functions from among similar genes. This differentiation was not recognized using only a semantic similarity measure. Semantic particularity should be used in conjunction with semantic similarity to perform functional analysis of GO-annotated gene sets. The principle is generalizable to other ontologies.

  10. Identifying disease feature genes based on cellular localized gene functional modules and regulation networks

    Institute of Scientific and Technical Information of China (English)

    ZHANG Min; ZHU Jing; GUO Zheng; LI Xia; YANG Da; WANG Lei; RAO Shaoqi

    2006-01-01

    Identifying disease-relevant genes and functional modules, based on gene expression profiles and gene functional knowledge, is of high importance for studying disease mechanisms and subtyping disease phenotypes. Using gene categories of biological process and cellular component in Gene Ontology, we propose an approach to selecting functional modules enriched with differentially expressed genes, and identifying the feature functional modules of high disease discriminating abilities. Using the differentially expressed genes in each feature module as the feature genes, we reveal the relevance of the modules to the studied diseases. Using three datasets for prostate cancer, gastric cancer, and leukemia, we have demonstrated that the proposed modular approach is of high power in identifying functionally integrated feature gene subsets that are highly relevant to the disease mechanisms. Our analysis has also shown that the critical disease-relevant genes might be better recognized from the gene regulation network, which is constructed using the characterized functional modules, giving important clues to the concerted mechanisms of the modules responding to complex disease states. In addition, the proposed approach to selecting the disease-relevant genes by jointly considering the gene functional knowledge suggests a new way for precisely classifying disease samples with clear biological interpretations, which is critical for the clinical diagnosis and the elucidation of the pathogenic basis of complex diseases.

  11. HLA Immune Function Genes in Autism

    Directory of Open Access Journals (Sweden)

    Anthony R. Torres

    2012-01-01

    Full Text Available The human leukocyte antigen (HLA genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects.

  12. Pdx1 and BETA2/NeuroD1 participate in a transcriptional complex that mediates short-range DNA looping at the insulin gene.

    Science.gov (United States)

    Babu, Daniella A; Chakrabarti, Swarup K; Garmey, James C; Mirmira, Raghavendra G

    2008-03-28

    The activity of the insulin gene, Ins, in islet beta cells is thought to arise in part from the synergistic action of the transcription factors Pdx1 and BETA2/NeuroD1. We asked how the binding of these factors to A and E elements many tens or hundreds of base pairs upstream of the start site could influence activity of transcriptional machinery. We therefore tested the hypothesis that the complex of Pdx1 and BETA2/NeuroD1 maintains a DNA conformation such that distal regions of the gene are brought into proximity of the promoter and coding region. We show by coimmunoprecipitation that Pdx1 and BETA2/NeuroD1 exist within a complex and that the two physically interact with one another in this complex as assessed by fluorescence resonance energy transfer. Consistent with this interaction, we found that the two factors simultaneously occupy the same fragment of the Ins gene in beta cell lines using the chromatin immunoprecipitation/re-chromatin immunoprecipitation assay. Using a modification of the chromosome conformation capture assay in vitro and in beta cells, we observed that Pdx1 and BETA2/NeuroD1 mediate looping of a segment of Ins that brings EcoRI sites located at -623 and +761 bp (relative to the transcriptional start site) in proximity to one another. This looping appears to be dependent in vitro upon an intact A3 binding element, but not upon the E2 element. Based on our findings, we propose a model whereby Pdx1 and BETA2/NeuroD1 physically interact to form a nucleoprotein complex on the Ins gene that mediates formation of a short DNA loop. Our results suggest that such short loop conformations may be a general mechanism to permit interactions between transcription factors and basal transcriptional machinery.

  13. Tracing evolutionary footprints to identify novel gene functional linkages.

    Directory of Open Access Journals (Sweden)

    Yong Chen

    Full Text Available Systematic determination of gene function is an essential step in fully understanding the precise contribution of each gene for the proper execution of molecular functions in the cell. Gene functional linkage is defined as to describe the relationship of a group of genes with similar functions. With thousands of genomes sequenced, there arises a great opportunity to utilize gene evolutionary information to identify gene functional linkages. To this end, we established a computational method (called TRACE to trace gene footprints through a gene functional network constructed from 341 prokaryotic genomes. TRACE performance was validated and successfully tested to predict enzyme functions as well as components of pathway. A so far undescribed chromosome partitioning-like protein ro03654 of an oleaginous bacteria Rhodococcus sp. RHA1 (RHA1 was predicted and verified experimentally with its deletion mutant showing growth inhibition compared to RHA1 wild type. In addition, four proteins were predicted to act as prokaryotic SNARE-like proteins, and two of them were shown to be localized at the plasma membrane. Thus, we believe that TRACE is an effective new method to infer prokaryotic gene functional linkages by tracing evolutionary events.

  14. FSim: A Novel Functional Similarity Search Algorithm and Tool for Discovering Functionally Related Gene Products

    Directory of Open Access Journals (Sweden)

    Qiang Hu

    2014-01-01

    Full Text Available Background. During the analysis of genomics data, it is often required to quantify the functional similarity of genes and their products based on the annotation information from gene ontology (GO with hierarchical structure. A flexible and user-friendly way to estimate the functional similarity of genes utilizing GO annotation is therefore highly desired. Results. We proposed a novel algorithm using a level coefficient-weighted model to measure the functional similarity of gene products based on multiple ontologies of hierarchical GO annotations. The performance of our algorithm was evaluated and found to be superior to the other tested methods. We implemented the proposed algorithm in a software package, FSim, based on R statistical and computing environment. It can be used to discover functionally related genes for a given gene, group of genes, or set of function terms. Conclusions. FSim is a flexible tool to analyze functional gene groups based on the GO annotation databases.

  15. Autism and genius: is there a link? The involvement of central brain loops and hypotheses for functional testing.

    Science.gov (United States)

    Boso, M; Emanuele, E; Prestori, Francesca; Politi, P; Barale, F; D'Angelo, E

    2010-01-01

    Mental processing is the product of the huge number of synaptic interactions that occur in the brain. It is easier to understand how brain functions can deteriorate than how they might be boosted. Lying at the border between the humanities, cognitive science and neurophysiology, some mental diseases offer new angles on this problematic issue. Despite their social deficits, autistic subjects can display unexpected and extraordinary skills in numerous fields, including music, the arts, calculation and memory. The advanced skills found in a subgroup of people with autism may be explained by their special mental functioning, in particular by their weak central coherence, one of the pivotal characteristics of the disorder. As a result of the increasing interest in autistic talent, there has recently emerged a tendency to screen any eccentric artist or scientist for traits of the autistic spectrum. Following this trend, we analyze the eccentricity of the popular pianist Glenn Gould and briefly discuss the major functional hypotheses on autistic hyperfunctioning, advancing proposals for functional testing. In particular, the potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens up new perspectives for the investigation of autistic disorders and brain hyperfunctioning.

  16. An improved method for functional similarity analysis of genes based on Gene Ontology.

    Science.gov (United States)

    Tian, Zhen; Wang, Chunyu; Guo, Maozu; Liu, Xiaoyan; Teng, Zhixia

    2016-12-23

    Measures of gene functional similarity are essential tools for gene clustering, gene function prediction, evaluation of protein-protein interaction, disease gene prioritization and other applications. In recent years, many gene functional similarity methods have been proposed based on the semantic similarity of GO terms. However, these leading approaches may make errorprone judgments especially when they measure the specificity of GO terms as well as the IC of a term set. Therefore, how to estimate the gene functional similarity reliably is still a challenging problem. We propose WIS, an effective method to measure the gene functional similarity. First of all, WIS computes the IC of a term by employing its depth, the number of its ancestors as well as the topology of its descendants in the GO graph. Secondly, WIS calculates the IC of a term set by means of considering the weighted inherited semantics of terms. Finally, WIS estimates the gene functional similarity based on the IC overlap ratio of term sets. WIS is superior to some other representative measures on the experiments of functional classification of genes in a biological pathway, collaborative evaluation of GO-based semantic similarity measures, protein-protein interaction prediction and correlation with gene expression. Further analysis suggests that WIS takes fully into account the specificity of terms and the weighted inherited semantics of terms between GO terms. The proposed WIS method is an effective and reliable way to compare gene function. The web service of WIS is freely available at http://nclab.hit.edu.cn/WIS/ .

  17. Maternal Betaine Supplementation during Gestation Enhances Expression of mtDNA-Encoded Genes through D-Loop DNA Hypomethylation in the Skeletal Muscle of Newborn Piglets.

    Science.gov (United States)

    Jia, Yimin; Song, Haogang; Gao, Guichao; Cai, Demin; Yang, Xiaojing; Zhao, Ruqian

    2015-11-25

    Betaine has been widely used in animal and human nutrition to promote muscle growth and performance, yet it remains unknown whether maternal betaine supplementation during gestation affects the metabolic characteristics of neonatal skeletal muscles. In the present study, feeding sows with betaine-supplemented diets throughout gestation significantly upregulated the expression of mtDNA-encoded OXPHOS genes (p betaine supplementation increased the plasma betaine concentration and muscle expression of methyl transfer enzymes (p betaine supplementation during gestation enhances expression of mtDNA-encoded genes through D-loop DNA hypomethylation in the skeletal muscle of newborn piglets.

  18. One loop partition function of six dimensional conformal gravity using heat kernel on AdS

    Energy Technology Data Exchange (ETDEWEB)

    Lovreković, Iva [Institute for Theoretical Physics, Technische Universität Wien,Wiedner Hauptstrasse 8-10/136, A-1040 Vienna (Austria)

    2016-10-13

    We compute the heat kernel for the Laplacians of symmetric transverse traceless fields of arbitrary spin on the AdS background in even number of dimensions using the group theoretic approach introduced in http://dx.doi.org/10.1007/JHEP11(2011)010 and apply it on the partition function of six dimensional conformal gravity. The obtained partition function consists of the Einstein gravity, conformal ghost and two modes that contain mass.

  19. The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner

    NARCIS (Netherlands)

    F. Sleutels (Frank); W.S.W. Soochit (Widia); M. Bartkuhn (Marek); H. Heath (Helen); S. Dienstbach (Sven); P. Bergmaier (Philipp); V. Franke (Vedran); M. Rosa-Garrido (Manuel); S. van de Nobelen (Suzanne); L. Caesar (Lisa); M. van der Reijden (Michael); J.C. Bryne; W.F.J. van IJcken (Wilfred); J.A. Grootegoed (Anton); M.D. Delgado (Dolores); B. Lenhard (Boris); R. Renkawitz (Rainer); F.G. Grosveld (Frank); N.J. Galjart (Niels)

    2012-01-01

    textabstractBackground: CTCF is a highly conserved and essential zinc finger protein expressed in virtually all cell types. In conjunction with cohesin, it organizes chromatin into loops, thereby regulating gene expression and epigenetic events. The function of CTCFL or BORIS, the testis-specific pa

  20. The 3-Loop Pure Singlet Heavy Flavor Contributions to the Structure Function $F_2(x,Q^2)$ and the Anomalous Dimension

    CERN Document Server

    Ablinger, J; Blümlein, J; De Freitas, A; von Manteuffel, A; Schneider, C

    2014-01-01

    The pure singlet asymptotic heavy flavor corrections to 3-loop order for the deep-inelastic scattering structure function $F_2(x,Q^2)$ and the corresponding transition matrix element $A_{Qq}^{(3), \\sf PS}$ in the variable flavor number scheme are computed. In Mellin-$N$ space these inclusive quantities depend on generalized harmonic sums. We also recalculate the complete 3-loop pure singlet anomalous dimension for the first time. Numerical results for the Wilson coefficients, the operator matrix element and the contribution to the structure function $F_2(x,Q^2)$ are presented.

  1. The 3-loop pure singlet heavy flavor contributions to the structure function F2(x,Q2 and the anomalous dimension

    Directory of Open Access Journals (Sweden)

    J. Ablinger

    2015-01-01

    Full Text Available The pure singlet asymptotic heavy flavor corrections to 3-loop order for the deep-inelastic scattering structure function F2(x,Q2 and the corresponding transition matrix element AQq(3,PS in the variable flavor number scheme are computed. In Mellin-N space these inclusive quantities depend on generalized harmonic sums. We also recalculate the complete 3-loop pure singlet anomalous dimension for the first time. Numerical results for the Wilson coefficients, the operator matrix element and the contribution to the structure function F2(x,Q2 are presented.

  2. X-linked genes and mental functioning

    National Research Council Canada - National Science Library

    Skuse, David H

    2005-01-01

    ... (as indicated by the large number of X-linked mental retardation syndromes). In addition, there is evidence for relatively specific effects of X-linked genes on social-cognition and emotional regulation...

  3. The calculation of the two-loop spin splitting functions P{sub ij}{sup (1)}(x)

    Energy Technology Data Exchange (ETDEWEB)

    Mertig, R. [Nationaal Inst. voor Kernfysica en Hoge-Energiefysica (NIKHEF), Amsterdam (Netherlands). Sectie H; Neerven, W.L. van [Rijksuniversiteit Leiden (Netherlands). Inst. Lorentz voor Theoretische Natuurkunde

    1995-06-01

    We present the calculation of the two-loop spin splitting functions P{sub ij}{sup (1)}(x) (i, j=q, g) contributing to the next-to-leading order corrected spin structure function g{sub 1}(x, Q{sup 2}). These splitting functions, which are presented in the anti M anti S scheme, are derived from the order {alpha}{sub s}{sup 2} contribution to the anomalous dimensions {gamma}{sup m}{sub ij} (i, j=q, g). The latter correspond to the local operators which appear in the operator product expansion of two electromagnetic currents. Some of the properties of the anomalous dimensions will be discussed. In particular we find that in order {alpha}{sub s}{sup 2} the supersymmetric relation {gamma}{sup m}{sub qq}+{gamma}{sup m}{sub qg}-{gamma}{sup m}{sub qg}-{gamma}{sup m}{sub gg}=0 is violated. (orig.).

  4. Cfs1p, a Novel Membrane Protein in the PQ-Loop Family, Is Involved in Phospholipid Flippase Functions in Yeast

    Directory of Open Access Journals (Sweden)

    Takaharu Yamamoto

    2017-01-01

    Full Text Available Type 4 P-type ATPases (P4-ATPases function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer, to generate and maintain asymmetric distribution of phospholipids at the plasma membrane and endosomal/Golgi membranes. The budding yeast Saccharomyces cerevisiae has four heteromeric flippases (Drs2p, Dnf1p, Dnf2p, and Dnf3p, associated with the Cdc50p family noncatalytic subunit, and one monomeric flippase, Neo1p. They have been suggested to function in vesicle formation in membrane trafficking pathways, but details of their mechanisms remain to be clarified. Here, to search for novel factors that functionally interact with flippases, we screened transposon insertional mutants for strains that suppressed the cold-sensitive growth defect in the cdc50Δ mutant. We identified a mutation of YMR010W encoding a novel conserved membrane protein that belongs to the PQ-loop family including the cystine transporter cystinosin and the SWEET sugar transporters. We named this gene CFS1 (cdc fifty suppressor 1. GFP-tagged Cfs1p was partially colocalized with Drs2p and Neo1p to endosomal/late Golgi membranes. Interestingly, the cfs1Δ mutation suppressed growth defects in all flippase mutants. Accordingly, defects in membrane trafficking in the flippase mutants were also suppressed. These results suggest that Cfs1p and flippases function antagonistically in membrane trafficking pathways. A growth assay to assess sensitivity to duramycin, a phosphatidylethanolamine (PE-binding peptide, suggested that the cfs1Δ mutation changed PE asymmetry in the plasma membrane. Cfs1p may thus be a novel regulator of phospholipid asymmetry.

  5. Basic helix-loop-helix transcription factor BcbHLHpol functions as a positive regulator of pollen development in non-heading Chinese cabbage.

    Science.gov (United States)

    Liu, Tongkun; Li, Ying; Zhang, Changwei; Duan, Weike; Huang, Feiyi; Hou, Xilin

    2014-12-01

    Cytoplasmic male sterility (CMS) is a common trait in higher plants, and several transcription factors regulate pollen development. Previously, we obtained a basic helix-loop-helix transcription factor, BcbHLHpol, via suppression subtractive hybridization in non-heading Chinese cabbage. However, the regulatory function of BcbHLHpol during anther and pollen development remains unclear. In this study, BcbHLHpol was cloned, and its tissue-specific expression profile was analyzed. The results of real-time polymerase chain reaction showed that BcbHLHpol was highly expressed in maintainer buds and that the transcripts of BcbHLHpol significantly decreased in the buds of pol CMS. A virus-induced gene silencing vector that targets BcbHLHpol was constructed and transformed into Brassica campestris plants to further explore the function of BcbHLHpol. Male sterility and short stature were observed in BcbHLHpol-silenced plants. The degradation of tapetal cells was inhibited in BcbHLHpol-silenced plants, and nutrients were insufficiently supplied to the microspore. These phenomena resulted in pollen abortion. This result indicates that BcbHLHpol functions as a positive regulator in pollen development. Yeast two-hybrid and bimolecular fluorescence complementation assays revealed that BcbHLHpol interacted with BcSKP1 in the nucleus. This finding suggests that BcbHLHpol and BcSKP1 are positive coordinating regulators of pollen development. Quantitative real-time PCR indicated that BcbHLHpol and BcSKP1 can be induced at low temperatures. Thus, we propose that BcbHLHpol is necessary for meiosis. This study provides insights into the regulatory functions of the BcbHLHpol network during anther development.

  6. A functional profile of gene expression in ARPE-19 cells

    Directory of Open Access Journals (Sweden)

    Johnson Dianna A

    2005-11-01

    Full Text Available Abstract Background Retinal pigment epithelium cells play an important role in the pathogenesis of age related macular degeneration. Their morphological, molecular and functional phenotype changes in response to various stresses. Functional profiling of genes can provide useful information about the physiological state of cells and how this state changes in response to disease or treatment. In this study, we have constructed a functional profile of the genes expressed by the ARPE-19 cell line of retinal pigment epithelium. Methods Using Affymetrix MAS 5.0 microarray analysis, genes expressed by ARPE-19 cells were identified. Using GeneChip® annotations, these genes were classified according to their known functions to generate a functional gene expression profile. Results We have determined that of approximately 19,044 unique gene sequences represented on the HG-U133A GeneChip® , 6,438 were expressed in ARPE-19 cells irrespective of the substrate on which they were grown (plastic, fibronectin, collagen, or Matrigel. Rather than focus our subsequent analysis on the identity or level of expression of each individual gene in this large data set, we examined the number of genes expressed within 130 functional categories. These categories were selected from a library of HG-U133A GeneChip® annotations linked to the Affymetrix MAS 5.0 data sets. Using this functional classification scheme, we were able to categorize about 70% of the expressed genes and condense the original data set of over 6,000 data points into a format with 130 data points. The resulting ARPE-19 Functional Gene Expression Profile is displayed as a percentage of ARPE-19-expressed genes. Conclusion The Profile can readily be compared with equivalent microarray data from other appropriate samples in order to highlight cell-specific attributes or treatment-induced changes in gene expression. The usefulness of these analyses is based on the assumption that the numbers of genes

  7. Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?

    Science.gov (United States)

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Peterson, Lindsy M; Mai, Katherine; McHale, Quinn; Jenkins, Michael W; Linask, Kersti K; Rollins, Andrew M; Watanabe, Michiko

    2014-02-01

    Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities.

  8. From Loops to Surfaces

    CERN Document Server

    Neuberger, H

    2010-01-01

    The generating function for all antisymmetric characters of a Wilson loop matrix in SU(N) Yang Mills theory is the partition function of a fermion living on the curve describing the loop. This generalizes to fermion subsystems living on higher dimensional submanifolds, for example, surfaces. This write-up also contains some extra background, in response to some questions raised during the oral presentation.

  9. When natural selection gives gene function the cold shoulder.

    Science.gov (United States)

    Cutter, Asher D; Jovelin, Richard

    2015-11-01

    It is tempting to invoke organismal selection as perpetually optimizing the function of any given gene. However, natural selection can drive genic functional change without improvement of biochemical activity, even to the extinction of gene activity. Detrimental mutations can creep in owing to linkage with other selectively favored loci. Selection can promote functional degradation, irrespective of genetic drift, when adaptation occurs by loss of gene function. Even stabilizing selection on a trait can lead to divergence of the underlying molecular constituents. Selfish genetic elements can also proliferate independent of any functional benefits to the host genome. Here we review the logic and evidence for these diverse processes acting in genome evolution. This collection of distinct evolutionary phenomena - while operating through easily understandable mechanisms - all contribute to the seemingly counterintuitive notion that maintenance or improvement of a gene's biochemical function sometimes do not determine its evolutionary fate.

  10. [Effects of a series of food substances on motor and emptying function of the gastric stump and diverting intestinal loop after stomach resection and truncal vagotomy].

    Science.gov (United States)

    Loranskaia, T I; Khoromskiĭ, L N; Benedikt, V V

    1986-01-01

    Altogether 253 patients operated on for peptic ulcer were examined for the action of 30 foods on motor and evacuatory function of the gastric stump and efferent intestinal loop. 213 patients were subjected to gastric resection after Hofmeister-Finsterer and 40 patients to antrum resection and truncal vagotomy. Proceeding from the action on motor function of the gastric stump and efferent intestinal loop the foods were distributed into three groups: with a stimulation, inhibitory of weak effects on the function. The first group included beef and fish broths, boiled meat, rye bread, cabbage, tomato, apple, cherry and black currant juices, rhubarb infusion, fresh kefir, carrot and pumpkin purees. The group of foods producing an inhibitory action comprised milk and milk whey, cottage cheese, sugar, butter, sunflower oil, lard, rice and oat decoctions, mashed potatoes and potato juice, buckwheat porridge and semolina, wheat bread, raw eggs, and honey. The action of the same foods was found to be different as regards the effect on the gastric stump and efferent intestinal loop, on tonic and contractile functions of the organs. The dietetic management of patients undergoing gastric operations should be carried out on a strictly individualized basis with allowance made for the functions of the gastric stump and intestinal loop and for the action of foods on the organs.

  11. The renormalised quark mass in the Schroedinger functional of lattice QCD. A one-loop calculation with a non-vanishing background field

    Energy Technology Data Exchange (ETDEWEB)

    Kurth, S.

    2002-09-04

    The renormalised quark mass in the Schroedinger functional is studied perturbatively with a non-vanishing background field. The framework in which the calculations are done is the Schroedinger functional. Its definition and basic properties are reviewed and it is shown how to make the theory converge faster towards its continuum limit by O(a) improvement. It is explained how the Schroedinger functional scheme avoids the implications of treating a large energy range on a single lattice in order to determine the scale dependence of renormalised quantities. The description of the scale dependence by the step scaling function is introduced both for the renormalised coupling and the renormalised quark masses. The definition of the renormalised coupling in the Schroedinger functional is reviewed, and the concept of the renormalised mass being defined by the axial current and density via the PCAC-relation is explained. The running of the renormalised mass described by its step scaling function is presented as a consequence of the fact that the renormalisation constant of the axial density is scale dependent. The central part of the thesis is the expansion of several correlation functions up to 1-loop order. The expansion coefficients are used to compute the critical quark mass at which the renormalised mass vanishes, as well as the 1-loop coefficient of the renormalisation constant of the axial density. Using the result for this renormalisation constant, the 2-loop anomalous dimension is obtained by conversion from the MS-scheme. Another important application of perturbation theory carried out in this thesis is the determination of discretisation errors. The critical quark mass at 1-loop order is used to compute the deviation of the coupling's step scaling function from its continuum limit at 2-loop order. Several lattice artefacts of the current quark mass, defined by the PCAC relation with the unrenormalised axial current and density, are computed at 1-loop order

  12. Methods for transient assay of gene function in floral tissues

    Directory of Open Access Journals (Sweden)

    Pathirana Nilangani N

    2007-01-01

    Full Text Available Abstract Background There is considerable interest in rapid assays or screening systems for assigning gene function. However, analysis of gene function in the flowers of some species is restricted due to the difficulty of producing stably transformed transgenic plants. As a result, experimental approaches based on transient gene expression assays are frequently used. Biolistics has long been used for transient over-expression of genes of interest, but has not been exploited for gene silencing studies. Agrobacterium-infiltration has also been used, but the focus primarily has been on the transient transformation of leaf tissue. Results Two constructs, one expressing an inverted repeat of the Antirrhinum majus (Antirrhinum chalcone synthase gene (CHS and the other an inverted repeat of the Antirrhinum transcription factor gene Rosea1, were shown to effectively induce CHS and Rosea1 gene silencing, respectively, when introduced biolistically into petal tissue of Antirrhinum flowers developing in vitro. A high-throughput vector expressing the Antirrhinum CHS gene attached to an inverted repeat of the nos terminator was also shown to be effective. Silencing spread systemically to create large zones of petal tissue lacking pigmentation, with transmission of the silenced state spreading both laterally within the affected epidermal cell layer and into lower cell layers, including the epidermis of the other petal surface. Transient Agrobacterium-mediated transformation of petal tissue of tobacco and petunia flowers in situ or detached was also achieved, using expression of the reporter genes GUS and GFP to visualise transgene expression. Conclusion We demonstrate the feasibility of using biolistics-based transient RNAi, and transient transformation of petal tissue via Agrobacterium infiltration to study gene function in petals. We have also produced a vector for high throughput gene silencing studies, incorporating the option of using T-A cloning to

  13. Two-point Functions at Two Loops in Three Flavour Chiral Perturbation Theory

    CERN Document Server

    Amorós, G; Talavera, P; Amoros, Gabriel; Bijnens, Johan; Talavera, Pere

    2000-01-01

    The vector and axial-vector two-point functions are calculated to next-to-next-to-leading order in Chiral Perturbation Theory for three light flavours. We also obtain expressions at the same order for the masses, $m_\\pi^2$, $m_K^2$ and $m_\\eta^2$, and the decay constants, $F_\\pi$, $F_K$ and $F_\\eta$. We present some numerical results after a simple resonance estimate of some of the new ${\\cal O}(p^6)$ constants.

  14. Optimal transportation network with concave cost functions: loop analysis and algorithms.

    Science.gov (United States)

    Shao, Zhen; Zhou, Haijun

    2007-06-01

    Transportation networks play a vital role in modern societies. Structural optimization of a transportation system under a given set of constraints is an issue of great practical importance. For a general transportation system whose total cost C is determined by C = Sigma(ioptimal network topology is a tree if C(ij) proportional |I(ij)|(gamma) with 0 optimality of tree-formed networks is given. The simple intuitive picture of this proof then leads to an efficient global algorithm for the searching of optimal structures for a given transportation system with concave cost functions.

  15. Horizontal functional gene transfer from bacteria to fishes.

    Science.gov (United States)

    Sun, Bao-Fa; Li, Tong; Xiao, Jin-Hua; Jia, Ling-Yi; Liu, Li; Zhang, Peng; Murphy, Robert W; He, Shun-Min; Huang, Da-Wei

    2015-12-22

    Invertebrates can acquire functional genes via horizontal gene transfer (HGT) from bacteria but fishes are not known to do so. We provide the first reliable evidence of one HGT event from marine bacteria to fishes. The HGT appears to have occurred after emergence of the teleosts. The transferred gene is expressed and regulated developmentally. Its successful integration and expression may change the genetic and metabolic repertoire of fishes. In addition, this gene contains conserved domains and similar tertiary structures in fishes and their putative donor bacteria. Thus, it may function similarly in both groups. Evolutionary analyses indicate that it evolved under purifying selection, further indicating its conserved function. We document the first likely case of HGT of functional gene from prokaryote to fishes. This discovery certifies that HGT can influence vertebrate evolution.

  16. Calculation of PDS-XADS core closed-loop transfer function by using feedback with the lumped-model

    Energy Technology Data Exchange (ETDEWEB)

    Moghassem, Alireza; Payirandeh, Ali; Abbaspour, Ali [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Nuclear Engineering Dept.

    2016-03-15

    In this paper, the PDS-XADS LBE-cooled core open-loop transfer function was calculated by considering the source importance in point-kinetic equations. For this purpose, the overall-feedback transfer function was calculated considering the lumped-model for 14-steps of subcritical levels. Following effects were considered in three steps: 1. Doppler broadening, fuel expansion, coolant density and structure expansion, 2. Delayed-reactivity and void-worth inserted to prior step, 3. Severe-accident condition, inserted to prior steps. The linear stability analysis was modeled by using the Bode diagrams, Nyquist stability criterion and Nichols chart in MATLAB for each subcritical level and six groups of delayed neutrons. For optimized subcritical level determination, a conservative severe accident was considered. According to calculation results and analysis, the PDS-XADS core is stable and in optimized subcritical level, has the higher safety margin. The results are in good agreement with SIMMER-III code and main neutronic results. The optimized subcritical level by using the lumped-model is 0.97687.

  17. AV interval optimization using pressure volume loops in dual chamber pacemaker patients with maintained systolic left ventricular function.

    Science.gov (United States)

    Eberhardt, Frank; Hanke, Thorsten; Fitschen, Joern; Heringlake, Matthias; Bode, Frank; Schunkert, Heribert; Wiegand, Uwe K H

    2012-08-01

    Atrioventricular (AV) interval optimization is often deemed too time-consuming in dual-chamber pacemaker patients with maintained LV function. Thus the majority of patients are left at their default AV interval. To quantify the magnitude of hemodynamic improvement following AV interval optimization in chronically paced dual chamber pacemaker patients. A pressure volume catheter was placed in the left ventricle of 19 patients with chronic dual chamber pacing and an ejection fraction >45 % undergoing elective coronary angiography. AV interval was varied in 10 ms steps from 80 to 300 ms, and pressure volume loops were recorded during breath hold. The average optimal AV interval was 152 ± 39 ms compared to 155 ± 8 ms for the average default AV interval (range 100-240 ms). The average improvement in stroke work following AV interval optimization was 935 ± 760 mmHg/ml (range 0-2,908; p AV interval changes the average stroke work by 207 ± 162 mmHg/ml. AV interval optimization also leads to improved systolic dyssynchrony indices (17.7 ± 7.0 vs. 19.4 ± 7.1 %; p = 0.01). The overall hemodynamic effect of AV interval optimization in patients with maintained LV function is in the same range as for patients undergoing cardiac resynchronization therapy for several parameters. The positive effect of AV interval optimization also applies to patients who have been chronically paced for years.

  18. Saliva microbiota carry caries-specific functional gene signatures.

    Directory of Open Access Journals (Sweden)

    Fang Yang

    Full Text Available Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as Diaminopimelate epimerase, Prephenate dehydrogenase, Pyruvate-formate lyase and N-acetylmuramoyl-L-alanine amidase were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis.

  19. Design and test of a closed-loop FES system for supporting function of the hemiparetic hand based on automatic detection using the Microsoft Kinect sensor

    DEFF Research Database (Denmark)

    Simonsen, Daniel; Spaich, Erika G.; Hansen, John

    2017-01-01

    This paper describes the design of a FES system automatically controlled in a closed loop using a Microsoft Kinect sensor, for assisting both cylindrical grasping and hand opening. The feasibility of the system was evaluated in real-time in stroke patients with hand function deficits. A hand...

  20. The three-loop splitting functions P{sup (2)}{sub qg} and P{sup (2,N{sub F})}{sub gg}

    Energy Technology Data Exchange (ETDEWEB)

    Ablinger, J.; Schneider, C. [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation (RISC); Behring, A. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); RWTH Aachen Univ. (Germany). Inst. fuer Theoretische Teilchenphysik und Kosmologie; Bluemlein, J.; Freitas, A. de [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Von Manteuffel, A. [Michigan State Univ., East Lansing, MI (United States). Dept. of Physics and Astronomy

    2017-04-15

    We calculate the unpolarized twist-2 three-loop splitting functions P{sup (2)}{sub qg}(x) and P{sup (2,N{sub F})}{sub gg}(x) and the associated anomalous dimensions using massive three-loop operator matrix elements. While we calculate P{sup (2,N{sub F})}{sub gg}(x) directly, P{sup (2)}{sub qg}(x) is computed from 1200 even moments, without any structural prejudice, using a hierarchy of recurrences obtained for the corresponding operator matrix element. The largest recurrence to be solved is of order 12 and degree 191. We confirm results in the foregoing literature.

  1. Functional expression of human heme oxygenase-1 gene in renal structure of spontaneously hypertensive rats.

    Science.gov (United States)

    Goodman, Alvin I; Quan, Shou; Yang, Liming; Synghal, Arika; Abraham, Nader G

    2003-05-01

    Heme oxygenase (HO), by catabolizing heme to bile pigments, regulates the levels and activity of cellular hemoprotein and HO activity. We examined the effect of delivery of the human HO-1 gene on cellular heme in renal tissue using a retroviral vector. We used a single intracardiac injection of the concentrated infectious viral particles in 5-day-old spontaneously hypertensive rats; 25 were transduced with empty vector and 25 were transduced with the human HO-1 gene. Functional expression of human and rat HO-1 was measured after 2 and 4 weeks. Reverse transcription polymerase chain reaction showed that human HO-1 mRNA was expressed as early as 2 weeks, with the highest levels in the kidney. Western blot analysis showed distribution of human HO-1 protein in rat kidney structures, predominantly in the thick ascending limb of the loop of Henle as well as in proximal tubules and preglomerular arterioles. These areas also demonstrated higher HO activity as measured by increased conversion of heme to bilirubin and carbon monoxide. Functional expression of the human HO-1 gene was associated with a decrease in blood pressure in 4- and 8-week-old spontaneously hypertensive rats. Compared with nontransduced rats, human HO-1 gene overexpression in transduced rats was associated with a 35% decrease in urinary 20-hydroxyeicosatetraenoic acid, a potent vasoconstrictor and an inhibitor of tubular Na(+) transport, which may be related to the decrease in blood pressure.

  2. Functions of Replication Protein A as a Sensor of R Loops and a Regulator of RNaseH1.

    Science.gov (United States)

    Nguyen, Hai Dang; Yadav, Tribhuwan; Giri, Sumanprava; Saez, Borja; Graubert, Timothy A; Zou, Lee

    2017-03-02

    R loop, a transcription intermediate containing RNA:DNA hybrids and displaced single-stranded DNA (ssDNA), has emerged as a major source of genomic instability. RNaseH1, which cleaves the RNA in RNA:DNA hybrids, plays an important role in R loop suppression. Here we show that replication protein A (RPA), an ssDNA-binding protein, interacts with RNaseH1 and colocalizes with both RNaseH1 and R loops in cells. In vitro, purified RPA directly enhances the association of RNaseH1 with RNA:DNA hybrids and stimulates the activity of RNaseH1 on R loops. An RPA binding-defective RNaseH1 mutant is not efficiently stimulated by RPA in vitro, fails to accumulate at R loops in cells, and loses the ability to suppress R loops and associated genomic instability. Thus, in addition to sensing DNA damage and replication stress, RPA is a sensor of R loops and a regulator of RNaseH1, extending the versatile role of RPA in suppression of genomic instability. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. An improved method for detection of Edwardsiella tarda by loop-mediated isothermal amplification by targeting the EsrB gene

    Institute of Scientific and Technical Information of China (English)

    XIE Guosi; ZHANG Qingli; HAN Nana; SHI Chengyin; WANG Xiuhua; LIU Qinghui; HUANG Jie

    2012-01-01

    Edwardsiella tarda is a major pathogen in aquatic environments that can cause heavy economic losses.An improved method for quick and accurate detection of E.tarda by loop-mediated isothermal amplification (LAMP) with two additional loop primers was developed by targeting the EsrB gene (EsrBLAMP).In this method,the Mg2+ concentration,reaction temperature,and reaction time were optimized to 8 mmol/L,61℃,and 40 min,respectively.The detection limit with the EsrB gene was as low as 10 copies,which is 100 times more sensitive than that of conventional polymerase chain reaction (PCR).The EsrB-LAMP assay was shown more sensitive and rapid than previously reported LAMP assays targeting the hemolysin gene (hemolysin-LAMP) for detection ofE.tarda.The EsrB-LAMP was also highly specific to E.tarda and had no cross-reaction with 13 other strains of bacteria.The assay can be carried out in a simple heating device and the EsrB-LAMP products can be visually detected by adding fluorescent dye to the reaction mixture.Taken together,the improved EsrB-LAMP diagnostic protocol has the potential for detection ofE.tarda from indoor and outdoor samples.

  4. Chiral and deconfinement transitions in a magnetic background using the functional renormalization group with the Polyakov loop

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Jens O.; Naylor, William R. [Department of Physics, Norwegian University of Science and Technology, Høgskoleringen 5, N-7491 Trondheim (Norway); Tranberg, Anders [Faculty of Science and Technology, University of Stavanger, N-4036 Stavanger (Norway)

    2014-04-30

    We use the Polyakov loop coupled quark-meson model to approximate low energy QCD and present results for the chiral and deconfinement transitions in the presence of a constant magnetic background B at finite temperature T and baryon chemical potential μ{sub B}. We investigate effects of various gluonic potentials on the deconfinement transition with and without a fermionic backreaction at finite B. Additionally we investigate the effect of the Polyakov loop on the chiral phase transition, finding that magnetic catalysis at low μ{sub B} is present, but weakened by the Polyakov loop.

  5. Monitoring aromatic hydrocarbon biodegradation by functional marker genes

    Energy Technology Data Exchange (ETDEWEB)

    Nyyssoenen, Mari [Technical Research Centre of Finland, Espoo (Finland)], E-mail: mari.nyyssonen@vtt.fi; Piskonen, Reetta; Itaevaara, Merja [Technical Research Centre of Finland, Espoo (Finland)

    2008-07-15

    The development of biological treatment technologies for contaminated environments requires tools for obtaining direct information about the biodegradation of specific contaminants. The potential of functional gene array analysis to monitor changes in the amount of functional marker genes as indicators of contaminant biodegradation was investigated. A prototype functional gene array was developed for targeting key functions in the biodegradation of naphthalene, toluene and xylenes. Internal standard probe based normalization was introduced to facilitate comparison across multiple samples. Coupled with one-colour hybridization, the signal normalization improved the consistency among replicate hybridizations resulting in better discrimination for the differences in the amount of target DNA. During the naphthalene biodegradation in a PAH-contaminated soil slurry microcosm, the normalized hybridization signals in naphthalene catabolic gene probes were in good agreement with the amount of naphthalene-degradation genes and the production of {sup 14}CO{sub 2}. Gene arrays provide efficient means for monitoring of contaminant biodegradation in the environment. - Functional gene array analysis coupled with one-colour hybridization and internal standard based signal normalization provides efficient tool for monitoring contaminant biodegradation processes.

  6. LoopIng: a template-based tool for predicting the structure of protein loops.

    KAUST Repository

    Messih, Mario Abdel

    2015-08-06

    Predicting the structure of protein loops is very challenging, mainly because they are not necessarily subject to strong evolutionary pressure. This implies that, unlike the rest of the protein, standard homology modeling techniques are not very effective in modeling their structure. However, loops are often involved in protein function, hence inferring their structure is important for predicting protein structure as well as function.We describe a method, LoopIng, based on the Random Forest automated learning technique, which, given a target loop, selects a structural template for it from a database of loop candidates. Compared to the most recently available methods, LoopIng is able to achieve similar accuracy for short loops (4-10 residues) and significant enhancements for long loops (11-20 residues). The quality of the predictions is robust to errors that unavoidably affect the stem regions when these are modeled. The method returns a confidence score for the predicted template loops and has the advantage of being very fast (on average: 1 min/loop).www.biocomputing.it/loopinganna.tramontano@uniroma1.itSupplementary data are available at Bioinformatics online.

  7. Measuring semantic similarities by combining gene ontology annotations and gene co-function networks.

    Science.gov (United States)

    Peng, Jiajie; Uygun, Sahra; Kim, Taehyong; Wang, Yadong; Rhee, Seung Y; Chen, Jin

    2015-02-14

    Gene Ontology (GO) has been used widely to study functional relationships between genes. The current semantic similarity measures rely only on GO annotations and GO structure. This limits the power of GO-based similarity because of the limited proportion of genes that are annotated to GO in most organisms. We introduce a novel approach called NETSIM (network-based similarity measure) that incorporates information from gene co-function networks in addition to using the GO structure and annotations. Using metabolic reaction maps of yeast, Arabidopsis, and human, we demonstrate that NETSIM can improve the accuracy of GO term similarities. We also demonstrate that NETSIM works well even for genomes with sparser gene annotation data. We applied NETSIM on large Arabidopsis gene families such as cytochrome P450 monooxygenases to group the members functionally and show that this grouping could facilitate functional characterization of genes in these families. Using NETSIM as an example, we demonstrated that the performance of a semantic similarity measure could be significantly improved after incorporating genome-specific information. NETSIM incorporates both GO annotations and gene co-function network data as a priori knowledge in the model. Therefore, functional similarities of GO terms that are not explicitly encoded in GO but are relevant in a taxon-specific manner become measurable when GO annotations are limited. Supplementary information and software are available at http://www.msu.edu/~jinchen/NETSIM .

  8. Functional Insight From Fruit Flies on Human ADHD Candidate Genes

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Arvidson, Sandra Marie Neumann

    2015-01-01

    , and increased risk of mental comorbidities, makes ADHD a disorder with high individual and societal costs. We use Drosophila melanogaster as a model to investigate the phenotypic consequences of gene disruption of 14 genes with human orthologs, selected by their proposed contribution to increased risk...... for other mutants. Decreased activity level, when treated with dexamphetamine, is seen when using other ADHD animal models. Our findings suggest involvement of the proposed candidate genes Genes, Brain, and Behavior 2015 36 Talk Abstracts in hyperactivity in D. melanogaster, providing functional evidence...

  9. Integrase-directed recovery of functional genes from genomic libraries.

    Science.gov (United States)

    Rowe-Magnus, Dean A

    2009-09-01

    Large population sizes, rapid growth and 3.8 billion years of evolution firmly establish microorganisms as a major source of the planet's biological and genetic diversity. However, up to 99% of the microorganisms in a given environment cannot be cultured. Culture-independent methods that directly access the genetic potential of an environmental sample can unveil new proteins with diverse functions, but the sequencing of random DNA can generate enormous amounts of extraneous data. Integrons are recombination systems that accumulate open reading frames (gene cassettes), many of which code for functional proteins with enormous adaptive potential. Some integrons harbor hundreds of gene cassettes and evidence suggests that the gene cassette pool may be limitless in size. Accessing this genetic pool has been hampered since sequence-based techniques, such as hybridization or PCR, often recover only partial genes or a small subset of those present in the sample. Here, a three-plasmid genetic strategy for the sequence-independent recovery of gene cassettes from genomic libraries is described and its use by retrieving functional gene cassettes from the chromosomal integron of Vibrio vulnificus ATCC 27562 is demonstrated. By manipulating the natural activity of integrons, we can gain access to the caches of functional genes amassed by these structures.

  10. Ranking, selecting, and prioritising genes with desirability functions

    Directory of Open Access Journals (Sweden)

    Stanley E. Lazic

    2015-11-01

    Full Text Available In functional genomics experiments, researchers often select genes to follow-up or validate from a long list of differentially expressed genes. Typically, sharp thresholds are used to bin genes into groups such as significant/non-significant or fold change above/below a cut-off value, and ad hoc criteria are also used such as favouring well-known genes. Binning, however, is inefficient and does not take the uncertainty of the measurements into account. Furthermore, p-values, fold-changes, and other outcomes are treated as equally important, and relevant genes may be overlooked with such an approach. Desirability functions are proposed as a way to integrate multiple selection criteria for ranking, selecting, and prioritising genes. These functions map any variable to a continuous 0–1 scale, where one is maximally desirable and zero is unacceptable. Multiple selection criteria are then combined to provide an overall desirability that is used to rank genes. In addition to p-values and fold-changes, further experimental results and information contained in databases can be easily included as criteria. The approach is demonstrated with a breast cancer microarray data set. The functions and an example data set can be found in the desiR package on CRAN (https://cran.r-project.org/web/packages/desiR/ and the development version is available on GitHub (https://github.com/stanlazic/desiR.

  11. Dipole factorization for DIS at NLO I: Loop correction to the photon to quark-antiquark light-front wave-functions

    CERN Document Server

    Beuf, Guillaume

    2016-01-01

    The one-loop QCD corrections to the light-front wave-function for the quark-antiquark Fock state inside a transverse or longitudinal off-shell photon are explicitly calculated, both in full momentum space and in mixed space (a.k.a. dipole space). These results provide one of the main contributions to virtual NLO corrections to many DIS observables (inclusive or not) in the dipole factorization formalism at low Bjorken x. In a follow-up article, these one-loop corrections are combined with earlier results on the wave-function for the quark-antiquark-gluon Fock state, in order to get the full set of NLO corrections to the DIS structure functions $F_2$ and $F_L$ in the dipole factorization formalism, valid at low Bjorken x.

  12. FUNCTIONAL SPECIALIZATION OF DUPLICATED FLAVONOID BIOSYNTHESIS GENES IN WHEAT

    Directory of Open Access Journals (Sweden)

    Khlestkina E.

    2012-08-01

    Full Text Available Gene duplication followed by subfunctionalization and neofunctionalization is of a great evolutionary importance. In plant genomes, duplicated genes may result from either polyploidization (homoeologous genes or segmental chromosome duplications (paralogous genes. In allohexaploid wheat Triticum aestivum L. (2n=6x=42, genome BBAADD, both homoeologous and paralogous copies were found for the regulatory gene Myc encoding MYC-like transcriptional factor in the biosynthesis of flavonoid pigments, anthocyanins, and for the structural gene F3h encoding one of the key enzymes of flavonoid biosynthesis, flavanone 3-hydroxylase. From the 5 copies (3 homoeologous and 2 paralogous of the Myc gene found in T. aestivum, only one plays a regulatory role in anthocyanin biosynthesis, interacting complementary with another transcriptional factor (MYB-like to confer purple pigmentation of grain pericarp in wheat. The role and functionality of the other 4 copies of the Myc gene remain unknown. From the 4 functional copies of the F3h gene in T. aestivum, three homoeologues have similar function. They are expressed in wheat organs colored with anthocyanins or in the endosperm, participating there in biosynthesis of uncolored flavonoid substances. The fourth copy (the B-genomic paralogue is transcribed neither in wheat organs colored with anthocyanins nor in seeds, however, it’s expression has been noticed in roots of aluminium-stressed plants, where the three homoeologous copies are not active. Functional diversification of the duplicated flavonoid biosynthesis genes in wheat may be a reason for maintenance of the duplicated copies and preventing them from pseudogenization.The study was supported by RFBR (11-04-92707. We also thank Ms. Galina Generalova for technical assistance.

  13. Recent Achievement in Gene Cloning and Functional Genomics in Soybean

    Directory of Open Access Journals (Sweden)

    Zhengjun Xia

    2013-01-01

    Full Text Available Soybean is a model plant for photoperiodism as well as for symbiotic nitrogen fixation. However, a rather low efficiency in soybean transformation hampers functional analysis of genes isolated from soybean. In comparison, rapid development and progress in flowering time and photoperiodic response have been achieved in Arabidopsis and rice. As the soybean genomic information has been released since 2008, gene cloning and functional genomic studies have been revived as indicated by successfully characterizing genes involved in maturity and nematode resistance. Here, we review some major achievements in the cloning of some important genes and some specific features at genetic or genomic levels revealed by the analysis of functional genomics of soybean.

  14. The identification of elephant ivory evidences of illegal trade with mitochondrial cytochrome b gene and hypervariable D-loop region.

    Science.gov (United States)

    Lee, Eun-jung; Lee, Yang-han; Moon, Seo-hyun; Kim, Nam-ye; Kim, Soon-hee; Yang, Moon-sik; Choi, Dong-ho; Han, Myun-soo

    2013-04-01

    DNA analysis of elephant ivory of illegal trade was handled in this work. The speciation and geographical origin of nine specimens of elephant ivory were requested by the police. Without national authorization, the suspect had purchased processed ivory seals from January to May, 2011 by Internet transactions from a site in a neighboring country. The DNA of decalcified ivory evidences was isolated with QIAGEN Micro Kit. The total 844-904 base pair sized sequences of mitochondrial cytochrome b and D-loop region could be acquired using direct sequencing analysis. They were compared with the sequences registered in GenBank. It was confirmed that most specimens were likely from African forest elephants (Loxodonta cyclotis), one from African savanna elephant (Loxodonta africana) and one from Asian elephant (Elephas maximus). Analysis of the mitochondrial hypervariable D-loop region sequence of elephants verified that one African savanna elephant might be from South Africa and one Asian elephant from Laos. Cytochrome b and D-loop region located in the mitochondrial DNA resulted in the successful determination of elephant DNA from nine processed ivory specimens.

  15. Expression and evolution of functionally distinct haemoglobin genes in plants.

    Science.gov (United States)

    Hunt, P W; Watts, R A; Trevaskis, B; Llewelyn, D J; Burnell, J; Dennis, E S; Peacock, W J

    2001-11-01

    Haemoglobin genes have been found in a number of plant species, but the number of genes known has been too small to allow effective evolutionary inferences. We present nine new non-symbiotic haemoglobin sequences from a range of plants, including class 1 haemoglobins from cotton, Citrus and tomato, class 2 haemoglobins from cotton, tomato, sugar beet and canola and two haemoglobins from the non-vascular plants, Marchantia polymorpha (a liverwort) and Physcomitrella patens (a moss). Our molecular phylogenetic analysis of all currently known non-symbiotic haemoglobin genes and a selection of symbiotic haemoglobins have confirmed the existence of two distinct classes of haemoglobin genes in the dicots. It is likely that all dicots have both class 1 and class 2 non-symbiotic haemoglobin genes whereas in monocots we have detected only class 1 genes. The symbiotic haemoglobins from legumes and Casuarina are related to the class 2 non-symbiotic haemoglobins, whilst the symbiotic haemoglobin from Parasponia groups with the class 1 non-symbiotic genes. Probably, there have been two independent recruitments of symbiotic haemoglobins. Although the functions of the two non-symbiotic haemoglobins remain unknown, their patterns of expression within plants suggest different functions. We examined the expression in transgenic plants of the two non-symbiotic haemoglobins from Arabidopsis using promoter fusions to a GUS reporter gene. The Arabidopsis GLB1 and GLB2 genes are likely to be functionally distinct. The class 2 haemoglobin gene (GLB2) is expressed in the roots, leaves and inflorescence and can be induced in young plants by cytokinin treatment in contrast to the class 1 gene (GLB1) which is active in germinating seedlings and can be induced by hypoxia and increased sucrose supply, but not by cytokinin treatment.

  16. A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

    Science.gov (United States)

    Noël, Emily S.; Verhoeven, Manon; Lagendijk, Anne Karine; Tessadori, Federico; Smith, Kelly; Choorapoikayil, Suma; den Hertog, Jeroen; Bakkers, Jeroen

    2013-11-01

    Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.

  17. Calcitonin gene related peptide and its functions

    Directory of Open Access Journals (Sweden)

    Karimian M

    1998-07-01

    Full Text Available Calcitonin Gene Related Peptide (CGRP was first reported in 1982. This peptide contains 37 amino acids which could be found in Alpha and Beta forms. CGRP shows diversity both in its receptors and biological effects and up to now four different types of receptors have been reported. It can act like a neurotransmitter, local hormone and neuromodulator. They have a variety of effects on different organs such as a potent effect on vasodilation and smooth muscle relaxation. Ability of CGRP for induction of protein extravasation from blood vessels was uncertain. In this study intra-articular infusion of 10^-6 M CGRP to the rat knee joint induced significant protein extravasation into the rat knee joint space. The amount of protein was detected by modified Iawata method which could detect amount of protein between 5-500 mg/L. Higher and lower concentrations failed to induce protein extravasation. Failure in higher concentration was likely due to significant fall in blood pressure. In the presence of an arterial hypotension induced by an ? adenoreceptor antagonist, 10^-6 M of CGRP failed to produce protein extravasation. This effect of CGRP was a specific active effect and not a passive effect due to its potent vasodilation effect, as similar vasodilatory response induced by a ?-adrenoreceptor agonist failed to induce protein extravasation. There is more than 50% of sensory neurons which contain CGRP and they are spread in all over the body and joints, therefore CGRP induced protein extravasation can potentiate inflammation in different organs.

  18. Gene function in early mouse embryonic stem cell differentiation

    Directory of Open Access Journals (Sweden)

    Campbell Pearl A

    2007-03-01

    Full Text Available Abstract Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5 undergoing undirected differentiation into embryoid bodies (EBs over a period of two weeks. Results We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1, our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2 that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. Conclusion Our analysis profiles for the first time gene expression at a very early stage of m

  19. Primary functional identification of gene TMSG-1

    Institute of Scientific and Technical Information of China (English)

    MA; Chunshu; (马春树); NING; Junyu; (宁钧宇); YOU; Jiangfeng; (由江峰); LIU; Lin; (柳林); WANG; Jieliang; (王洁良); CUI; Xianglin; (崔湘琳); WU; Bingquan; (吴秉铨); ZHENG; Jie; (郑杰)

    2003-01-01

    TMSG-1 was a tumor metastasis-related gene identified using mRNA differential display, whose expression level was lower in cancer cell lines with higher metastatic potential and in tumor tissue with metastasis. TMSG-1 was transfected to prostate cancer cell line (PC-3M-1E8) with high metastatic potential to observe the effects of increased expression of TMSG-1 on V-ATPase activity, intracellular pH and cell apoptosis. Subcellular localization of the encoded protein of TMSG-1 was determined by using GFP. Results showed that there were no differences of V-ATPase activity among parental PC-3M-1E8 cell line, pcDNA3 transfectant and anti-TMSG-1 transfectant, whereas the V-ATPase activity was significantly higher in TMSG-1 transfectant than that in parental PC-3M-1E8 cell line, pcDNA3 transfectant and Anti-TMSG-1 transfectant (p<0.001). Intracellular pH (pHi) was detected by using the pH-dependent fluorescence probe BECEF. Results showed the pHi was significantly increased in TMSG-1 transfectant. Cell apoptosis assay demonstrated cell apoptosis was significantly higher in -1 transfectant (p<0.01) and BCL2 expression was down regulated. Subcellular localization of TMSG-1 protein showed TMSG-1 was a transmembrane protein, which predicted TMSG-1 protein was located in cytoplasm system, such as endoplasmic reticulum and mitochondrial. These results indicated TMSG-1 up regulation in prostate cancer cell line could promote V-ATPase activity, increase pHi and cell apoptosis, and inhibit the expression of BCL2.

  20. Annotation of gene function in citrus using gene expression information and co-expression networks.

    Science.gov (United States)

    Wong, Darren C J; Sweetman, Crystal; Ford, Christopher M

    2014-07-15

    The genus Citrus encompasses major cultivated plants such as sweet orange, mandarin, lemon and grapefruit, among the world's most economically important fruit crops. With increasing volumes of transcriptomics data available for these species, Gene Co-expression Network (GCN) analysis is a viable option for predicting gene function at a genome-wide scale. GCN analysis is based on a "guilt-by-association" principle whereby genes encoding proteins involved in similar and/or related biological processes may exhibit similar expression patterns across diverse sets of experimental conditions. While bioinformatics resources such as GCN analysis are widely available for efficient gene function prediction in model plant species including Arabidopsis, soybean and rice, in citrus these tools are not yet developed. We have constructed a comprehensive GCN for citrus inferred from 297 publicly available Affymetrix Genechip Citrus Genome microarray datasets, providing gene co-expression relationships at a genome-wide scale (33,000 transcripts). The comprehensive citrus GCN consists of a global GCN (condition-independent) and four condition-dependent GCNs that survey the sweet orange species only, all citrus fruit tissues, all citrus leaf tissues, or stress-exposed plants. All of these GCNs are clustered using genome-wide, gene-centric (guide) and graph clustering algorithms for flexibility of gene function prediction. For each putative cluster, gene ontology (GO) enrichment and gene expression specificity analyses were performed to enhance gene function, expression and regulation pattern prediction. The guide-gene approach was used to infer novel roles of genes involved in disease susceptibility and vitamin C metabolism, and graph-clustering approaches were used to investigate isoprenoid/phenylpropanoid metabolism in citrus peel, and citric acid catabolism via the GABA shunt in citrus fruit. Integration of citrus gene co-expression networks, functional enrichment analysis and gene

  1. Annotation of gene function in citrus using gene expression information and co-expression networks

    OpenAIRE

    Wong, Darren CJ; Sweetman, Crystal; Ford, Christopher M.

    2014-01-01

    Background The genus Citrus encompasses major cultivated plants such as sweet orange, mandarin, lemon and grapefruit, among the world’s most economically important fruit crops. With increasing volumes of transcriptomics data available for these species, Gene Co-expression Network (GCN) analysis is a viable option for predicting gene function at a genome-wide scale. GCN analysis is based on a “guilt-by-association” principle whereby genes encoding proteins involved in similar and/or related bi...

  2. Annotation of gene function in citrus using gene expression information and co-expression networks

    OpenAIRE

    Wong, Darren CJ; Sweetman, Crystal; Ford, Christopher M.

    2014-01-01

    Background The genus Citrus encompasses major cultivated plants such as sweet orange, mandarin, lemon and grapefruit, among the world’s most economically important fruit crops. With increasing volumes of transcriptomics data available for these species, Gene Co-expression Network (GCN) analysis is a viable option for predicting gene function at a genome-wide scale. GCN analysis is based on a “guilt-by-association” principle whereby genes encoding proteins involved in similar and/or related bi...

  3. Sucrose metabolism gene families and their biological functions.

    Science.gov (United States)

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-11-30

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions.

  4. Bioinformatic prediction and functional characterization of human KIAA0100 gene

    Directory of Open Access Journals (Sweden)

    He Cui

    2017-02-01

    Full Text Available Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated (Cas 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil , and four domains from mitochondrial protein 27 (FMP27. The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.

  5. Automated discovery of functional generality of human gene expression programs.

    Directory of Open Access Journals (Sweden)

    Georg K Gerber

    2007-08-01

    Full Text Available An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-kappaB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal

  6. Loop-Mediated Isothermal Amplification (LAMP) for Rapid Detection and Quantification of Dehalococcoides Biomarker Genes in Commercial Reductive Dechlorinating Cultures KB-1 and SDC-9.

    Science.gov (United States)

    Kanitkar, Yogendra H; Stedtfeld, Robert D; Steffan, Robert J; Hashsham, Syed A; Cupples, Alison M

    2016-01-08

    Real-time quantitative PCR (qPCR) protocols specific to the reductive dehalogenase (RDase) genes vcrA, bvcA, and tceA are commonly used to quantify Dehalococcoides spp. in groundwater from chlorinated solvent-contaminated sites. In this study, loop-mediated isothermal amplification (LAMP) was developed as an alternative approach for the quantification of these genes. LAMP does not require a real-time thermal cycler (i.e., amplification is isothermal), allowing the method to be performed using less-expensive and potentially field-deployable detection devices. Six LAMP primers were designed for each of three RDase genes (vcrA, bvcA, and tceA) using Primer Explorer V4. The LAMP assays were compared to conventional qPCR approaches using plasmid standards, two commercially available bioaugmentation cultures, KB-1 and SDC-9 (both contain Dehalococcoides species). DNA was extracted over a growth cycle from KB-1 and SDC-9 cultures amended with trichloroethene and vinyl chloride, respectively. All three genes were quantified for KB-1, whereas only vcrA was quantified for SDC-9. A comparison of LAMP and qPCR using standard plasmids indicated that quantification results were similar over a large range of gene concentrations. In addition, the quantitative increase in gene concentrations over one growth cycle of KB-1 and SDC-9 using LAMP was comparable to that of qPCR. The developed LAMP assays for vcrA and tceA genes were validated by comparing quantification on the Gene-Z handheld platform and a real-time thermal cycler using DNA isolated from eight groundwater samples obtained from an SDC-9-bioaugmented site (Tulsa, OK). These assays will be particularly useful at sites subject to bioaugmentation with these two commonly used Dehalococcoides species-containing cultures.

  7. The use of multiple hierarchically independent gene ontology terms in gene function prediction and genome annotation

    NARCIS (Netherlands)

    Kourmpetis, Y.I.A.; Burgt, van der A.; Bink, M.C.A.M.; Braak, ter C.J.F.; Ham, van R.C.H.J.

    2007-01-01

    The Gene Ontology (GO) is a widely used controlled vocabulary for the description of gene function. In this study we quantify the usage of multiple and hierarchically independent GO terms in the curated genome annotations of seven well-studied species. In most genomes, significant proportions (6 -

  8. Gene analogue finder: a GRID solution for finding functionally analogous gene products

    Directory of Open Access Journals (Sweden)

    Licciulli Flavio

    2007-09-01

    Full Text Available Abstract Background To date more than 2,1 million gene products from more than 100000 different species have been described specifying their function, the processes they are involved in and their cellular localization using a very well defined and structured vocabulary, the gene ontology (GO. Such vast, well defined knowledge opens the possibility of compare gene products at the level of functionality, finding gene products which have a similar function or are involved in similar biological processes without relying on the conventional sequence similarity approach. Comparisons within such a large space of knowledge are highly data and computing intensive. For this reason this project was based upon the use of the computational GRID, a technology offering large computing and storage resources. Results We have developed a tool, GENe AnaloGue FINdEr (ENGINE that parallelizes the search process and distributes the calculation and data over the computational GRID, splitting the process into many sub-processes and joining the calculation and the data on the same machine and therefore completing the whole search in about 3 days instead of occupying one single machine for more than 5 CPU years. The results of the functional comparison contain potential functional analogues for more than 79000 gene products from the most important species. 46% of the analyzed gene products are well enough described for such an analysis to individuate functional analogues, such as well-known members of the same gene family, or gene products with similar functions which would never have been associated by standard methods. Conclusion ENGINE has produced a list of potential functionally analogous relations between gene products within and between species using, in place of the sequence, the gene description of the GO, thus demonstrating the potential of the GO. However, the current limiting factor is the quality of the associations of many gene products from non

  9. Inter-MAR association contributes to transcriptionally active looping events in human beta-globin gene cluster.

    Science.gov (United States)

    Wang, Li; Di, Li-Jun; Lv, Xiang; Zheng, Wei; Xue, Zheng; Guo, Zhi-Chen; Liu, De-Pei; Liang, Chi-Chuan

    2009-01-01

    Matrix attachment regions (MARs) are important in chromatin organization and gene regulation. Although it is known that there are a number of MAR elements in the beta-globin gene cluster, it is unclear that how these MAR elements are involved in regulating beta-globin genes expression. Here, we report the identification of a new MAR element at the LCR (locus control region) of human beta-globin gene cluster and the detection of the inter-MAR association within the beta-globin gene cluster. Also, we demonstrate that SATB1, a protein factor that has been implicated in the formation of network like higher order chromatin structures at some gene loci, takes part in beta-globin specific inter-MAR association through binding the specific MARs. Knocking down of SATB1 obviously reduces the binding of SATB1 to the MARs and diminishes the frequency of the inter-MAR association. As a result, the ACH establishment and the alpha-like globin genes and beta-like globin genes expressions are affected either. In summary, our results suggest that SATB1 is a regulatory factor of hemoglobin genes, especially the early differentiation genes at least through affecting the higher order chromatin structure.

  10. Concentration and length dependence of DNA looping in transcriptional regulation.

    Directory of Open Access Journals (Sweden)

    Lin Han

    Full Text Available In many cases, transcriptional regulation involves the binding of transcription factors at sites on the DNA that are not immediately adjacent to the promoter of interest. This action at a distance is often mediated by the formation of DNA loops: Binding at two or more sites on the DNA results in the formation of a loop, which can bring the transcription factor into the immediate neighborhood of the relevant promoter. These processes are important in settings ranging from the historic bacterial examples (bacterial metabolism and the lytic-lysogeny decision in bacteriophage, to the modern concept of gene regulation to regulatory processes central to pattern formation during development of multicellular organisms. Though there have been a variety of insights into the combinatorial aspects of transcriptional control, the mechanism of DNA looping as an agent of combinatorial control in both prokaryotes and eukaryotes remains unclear. We use single-molecule techniques to dissect DNA looping in the lac operon. In particular, we measure the propensity for DNA looping by the Lac repressor as a function of the concentration of repressor protein and as a function of the distance between repressor binding sites. As with earlier single-molecule studies, we find (at least two distinct looped states and demonstrate that the presence of these two states depends both upon the concentration of repressor protein and the distance between the two repressor binding sites. We find that loops form even at interoperator spacings considerably shorter than the DNA persistence length, without the intervention of any other proteins to prebend the DNA. The concentration measurements also permit us to use a simple statistical mechanical model of DNA loop formation to determine the free energy of DNA looping, or equivalently, the for looping.

  11. Consistent Momentum Space Regularization/Renormalization of Supersymmetric Quantum Field Theories: The 3-loop beta function for the Wess-Zumino Model

    CERN Document Server

    Carneiro, D F; Sampaio, M D; Nemes, M C

    2003-01-01

    We compute the three loop $\\beta$ function of the Wess-Zumino model to motivate implicit regularization (IR) as a consistent and practical momentum-space framework to study supersymmetric quantum field theories. In this framework which works essentially in the physical dimension of the theory we show that ultraviolet are clearly disantangled from infrared divergences. We obtain consistent results which motivate the method as a good choice to study supersymmetry anomalies in quantum field theories.

  12. Cellular functions of genetically imprinted genes in human and mouse as annotated in the gene ontology.

    Science.gov (United States)

    Hamed, Mohamed; Ismael, Siba; Paulsen, Martina; Helms, Volkhard

    2012-01-01

    By analyzing the cellular functions of genetically imprinted genes as annotated in the Gene Ontology for human and mouse, we found that imprinted genes are often involved in developmental, transport and regulatory processes. In the human, paternally expressed genes are enriched in GO terms related to the development of organs and of anatomical structures. In the mouse, maternally expressed genes regulate cation transport as well as G-protein signaling processes. Furthermore, we investigated if imprinted genes are regulated by common transcription factors. We identified 25 TF families that showed an enrichment of binding sites in the set of imprinted genes in human and 40 TF families in mouse. In general, maternally and paternally expressed genes are not regulated by different transcription factors. The genes Nnat, Klf14, Blcap, Gnas and Ube3a contribute most to the enrichment of TF families. In the mouse, genes that are maternally expressed in placenta are enriched for AP1 binding sites. In the human, we found that these genes possessed binding sites for both, AP1 and SP1.

  13. Global properties and functional complexity of human gene regulatory variation.

    Directory of Open Access Journals (Sweden)

    Daniel J Gaffney

    2013-05-01

    Full Text Available Identification and functional interpretation of gene regulatory variants is a major focus of modern genomics. The application of genetic mapping to molecular and cellular traits has enabled the detection of regulatory variation on genome-wide scales and revealed an enormous diversity of regulatory architecture in humans and other species. In this review I summarise the insights gained and questions raised by a decade of genetic mapping of gene expression variation. I discuss recent extensions of this approach using alternative molecular phenotypes that have revealed some of the biological mechanisms that drive gene expression variation between individuals. Finally, I highlight outstanding problems and future directions for development.

  14. Structure and function of Rac genes in higher plants

    Institute of Scientific and Technical Information of China (English)

    LUO Min; WU Naihu

    2003-01-01

    As the sole ubiquitous signal GTP-binding protein in higher plants, Rac genes act as pivotal molecular switches and participate in regulations of many life activities, such as cell morphogenesis and polarity growth, programmed cell death, production of H2O2, cell differentiation, and hormone reaction. Based on our work on rice Rac genes, this paper summarizes the researches on Rac genes in higher plant of the last ten years. It will help us to understand the relation between the signal tranduction and the biological functions of plant Rac.

  15. Diverse functions of spindle assembly checkpoint genes in Saccharomyces cerevisiae.

    Science.gov (United States)

    Daniel, Jewel A; Keyes, Brice E; Ng, Yvonne P Y; Freeman, C Onyi; Burke, Daniel J

    2006-01-01

    The spindle assembly checkpoint regulates the metaphase-to-anaphase transition from yeast to humans. We examined the genetic interactions with four spindle assembly checkpoint genes to identify nonessential genes involved in chromosome segregation, to identify the individual roles of the spindle assembly checkpoint genes within the checkpoint, and to reveal potential complexity that may exist. We used synthetic genetic array (SGA) analysis using spindle assembly checkpoint mutants mad1, mad2, mad3, and bub3. We found 228 synthetic interactions with the four spindle assembly checkpoint mutants with substantial overlap in the spectrum of interactions between mad1, mad2, and bub3. In contrast, there were many synthetic interactions that were common to mad1, mad2, and bub3 that were not shared by mad3. We found shared interactions between pairs of spindle assembly checkpoint mutants, suggesting additional complexity within the checkpoint and unique interactions for all of the spindle assembly checkpoint genes. We show that most genes in the interaction network, including ones with unique interactions, affect chromosome transmission or microtubule function, suggesting that the complexity of interactions reflects diverse roles for the checkpoint genes within the checkpoint. Our analysis expands our understanding of the spindle assembly checkpoint and identifies new candidate genes with possible roles in chromosome transmission and mitotic spindle function.

  16. R-loopDB: a database for R-loop forming sequences (RLFS) and R-loops

    Science.gov (United States)

    Jenjaroenpun, Piroon; Wongsurawat, Thidathip; Sutheeworapong, Sawannee; Kuznetsov, Vladimir A.

    2017-01-01

    R-loopDB (http://rloop.bii.a-star.edu.sg) was originally constructed as a collection of computationally predicted R-loop forming sequences (RLFSs) in the human genic regions. The renewed R-loopDB provides updates, improvements and new options, including access to recent experimental data. It includes genome-scale prediction of RLFSs for humans, six other animals and yeast. Using the extended quantitative model of RLFSs (QmRLFS), we significantly increased the number of RLFSs predicted in the human genes and identified RLFSs in other organism genomes. R-loopDB allows searching of RLFSs in the genes and in the 2 kb upstream and downstream flanking sequences of any gene. R-loopDB exploits the Ensembl gene annotation system, providing users with chromosome coordinates, sequences, gene and genomic data of the 1 565 795 RLFSs distributed in 121 056 genic or proximal gene regions of the covered organisms. It provides a comprehensive annotation of Ensembl RLFS-positive genes including 93 454 protein coding genes, 12 480 long non-coding RNA and 7 568 small non-coding RNA genes and 7 554 pseudogenes. Using new interface and genome viewers of R-loopDB, users can search the gene(s) in multiple species with keywords in a single query. R-loopDB provides tools to carry out comparative evolution and genome-scale analyses in R-loop biology. PMID:27899586

  17. A new gene ontology-based measure for the functional similarity of gene products

    Institute of Scientific and Technical Information of China (English)

    QI Guo-long; QIAN Shi-yu; FANG Ji-qian

    2013-01-01

    Background Although biomedical ontologies have standardized the representation of gene products across species and databases,a method for determining the functional similarities of gene products has not yet been developed.Methods We proposed a new semantic similarity measure based on Gene Ontology that considers the semantic influences from all of the ancestor terms in a graph.Our measure was compared with Resnik's measure in two applications,which were based on the association of the measure used with the gene co-expression and the proteinprotein interactions.Results The results showed a considerable association between the semantic similarity and the expression correlation and between the semantic similarity and the protein-protein interactions,and our measure performed the best overall.Conclusion These results revealed the potential value of our newly proposed semantic similarity measure in studying the functional relevance of gene products.

  18. PHYLOGENOMICS - GUIDED VALIDATION OF FUNCTION FOR CONSERVED UNKNOWN GENES

    Energy Technology Data Exchange (ETDEWEB)

    V, DE CRECY-LAGARD; D, HANSON A

    2012-01-03

    Identifying functions for all gene products in all sequenced organisms is a central challenge of the post-genomic era. However, at least 30-50% of the proteins encoded by any given genome are of unknown function, or wrongly or vaguely annotated. Many of these 'unknown' proteins are common to prokaryotes and plants. We accordingly set out to predict and experimentally test the functions of such proteins. Our approach to functional prediction is integrative, coupling the extensive post-genomic resources available for plants with comparative genomics based on hundreds of microbial genomes, and functional genomic datasets from model microorganisms. The early phase is computer-assisted; later phases incorporate intellectual input from expert plant and microbial biochemists. The approach thus bridges the gap between automated homology-based annotations and the classical gene discovery efforts of experimentalists, and is much more powerful than purely computational approaches to identifying gene-function associations. Among Arabidopsis genes, we focused on those (2,325 in total) that (i) are unique or belong to families with no more than three members, (ii) are conserved between plants and prokaryotes, and (iii) have unknown or poorly known functions. Computer-assisted selection of promising targets for deeper analysis was based on homology .. independent characteristics associated in the SEED database with the prokaryotic members of each family, specifically gene clustering and phyletic spread, as well as availability of functional genomics data, and publications that could link candidate families to general metabolic areas, or to specific functions. In-depth comparative genomic analysis was then performed for about 500 top candidate families, which connected ~55 of them to general areas of metabolism and led to specific functional predictions for a subset of ~25 more. Twenty predicted functions were experimentally tested in at least one prokaryotic organism

  19. Ontology-Based Prediction and Prioritization of Gene Functional Annotations.

    Science.gov (United States)

    Chicco, Davide; Masseroli, Marco

    2016-01-01

    Genes and their protein products are essential molecular units of a living organism. The knowledge of their functions is key for the understanding of physiological and pathological biological processes, as well as in the development of new drugs and therapies. The association of a gene or protein with its functions, described by controlled terms of biomolecular terminologies or ontologies, is named gene functional annotation. Very many and valuable gene annotations expressed through terminologies and ontologies are available. Nevertheless, they might include some erroneous information, since only a subset of annotations are reviewed by curators. Furthermore, they are incomplete by definition, given the rapidly evolving pace of biomolecular knowledge. In this scenario, computational methods that are able to quicken the annotation curation process and reliably suggest new annotations are very important. Here, we first propose a computational pipeline that uses different semantic and machine learning methods to predict novel ontology-based gene functional annotations; then, we introduce a new semantic prioritization rule to categorize the predicted annotations by their likelihood of being correct. Our tests and validations proved the effectiveness of our pipeline and prioritization of predicted annotations, by selecting as most likely manifold predicted annotations that were later confirmed.

  20. Cognitive analysis of schizophrenia risk genes that function as epigenetic regulators of gene expression.

    Science.gov (United States)

    Whitton, Laura; Cosgrove, Donna; Clarkson, Christopher; Harold, Denise; Kendall, Kimberley; Richards, Alex; Mantripragada, Kiran; Owen, Michael J; O'Donovan, Michael C; Walters, James; Hartmann, Annette; Konte, Betina; Rujescu, Dan; Gill, Michael; Corvin, Aiden; Rea, Stephen; Donohoe, Gary; Morris, Derek W

    2016-12-01

    Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription. Evidence now supports some shared genetic aetiology between schizophrenia and intellectual disability. GWAS have identified 108 chromosomal regions associated with schizophrenia risk that span 350 genes. This study identified genes mapping to those loci that have epigenetic functions, and tested the risk alleles defining those loci for association with cognitive deficits. We developed a list of 350 genes with epigenetic functions and cross-referenced this with the GWAS loci. This identified eight candidate genes: BCL11B, CHD7, EP300, EPC2, GATAD2A, KDM3B, RERE, SATB2. Using a dataset of Irish psychosis cases and controls (n = 1235), the schizophrenia risk SNPs at these loci were tested for effects on IQ, working memory, episodic memory, and attention. Strongest associations were for rs6984242 with both measures of IQ (P = 0.001) and episodic memory (P = 0.007). We link rs6984242 to CHD7 via a long range eQTL. These associations were not replicated in independent samples. Our study highlights that a number of genes mapping to risk loci for schizophrenia may function as epigenetic regulators of gene expression but further studies are required to establish a role for these genes in cognition. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Loop-to-loop coupling.

    Energy Technology Data Exchange (ETDEWEB)

    Warne, Larry Kevin; Lucero, Larry Martin; Langston, William L.; Salazar, Robert Austin; Coleman, Phillip Dale; Basilio, Lorena I.; Bacon, Larry Donald

    2012-05-01

    This report estimates inductively-coupled energy to a low-impedance load in a loop-to-loop arrangement. Both analytical models and full-wave numerical simulations are used and the resulting fields, coupled powers and energies are compared. The energies are simply estimated from the coupled powers through approximations to the energy theorem. The transmitter loop is taken to be either a circular geometry or a rectangular-loop (stripline-type) geometry that was used in an experimental setup. Simple magnetic field models are constructed and used to estimate the mutual inductance to the receiving loop, which is taken to be circular with one or several turns. Circuit elements are estimated and used to determine the coupled current and power (an equivalent antenna picture is also given). These results are compared to an electromagnetic simulation of the transmitter geometry. Simple approximate relations are also given to estimate coupled energy from the power. The effect of additional loads in the form of attached leads, forming transmission lines, are considered. The results are summarized in a set of susceptibility-type curves. Finally, we also consider drives to the cables themselves and the resulting common-to-differential mode currents in the load.

  2. The Drosophila melanogaster methuselah gene: a novel gene with ancient functions.

    Directory of Open Access Journals (Sweden)

    Ana Rita Araújo

    Full Text Available The Drosophila melanogaster G protein-coupled receptor gene, methuselah (mth, has been described as a novel gene that is less than 10 million years old. Nevertheless, it shows a highly specific expression pattern in embryos, larvae, and adults, and has been implicated in larval development, stress resistance, and in the setting of adult lifespan, among others. Although mth belongs to a gene subfamily with 16 members in D. melanogaster, there is no evidence for functional redundancy in this subfamily. Therefore, it is surprising that a novel gene influences so many traits. Here, we explore the alternative hypothesis that mth is an old gene. Under this hypothesis, in species distantly related to D. melanogaster, there should be a gene with features similar to those of mth. By performing detailed phylogenetic, synteny, protein structure, and gene expression analyses we show that the D. virilis GJ12490 gene is the orthologous of mth in species distantly related to D. melanogaster. We also show that, in D. americana (a species of the virilis group of Drosophila, a common amino acid polymorphism at the GJ12490 orthologous gene is significantly associated with developmental time, size, and lifespan differences. Our results imply that GJ12490 orthologous genes are candidates for developmental time and lifespan differences in Drosophila in general.

  3. DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis

    Directory of Open Access Journals (Sweden)

    Baseler Michael W

    2007-11-01

    Full Text Available Abstract Background Due to the complex and distributed nature of biological research, our current biological knowledge is spread over many redundant annotation databases maintained by many independent groups. Analysts usually need to visit many of these bioinformatics databases in order to integrate comprehensive annotation information for their genes, which becomes one of the bottlenecks, particularly for the analytic task associated with a large gene list. Thus, a highly centralized and ready-to-use gene-annotation knowledgebase is in demand for high throughput gene functional analysis. Description The DAVID Knowledgebase is built around the DAVID Gene Concept, a single-linkage method to agglomerate tens of millions of gene/protein identifiers from a variety of public genomic resources into DAVID gene clusters. The grouping of such identifiers improves the cross-reference capability, particularly across NCBI and UniProt systems, enabling more than 40 publicly available functional annotation sources to be comprehensively integrated and centralized by the DAVID gene clusters. The simple, pair-wise, text format files which make up the DAVID Knowledgebase are freely downloadable for various data analysis uses. In addition, a well organized web interface allows users to query different types of heterogeneous annotations in a high-throughput manner. Conclusion The DAVID Knowledgebase is designed to facilitate high throughput gene functional analysis. For a given gene list, it not only provides the quick accessibility to a wide range of heterogeneous annotation data in a centralized location, but also enriches the level of biological information for an individual gene. Moreover, the entire DAVID Knowledgebase is freely downloadable or searchable at http://david.abcc.ncifcrf.gov/knowledgebase/.

  4. Development of a loop-mediated isothermal amplification assay for sensitive and rapid detection of the tdh and trh genes of Vibrio parahaemolyticus and related Vibrio species.

    Science.gov (United States)

    Yamazaki, Wataru; Kumeda, Yuko; Misawa, Naoaki; Nakaguchi, Yoshitsugu; Nishibuchi, Mitsuaki

    2010-02-01

    Thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) are the major virulence determinants of Vibrio parahaemolyticus. TRH is further differentiated into TRH1 and TRH2 on the basis of genetic and phenotypic differences. We developed a novel and highly specific loop-mediated isothermal amplification (LAMP) assay for sensitive and rapid detection of the tdh, trh1, and trh2 genes of V. parahaemolyticus. The LAMP assay was designed for both combined and individual detection of the tdh, trh1, and trh2 genes and combined detection of the trh1 and trh2 genes. Our results showed that it gave the same results as DNA probes and conventional PCR assays for 125 strains of V. parahaemolyticus, 3 strains of Grimontia hollisae, and 2 strains of Vibrio mimicus carrying the tdh, trh1, and trh2 genes in various combinations. No LAMP products were detected for any of the 20 bacterial strains lacking the tdh, trh1, and trh2 genes. The sensitivities of the LAMP assay for detection of tdh-, trh1-, and trh2-carrying V. parahaemolyticus strains in spiked shrimp samples were 0.8, 21.3, and 5.0 CFU per LAMP reaction tube, respectively. Starting with DNA extraction from a single colony and from spiked shrimp samples, the LAMP assay required only 27 to 60 min and less than 80 min, respectively. This is the first report of a rapid and specific LAMP assay for detection and differentiation of the tdh, trh1, and trh2 genes of V. parahaemolyticus and related Vibrio species.

  5. Development and Application of Loop-Mediated Isothermal Amplification Assays for Rapid Visual Detection of cry2Ab and cry3A Genes in Genetically-Modified Crops

    Directory of Open Access Journals (Sweden)

    Feiwu Li

    2014-08-01

    Full Text Available The cry2Ab and cry3A genes are two of the most important insect-resistant exogenous genes and had been widely used in genetically-modified crops. To develop more effective alternatives for the quick identification of genetically-modified organisms (GMOs containing these genes, a rapid and visual loop-mediated isothermal amplification (LAMP method to detect the cry2Ab and cry3A genes is described in this study. The LAMP assay can be finished within 60 min at an isothermal condition of 63 °C. The derived LAMP products can be obtained by a real-time turbidimeter via monitoring the white turbidity or directly observed by the naked eye through adding SYBR Green I dye. The specificity of the LAMP assay was determined by analyzing thirteen insect-resistant genetically-modified (GM crop events with different Bt genes. Furthermore, the sensitivity of the LAMP assay was evaluated by diluting the template genomic DNA. Results showed that the limit of detection of the established LAMP assays was approximately five copies of haploid genomic DNA, about five-fold greater than that of conventional PCR assays. All of the results indicated that this established rapid and visual LAMP assay was quick, accurate and cost effective, with high specificity and sensitivity. In addition, this method does not need specific expensive instruments or facilities, which can provide a simpler and quicker approach to detecting the cry2Ab and cry3A genes in GM crops, especially for on-site, large-scale test purposes in the field.

  6. Gene network analysis in a pediatric cohort identifies novel lung function genes.

    Directory of Open Access Journals (Sweden)

    Bruce A Ong

    Full Text Available Lung function is a heritable trait and serves as an important clinical predictor of morbidity and mortality for pulmonary conditions in adults, however, despite its importance, no studies have focused on uncovering pediatric-specific loci influencing lung function. To identify novel genetic determinants of pediatric lung function, we conducted a genome-wide association study (GWAS of four pulmonary function traits, including FVC, FEV1, FEV1/FVC and FEF25-75% in 1556 children. Further, we carried out gene network analyses for each trait including all SNPs with a P-value of <1.0 × 10(-3 from the individual GWAS. The GWAS identified SNPs with notable trends towards association with the pulmonary function measures, including the previously described INTS12 locus association with FEV1 (pmeta=1.41 × 10(-7. The gene network analyses identified 34 networks of genes associated with pulmonary function variables in Caucasians. Of those, the glycoprotein gene network reached genome-wide significance for all four variables. P-value range pmeta=6.29 × 10(-4 - 2.80 × 10(-8 on meta-analysis. In this study, we report on specific pathways that are significantly associated with pediatric lung function at genome-wide significance. In addition, we report the first loci associated with lung function in both pediatric Caucasian and African American populations.

  7. Primer Sets Developed for Functional Genes Reveal Shifts in Functionality of Fungal Community in Soils

    NARCIS (Netherlands)

    Hannula, S.E.; van Veen, J.A.

    2016-01-01

    Phylogenetic diversity of soil microbes is a hot topic at the moment. However, the molecular tools for the assessment of functional diversity in the fungal community are less developed than tools based on genes encoding the ribosomal operon. Here 20 sets of primers targeting genes involved mainly in

  8. A functional gene array for detection of bacterial virulence elements.

    Directory of Open Access Journals (Sweden)

    Crystal Jaing

    Full Text Available Emerging known and unknown pathogens create profound threats to public health. Platforms for rapid detection and characterization of microbial agents are critically needed to prevent and respond to disease outbreaks. Available detection technologies cannot provide broad functional information about known or novel organisms. As a step toward developing such a system, we have produced and tested a series of high-density functional gene arrays to detect elements of virulence and antibiotic resistance mechanisms. Our first generation array targets genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for gene family detection and discrimination. When tested with organisms at varying phylogenetic distances from the four target strains, the array detected orthologs for the majority of targeted gene families present in bacteria belonging to the same taxonomic family. In combination with whole-genome amplification, the array detects femtogram concentrations of purified DNA, either spiked in to an aerosol sample background, or in combinations from one or more of the four target organisms. This is the first report of a high density NimbleGen microarray system targeting microbial antibiotic resistance and virulence mechanisms. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples.

  9. Sponge microbiota are a reservoir of functional antibiotic resistance genes

    Directory of Open Access Journals (Sweden)

    Dennis Versluis

    2016-11-01

    Full Text Available Wide application of antibiotics has contributed to the evolution of multi-drug resistant human pathogens, resulting in poorer treatment outcomes for infections. In the marine environment, seawater samples have been investigated as a resistance reservoir; however, no studies have methodically examined sponges as a reservoir of antibiotic resistance. Sponges could be important in this respect because they often contain diverse microbial communities that have the capacity to produce bioactive metabolites. Here, we applied functional metagenomics to study the presence and diversity of functional resistance genes in the sponges Aplysina aerophoba, Petrosia ficiformis and Corticium candelabrum. We obtained 37 insert sequences facilitating resistance to D-cycloserine (n=6, gentamicin (n=1, amikacin (n=7, trimethoprim (n=17, chloramphenicol (n=1, rifampicin (n=2 and ampicillin (n=3. Fifteen of 37 inserts harboured resistance genes that shared <90% amino acid identity with known gene products, whereas on 13 inserts no resistance gene could be identified with high confidence, in which case we predicted resistance to be mainly mediated by antibiotic efflux. One marine-specific ampicillin-resistance-conferring β-lactamase was identified in the genus Pseudovibrio with 41% global amino acid identity to the closest β-lactamase with demonstrated functionality, and subsequently classified into a new family termed PSV. Taken together, our results show that sponge microbiota host diverse and novel resistance genes that may be harnessed by phylogenetically distinct bacteria.

  10. New gene functions in megakaryopoiesis and platelet formation

    Science.gov (United States)

    Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O’Reilly, Paul F.; Shin, So-Youn; Esko, Tõnu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, François; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amélie; Cambien, François; Chambers, John C.; Cucca, Francesco; D’Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Döring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kühnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Leach, Irene Mateo; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nöthlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Tönjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Völker, Uwe; Wichmann, H.-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole

    2012-01-01

    Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. PMID:22139419

  11. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

    Directory of Open Access Journals (Sweden)

    Leah Y. Liu

    2013-09-01

    Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

  12. Streptomycin affinity depends on 13 amino acids forming a loop in homology modelled ribosomal S12 protein (rpsL gene) of Lysinibacillus sphaericus DSLS5 associated with marine sponge (Tedania anhelans).

    Science.gov (United States)

    Suriyanarayanan, Balasubramanian; Lakshmi, Praveena Pothuraju; Santhosh, Ramachandran Sarojini; Dhevendaran, Kandasamy; Priya, Balakrishnan; Krishna, Shivaani

    2016-06-01

    Streptomycin, an antibiotic used against microbial infections, inhibits the protein synthesis by binding to ribosomal protein S12, encoded by rpsL12 gene, and associated mutations cause streptomycin resistance. A streptomycin resistant, Lysinibacillus sphaericus DSLS5 (MIC >300 µg/mL for streptomycin), was isolated from a marine sponge (Tedania anhelans). The characterisation of rpsL12 gene showed a region having similarity to long terminal repeat sequences of murine lukemia virus which added 13 amino acids for loop formation in RpsL12; in addition, a K56R mutation which corresponds to K43R mutation present in streptomycin-resistant Escherichia coli is also present. The RpsL12 protein was modelled and compared with that of Lysinibacillus boronitolerans, Escherichia coli and Mycobacterium tuberculosis. The modelled proteins docked with streptomycin indicate compound had less affinity. The effect of loop on streptomycin resistance was analysed by constructing three different models of RpsL12 by, (i) removing both loop and mutation, (ii) removing the loop alone while retaining the mutation and (iii) without mutation having loop. The results showed that the presence of loop causes streptomycin resistance (decreases the affinity), and it further enhanced in the presence of mutation at 56th codon. Further study will help in understanding the evolution of streptomycin resistance in organisms.

  13. Investigation of gene expression profiles in coronary heart disease and functional analysis of target gene

    Institute of Scientific and Technical Information of China (English)

    YIN HuiJun; MA Xiaoduan; JIANG YueRong; SHI DaZhuo; CHEN KeJi

    2009-01-01

    The research outlined here includes constitution of the differential gene expression profile by means of oligonucleotide gene microarray and functional analysis of the target gene for coronary heart disease (CHD). In a microarray screening experiment, the predominance of inflammation-and immune-related genes is presented in the expression profile of 107 differential genes based on the analysis of gene ontology and gene pathway. IL-8, an inflammatory factor, is identified as one of the genes that were markedly up-regulated in CHD. The plasma level of IL-8 is significantly raised in patients with CHD (n = 30) compared with healthy controls (n = 40), which underscores the clinical relevance of the in vitro finding. The further functional analysis shows that IL-8 affects platelet aggregation percentage, ex-pression of CD62p and platelet aggregation morphology in 12 healthy volunteers to some extent. These findings suggest the relevance of inflammation and immune responses to CHD at the DNA level. Moreover, IL-8 may be involved in the pathogenesis of CHD through the pathway of platelet activation.

  14. Three-point functions in planar N=4 super Yang-Mills Theory for scalar operators up to length five at the one-loop order

    CERN Document Server

    Georgiou, George; Grossardt, Andre; Plefka, Jan

    2012-01-01

    We report on a systematic perturbative study of three-point functions in planar SU(N) N=4 super Yang-Mills theory at the one-loop level involving scalar field operators up to length five. For this we have computed a sample of 40 structure constants involving primary operators of up to and including length five which are built entirely from scalar fields. A combinatorial dressing technique has been developed to promote tree-level correlators to one-loop level. In addition we have resolved the mixing up to the order (g_YM)^2 level of the operators involved, which amounts to mixings with bi-fermions, with bi-derivative insertions as well as self-mixing contributions in the scalar sector. This work supersedes a preprint by two of the authors from 2010 which had neglected the mixing contributions.

  15. Information theory applied to the sparse gene ontology annotation network to predict novel gene function

    Science.gov (United States)

    Tao, Ying; Li, Jianrong

    2010-01-01

    Motivation Despite advances in the gene annotation process, the functions of a large portion of the gene products remain insufficiently characterized. In addition, the “in silico” prediction of novel Gene Ontology (GO) annotations for partially characterized gene functions or processes is highly dependent on reverse genetic or function genomics approaches. Results We propose a novel approach, Information Theory-based Semantic Similarity (ITSS), to automatically predict molecular functions of genes based on Gene Ontology annotations. We have demonstrated using a 10-fold cross-validation that the ITSS algorithm obtains prediction accuracies (Precision 97%, Recall 77%) comparable to other machine learning algorithms when applied to similarly dense annotated portions of the GO datasets. In addition, such method can generate highly accurate predictions in sparsely annotated portions of GO, in which previous algorithm failed to do so. As a result, our technique generates an order of magnitude more gene function predictions than previous methods. Further, this paper presents the first historical rollback validation for the predicted GO annotations, which may represent more realistic conditions for an evaluation than generally used cross-validations type of evaluations. By manually assessing a random sample of 100 predictions conducted in a historical roll-back evaluation, we estimate that a minimum precision of 51% (95% confidence interval: 43%–58%) can be achieved for the human GO Annotation file dated 2003. Availability The program is available on request. The 97,732 positive predictions of novel gene annotations from the 2005 GO Annotation dataset are available at http://phenos.bsd.uchicago.edu/mphenogo/prediction_result_2005.txt. PMID:17646340

  16. Predictive screening for regulators of conserved functional gene modules (gene batteries in mammals

    Directory of Open Access Journals (Sweden)

    Sigvardsson Mikael

    2005-05-01

    Full Text Available Abstract Background The expression of gene batteries, genomic units of functionally linked genes which are activated by similar sets of cis- and trans-acting regulators, has been proposed as a major determinant of cell specialization in metazoans. We developed a predictive procedure to screen the mouse and human genomes and transcriptomes for cases of gene-battery-like regulation. Results In a screen that covered ~40 per cent of all annotated protein-coding genes, we identified 21 co-expressed gene clusters with statistically supported sharing of cis-regulatory sequence elements. 66 predicted cases of over-represented transcription factor binding motifs were validated against the literature and fell into three categories: (i previously described cases of gene battery-like regulation, (ii previously unreported cases of gene battery-like regulation with some support in a limited number of genes, and (iii predicted cases that currently lack experimental support. The novel predictions include for example Sox 17 and RFX transcription factor binding sites that were detected in ~10% of all testis specific genes, and HNF-1 and 4 binding sites that were detected in ~30% of all kidney specific genes respectively. The results are publicly available at http://www.wlab.gu.se/lindahl/genebatteries. Conclusion 21 co-expressed gene clusters were enriched for a total of 66 shared cis-regulatory sequence elements. A majority of these predictions represent novel cases of potential co-regulation of functionally coupled proteins. Critical technical parameters were evaluated, and the results and the methods provide a valuable resource for future experimental design.

  17. PRODH gene is associated with executive function in schizophrenic families.

    Science.gov (United States)

    Li, Tao; Ma, Xiaohong; Hu, Xun; Wang, Yingcheng; Yan, Chengying; Meng, Huaqing; Liu, Xiehe; Toulopoulou, Timothea; Murray, Robin M; Collier, David A

    2008-07-05

    The aim of this study was to investigate the relationship between polymorphisms in the PRODH and COMT genes and selected neurocognitive functions. Six SNPs in PRODH and two SNPs in COMT were genotyped in 167 first-episode schizophrenic families who had been assessed by a set of 14 neuropsychological tests. Neuropsychological measures were selected as quantitative traits for association analysis. The haplotype of SNPs PRODH 1945T/C and PRODH 1852G/A was associated with impaired performance on the Tower of Hanoi, a problem-solving task mainly reflecting planning capacity. There was no significant evidence for association with any other neuropsychological traits for other SNPs or haplotypes of paired SNPs in the two genes. This study takes previous findings of association between PRODH and schizophrenia further by associating variation within the gene with performance on a neurocognitive trait characteristic of the illness. It fails to confirm previous reports of an association between COMT and cognitive function.

  18. Prediction of human protein function according to Gene Ontology categories

    DEFF Research Database (Denmark)

    Jensen, Lars Juhl; Gupta, Ramneek; Stærfeldt, Hans Henrik

    2003-01-01

    developed a method for prediction of protein function for a subset of classes from the Gene Ontology classification scheme. This subset includes several pharmaceutically interesting categories-transcription factors, receptors, ion channels, stress and immune response proteins, hormones and growth factors...

  19. The dystrophin gene and cognitive function in the general population

    NARCIS (Netherlands)

    D. Vojinovic (Dina); H.H.H. Adams (Hieab); S. van der Lee (Sven); C.A. Ibrahim-Verbaas (Carla); R.W.W. Brouwer (Rutger); M.C.G.N. van den hout (Mirjam); E. Oole (Edwin); J. van Rooij (Jeroen); A.G. Uitterlinden (André); A. Hofman (Albert); W.F.J. van IJcken (Wilfred); A. Aartsma-Rus (Annemieke); G.-J.B. Van Ommen (Gert-Jan B.); M.A. Ikram (Arfan); C.M. van Duijn (Cornelia M.); N. Amin (Najaf)

    2015-01-01

    textabstractThe aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterd

  20. Gene Discovery and Functional Analyses in the Model Plant Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Cai-Ping Feng; John Mundy

    2006-01-01

    The present mini-review describes newer methods and strategies, including transposon and T-DNA insertions,TILLING, Deleteagene, and RNA interference, to functionally analyze genes of interest in the model plant Arabidopsis. The relative advantages and disadvantages of the systems are also discussed.

  1. Gene Discovery and Functional Analyses in the Model Plant Arabidopsis

    DEFF Research Database (Denmark)

    Feng, Cai-ping; Mundy, J.

    2006-01-01

    The present mini-review describes newer methods and strategies, including transposon and T-DNA insertions, TILLING, Deleteagene, and RNA interference, to functionally analyze genes of interest in the model plant Arabidopsis. The relative advantages and disadvantages of the systems are also...

  2. A2 gene of Old World cutaneous Leishmania is a single highly conserved functional gene

    Directory of Open Access Journals (Sweden)

    Derouin Francis

    2005-03-01

    Full Text Available Abstract Background Leishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. The various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. Among the candidate factors of parasite virulence are the A2 genes, a family of multiple genes that are developmentally expressed in species of the Leishmania donovani group responsible for visceral diseases (VL. By contrast, in L. major determining cutaneous infections (CL we showed that A2 genes are present in a truncated form only. Furthermore, the A2 genomic sequences of L. major were considered subsequently to represent non-expressed pseudogenes 1. Consequently, it was suggested that the structural and functional properties of A2 genes could play a role in the differential tropism of CL and VL leishmanias. On this basis, it was of importance to determine whether the observed structural/functional particularities of the L. major A2 genes were shared by other CL Leishmania, therefore representing a proper characteristic of CL A2 genes as opposed to those of VL isolates. Methods In the present study we amplified by PCR and sequenced the A2 genes from genomic DNA and from clonal libraries of the four Old World CL species comparatively to a clonal population of L. infantum VL parasites. Using RT-PCR we also amplified and sequenced A2 mRNA transcripts from L. major. Results A unique A2 sequence was identified in Old World cutaneous Leishmania by sequencing. The shared sequence was highly conserved among the various CL strains and species analysed, showing a single polymorphism C/G at position 58. The CL A2 gene was found to be functionally transcribed at both parasite stages. Conclusion The present study shows that cutaneous strains of leishmania share a conserved functional A2 gene. As opposed to the multiple A2 genes described in VL isolates

  3. Two-loop two-point functions with masses asymptotic expansions and Taylor series, in any dimension

    CERN Document Server

    Broadhurst, D J; Tarasov, O V

    1993-01-01

    In all mass cases needed for quark and gluon self-energies, the two-loop master diagram is expanded at large and small $q^2$, in $d$ dimensions, using identities derived from integration by parts. Expansions are given, in terms of hypergeometric series, for all gluon diagrams and for all but one of the quark diagrams; expansions of the latter are obtained from differential equations. Pad\\'{e} approximants to truncations of the expansions are shown to be of great utility. As an application, we obtain the two-loop photon self-energy, for all $d$, and achieve highly accelerated convergence of its expansions in powers of $q^2/m^2$ or $m^2/q^2$, for $d=4$.

  4. Elucidating gene function and function evolution through comparison of co-expression networks in plants

    Directory of Open Access Journals (Sweden)

    Marek eMutwil

    2014-08-01

    Full Text Available The analysis of gene expression data has shown that transcriptionally coordinated (co-expressed genes are often functionally related, enabling scientists to use expression data in gene function prediction. This Focused Review discusses our original paper (Large-scale co-expression approach to dissect secondary cell wall formation across plant species, Frontiers in Plant Science 2:23. In this paper we applied cross-species analysis to co-expression networks of genes involved in cellulose biosynthesis. We show that the co-expression networks from different species are highly similar, indicating that whole biological pathways are conserved across species. This finding has two important implications. First, the analysis can transfer gene function annotation from well-studied plants, such as Arabidopsis, to other, uncharacterized plant species. As the analysis finds genes that have similar sequence and similar expression pattern across different organisms, functionally equivalent genes can be identified. Second, since co-expression analyses are often noisy, a comparative analysis should have higher performance, as parts of co-expression networks that are conserved are more likely to be functionally relevant. In this Focused Review, we outline the comparative analysis done in the original paper and comment on the recent advances and approaches that allow comparative analyses of co-function networks. We hypothesize that, in comparison to simple co-expression analysis, comparative analysis would yield more accurate gene function predictions. Finally, by combining comparative analysis with genomic information of green plants, we propose a possible composition of cellulose biosynthesis machinery during earlier stages of plant evolution.

  5. Functional significance of four successive glycine residues in the pyrophosphate binding loop of fungal 6-oxopurine phosphoribosyltransferases.

    Science.gov (United States)

    Moynié, Lucile; Giraud, Marie-France; Breton, Annick; Boissier, Fanny; Daignan-Fornier, Bertrand; Dautant, Alain

    2012-08-01

    Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the purine recycling pathway that catalyzes the conversion of 5-phospho-ribosyl-α-1-pyrophosphate and guanine or hypoxanthine to guanosine monophosphate (GMP) or inosine monophosphate (IMP), respectively, and pyrophosphate (PPi). We report the first crystal structure of a fungal 6-oxopurine phosphoribosyltransferase, the Saccharomyces cerevisiae HGPRT (Sc-HGPRT) in complex with GMP. The crystal structures of full length protein with (WT1) or without (WT2) sulfate that mimics the phosphate group in the PPi binding site were solved by molecular replacement using the structure of a truncated version (Δ7) solved beforehand by multiwavelength anomalous diffusion. Sc-HGPRT is a dimer and adopts the overall structure of class I phosphoribosyltransferases (PRTs) with a smaller hood domain and a short two-stranded parallel β-sheet linking the N- to the C-terminal end. The catalytic loops in WT1 and WT2 are in an open form while in Δ7, due to an inter-subunit disulfide bridge, the catalytic loop is in either an open or closed form. The closure is concomitant with a peptide plane flipping in the PPi binding loop. Moreover, owing the flexibility of a GGGG motif conserved in fungi, all the peptide bonds of the phosphate binding loop are in trans conformation whereas in nonfungal 6-oxopurine PRTs, one cis-peptide bond is required for phosphate binding. Mutations affecting the enzyme activity or the previously characterized feedback inhibition by GMP are located at the nucleotide binding site and the dimer interface. Copyright © 2012 The Protein Society.

  6. The Role of Entropic Effects on DNA Loop Formation

    Science.gov (United States)

    Wilson, David; Tkachenko, Alexei; Lillian, Todd; Perkins, Noel; Meiners, Jens Christian

    2009-03-01

    The formation of protein mediated DNA loops often regulates gene expression. Typically, a protein is simultaneously bound to two DNA operator sites. An example is the lactose repressor which binds to the Lac operon of E. coli. We characterize the mechanics of this system by calculating the free energy cost of loop formation. We construct a Hamiltonian that describes the change in DNA bending energy due to linear perturbations about the looped and open states, starting from a non-linear mechanical rod model that determines the shape and bending energy of the inter-operator DNA loop while capturing the intrinsic curvature and sequence-dependent elasticity of the DNA. The crystal structure of the LacI protein provides the boundary conditions for the DNA. We then calculate normal modes of the open and closed loops to account for the thermal fluctuations. The ratio of determinants of the two Hamiltonians yields the partition function, and the enthalphic and entropic cost of looping. This calculation goes beyond standard elastic energy models because it fully accounts for the substantial entropic differences between the two states. It also includes effects of sequence dependent curvature and stiffness and allows anisotropic variations in persistence length. From the free energy we then calculate the J-factor and ratio of loop lifetimes.

  7. Formation of chromosomal domains in interphase by loop extrusion

    Science.gov (United States)

    Fudenberg, Geoffrey

    While genomes are often considered as one-dimensional sequences, interphase chromosomes are organized in three dimensions with an essential role for regulating gene expression. Recent studies have shown that Topologically Associating Domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes. Despite observations that architectural proteins, including CTCF, demarcate and maintain the borders of TADs, the mechanisms underlying TAD formation remain unknown. Here we propose that loop extrusion underlies the formation TADs. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops, but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. This process dynamically forms loops of various sizes within but not between TADs. Using polymer simulations, we find that loop extrusion can produce TADs as determined by our analyses of the highest-resolution experimental data. Moreover, we find that loop extrusion can explain many diverse experimental observations, including: the preferential orientation of CTCF motifs and enrichments of architectural proteins at TAD boundaries; TAD boundary deletion experiments; and experiments with knockdown or depletion of CTCF, cohesin, and cohesin-loading factors. Together, the emerging picture from our work is that TADs are formed by rapidly associating, growing, and dissociating loops, presenting a clear framework for understanding interphase chromosomal organization.

  8. Primer Sets Developed for Functional Genes Reveal Shifts in Functionality of Fungal Community in Soils

    Science.gov (United States)

    Hannula, S. Emilia; van Veen, Johannes A.

    2016-01-01

    Phylogenetic diversity of soil microbes is a hot topic at the moment. However, the molecular tools for the assessment of functional diversity in the fungal community are less developed than tools based on genes encoding the ribosomal operon. Here 20 sets of primers targeting genes involved mainly in carbon cycling were designed and/or validated and the functioning of soil fungal communities along a chronosequence of land abandonment from agriculture was evaluated using them. We hypothesized that changes in fungal community structure during secondary succession would lead to difference in the types of genes present in soils and that these changes would be directional. We expected an increase in genes involved in degradation of recalcitrant organic matter in time since agriculture. Out of the investigated genes, the richness of the genes related to carbon cycling was significantly higher in fields abandoned for longer time. The composition of six of the genes analyzed revealed significant differences between fields abandoned for shorter and longer time. However, all genes revealed significant variance over the fields studied, and this could be related to other parameters than the time since agriculture such as pH, organic matter, and the amount of available nitrogen. Contrary to our initial hypothesis, the genes significantly different between fields were not related to the decomposition of more recalcitrant matter but rather involved in degradation of cellulose and hemicellulose. PMID:27965632

  9. Primer Sets Developed for Functional Genes Reveal Shifts in Functionality of Fungal Community in Soils.

    Science.gov (United States)

    Hannula, S Emilia; van Veen, Johannes A

    2016-01-01

    Phylogenetic diversity of soil microbes is a hot topic at the moment. However, the molecular tools for the assessment of functional diversity in the fungal community are less developed than tools based on genes encoding the ribosomal operon. Here 20 sets of primers targeting genes involved mainly in carbon cycling were designed and/or validated and the functioning of soil fungal communities along a chronosequence of land abandonment from agriculture was evaluated using them. We hypothesized that changes in fungal community structure during secondary succession would lead to difference in the types of genes present in soils and that these changes would be directional. We expected an increase in genes involved in degradation of recalcitrant organic matter in time since agriculture. Out of the investigated genes, the richness of the genes related to carbon cycling was significantly higher in fields abandoned for longer time. The composition of six of the genes analyzed revealed significant differences between fields abandoned for shorter and longer time. However, all genes revealed significant variance over the fields studied, and this could be related to other parameters than the time since agriculture such as pH, organic matter, and the amount of available nitrogen. Contrary to our initial hypothesis, the genes significantly different between fields were not related to the decomposition of more recalcitrant matter but rather involved in degradation of cellulose and hemicellulose.

  10. Primer sets developed for fungal functional genes reveal shifts in functionality of fungal community in soils

    Directory of Open Access Journals (Sweden)

    Emilia Silja Hannula

    2016-11-01

    Full Text Available Phylogenetic diversity of soil microbes is a hot topic at the moment. However, the molecular tools for the assessment of functional diversity in the fungal community are less developed than tools based on genes encoding the ribosomal operon. Here 20 sets of primers targeting genes involved mainly in carbon cycling were designed and/or validated and the functioning of soil fungal communities along a chronosequence of land abandonment from agriculture was evaluated using them. We hypothesized that changes in fungal community structure during secondary succession would lead to difference in the types of genes present in soils and that these changes would be directional. We expected an increase in genes involved in degradation of recalcitrant organic matter in time since agriculture. Out of the investigated genes, the richness of the genes related to carbon cycling was significantly higher in fields abandoned for longer time. The composition of six of the genes analyzed revealed significant differences between fields abandoned for shorter and longer time. However, all genes revealed significant variance over the fields studied, and this could be related to other parameters than the time since agriculture such as pH, organic matter and the amount of available nitrogen. Contrary to our initial hypothesis, the genes significantly different between fields were not related to the decomposition of more recalcitrant matter but rather involved in degradation of cellulose and hemicellulose.

  11. Sediment denitrifier community composition and nirS gene expression investigated with functional gene microarrays

    DEFF Research Database (Denmark)

    Francis, C.A.; Jackson, G.A.; Ward, B.B.

    2008-01-01

    total RNA extracts) targets were hybridized to the same array to compare the profiles of community composition at the DNA (relative abundance) and mRNA (gene expression) levels. Only the three dominant denitrifying groups (in terms of relative strength of DNA hybridization signal) were detected at the m......A functional gene microarray was used to investigate denitrifier community composition and nitrite reductase (nirS) gene expression in sediments along the estuarine gradient in Chesapeake Bay, USA. The nirS oligonucleotide probe set was designed to represent a sequence database containing 539...

  12. The microRNA (miRNA): overview of the RNA genes that modulate gene function.

    Science.gov (United States)

    Ying, Shao-Yao; Chang, Donald C; Lin, Shi-Lung

    2008-03-01

    MicroRNAs (miRNAs), widely distributed, small regulatory RNA genes, target both messenger RNA (mRNA) degradation and suppression of protein translation based on sequence complementarity between the miRNA and its targeted mRNA. Different names have been used to describe various types of miRNA. During evolution, RNA retroviruses or transgenes invaded the eukaryotic genome and inserted in the non-coding regions of DNA, conceivably acting as transposon-like jumping genes, providing defense from viral invasion and fine-tuning of gene expression as a secondary level of gene modulation in eukaryotes. When a transposon is inserted in the intron, it becomes an intronic miRNA, taking advantage of the protein synthesis machinery, i.e., mRNA transcription and splicing, as a means for processing and maturation. Recently, miRNAs have been found to play an important, but not life-threatening, role in embryonic development. They might play a pivotal role in diverse biological systems in various organisms, facilitating a quick response and accurate plotting of body physiology and structures. Based on these unique properties, man-made intronic miRNAs have been developed for in vitro evaluation of gene function, in vivo gene therapy and generation of transgenic animal models. The biogenesis and identification of miRNAs, potential applications, and future directions for research are presented, hopefully providing a guideline for further miRNA and gene function studies.

  13. Syntenator: Multiple gene order alignments with a gene-specific scoring function

    Directory of Open Access Journals (Sweden)

    Dieterich Christoph

    2008-11-01

    Full Text Available Abstract Background Identification of homologous regions or conserved syntenies across genomes is one crucial step in comparative genomics. This task is usually performed by genome alignment softwares like WABA or blastz. In case of conserved syntenies, such regions are defined as conserved gene orders. On the gene order level, homologous regions can even be found between distantly related genomes, which do not align on the nucleotide sequence level. Results We present a novel approach to identify regions of conserved synteny across multiple genomes. Syntenator represents genomes and alignments thereof as partial order graphs (POGs. These POGs are aligned by a dynamic programming approach employing a gene-specific scoring function. The scoring function reflects the level of protein sequence similarity for each possible gene pair. Our method consistently defines larger homologous regions in pairwise gene order alignments than nucleotide-level comparisons. Our method is superior to methods that work on predefined homology gene sets (as implemented in Blockfinder. Syntenator successfully reproduces 80% of the EnsEMBL man-mouse conserved syntenic blocks. The full potential of our method becomes visible by comparing remotely related genomes and multiple genomes. Gene order alignments potentially resolve up to 75% of the EnsEMBL 1:many orthology relations and 27% of the many:many orthology relations. Conclusion We propose Syntenator as a software solution to reliably infer conserved syntenies among distantly related genomes. The software is available from http://www2.tuebingen.mpg.de/abt4/plone.

  14. Predictability of Genetic Interactions from Functional Gene Modules

    Directory of Open Access Journals (Sweden)

    Jonathan H. Young

    2017-02-01

    Full Text Available Characterizing genetic interactions is crucial to understanding cellular and organismal response to gene-level perturbations. Such knowledge can inform the selection of candidate disease therapy targets, yet experimentally determining whether genes interact is technically nontrivial and time-consuming. High-fidelity prediction of different classes of genetic interactions in multiple organisms would substantially alleviate this experimental burden. Under the hypothesis that functionally related genes tend to share common genetic interaction partners, we evaluate a computational approach to predict genetic interactions in Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae. By leveraging knowledge of functional relationships between genes, we cross-validate predictions on known genetic interactions and observe high predictive power of multiple classes of genetic interactions in all three organisms. Additionally, our method suggests high-confidence candidate interaction pairs that can be directly experimentally tested. A web application is provided for users to query genes for predicted novel genetic interaction partners. Finally, by subsampling the known yeast genetic interaction network, we found that novel genetic interactions are predictable even when knowledge of currently known interactions is minimal.

  15. Towards revealing the functions of all genes in plants.

    Science.gov (United States)

    Rhee, Seung Yon; Mutwil, Marek

    2014-04-01

    The great recent progress made in identifying the molecular parts lists of organisms revealed the paucity of our understanding of what most of the parts do. In this review, we introduce computational and statistical approaches and omics data used for inferring gene function in plants, with an emphasis on network-based inference. We also discuss caveats associated with network-based function predictions such as performance assessment, annotation propagation, the guilt-by-association concept, and the meaning of hubs. Finally, we note the current limitations and possible future directions such as the need for gold standard data from several species, unified access to data and tools, quantitative comparison of data and tool quality, and high-throughput experimental validation platforms for systematic gene function elucidation in plants.

  16. Use of functional gene arrays for elucidating in situ biodegradation

    Directory of Open Access Journals (Sweden)

    Joy D. Van Nostrand

    2012-09-01

    Full Text Available Microarrays have revolutionized the study of microbiology by providing a high-throughput method for examining thousands of genes with a single test and overcome the limitations of many culture-independent approaches. Functional gene arrays (FGA probe a wide range of genes involved in a variety of functions of interest to microbial ecology (e.g., carbon degradation, N-fixation, metal resistance from many different microorganisms, cultured and uncultured. The most comprehensive FGA to date is the GeoChip array, which targets tens of thousands of genes involved in the geochemical cycling of carbon, nitrogen, phosphorus, and sulphur, metal resistance and reduction, energy processing, antibiotic resistance and contaminant degradation as well as phylogenetic information (gyrB. Since the development of GeoChips, many studies have been performed using this FGA and have shown it to be a powerful tool for rapid, sensitive and specific examination of microbial communities in a high-throughput manner. As such, the GeoChip is well-suited for linking geochemical processes with microbial community function and structure. This technology has been used successfully to examine microbial communities before, during and after in situ bioremediation at a variety of contaminated sites. These studies have expanded our understanding of biodegradation and bioremediation processes and the associated microorganisms and environmental conditions responsible. This review provides an overview of FGA development with a focus on the GeoChip and highlights specific GeoChip studies involving in situ bioremediation.

  17. Rapid, Sensitive Detection of Bartonella quintana by Loop-Mediated Isothermal Amplification of the groEL Gene

    Science.gov (United States)

    Hu, Shoukui; Niu, Lina; Luo, Lijuan; Song, Xiuping; Sun, Jimin; Liu, Qiyong

    2016-01-01

    Trench fever, caused by Bartonella quintana, is recognized as a re-emerging and neglected disease. Rapid and sensitive detection approaches are urgently required to monitor and help control B. quintana infections. Here, loop-mediated isothermal amplification (LAMP), which amplifies target DNA at a fixed temperature with high sensitivity, specificity and rapidity, was employed to detect B. quintana. Thirty-six strains, including 10 B. quintana, 13 other Bartonella spp., and 13 other common pathogens, were applied to verify and evaluate the LAMP assay. The specificity of the LAMP assay was 100%, and the limit of detection was 125 fg/reaction. The LAMP assay was compared with qPCR in the examination of 100 rhesus and 20 rhesus-feeder blood samples; the diagnostic accuracy was found to be 100% when LAMP was compared to qPCR, but the LAMP assay was significantly more sensitive (p < 0.05). Thus, LAMP methodology is a useful for diagnosis of trench fever in humans and primates, especially in low-resource settings, because of its rapid, sensitive detection that does not require sophisticated equipment. PMID:27916953

  18. Rapid, Sensitive Detection of Bartonella quintana by Loop-Mediated Isothermal Amplification of the groEL Gene

    Directory of Open Access Journals (Sweden)

    Shoukui Hu

    2016-12-01

    Full Text Available Trench fever, caused by Bartonella quintana, is recognized as a re-emerging and neglected disease. Rapid and sensitive detection approaches are urgently required to monitor and help control B. quintana infections. Here, loop-mediated isothermal amplification (LAMP, which amplifies target DNA at a fixed temperature with high sensitivity, specificity and rapidity, was employed to detect B. quintana. Thirty-six strains, including 10 B. quintana, 13 other Bartonella spp., and 13 other common pathogens, were applied to verify and evaluate the LAMP assay. The specificity of the LAMP assay was 100%, and the limit of detection was 125 fg/reaction. The LAMP assay was compared with qPCR in the examination of 100 rhesus and 20 rhesus-feeder blood samples; the diagnostic accuracy was found to be 100% when LAMP was compared to qPCR, but the LAMP assay was significantly more sensitive (p < 0.05. Thus, LAMP methodology is a useful for diagnosis of trench fever in humans and primates, especially in low-resource settings, because of its rapid, sensitive detection that does not require sophisticated equipment.

  19. The 3-loop non-singlet heavy flavor contributions and anomalous dimensions for the structure function F2(x,Q2) and transversity

    Science.gov (United States)

    Ablinger, J.; Behring, A.; Blümlein, J.; De Freitas, A.; Hasselhuhn, A.; von Manteuffel, A.; Round, M.; Schneider, C.; Wißbrock, F.

    2014-09-01

    We calculate the massive flavor non-singlet Wilson coefficient for the heavy flavor contributions to the structure function F2(x,Q2) in the asymptotic region Q2≫m2 and the associated operator matrix element Aqq,Q(3),NS(N) to 3-loop order in Quantum Chromodynamics at general values of the Mellin variable N. This matrix element is associated with the vector current and axial vector current for the even and the odd moments N, respectively. We also calculate the corresponding operator matrix elements for transversity, compute the contributions to the 3-loop anomalous dimensions to O(NF) and compare to results in the literature. The 3-loop matching of the flavor non-singlet distribution in the variable flavor number scheme is derived. All results can be expressed in terms of nested harmonic sums in N space and harmonic polylogarithms in x-space. Numerical results are presented for the non-singlet charm quark contribution to F2(x,Q2).

  20. The 3-loop non-singlet heavy flavor contributions and anomalous dimensions for the structure function F2(x,Q2 and transversity

    Directory of Open Access Journals (Sweden)

    J. Ablinger

    2014-09-01

    Full Text Available We calculate the massive flavor non-singlet Wilson coefficient for the heavy flavor contributions to the structure function F2(x,Q2 in the asymptotic region Q2≫m2 and the associated operator matrix element Aqq,Q(3,NS(N to 3-loop order in Quantum Chromodynamics at general values of the Mellin variable N. This matrix element is associated with the vector current and axial vector current for the even and the odd moments N, respectively. We also calculate the corresponding operator matrix elements for transversity, compute the contributions to the 3-loop anomalous dimensions to O(NF and compare to results in the literature. The 3-loop matching of the flavor non-singlet distribution in the variable flavor number scheme is derived. All results can be expressed in terms of nested harmonic sums in N space and harmonic polylogarithms in x-space. Numerical results are presented for the non-singlet charm quark contribution to F2(x,Q2.

  1. The 3-loop non-singlet heavy flavor contributions and anomalous dimensions for the structure function F{sub 2}(x,Q{sup 2}) and transversity

    Energy Technology Data Exchange (ETDEWEB)

    Ablinger, J.; Hasselhuhn, A.; Schneider, C. [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation; Behring, A.; Bluemlein, J.; Freitas, A. de [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Manteuffel, A. von [Mainz Univ. (Germany). PRISMA Cluster of Excellence; Mainz Univ. (Germany). Inst. fuer Physik; Round, M.; Wissbrock, F. [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation; Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany)

    2014-06-15

    We calculate the massive flavor non-singlet Wilson coefficient for the heavy flavor contributions to the structure function F{sub 2}(x,Q{sup 2}) in the asymptotic region Q{sup 2}>>m{sup 2} and the associated operator matrix element A{sup (3),NS}{sub qq,Q} (N) to 3-loop order in Quantum Chromodynamics at general values of the Mellin variable N. This matrix element is associated to the vector current and axial vector current for the even and the odd moments N, respectively. We also calculate the corresponding operator matrix elements for transversity, compute the contributions to the 3-loop anomalous dimensions to O(N{sub F}) and compare to results in the literature. The 3-loop matching of the flavor non-singlet distribution in the variable flavor number scheme is derived. All results can be expressed in terms of nested harmonic sums in N space and harmonic polylogarithms in x-space. Numerical results are presented for the non-singlet charm quark contribution to F{sub 2}(x,Q{sup 2}).

  2. The 3-loop non-singlet heavy flavor contributions and anomalous dimensions for the structure function F{sub 2}(x,Q{sup 2}) and transversity

    Energy Technology Data Exchange (ETDEWEB)

    Ablinger, J. [Research Institute for Symbolic Computation (RISC), Johannes Kepler University, Altenbergerstraße 69, A-4040 Linz (Austria); Behring, A.; Blümlein, J.; De Freitas, A. [Deutsches Elektronen-Synchrotron, DESY, Platanenallee 6, D-15738 Zeuthen (Germany); Hasselhuhn, A. [Research Institute for Symbolic Computation (RISC), Johannes Kepler University, Altenbergerstraße 69, A-4040 Linz (Austria); Manteuffel, A. von [PRISMA Cluster of Excellence and Institute of Physics, J. Gutenberg University, D-55099 Mainz (Germany); Round, M. [Research Institute for Symbolic Computation (RISC), Johannes Kepler University, Altenbergerstraße 69, A-4040 Linz (Austria); Deutsches Elektronen-Synchrotron, DESY, Platanenallee 6, D-15738 Zeuthen (Germany); Schneider, C. [Research Institute for Symbolic Computation (RISC), Johannes Kepler University, Altenbergerstraße 69, A-4040 Linz (Austria); Wißbrock, F. [Research Institute for Symbolic Computation (RISC), Johannes Kepler University, Altenbergerstraße 69, A-4040 Linz (Austria); Deutsches Elektronen-Synchrotron, DESY, Platanenallee 6, D-15738 Zeuthen (Germany)

    2014-09-15

    We calculate the massive flavor non-singlet Wilson coefficient for the heavy flavor contributions to the structure function F{sub 2}(x,Q{sup 2}) in the asymptotic region Q{sup 2}≫m{sup 2} and the associated operator matrix element A{sub qq,Q}{sup (3),NS}(N) to 3-loop order in Quantum Chromodynamics at general values of the Mellin variable N. This matrix element is associated with the vector current and axial vector current for the even and the odd moments N, respectively. We also calculate the corresponding operator matrix elements for transversity, compute the contributions to the 3-loop anomalous dimensions to O(N{sub F}) and compare to results in the literature. The 3-loop matching of the flavor non-singlet distribution in the variable flavor number scheme is derived. All results can be expressed in terms of nested harmonic sums in N space and harmonic polylogarithms in x-space. Numerical results are presented for the non-singlet charm quark contribution to F{sub 2}(x,Q{sup 2})

  3. The 3-Loop Non-Singlet Heavy Flavor Contributions and Anomalous Dimensions for the Structure Function $F_2(x,Q^2)$ and Transversity

    CERN Document Server

    Ablinger, J; Blümlein, J; De Freitas, A; Hasselhuhn, A; von Manteuffel, A; Round, M; Schneider, C; Wißbrock, F

    2014-01-01

    We calculate the massive flavor non-singlet Wilson coefficient for the heavy flavor contributions to the structure function $F_2(x,Q^2)$ in the asymptotic region $Q^2 \\gg m^2$ and the associated operator matrix element $A_{qq,Q}^{(3), \\rm NS}(N)$ to 3-loop order in Quantum Chromodynamics at general values of the Mellin variable $N$. This matrix element is associated to the vector current and axial vector current for the even and the odd moments $N$, respectively. We also calculate the corresponding operator matrix elements for transversity, compute the contributions to the 3-loop anomalous dimensions to $O(N_F)$ and compare to results in the literature. The 3-loop matching of the flavor non-singlet distribution in the variable flavor number scheme is derived. All results can be expressed in terms of nested harmonic sums in $N$ space and harmonic polylogarithms in $x$-space. Numerical results are presented for the non-singlet charm quark contribution to $F_2(x,Q^2)$.

  4. High-throughput Binary Vectors for Plant Gene Function Analysis

    Institute of Scientific and Technical Information of China (English)

    Zhi-Yong Lei; Ping Zhao; Min-Jie Cao; Rong Cui; Xi Chen; Li-Zhong Xiong; Qi-Fa Zhang; David J. Oliver; Cheng-Bin Xiang

    2007-01-01

    A series of high-throughput binary cloning vectors were constructed to facilitate gene function analysis in higher plants. This vector series consists of plasmids designed for plant expression, promoter analysis, gene silencing,and green fluorescent protein fusions for protein localization. These vectors provide for high-throughput and efficient cloning utilizing sites for λ phage integrase/excisionase. In addition, unique restriction sites are incorporated in a multiple cloning site and enable promoter replacement. The entire vector series are available with complete sequence information and detailed annotations and are freely distributed to the scientific community for non-commercial uses.

  5. The Apolipoprotein E Gene, Attention, and Brain Function

    OpenAIRE

    Parasuraman, Raja; Pamela M Greenwood; Sunderland, Trey

    2002-01-01

    The ɛ4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer’s disease (AD). Changes in components of visuospatial attention with ApoE-ɛ4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-ɛ4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE p...

  6. Comparative genomics of Geobacter chemotaxis genes reveals diverse signaling function

    Directory of Open Access Journals (Sweden)

    Antommattei Frances M

    2008-10-01

    Full Text Available Abstract Background Geobacter species are δ-Proteobacteria and are often the predominant species in a variety of sedimentary environments where Fe(III reduction is important. Their ability to remediate contaminated environments and produce electricity makes them attractive for further study. Cell motility, biofilm formation, and type IV pili all appear important for the growth of Geobacter in changing environments and for electricity production. Recent studies in other bacteria have demonstrated that signaling pathways homologous to the paradigm established for Escherichia coli chemotaxis can regulate type IV pili-dependent motility, the synthesis of flagella and type IV pili, the production of extracellular matrix material, and biofilm formation. The classification of these pathways by comparative genomics improves the ability to understand how Geobacter thrives in natural environments and better their use in microbial fuel cells. Results The genomes of G. sulfurreducens, G. metallireducens, and G. uraniireducens contain multiple (~70 homologs of chemotaxis genes arranged in several major clusters (six, seven, and seven, respectively. Unlike the single gene cluster of E. coli, the Geobacter clusters are not all located near the flagellar genes. The probable functions of some Geobacter clusters are assignable by homology to known pathways; others appear to be unique to the Geobacter sp. and contain genes of unknown function. We identified large numbers of methyl-accepting chemotaxis protein (MCP homologs that have diverse sensing domain architectures and generate a potential for sensing a great variety of environmental signals. We discuss mechanisms for class-specific segregation of the MCPs in the cell membrane, which serve to maintain pathway specificity and diminish crosstalk. Finally, the regulation of gene expression in Geobacter differs from E. coli. The sequences of predicted promoter elements suggest that the alternative sigma factors

  7. Analysis and improvement of missile three-loop autopilots

    Institute of Scientific and Technical Information of China (English)

    Lin Defu; Fan Junfang; Qi Zaikang; Mou Yu

    2009-01-01

    characteristics from a two-loop autopilot with PI compensator.Both the two-loop and three-loop topologies can stabilize a static unstable missile.However,the finite actuator resource is the crucial factor dominating autopilot function.

  8. Functional epigenomics identifies genes frequently silenced in prostate cancer.

    Science.gov (United States)

    Lodygin, Dimitri; Epanchintsev, Alexey; Menssen, Antje; Diebold, Joachim; Hermeking, Heiko

    2005-05-15

    In many cases, silencing of gene expression by CpG methylation is causally involved in carcinogenesis. Furthermore, cancer-specific CpG methylation may serve as a tumor marker. In order to identify candidate genes for inactivation by CpG methylation in prostate cancer, the prostate cancer cell lines LNCaP, PC3, and Du-145 were treated with 5-aza-2' deoxycytidine and trichostatin A, which leads to reversion of epigenetic silencing. By microarray analysis of 18,400 individual transcripts, several hundred genes were found to be induced when compared with cells treated with trichostatin A. Fifty re-expressed genes were selected for further analysis based on their known function, which implied a possible involvement in tumor suppression. Twelve of these genes showed a significant degree of CpG methylation in their promoters. Six genes were silenced by CpG methylation in the majority of five analyzed prostate cancer cell lines, although they displayed robust mRNA expression in normal prostate epithelial cells obtained from four different donors. In primary prostate cancer samples derived from 41 patients, the frequencies of CpG methylation detected in the promoter regions of these genes were: GPX3, 93%; SFRP1, 83%; COX2, 78%; DKK3, 68%; GSTM1, 58%; and KIP2/p57, 56%. Ectopic expression of SFRP1 or DKK3 resulted in decreased proliferation. The expression of DKK3 was accompanied by attenuation of the mitogen-activated protein kinase pathway. The high frequency of CpG methylation detected in the promoters of the identified genes suggests a potential causal involvement in prostate cancer and may prove useful for diagnostic purposes.

  9. Functional discrimination of gene expression patterns in terms of the gene ontology.

    Science.gov (United States)

    Badea, Liviu

    2003-01-01

    The ever-growing amount of experimental data in molecular biology and genetics requires its automated analysis, by employing sophisticated knowledge discovery tools. We use an Inductive Logic Programming (ILP) learner to induce functional discrimination rules between genes studied using microarrays and found to be differentially expressed in three recently discovered subtypes of adenocarcinoma of the lung. The discrimination rules involve functional annotations from the Proteome HumanPSD database in terms of the Gene Ontology, whose hierarchical structure is essential for this task. While most of the lower levels of gene expression data (pre)processing have been automated, our work can be seen as a step toward automating the higher level functional analysis of the data. We view our application not just as a prototypical example of applying more sophisticated machine learning techniques to the functional analysis of genes, but also as an incentive for developing increasingly more sophisticated functional annotations and ontologies, that can be automatically processed by such learning algorithms.

  10. miRNA-mediated functional changes through co-regulating function related genes.

    Directory of Open Access Journals (Sweden)

    Jie He

    Full Text Available BACKGROUND: MicroRNAs play important roles in various biological processes involving fairly complex mechanism. Analysis of genome-wide miRNA microarray demonstrate that a single miRNA can regulate hundreds of genes, but the regulative extent on most individual genes is surprisingly mild so that it is difficult to understand how a miRNA provokes detectable functional changes with such mild regulation. RESULTS: To explore the internal mechanism of miRNA-mediated regulation, we re-analyzed the data collected from genome-wide miRNA microarray with bioinformatics assay, and found that the transfection of miR-181b and miR-34a in Hela and HCT-116 tumor cells regulated large numbers of genes, among which, the genes related to cell growth and cell death demonstrated high Enrichment scores, suggesting that these miRNAs may be important in cell growth and cell death. MiR-181b induced changes in protein expression of most genes that were seemingly related to enhancing cell growth and decreasing cell death, while miR-34a mediated contrary changes of gene expression. Cell growth assays further confirmed this finding. In further study on miR-20b-mediated osteogenesis in hMSCs, miR-20b was found to enhance osteogenesis by activating BMPs/Runx2 signaling pathway in several stages by co-repressing of PPARγ, Bambi and Crim1. CONCLUSIONS: With its multi-target characteristics, miR-181b, miR-34a and miR-20b provoked detectable functional changes by co-regulating functionally-related gene groups or several genes in the same signaling pathway, and thus mild regulation from individual miRNA targeting genes could have contributed to an additive effect. This might also be one of the modes of miRNA-mediated gene regulation.

  11. Functions of genes and enzymes involved in phenalinolactone biosynthesis.

    Science.gov (United States)

    Daum, Martina; Schnell, Hans-Jörg; Herrmann, Simone; Günther, Andreas; Murillo, Renato; Müller, Rolf; Bisel, Philippe; Müller, Michael; Bechthold, Andreas

    2010-07-05

    Phenalinolactones are novel terpene glycoside antibiotics produced by Streptomyces sp. Tü6071. Inactivation of three oxygenase genes (plaO2, plaO3 and plaO5), two dehydrogenase genes (plaU, plaZ) and one putative acetyltransferase gene (plaV) led to the production of novel phenalinolactone derivatives (PL HS6, PL HS7, PL HS2 and PL X1). Furthermore, the exact biosynthetic functions of two enzymes were determined, and their in vitro activities were demonstrated. PlaO1, an Fe(II)/alpha-ketoglutarate-dependent dioxygenase, is responsible for the key step in gamma-butyrolactone formation, whereas PlaO5, a cytochrome P450-dependent monooxygenase, catalyses the 1-C-hydroxylation of phenalinolactone D. In addition, stable isotope feeding experiments with biosynthetic precursors shed light on the origin of the carbons in the gamma-butyrolactone moiety.

  12. Functional analysis of prognostic gene expression network genes in metastatic breast cancer models.

    Directory of Open Access Journals (Sweden)

    Thomas R Geiger

    Full Text Available Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+ breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease.

  13. Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia.

    Science.gov (United States)

    Lips, E S; Cornelisse, L N; Toonen, R F; Min, J L; Hultman, C M; Holmans, P A; O'Donovan, M C; Purcell, S M; Smit, A B; Verhage, M; Sullivan, P F; Visscher, P M; Posthuma, D

    2012-10-01

    Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of ~1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 cases and 4965 healthy controls, using functional gene group analysis. Identifying groups of genes with similar cellular function rather than genes in isolation may have clinical implications for finding additional drug targets. We found that a group of 1026 synaptic genes was significantly associated with the risk of schizophrenia (P=7.6 × 10(-11)) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P<0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P=2.0 × 10(-4)), excitability (P=9.0 × 10(-4)) and cell adhesion and trans-synaptic signaling (P=2.4 × 10(-3)). These results are consistent with a role of synaptic dysfunction in schizophrenia and imply that impaired intracellular signal transduction in synapses, synaptic excitability and cell adhesion and trans-synaptic signaling play a role in the pathology of schizophrenia.

  14. A multicolor panel of novel lentiviral "gene ontology" (LeGO) vectors for functional gene analysis.

    Science.gov (United States)

    Weber, Kristoffer; Bartsch, Udo; Stocking, Carol; Fehse, Boris

    2008-04-01

    Functional gene analysis requires the possibility of overexpression, as well as downregulation of one, or ideally several, potentially interacting genes. Lentiviral vectors are well suited for this purpose as they ensure stable expression of complementary DNAs (cDNAs), as well as short-hairpin RNAs (shRNAs), and can efficiently transduce a wide spectrum of cell targets when packaged within the coat proteins of other viruses. Here we introduce a multicolor panel of novel lentiviral "gene ontology" (LeGO) vectors designed according to the "building blocks" principle. Using a wide spectrum of different fluorescent markers, including drug-selectable enhanced green fluorescent protein (eGFP)- and dTomato-blasticidin-S resistance fusion proteins, LeGO vectors allow simultaneous analysis of multiple genes and shRNAs of interest within single, easily identifiable cells. Furthermore, each functional module is flanked by unique cloning sites, ensuring flexibility and individual optimization. The efficacy of these vectors for analyzing multiple genes in a single cell was demonstrated in several different cell types, including hematopoietic, endothelial, and neural stem and progenitor cells, as well as hepatocytes. LeGO vectors thus represent a valuable tool for investigating gene networks using conditional ectopic expression and knock-down approaches simultaneously.

  15. Non-Maxwellian distribution functions in flaring coronal loops - Comparison of Landau-Fokker-Planck and BGK solutions

    Science.gov (United States)

    Ljepojevic, N. N.; Macneice, P.

    1988-01-01

    The high-velocity tail of the electron distribution has been calculated by solving the high-velocity form of the Landau equation for a thermal structure representative of a flaring coronal loop. These calculations show an enhancement of the tail population above Maxwellian for electrons moving down the temperature gradient. The results obtained are used to test the reliability of the BGK approximation. The comparison shows that the BGK technique can estimate contributions to the heat flux from the high-energy tail to within an order of magnitude.

  16. Functional analysis of the Myostatin gene promoter in sheep

    Institute of Scientific and Technical Information of China (English)

    DU; Rong; AN; XiaoRong; CHEN; YongFu; QIN; Jian

    2007-01-01

    Compared with the understanding for the functional mechanism of the myostatin gene, little is known about the regulatory mechanism of the myostatin gene transcription and expression. To better understand the function of the myostatin gene promoter (MSTNpro) in the transcriptional regulation of the myostatin gene and to further investigate the transcriptional regulation mechanism of the myostatin gene, the promoter region of the myostatin gene in sheep has been cloned in our recent study (AY918121). In this study, the wild (W) type MSTNProW-EGFP vectors and E-box (E) (CANNTG) mutant (M) type MSTNProE(3+5+7)M-EGFP vectors were constructed and the transcriptional regulation activities were compared by detecting the fluorescent strength of EGFP (enhanced green fluorescent protein) in C2C12 myoblasts (or myotubes) and sheep fibroblasts transfected with the vectors. Results showed that the 0.3―1.2 kb sheep myostatin promoter could activate the transcription and expression of EGFP gene in C2C12 myoblasts to different extent and the 1.2 kb promoter was the strongest. However, fluorescence was not observed in the sheep fibroblasts transfected with the 1.2 kb sheep myostatin promoter. These results suggested that the specific nature of the myostatin gene expression in skeletal muscle was attributed to the specific nature of the myostatin promoter activity. The increasing growth density of C2C12 myoblasts inhibited the transcriptional regulation activity of the wild type sheep myostatin promoter by a mechanism of feedback. The transcriptional regulation activity of the 1.2 kb wild type sheep myostatin promoter increased significantly after C2C12 myoblasts were differentiated, while the activity of 1.2 kb E(3+5+7)-mutant type myostatin promoter had no obvious change. This result suggested that MyoD may be responsible for the difference of the myostatin gene transcription and expression between growing and differentiating conditions by binding to E-box of the myostatin

  17. Functional genomics and structural biology in the definition of gene function.

    Science.gov (United States)

    Hrmova, Maria; Fincher, Geoffrey B

    2009-01-01

    By mid-2007, the three-dimensional (3D) structures of some 45,000 proteins have been solved, over a period where the linear structures of millions of genes have been defined. Technical challenges associated with X-ray crystallography are being overcome and high-throughput methods both for crystallization of proteins and for solving their 3D structures are under development. The question arises as to how structural biology can be integrated with and adds value to functional genomics programs. Structural biology will assist in the definition of gene function through the identification of the likely function of the protein products of genes. The 3D information allows protein sequences predicted from DNA sequences to be classified into broad groups, according to the overall 'fold', or 3D shape, of the protein. Structural information can be used to predict the preferred substrate of a protein, and thereby greatly enhance the accurate annotation of the corresponding gene. Furthermore, it will enable the effects of amino acid substitutions in enzymes to be better understood with respect to enzyme function and could thereby provide insights into natural variation in genes. If the molecular basis of transcription factor-DNA interactions were defined through precise 3D knowledge of the protein-DNA binding site, it would be possible to predict the effects of base substitutions within the motif on the specificity and/or kinetics of binding. In this chapter, we present specific examples of how structural biology can provide valuable information for functional genomics programs.

  18. Loop-Mediated Isothermal Amplification of the sefA Gene for Rapid Detection of Salmonella Enteritidis and Salmonella Gallinarum in Chickens.

    Science.gov (United States)

    Gong, Jiansen; Zhuang, Linlin; Zhu, Chunhong; Shi, Shourong; Zhang, Di; Zhang, Linji; Yu, Yan; Dou, Xinhong; Xu, Bu; Wang, Chengming

    2016-04-01

    Salmonella spp. pose a threat to both human and animal health, with more than 2600 serovars having been reported to date. Salmonella serovars are usually identified by slide agglutination tests, which are labor intensive and time consuming. In an attempt to develop a more rapid screening method for the major poultry Salmonella serovars, we developed a loop-mediated isothermal amplification (LAMP) assay, which directly detected the sefA gene, a fimbrial operon gene existing in several specific serovars of Salmonella enterica including the major poultry serovars, namely Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) and Salmonella enterica serovar Gallinarum (Salmonella Gallinarum). With the 177 bacterial strains we tested, positive reactions were only observed with 85 strains of serovar Salmonella Enteritidis and Salmonella Gallinarum. The detection limit of the LAMP assay was 4 CFU/reaction with genomic DNAs of Salmonella Enteritidis (ATCC 13076) from pure culture and 400 CFU/ reaction with DNA extracted from spiked chicken feces. The LAMP assay was more sensitive than conventional culture, especially without enrichment, in detecting Salmonella Enteritidis (CMCC 50041) in the spiked fecal samples. The results show the sefA LAMP method is a rapid, sensitive, specific, and practical method for directly detection of Salmonella Enteritidis and Salmonella Gallinarum in chickens. The sefA LAMP assay can potentially serve as new on-site diagnostics in the poultry industry.

  19. Development and application of loop-mediated isothermal amplification methods targeting the seM gene for detection of Streptococcus equi subsp. equi.

    Science.gov (United States)

    Hobo, Seiji; Niwa, Hidekazu; Oku, Kazuomi

    2012-03-01

    Loop-mediated isothermal amplification (LAMP) constitutes a potentially valuable diagnostic tool for rapid diagnosis of contagious diseases. In this study, we developed a novel LAMP method (seM-LAMP) to detect the seM gene of Streptococcus equi subsp. equi (S. equi), the causative agent of strangles in equids. The seM-LAMP successfully amplified the target sequence of the seM gene at 63°C within 60 min. The sensitivity of the seM-LAMP was slightly lower than the 2nd reaction of the seM semi-nested PCR. To evaluate the species specificity of the seM-LAMP, we tested 100 S. equi and 189 non-S. equi strains. Significant amplification of the DNA originating from S. equi was observed within 60 min incubation, but no amplification of non-S. equi DNA occurred. The results were identical to those of seM semi-nested PCR. To investigate the clinical usefulness of the methods, the seM-LAMP and the seM semi-nested PCR were used to screen 590 nasal swabs obtained during an outbreak of strangles. Both methods showed that 79 and 511 swabs were S. equi positive and negative, respectively, and the results were identical to those of the culture examination. These results indicate that the seM-LAMP is potentially useful for the reliable routine diagnosis of Streptococcus equi subsp. equi infections.

  20. Analytic Evaluation of Three Different Five-Electron Atomic Integrals Involving Exponentially Correlated Functions of $r_{ij}$ With $r_{ij}$'s Not Forming A Closed Loop

    CERN Document Server

    Padhy, B

    2016-01-01

    The simple method outlined in our earlier paper [B.Padhy, Orissa Journal of Physics, vol.19, No.1, p.1, February 2012] has been utilized here for analytic evaluation of three different five-electron atomic integrals with integrands involving products of s Slater-type orbitals and exponentially correlated functions of the form $r_{ij} exp(-\\lambda_{ij} r_{ij})$. Only products of those $r_{ij}$'s which do not form a closed loop by themselves, are considered.

  1. The two-loop sunrise integral around four space-time dimensions and generalisations of the Clausen and Glaisher functions towards the elliptic case

    Science.gov (United States)

    Adams, Luise; Bogner, Christian; Weinzierl, Stefan

    2015-07-01

    We present the result for the finite part of the two-loop sunrise integral with unequal masses in four space-time dimensions in terms of the O ( ɛ0) -part and the O ( ɛ1) -part of the sunrise integral around two space-time dimensions. The latter two integrals are given in terms of elliptic generalisations of Clausen and Glaisher functions. Interesting aspects of the result for the O ( ɛ1 ) -part of the sunrise integral around two space-time dimensions are the occurrence of depth two elliptic objects and the weights of the individual terms.

  2. The two-loop sunrise integral around four space-time dimensions and generalisations of the Clausen and Glaisher functions towards the elliptic case

    CERN Document Server

    Adams, Luise; Weinzierl, Stefan

    2015-01-01

    We present the result for the finite part of the two-loop sunrise integral with unequal masses in four space-time dimensions in terms of the ${\\mathcal O}(\\varepsilon^0)$-part and the ${\\mathcal O}(\\varepsilon^1)$-part of the sunrise integral around two space-time dimensions. The latter two integrals are given in terms of elliptic generalisations of Clausen and Glaisher functions. Interesting aspects of the result for the ${\\mathcal O}(\\varepsilon^1)$-part of the sunrise integral around two space-time dimensions are the occurrence of depth two elliptic objects and the weights of the individual terms.

  3. Gene therapy rescues cone function in congenital achromatopsia

    Science.gov (United States)

    Komáromy, András M.; Alexander, John J.; Rowlan, Jessica S.; Garcia, Monique M.; Chiodo, Vince A.; Kaya, Asli; Tanaka, Jacqueline C.; Acland, Gregory M.; Hauswirth, William W.; Aguirre, Gustavo D.

    2010-01-01

    The successful restoration of visual function with recombinant adeno-associated virus (rAAV)-mediated gene replacement therapy in animals and humans with an inherited disease of the retinal pigment epithelium has ushered in a new era of retinal therapeutics. For many retinal disorders, however, targeting of therapeutic vectors to mutant rods and/or cones will be required. In this study, the primary cone photoreceptor disorder achromatopsia served as the ideal translational model to develop gene therapy directed to cone photoreceptors. We demonstrate that rAAV-mediated gene replacement therapy with different forms of the human red cone opsin promoter led to the restoration of cone function and day vision in two canine models of CNGB3 achromatopsia, a neuronal channelopathy that is the most common form of achromatopsia in man. The robustness and stability of the observed treatment effect was mutation independent, but promoter and age dependent. Subretinal administration of rAAV5–hCNGB3 with a long version of the red cone opsin promoter in younger animals led to a stable therapeutic effect for at least 33 months. Our results hold promise for future clinical trials of cone-directed gene therapy in achromatopsia and other cone-specific disorders. PMID:20378608

  4. Ectopic expression of a basic helix-loop-helix gene transactivates parallel pathways of proanthocyanidin biosynthesis. structure, expression analysis, and genetic control of leucoanthocyanidin 4-reductase and anthocyanidin reductase genes in Lotus corniculatus.

    Science.gov (United States)

    Paolocci, Francesco; Robbins, Mark P; Madeo, Laura; Arcioni, Sergio; Martens, Stefan; Damiani, Francesco

    2007-01-01

    Proanthocyanidins (PAs) are plant secondary metabolites and are composed primarily of catechin and epicatechin units in higher plant species. Due to the ability of PAs to bind reversibly with plant proteins to improve digestion and reduce bloat, engineering this pathway in leaves is a major goal for forage breeders. Here, we report the cloning and expression analysis of anthocyanidin reductase (ANR) and leucoanthocyanidin 4-reductase (LAR), two genes encoding enzymes committed to epicatechin and catechin biosynthesis, respectively, in Lotus corniculatus. We show the presence of two LAR gene families (LAR1 and LAR2) and that the steady-state levels of ANR and LAR1 genes correlate with the levels of PAs in leaves of wild-type and transgenic plants. Interestingly, ANR and LAR1, but not LAR2, genes produced active proteins following heterologous expression in Escherichia coli and are affected by the same basic helix-loop-helix transcription factor that promotes PA accumulation in cells of palisade and spongy mesophyll. This study provides direct evidence that the same subclass of transcription factors can mediate the expression of the structural genes of both branches of PA biosynthesis.

  5. Sponge Microbiota are a Reservoir of Functional Antibiotic Resistance Genes

    DEFF Research Database (Denmark)

    Versluis, Dennis; de Evgrafov, Mari Cristina Rodriguez; Sommer, Morten Otto Alexander

    2016-01-01

    Wide application of antibiotics has contributed to the evolution of multi-drug resistant human pathogens, resulting in poorer treatment outcomes for infections. In the marine environment, seawater samples have been investigated as a resistance reservoir; however, no studies have methodically...... examined sponges as a reservoir of antibiotic resistance. Sponges could be important in this respect because they often contain diverse microbial communities that have the capacity to produce bioactive metabolites. Here, we applied functional metagenomics to study the presence and diversity of functional......). Fifteen of 37 inserts harbored resistance genes that shared resistance gene could be identified with high confidence, in which case we predicted resistance to be mainly mediated by antibiotic efflux. One marine-specific ampicillin-resistance...

  6. Vertebrate pigmentation: from underlying genes to adaptive function.

    Science.gov (United States)

    Hubbard, Joanna K; Uy, J Albert C; Hauber, Mark E; Hoekstra, Hopi E; Safran, Rebecca J

    2010-05-01

    Animal coloration is a powerful model for studying the genetic mechanisms that determine phenotype. Genetic crosses of laboratory mice have provided extensive information about the patterns of inheritance and pleiotropic effects of loci involved in pigmentation. Recently, the study of pigmentation genes and their functions has extended into wild populations, providing additional evidence that pigment gene function is largely conserved across disparate vertebrate taxa and can influence adaptive coloration, often in predictable ways. These new and integrative studies, along with those using a genetic approach to understand color perception, raise some important questions. Most notably, how does selection shape both phenotypic and genetic variation, and how can we use this information to further understand the phenotypic diversity generated by evolutionary processes? Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Bacterial genes in the aphid genome: absence of functional gene transfer from Buchnera to its host.

    Directory of Open Access Journals (Sweden)

    Naruo Nikoh

    2010-02-01

    Full Text Available Genome reduction is typical of obligate symbionts. In cellular organelles, this reduction partly reflects transfer of ancestral bacterial genes to the host genome, but little is known about gene transfer in other obligate symbioses. Aphids harbor anciently acquired obligate mutualists, Buchnera aphidicola (Gammaproteobacteria, which have highly reduced genomes (420-650 kb, raising the possibility of gene transfer from ancestral Buchnera to the aphid genome. In addition, aphids often harbor other bacteria that also are potential sources of transferred genes. Previous limited sampling of genes expressed in bacteriocytes, the specialized cells that harbor Buchnera, revealed that aphids acquired at least two genes from bacteria. The newly sequenced genome of the pea aphid, Acyrthosiphon pisum, presents the first opportunity for a complete inventory of genes transferred from bacteria to the host genome in the context of an ancient obligate symbiosis. Computational screening of the entire A. pisum genome, followed by phylogenetic and experimental analyses, provided strong support for the transfer of 12 genes or gene fragments from bacteria to the aphid genome: three LD-carboxypeptidases (LdcA1, LdcA2,psiLdcA, five rare lipoprotein As (RlpA1-5, N-acetylmuramoyl-L-alanine amidase (AmiD, 1,4-beta-N-acetylmuramidase (bLys, DNA polymerase III alpha chain (psiDnaE, and ATP synthase delta chain (psiAtpH. Buchnera was the apparent source of two highly truncated pseudogenes (psiDnaE and psiAtpH. Most other transferred genes were closely related to genes from relatives of Wolbachia (Alphaproteobacteria. At least eight of the transferred genes (LdcA1, AmiD, RlpA1-5, bLys appear to be functional, and expression of seven (LdcA1, AmiD, RlpA1-5 are highly upregulated in bacteriocytes. The LdcAs and RlpAs appear to have been duplicated after transfer. Our results excluded the hypothesis that genome reduction in Buchnera has been accompanied by gene transfer to the

  8. Gene-specific function prediction for non-synonymous mutations in monogenic diabetes genes.

    Directory of Open Access Journals (Sweden)

    Quan Li

    Full Text Available The rapid progress of genomic technologies has been providing new opportunities to address the need of maturity-onset diabetes of the young (MODY molecular diagnosis. However, whether a new mutation causes MODY can be questionable. A number of in silico methods have been developed to predict functional effects of rare human mutations. The purpose of this study is to compare the performance of different bioinformatics methods in the functional prediction of nonsynonymous mutations in each MODY gene, and provides reference matrices to assist the molecular diagnosis of MODY. Our study showed that the prediction scores by different methods of the diabetes mutations were highly correlated, but were more complimentary than replacement to each other. The available in silico methods for the prediction of diabetes mutations had varied performances across different genes. Applying gene-specific thresholds defined by this study may be able to increase the performance of in silico prediction of disease-causing mutations.

  9. Functional analysis of soybean genes involved in flavonoid biosynthesis by virus-induced gene silencing.

    Science.gov (United States)

    Nagamatsu, Atsushi; Masuta, Chikara; Senda, Mineo; Matsuura, Hideyuki; Kasai, Atsushi; Hong, Jin-Sung; Kitamura, Keisuke; Abe, Jun; Kanazawa, Akira

    2007-11-01

    Virus-induced gene silencing (VIGS) is a powerful tool for functional analysis of genes in plants. A wide-host-range VIGS vector, which was developed based on the Cucumber mosaic virus (CMV), was tested for its ability to silence endogenous genes involved in flavonoid biosynthesis in soybean. Symptomless infection was established using a pseudorecombinant virus, which enabled detection of specific changes in metabolite content by VIGS. It has been demonstrated that the yellow seed coat phenotype of various cultivated soybean lines that lack anthocyanin pigmentation is induced by natural degradation of chalcone synthase (CHS) mRNA. When soybean plants with brown seed coats were infected with a virus that contains the CHS gene sequence, the colour of the seed coats changed to yellow, which indicates that the naturally occurring RNA silencing is reproduced by VIGS. In addition, CHS VIGS consequently led to a decrease in isoflavone content in seeds. VIGS was also tested on the putative flavonoid 3'-hydroxylase (F3'H) gene in the pathway. This experiment resulted in a decrease in the content of quercetin relative to kaempferol in the upper leaves after viral infection, which suggests that the putative gene actually encodes the F3'H protein. In both experiments, a marked decrease in the target mRNA and accumulation of short interfering RNAs were detected, indicating that sequence-specific mRNA degradation was induced. The present report is a successful demonstration of the application of VIGS for genes involved in flavonoid biosynthesis in plants; the CMV-based VIGS system provides an efficient tool for functional analysis of soybean genes.

  10. Using Causal Loop Diagramming to Explore the Drivers of the Sustained Functionality of Rural Water Services in Timor-Leste

    Directory of Open Access Journals (Sweden)

    Kate Neely

    2016-01-01

    Full Text Available It is recognized that international water sector development work has issues with a lack of sustained positive outcomes. A large driver of this outcome is how NGOs work with communities to implement and then manage water services. Many NGOs tend to focus their efforts on improving their reach and organisational growth by continually engaging in new projects. This behaviour is largely driven by short-term donor funding models that reward extended coverage, leaving little focus on sustained outcomes. Similarly, community-based management (CBM schemes often impede sustained services as a result of the community’s limited capacity to operate and maintain the technology. To explore these complicated drivers on water service sustainability, we used causal loop diagramming to analyse the key aspect influencing the combined dynamics between NGOs, donors and CBM. We demonstrate this methodology through a study in Timor-Leste, where we gathered data necessary to develop and apply causal loop diagrams to analyse rural water supply program outcomes. The analysis of these diagrams allowed identification of leverage points used to suggest structural changes for sustained benefits of water services. These structural changes emphasize the importance of increased robustness and reliability of water technology and the associated impact this has on community satisfaction and, conjointly, on water service sustainability.

  11. Cloning and functional expression of intracellular loop variants of the honey bee (Apis mellifera) RDL GABA receptor.

    Science.gov (United States)

    Taylor-Wells, Jennina; Hawkins, Joseph; Colombo, Claudia; Bermudez, Isabel; Jones, Andrew K

    2016-06-08

    The insect GABA receptor, RDL (resistance to dieldrin), plays central roles in neuronal signalling and is the target of several classes of insecticides. To study the GABA receptor from an important pollinator species, we cloned Rdl cDNA from the honey bee, Apis mellifera. Three Rdl variants were identified, arising from differential use of splice acceptor sites in the large intracellular loop between transmembrane regions 3 and 4. These variants were renamed from previously, as Amel_RDLvar1, Amel_RDLvar2 and Amel_RDLvar3. When expressed in Xenopus laevis oocytes, the three variants showed no difference in sensitivity to the agonist, GABA, with EC50s of 29μM, 20μM and 29μM respectively. Also, the potencies of the antagonists, fipronil and imidacloprid, were similar on all three variants. Fipronil IC50 values were 0.18μM, 0.31μM and 0.20μM whereas 100μM imidacloprid reduced the GABA response by 17%, 24% and 31%. The possibility that differential splicing of the RDL intracellular loop may represent a species-specific mechanism leading to insensitivity to insecticides is discussed.

  12. Evaluating Functional Annotations of Enzymes Using the Gene Ontology.

    Science.gov (United States)

    Holliday, Gemma L; Davidson, Rebecca; Akiva, Eyal; Babbitt, Patricia C

    2017-01-01

    The Gene Ontology (GO) (Ashburner et al., Nat Genet 25(1):25-29, 2000) is a powerful tool in the informatics arsenal of methods for evaluating annotations in a protein dataset. From identifying the nearest well annotated homologue of a protein of interest to predicting where misannotation has occurred to knowing how confident you can be in the annotations assigned to those proteins is critical. In this chapter we explore what makes an enzyme unique and how we can use GO to infer aspects of protein function based on sequence similarity. These can range from identification of misannotation or other errors in a predicted function to accurate function prediction for an enzyme of entirely unknown function. Although GO annotation applies to any gene products, we focus here a describing our approach for hierarchical classification of enzymes in the Structure-Function Linkage Database (SFLD) (Akiva et al., Nucleic Acids Res 42(Database issue):D521-530, 2014) as a guide for informed utilisation of annotation transfer based on GO terms.

  13. Frequency domain analysis of noise in autoregulated gene circuits

    OpenAIRE

    Simpson, Michael L.; Cox, Chris D.; Sayler, Gary S.

    2003-01-01

    We describe a frequency domain technique for the analysis of intrinsic noise within negatively autoregulated gene circuits. This approach is based on the transfer function around the feedback loop (loop transmission) and the equivalent noise bandwidth of the system. The loop transmission, T, is shown to be a determining factor of the dynamics and the noise behavior of autoregulated gene circuits, and this T-based technique provides a simple and flexible method for the analysis of noise arisin...

  14. Gene expression profiles in rat brain disclose CNS signature genes and regional patterns of functional specialisation

    Directory of Open Access Journals (Sweden)

    Breilid Harald

    2007-04-01

    Full Text Available Abstract Background The mammalian brain is divided into distinct regions with structural and neurophysiological differences. As a result, gene expression is likely to vary between regions in relation to their cellular composition and neuronal function. In order to improve our knowledge and understanding of regional patterns of gene expression in the CNS, we have generated a global map of gene expression in selected regions of the adult rat brain (frontomedial-, temporal- and occipital cortex, hippocampus, striatum and cerebellum; both right and left sides as well as in three major non-neural tissues (spleen, liver and kidney using the Applied Biosystems Rat Genome Survey Microarray. Results By unsupervised hierarchical clustering, we found that the transcriptome within a region was highly conserved among individual rats and that there were no systematic differences between the two hemispheres (right versus left side. Further, we identified distinct sets of genes showing significant regional enrichment. Functional annotation of each of these gene sets clearly reflected several important physiological features of the region in question, including synaptic transmission within the cortex, neurogenesis in hippocampus and G-protein-mediated signalling in striatum. In addition, we were able to reveal potentially new regional features, such as mRNA transcription- and neurogenesis-annotated activities in cerebellum and differential use of glutamate signalling between regions. Finally, we determined a set of 'CNS-signature' genes that uncover characteristics of several common neuronal processes in the CNS, with marked over-representation of specific features of synaptic transmission, ion transport and cell communication, as well as numerous novel unclassified genes. Conclusion We have generated a global map of gene expression in the rat brain and used this to determine functional processes and pathways that have a regional preference or ubiquitous

  15. Natively unstructured loops differ from other loops.

    Directory of Open Access Journals (Sweden)

    Avner Schlessinger

    2007-07-01

    Full Text Available Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%-70% of all worm proteins observed to have more than seven protein-protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested

  16. Natively unstructured loops differ from other loops.

    Science.gov (United States)

    Schlessinger, Avner; Liu, Jinfeng; Rost, Burkhard

    2007-07-01

    Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions) differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%-70% of all worm proteins observed to have more than seven protein-protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested that long

  17. Gene Perturbation Atlas (GPA): a single-gene perturbation repository for characterizing functional mechanisms of coding and non-coding genes.

    Science.gov (United States)

    Xiao, Yun; Gong, Yonghui; Lv, Yanling; Lan, Yujia; Hu, Jing; Li, Feng; Xu, Jinyuan; Bai, Jing; Deng, Yulan; Liu, Ling; Zhang, Guanxiong; Yu, Fulong; Li, Xia

    2015-06-03

    Genome-wide transcriptome profiling after gene perturbation is a powerful means of elucidating gene functional mechanisms in diverse contexts. The comprehensive collection and analysis of the resulting transcriptome profiles would help to systematically characterize context-dependent gene functional mechanisms and conduct experiments in biomedical research. To this end, we collected and curated over 3000 transcriptome profiles in human and mouse from diverse gene perturbation experiments, which involved 1585 different perturbed genes (microRNAs, lncRNAs and protein-coding genes) across 1170 different cell lines/tissues. For each profile, we identified differential genes and their associated functions and pathways, constructed perturbation networks, predicted transcription regulation and cancer/drug associations, and assessed cooperative perturbed genes. Based on these transcriptome analyses, the Gene Perturbation Atlas (GPA) can be used to detect (i) novel or cell-specific functions and pathways affected by perturbed genes, (ii) protein interactions and regulatory cascades affected by perturbed genes, and (iii) perturbed gene-mediated cooperative effects. The GPA is a user-friendly database to support the rapid searching and exploration of gene perturbations. Particularly, we visualized functional effects of perturbed genes from multiple perspectives. In summary, the GPA is a valuable resource for characterizing gene functions and regulatory mechanisms after single-gene perturbations. The GPA is freely accessible at http://biocc.hrbmu.edu.cn/GPA/.

  18. Basic helix-loop-helix transcription factor Bmsage is involved in regulation of fibroin H-chain gene via interaction with SGF1 in Bombyx mori.

    Science.gov (United States)

    Zhao, Xiao-Ming; Liu, Chun; Li, Qiong-Yan; Hu, Wen-Bo; Zhou, Meng-Ting; Nie, Hong-Yi; Zhang, Yin-Xia; Peng, Zhang-Chuan; Zhao, Ping; Xia, Qing-You

    2014-01-01

    Silk glands are specialized in the synthesis of several secretory proteins. Expression of genes encoding the silk proteins in Bombyx mori silk glands with strict territorial and developmental specificities is regulated by many transcription factors. In this study, we have characterized B. mori sage, which is closely related to sage in the fruitfly Drosophila melanogaster. It is termed Bmsage; it encodes transcription factor Bmsage, which belongs to the Mesp subfamily, containing a basic helix-loop-helix motif. Bmsage transcripts were detected specifically in the silk glands of B. mori larvae through RT-PCR analysis. Immunoblotting analysis confirmed the Bmsage protein existed exclusively in B. mori middle and posterior silk gland cells. Bmsage has a low level of expression in the 4th instar molting stages, which increases gradually in the 5th instar feeding stages and then declines from the wandering to the pupation stages. Quantitative PCR analysis suggested the expression level of Bmsage in a high silk strain was higher compared to a lower silk strain on day 3 of the larval 5th instar. Furthermore, far western blotting and co-immunoprecipitation assays showed the Bmsage protein interacted with the fork head transcription factor silk gland factor 1 (SGF1). An electrophoretic mobility shift assay showed the complex of Bmsage and SGF1 proteins bound to the A and B elements in the promoter of fibroin H-chain gene(fib-H), respectively. Luciferase reporter gene assays confirmed the complex of Bmsage and SGF1 proteins increased the expression of fib-H. Together, these results suggest Bmsage is involved in the regulation of the expression of fib-H by being together with SGF1 in B. mori PSG cells.

  19. Functional analysis of sirtuin genes in multiple Plasmodium falciparum strains.

    Directory of Open Access Journals (Sweden)

    Catherine J Merrick

    Full Text Available Plasmodium falciparum, the causative agent of severe human malaria, employs antigenic variation to avoid host immunity. Antigenic variation is achieved by transcriptional switching amongst polymorphic var genes, enforced by epigenetic modification of chromatin. The histone-modifying 'sirtuin' enzymes PfSir2a and PfSir2b have been implicated in this process. Disparate patterns of var expression have been reported in patient isolates as well as in cultured strains. We examined var expression in three commonly used laboratory strains (3D7, NF54 and FCR-3 in parallel. NF54 parasites express significantly lower levels of var genes compared to 3D7, despite the fact that 3D7 was originally a clone of the NF54 strain. To investigate whether this was linked to the expression of sirtuins, genetic disruption of both sirtuins was attempted in all three strains. No dramatic changes in var gene expression occurred in NF54 or FCR-3 following PfSir2b disruption, contrasting with previous observations in 3D7. In 3D7, complementation of the PfSir2a genetic disruption resulted in a significant decrease in previously-elevated var gene expression levels, but with the continued expression of multiple var genes. Finally, rearranged chromosomes were observed in the 3D7 PfSir2a knockout line. Our results focus on the potential for parasite genetic background to contribute to sirtuin function in regulating virulence gene expression and suggest a potential role for sirtuins in maintaining genome integrity.

  20. Functional analysis of sirtuin genes in multiple Plasmodium falciparum strains.

    Science.gov (United States)

    Merrick, Catherine J; Jiang, Rays H Y; Skillman, Kristen M; Samarakoon, Upeka; Moore, Rachel M; Dzikowski, Ron; Ferdig, Michael T; Duraisingh, Manoj T

    2015-01-01

    Plasmodium falciparum, the causative agent of severe human malaria, employs antigenic variation to avoid host immunity. Antigenic variation is achieved by transcriptional switching amongst polymorphic var genes, enforced by epigenetic modification of chromatin. The histone-modifying 'sirtuin' enzymes PfSir2a and PfSir2b have been implicated in this process. Disparate patterns of var expression have been reported in patient isolates as well as in cultured strains. We examined var expression in three commonly used laboratory strains (3D7, NF54 and FCR-3) in parallel. NF54 parasites express significantly lower levels of var genes compared to 3D7, despite the fact that 3D7 was originally a clone of the NF54 strain. To investigate whether this was linked to the expression of sirtuins, genetic disruption of both sirtuins was attempted in all three strains. No dramatic changes in var gene expression occurred in NF54 or FCR-3 following PfSir2b disruption, contrasting with previous observations in 3D7. In 3D7, complementation of the PfSir2a genetic disruption resulted in a significant decrease in previously-elevated var gene expression levels, but with the continued expression of multiple var genes. Finally, rearranged chromosomes were observed in the 3D7 PfSir2a knockout line. Our results focus on the potential for parasite genetic background to contribute to sirtuin function in regulating virulence gene expression and suggest a potential role for sirtuins in maintaining genome integrity.

  1. Differentiation of European wild boar (Sus scrofa scrofa) and domestic swine (Sus scrofa domestica) meats by PCR analysis targeting the mitochondrial D-loop and the nuclear melanocortin receptor 1 (MC1R) genes.

    Science.gov (United States)

    Fajardo, Violeta; González, Isabel; Martín, Irene; Rojas, Marı A; Hernández, Pablo E; Garcı A, Teresa; Martín, Rosario

    2008-03-01

    This work describes the differentiation of European wild boar (Sus scrofa scrofa) and domestic swine (Sus scrofa domestica) meats by PCR targeting sequences from two molecular markers: the mitochondrial displacement loop (D-loop) region and the nuclear melanocortin receptor 1 (MC1R) gene. A polymorphic D-loop fragment (∼270bp) was amplified and sequenced in a number of wild and domestic Sus scrofa meat samples, to find a nucleotide region suitable for PCR-RFLP analysis. Sequence data showed the presence of only a few point mutations across Sus scrofa D-loop sequences, not allowing direct discrimination between wild boar and domestic swine meats. Later, the MC1R gene was targeted and Sus scrofa-specific primers designed to amplify a 795bp MC1R fragment. Subsequent RFLP analysis of the MC1R swine-specific amplicons allowed selection of BspHI and BstUI endonucleases to carry out intraspecific Sus scrofa differentiation. Digestion of MC1R amplicons with the chosen enzymes generated characteristic PCR-RFLP profiles that allowed discrimination among meats from wild and domestic swine specimens. The technique also enabled the detection of samples that yielded heterozygous profiles, suggesting hybrids resulting from wild boar and domestic pig breeding. The PCR-RFLP reported here, targeting the MC1R gene may be routinely applied to verify the correct labelling of game products.

  2. Bending the Rules of Transcriptional Repression: Tightly Looped DNA Directly Represses T7 RNA Polymerase

    OpenAIRE

    Lionberger, Troy A.; Meyhöfer, Edgar

    2010-01-01

    From supercoiled DNA to the tight loops of DNA formed by some gene repressors, DNA in cells is often highly bent. Despite evidence that transcription by RNA polymerase (RNAP) is affected in systems where DNA is deformed significantly, the mechanistic details underlying the relationship between polymerase function and mechanically stressed DNA remain unclear. Seeking to gain additional insight into the regulatory consequences of highly bent DNA, we hypothesize that tightly looping DNA is alone...

  3. 中国地鼠线粒体D-loop基因的克隆及序列分析%Cloning and Sequence Analysis of Mitochondrial D-loop Gene in Chinese Hamster

    Institute of Scientific and Technical Information of China (English)

    宋国华; 陈朝阳; 庞文彪; 高继萍; 岳文斌

    2013-01-01

    The primer was designed according to the closest animal published partial sequences, the PCR products were se-quenced and determined. Combined with the known D-loop region sequence of other rodents,nucleotide composition were analyzed with DNAStar and genetic distance was analyzed with MEGA 4. 1. The phylogenetic tree was constructed by neighbor-joining methods (NJ) and minimum-evolution methods (ME). The D-loop sequence of Chinese hamster had 867 bp, the nucleotide composition were relatively T(31. 49%) , C(26.07%), A(29.53%), and G(12. 92%). The different clustering methods all showed a similar result. Chinese hamsters had the closest relationship with golden hamsters, but had relatively large difference from mice and rats, basically consistent with the traditional taxonomic status. D-loop gene might be genetic marker among species. The results of this study might be of importance for studies on evolution, structure and function of the mitochondria in Chinese hamsters.%本试验根据已知相近物种动物基因序列设计引物,PCR扩增获得中国地鼠线粒体D-loop基因序列.采用DNAS-tar软件计算序列碱基组成,分析遗传变异情况.用MEGA 4.1软件计算物种间遗传距离,采用邻接法(NJ)、最小进化法(ME)构建系统进化树.结果表明,中国地鼠线粒体D-loop区序列全长为867 bp,碱基A、T、C、G的含量分别为29.53%、31.49%、26.07%、12.92%,中国地鼠与啮齿类动物有相似的碱基组成.系统进化树结果显示,中国地鼠与金黄地鼠亲缘关系较近,与大鼠的关系最远,与传统的分类相一致.所获得的中国地鼠D-loop基因可作为种间遗传变异研究的标记,研究结果为进一步研究中国地鼠的群体遗传结构奠定了基础.

  4. Design and Test of a Closed-Loop FES System for Supporting Function of the Hemiparetic Hand Based on Automatic Detection using the Microsoft Kinect sensor.

    Science.gov (United States)

    Simonsen, Daniel; Spaich, Erika G; Hansen, John; Andersen, Ole K

    2016-10-26

    This paper describes the design of a FES system automatically controlled in a closed loop using a Microsoft Kinect sensor, for assisting both cylindrical grasping and hand opening. The feasibility of the system was evaluated in real-time in stroke patients with hand function deficits. A hand function exercise was designed in which the subjects performed an arm and hand exercise in sitting position. The subject had to grasp one of two differently sized cylindrical objects and move it forward or backwards in the sagittal plane. This exercise was performed with each cylinder with and without FES support. Results showed that the stroke patients were able to perform up to 29% more successful grasps when they were assisted by FES. Moreover, the hand grasp-and-hold and hold-and-release durations were shorter for the smaller of the two cylinders. FES was appropriately timed in more than 95% of all trials indicating successful closed loop FES control. Future studies should incorporate options for assisting forward reaching in order to target a larger group of stroke patients.

  5. Inferring hypotheses on functional relationships of genes: Analysis of the Arabidopsis thaliana subtilase gene family.

    Directory of Open Access Journals (Sweden)

    Carsten Rautengarten

    2005-09-01

    Full Text Available The gene family of subtilisin-like serine proteases (subtilases in Arabidopsis thaliana comprises 56 members, divided into six distinct subfamilies. Whereas the members of five subfamilies are similar to pyrolysins, two genes share stronger similarity to animal kexins. Mutant screens confirmed 144 T-DNA insertion lines with knockouts for 55 out of the 56 subtilases. Apart from SDD1, none of the confirmed homozygous mutants revealed any obvious visible phenotypic alteration during growth under standard conditions. Apart from this specific case, forward genetics gave us no hints about the function of the individual 54 non-characterized subtilase genes. Therefore, the main objective of our work was to overcome the shortcomings of the forward genetic approach and to infer alternative experimental approaches by using an integrative bioinformatics and biological approach. Computational analyses based on transcriptional co-expression and co-response pattern revealed at least two expression networks, suggesting that functional redundancy may exist among subtilases with limited similarity. Furthermore, two hubs were identified, which may be involved in signalling or may represent higher-order regulatory factors involved in responses to environmental cues. A particular enrichment of co-regulated genes with metabolic functions was observed for four subtilases possibly representing late responsive elements of environmental stress. The kexin homologs show stronger associations with genes of transcriptional regulation context. Based on the analyses presented here and in accordance with previously characterized subtilases, we propose three main functions of subtilases: involvement in (i control of development, (ii protein turnover, and (iii action as downstream components of signalling cascades. Supplemental material is available in the Plant Subtilase Database (PSDB (http://csbdb.mpimp-golm.mpg.de/psdb.html, as well as from the CSB.DB (http://csbdb.mpimp-golm.mpg.de.

  6. Inferring Hypotheses on Functional Relationships of Genes: Analysis of the Arabidopsis thaliana Subtilase Gene Family.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available The gene family of subtilisin-like serine proteases (subtilases in Arabidopsis thaliana comprises 56 members, divided into six distinct subfamilies. Whereas the members of five subfamilies are similar to pyrolysins, two genes share stronger similarity to animal kexins. Mutant screens confirmed 144 T-DNA insertion lines with knockouts for 55 out of the 56 subtilases. Apart from SDD1, none of the confirmed homozygous mutants revealed any obvious visible phenotypic alteration during growth under standard conditions. Apart from this specific case, forward genetics gave us no hints about the function of the individual 54 non-characterized subtilase genes. Therefore, the main objective of our work was to overcome the shortcomings of the forward genetic approach and to infer alternative experimental approaches by using an integrative bioinformatics and biological approach. Computational analyses based on transcriptional co-expression and co-response pattern revealed at least two expression networks, suggesting that functional redundancy may exist among subtilases with limited similarity. Furthermore, two hubs were identified, which may be involved in signalling or may represent higher-order regulatory factors involved in responses to environmental cues. A particular enrichment of co-regulated genes with metabolic functions was observed for four subtilases possibly representing late responsive elements of environmental stress. The kexin homologs show stronger associations with genes of transcriptional regulation context. Based on the analyses presented here and in accordance with previously characterized subtilases, we propose three main functions of subtilases: involvement in (i control of development, (ii protein turnover, and (iii action as downstream components of signalling cascades. Supplemental material is available in the Plant Subtilase Database (PSDB (http://csbdb.mpimp-golm.mpg.de/psdb.html , as well as from the CSB.DB (http://csbdb.mpimp-golm.mpg.de.

  7. Strigolactone biology: genes, functional genomics, epigenetics and applications.

    Science.gov (United States)

    Makhzoum, Abdullah; Yousefzadi, Morteza; Malik, Sonia; Gantet, Pascal; Tremouillaux-Guiller, Jocelyne

    2017-03-01

    Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional role in plant and rhizosphere interactions. These compounds stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. In addition, they are involved in the control of plant architecture by inhibiting bud outgrowth as well as many other morphological and developmental processes together with other plant hormones such as auxins and cytokinins. The biosynthetic pathway of SLs that are derived from carotenoids was partially decrypted based on the identification of mutants from a variety of plant species. Only a few SL biosynthetic and regulated genes and related regulatory transcription factors have been identified. However, functional genomics and epigenetic studies started to give first elements on the modality of the regulation of SLs related genes. Since they control plant architecture and plant-rhizosphere interaction, SLs start to be used for agronomical and biotechnological applications. Furthermore, the genes involved in the SL biosynthetic pathway and genes regulated by SL constitute interesting targets for plant breeding. Therefore, it is necessary to decipher and better understand the genetic determinants of their regulation at different levels.

  8. Association of lung function genes with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Kim, Woo Jin; Lim, Myoung Nam; Hong, Yoonki; Silverman, Edwin K; Lee, Ji-Hyun; Jung, Bock Hyun; Ra, Seung Won; Choi, Hye Sook; Jung, Young Ju; Park, Yong Bum; Park, Myung Jae; Lee, Sei Won; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang Do

    2014-08-01

    Spirometric measurements of pulmonary function are important in diagnosing and determining the severity of chronic obstructive pulmonary disease (COPD). We performed this study to determine whether candidate genes identified in genome-wide association studies of spirometric measurements were associated with COPD and if they interacted with smoking intensity. The current analysis included 1,000 COPD subjects and 1,000 controls recruited from 24 hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide association studies of spirometric measurements in the Korean population cohorts, were genotyped. Genetic association tests were performed, adjusting for age, sex, and smoking intensity, using models including a SNP-by-smoking interaction term. PID1 and FAM13A were significantly associated with COPD susceptibility. There were also significant interactions between SNPs in ACN9 and FAM13A and smoking pack-years, and an association of ACN9 with COPD in the lowest smoking tertile. The risk allele of FAM13A was associated with increased expression of FAM13A in the lung. We have validated associations of FAM13A and PID1 with COPD. ACN9 showed significant interaction with smoking and is a potential candidate gene for COPD. Significant associations of genetic variants of FAM13A with gene expression levels suggest that the associated loci may act as genetic regulatory elements for FAM13A gene expression.

  9. Targeted Gene Capture by Hybridization to Illuminate Ecosystem Functioning.

    Science.gov (United States)

    Ribière, Céline; Beugnot, Réjane; Parisot, Nicolas; Gasc, Cyrielle; Defois, Clémence; Denonfoux, Jérémie; Boucher, Delphine; Peyretaillade, Eric; Peyret, Pierre

    2016-01-01

    Microbial communities are extremely abundant and diverse on earth surface and play key role in the ecosystem functioning. Thus, although next-generation sequencing (NGS) technologies have greatly improved knowledge on microbial diversity, it is necessary to reduce the biological complexity to better understand the microorganism functions. To achieve this goal, we describe a promising approach, based on the solution hybrid selection (SHS) method for the selective enrichment in a target-specific biomarker from metagenomic and metatranscriptomic samples. The success of this method strongly depends on the determination of sensitive, specific, and explorative probes to assess the complete targeted gene repertoire. Indeed, in this method, RNA probes were used to capture large DNA or RNA fragments harboring biomarkers of interest that potentially allow to link structure and function of communities of interest.

  10. Functional characterization of a Penicillium chrysogenum mutanase gene induced upon co-cultivation with Bacillus subtilis

    NARCIS (Netherlands)

    Bajaj, I.; Veiga, T.; Van Dissel, D.; Pronk, J.T.; Daran, J.M.

    2014-01-01

    Background Microbial gene expression is strongly influenced by environmental growth conditions. Comparison of gene expression under different conditions is frequently used for functional analysis and to unravel regulatory networks, however, gene expression responses to co-cultivation with other micr

  11. Dissecting the gene network of dietary restriction to identify evolutionarily conserved pathways and new functional genes.

    Science.gov (United States)

    Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhães, João Pedro

    2012-01-01

    Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR-essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR-essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR-essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR-essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR-induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led

  12. Dissecting the gene network of dietary restriction to identify evolutionarily conserved pathways and new functional genes.

    Directory of Open Access Journals (Sweden)

    Daniel Wuttke

    Full Text Available Dietary restriction (DR, limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR-essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/. To dissect the interactions of DR-essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR-essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR-essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2 had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR-induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of

  13. Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes

    Science.gov (United States)

    Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhães, João Pedro

    2012-01-01

    Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple

  14. Primary function analysis of human mental retardation related gene CRBN.

    Science.gov (United States)

    Xin, Wang; Xiaohua, Ni; Peilin, Chen; Xin, Chen; Yaqiong, Sun; Qihan, Wu

    2008-06-01

    The mutation of human cereblon gene (CRBN) is revealed to be related with mild mental retardation. Since the molecular characteristics of CRBN have not been well presented, we investigated the general properties of CRBN. We analyzed its gene structure and protein homologues. The CRBN protein might belong to a family of adenosine triphosphate (ATP)-dependent Lon protease. We also found that CRBN was widely expressed in different tissues, and the expression level in testis is significantly higher than other tissues. This may suggested it could play some important roles in several other tissues besides brain. Transient transfection experiment in AD 293 cell lines suggested that both CRBN and CRBN mutant (nucleotide position 1,274(C > T)) are located in the whole cells. This may suggest new functions of CRBN in cell nucleolus besides its mitochondria protease activity in cytoplasm.

  15. Involvement of distinct PKC gene products in T cell functions

    Directory of Open Access Journals (Sweden)

    Gottfried eBaier

    2012-08-01

    Full Text Available It is well established that members of the Protein kinase C(PKC family seem to have important roles in T cells. Focusing on the physiological and non-redundant PKC functions established in primary mouse T cells via germline gene-targeting approaches, our current knowledge defines two particularly critical PKC gene products, PKCθ and PKCα, as the flavor of PKC in T cells that appear to have a positive role in signaling pathways that are necessary for full antigen receptor-mediated T cell activation ex vivo and T cell-mediated immunity in vivo. Consistently, in spite of the current dogma that PKCθ inhibition might be sufficient to achieve complete immunosuppressive effects, more recent results have indicated that the pharmacological inhibition of PKCθ, and additionally, at least PKCα, appears to be needed to provide a successful approach for the prevention of allograft rejection and treatment of autoimmune diseases.

  16. Constructing gene co-expression networks and predicting functions of unknown genes by random matrix theory

    Directory of Open Access Journals (Sweden)

    Gao Haichun

    2007-08-01

    Full Text Available Abstract Background Large-scale sequencing of entire genomes has ushered in a new age in biology. One of the next grand challenges is to dissect the cellular networks consisting of many individual functional modules. Defining co-expression networks without ambiguity based on genome-wide microarray data is difficult and current methods are not robust and consistent with different data sets. This is particularly problematic for little understood organisms since not much existing biological knowledge can be exploited for determining the threshold to differentiate true correlation from random noise. Random matrix theory (RMT, which has been widely and successfully used in physics, is a powerful approach to distinguish system-specific, non-random properties embedded in complex systems from random noise. Here, we have hypothesized that the universal predictions of RMT are also applicable to biological systems and the correlation threshold can be determined by characterizing the correlation matrix of microarray profiles using random matrix theory. Results Application of random matrix theory to microarray data of S. oneidensis, E. coli, yeast, A. thaliana, Drosophila, mouse and human indicates that there is a sharp transition of nearest neighbour spacing distribution (NNSD of correlation matrix after gradually removing certain elements insider the matrix. Testing on an in silico modular model has demonstrated that this transition can be used to determine the correlation threshold for revealing modular co-expression networks. The co-expression network derived from yeast cell cycling microarray data is supported by gene annotation. The topological properties of the resulting co-expression network agree well with the general properties of biological networks. Computational evaluations have showed that RMT approach is sensitive and robust. Furthermore, evaluation on sampled expression data of an in silico modular gene system has showed that under

  17. Functional annotation and identification of candidate disease genes by computational analysis of normal tissue gene expression data.

    Directory of Open Access Journals (Sweden)

    Laura Miozzi

    Full Text Available BACKGROUND: High-throughput gene expression data can predict gene function through the "guilt by association" principle: coexpressed genes are likely to be functionally associated. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed publicly available expression data on normal human tissues. The analysis is based on the integration of data obtained with two experimental platforms (microarrays and SAGE and of various measures of dissimilarity between expression profiles. The building blocks of the procedure are the Ranked Coexpression Groups (RCG, small sets of tightly coexpressed genes which are analyzed in terms of functional annotation. Functionally characterized RCGs are selected by means of the majority rule and used to predict new functional annotations. Functionally characterized RCGs are enriched in groups of genes associated to similar phenotypes. We exploit this fact to find new candidate disease genes for many OMIM phenotypes of unknown molecular origin. CONCLUSIONS/SIGNIFICANCE: We predict new functional annotations for many human genes, showing that the integration of different data sets and coexpression measures significantly improves the scope of the results. Combining gene expression data, functional annotation and known phenotype-gene associations we provide candidate genes for several genetic diseases of unknown molecular basis.

  18. RCD+: Fast loop modeling server.

    Science.gov (United States)

    López-Blanco, José Ramón; Canosa-Valls, Alejandro Jesús; Li, Yaohang; Chacón, Pablo

    2016-07-08

    Modeling loops is a critical and challenging step in protein modeling and prediction. We have developed a quick online service (http://rcd.chaconlab.org) for ab initio loop modeling combining a coarse-grained conformational search with a full-atom refinement. Our original Random Coordinate Descent (RCD) loop closure algorithm has been greatly improved to enrich the sampling distribution towards near-native conformations. These improvements include a new workflow optimization, MPI-parallelization and fast backbone angle sampling based on neighbor-dependent Ramachandran probability distributions. The server starts by efficiently searching the vast conformational space from only the loop sequence information and the environment atomic coordinates. The generated closed loop models are subsequently ranked using a fast distance-orientation dependent energy filter. Top ranked loops are refined with the Rosetta energy function to obtain accurate all-atom predictions that can be interactively inspected in an user-friendly web interface. Using standard benchmarks, the average root mean squared deviation (RMSD) is 0.8 and 1.4 Å for 8 and 12 residues loops, respectively, in the challenging modeling scenario in where the side chains of the loop environment are fully remodeled. These results are not only very competitive compared to those obtained with public state of the art methods, but also they are obtained ∼10-fold faster. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis.

    Directory of Open Access Journals (Sweden)

    Peter Jonas Grahn

    2014-09-01

    Full Text Available Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system’s state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles.

  20. Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis

    Science.gov (United States)

    Grahn, Peter J.; Mallory, Grant W.; Berry, B. Michael; Hachmann, Jan T.; Lobel, Darlene A.; Lujan, J. Luis

    2014-01-01

    Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI) can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system's state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles. PMID:25278830

  1. Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis.

    Science.gov (United States)

    Grahn, Peter J; Mallory, Grant W; Berry, B Michael; Hachmann, Jan T; Lobel, Darlene A; Lujan, J Luis

    2014-01-01

    Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI) can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system's state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles.

  2. Development and evaluation of a loop-mediated isothermal amplification (LAMP assay for rapid detection of Actinobacillus pleuropneumoniae based the dsbE-like gene

    Directory of Open Access Journals (Sweden)

    Hongwei Ji

    2012-08-01

    Full Text Available This paper reports on the development and validation of a loop-mediated isothermal amplification assay (LAMP for the rapid and specific detection of Actinobacillus pleuropneumoniae (A. pleuropneumoniae. A set of six primers were designed derived from the dsbE-like gene of A.pleuropneumoniae and validate the assay using 9 A. pleuropneumoniae reference/field strains, 132 clinical isolates and 9 other pathogens. The results indicated that positive reactions were confirmed for all A. pleuropneumoniae strains and specimens by LAMP at 63ºC for 60 min and no cross-reactivity were observed from other non-A.pleuropneumoniae including Haemophilus parasuis, Escherichia coli, Pasteurella multocida, Bordetella bronchiseptica, Streptococcus suis, Salmonella enterica, Staphylococcus, porcine reproductive and respiratory syndrome virus (PRRSV, and Pseudorabies virus. The detection limit of the conventional PCR was 10² CFU per PCR test tube, while that of the LAMP was 5 copies per tube. Therefore, the sensitivity of LAMP was higher than that of PCR. Moreover, the LAMP assay provided a rapid yet simple test of A. pleuropneumoniae suitable for laboratory diagnosis and pen-side detection due to ease of operation and the requirement of only a regular water bath or heat block for the reaction.

  3. Rapid and sensitive detection of Dasheen mosaic virus infecting elephant foot yam by reverse transcription loop mediated isothermal amplification of coat protein gene.

    Science.gov (United States)

    Kamala, S; Makeshkumar, T

    2015-09-15

    Dasheen mosaic virus (DsMV), the pathogen causing mosaic disease of elephant foot yam (Amorphophallus paeoniifoilius) is disseminated mainly through vegetative propagation of the tubers. For the rapid and sensitive detection of the virus, a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay based on the coat protein gene has been developed. A final concentration of 5.4 mM magnesium sulphate and 0.7 M betaine in the reaction mixture was found to be optimum for getting characteristic ladder like bands of the amplified product after gel electrophoresis. The reaction was set at 65°C for 50 min followed by reaction termination at 86°C for 5 min in a water bath. The sensitivity of the assay was found to be 100 times higher than that of RT-PCR. The virus was indexed successfully from tubers of elephant foot yam. In tube detection of the DsMV was carried out using fluorescence detection reagents. The assay was validated with field samples from various regions of Kerala state, India. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. A Loop-Mediated Isothermal Amplification Assay Targeting 16S rRNA Gene for Rapid Detection of Anaplasma phagocytophilum Infection in Sheep and Goats.

    Science.gov (United States)

    Wang, Jinhong; Zhang, Yan; Wang, Xiaoxing; Cui, Yanyan; Yan, Yaqun; Wang, Rongjun; Jian, Fuchun; Zhang, Longxian; Ning, Changshen

    2017-04-01

    Anaplasma phagocytophilum is a zoonotic pathogen and the causative agent of human granulocytic anaplasmosis in humans and tick-borne fever in various kinds of animals. In the present study, a loop-mediated isothermal amplification (LAMP) assay for rapid detection of A. phagocytophilum was developed using primers specific to 16S rRNA gene of this organism. The LAMP assay was performed at 65 C for 60 min and terminated at 80 C for 10 min. The optimal reaction conditions under which no cross-reaction was observed with other closely related tick-borne parasites ( Anaplasma bovis , Anaplasma ovis , Theileria luwenshuni, Babesia motasi, and Schistosoma japonicum ) were established. The assay exhibited much higher sensitivity compared with conventional polymerase chain reaction (PCR) (1 copy vs. 1,000 copies). To evaluate the applicability of the LAMP assay, 94 field samples of sheep blood were analyzed for A. phagocytophilum infection by using LAMP, nested PCR, and conventional PCR assays at the same time. A positive LAMP result was obtained from 53 (56.4%) of the 94 samples, whereas only 12 (12.8%) and 3 (3.2%) tested positive by nested and conventional PCR, respectively. In conclusion, this LAMP assay is a specific, sensitive, and rapid method for the detection of A. phagocytophilum in sheep/goats.

  5. Automatic annotation of protein motif function with Gene Ontology terms

    Directory of Open Access Journals (Sweden)

    Gopalakrishnan Vanathi

    2004-09-01

    Full Text Available Abstract Background Conserved protein sequence motifs are short stretches of amino acid sequence patterns that potentially encode the function of proteins. Several sequence pattern searching algorithms and programs exist foridentifying candidate protein motifs at the whole genome level. However, amuch needed and importanttask is to determine the functions of the newly identified protein motifs. The Gene Ontology (GO project is an endeavor to annotate the function of genes or protein sequences with terms from a dynamic, controlled vocabulary and these annotations serve well as a knowledge base. Results This paperpresents methods to mine the GO knowledge base and use the association between the GO terms assigned to a sequence and the motifs matched by the same sequence as evidence for predicting the functions of novel protein motifs automatically. The task of assigning GO terms to protein motifsis viewed as both a binary classification and information retrieval problem, where PROSITE motifs are used as samples for mode training and functional prediction. The mutual information of a motif and aGO term association isfound to be a very useful feature. We take advantageof the known motifs to train a logistic regression classifier, which allows us to combine mutual information with other frequency-based features and obtain a probability of correctassociation. The trained logistic regression model has intuitively meaningful and logically plausible parameter values, and performs very well empirically according to our evaluation criteria. Conclusions In this research, different methods for automatic annotation of protein motifs have been investigated. Empirical result demonstrated that the methods have a great potential for detecting and augmenting information about thefunctions of newly discovered candidate protein motifs.

  6. Development and evaluation of a loop-mediated isothermal amplification assay for detection of Ehrlichia canis DNA in naturally infected dogs using the p30 gene.

    Science.gov (United States)

    Pinhanelli, V C; Costa, P N M; Silva, G; Aguiar, D M; Silva, C M L; Fachin, A L; Marins, M

    2015-12-22

    Canine monocytic ehrlichiosis (CME) is a common tick-borne disease caused by the rickettsial bacterium Ehrlichia canis (Rickettsiales: Anaplasmataceae). In view of the different stages and variable clinical signs of CME, which can overlap with those of other infections, a conclusive diagnosis can more readily be obtained by combining clinical and hematological evaluations with molecular diagnostic methods. In this study, a loop-mediated isothermal amplification (LAMP) assay targeting the p30 gene of E. canis was developed. The assay was developed using DNA extracted from E. canis-infected cultures of the macrophage cell line DH82 and samples from dogs testing positive for E. canis DNA by PCR. The LAMP assay was compared to a p30-based PCR assay, using DNA extracted from EDTA-anticoagulated blood samples of 137 dogs from an endemic region in Brazil. The LAMP assay was sensitive enough to detect a single copy of the target gene, and identified 74 (54.0%) E. canis DNA-positive samples, while the p30 PCR assay detected 50 positive samples (36.5%) among the field samples. Agreement between the two assays was observed in 42 positive and 55 negative samples. However, 32 positive samples that were not detected by the PCR assay were identified by the LAMP assay, while eight samples identified as E. canis-positive by PCR showed negative results in LAMP. The developed E. canis LAMP assay showed the potential to maximize the use of nucleic acid tests in a veterinary clinical laboratory, and to improve the diagnosis of CME.

  7. Detection of pork adulteration in processed meat by species-specific PCR-QIAxcel procedure based on D-loop and cytb genes.

    Science.gov (United States)

    Barakat, Hassan; El-Garhy, Hoda A S; Moustafa, Mahmoud M A

    2014-12-01

    Detection of pork meat adulteration in "halal" meat products is a crucial issue in the fields of modern food inspection according to implementation of very strict procedures for halal food labelling. Present study aims at detecting and quantifying pork adulteration in both raw and cooked manufactured sausages. This is by applying an optimized species-specific PCR procedure followed by QIAxcel capillary electrophoresis system. Manufacturing experiment was designed by incorporating pork with beef meat at 0.01 to 10 % substitution levels beside beef and pork sausages as negative and positive controls, respectively. Subsequently, sausages were divided into raw and cooked sausages then subjected to DNA extraction. Results indicated that PCR amplifications of mitochondrial D-loop and cytochrome b (cytb) genes by porcine-specific primers produced 185 and 117 bp pork-specific DNA fragments in sausages, respectively. No DNA fragments were detected when PCR was applied on beef sausage DNA confirming primers specificity. For internal control, a 141-bp DNA fragment of eukaryotic 18S ribosomal RNA (rRNA) gene was amplified from pork and beef DNA templates. Although PCR followed by either QIAxcel or agarose techniques were efficient for targeted DNA fragments differentiation even as low as 0.01 % (pork/meat: w/w). For proficiency, adequacy, and performance, PCR-QIA procedure is highly sensitive, a time-saver, electronically documented, mutagenic-reagent free, of little manual errors, accurate in measuring PCR fragments length, and quantitative data supplier. In conclusion, it can be suggested that optimized PCR-QAI is considered as a rapid and sensitive method for routine pork detection and quantification in raw or processed meat.

  8. Prediction of human protein function according to Gene Ontology categories

    DEFF Research Database (Denmark)

    Jensen, Lars Juhl; Gupta, Ramneek; Stærfeldt, Hans Henrik

    2003-01-01

    developed a method for prediction of protein function for a subset of classes from the Gene Ontology classification scheme. This subset includes several pharmaceutically interesting categories-transcription factors, receptors, ion channels, stress and immune response proteins, hormones and growth factors...... can all be predicted. Although the method relies on protein sequences as the sole input, it does not rely on sequence similarity, but instead on sequence derived protein features such as predicted post translational modifications (PTMs), protein sorting signals and physical/chemical properties...

  9. Cloning of full-length cDNA of Microsporum canis membrane protein PQ-loop repeat protein gene%犬小孢子菌膜蛋白PQ-LRP基因全长cDNA的克隆

    Institute of Scientific and Technical Information of China (English)

    庞娟; 祝逸平; 杨国玲

    2012-01-01

    Objective To clone the full-length cDNA of Microsporum canis membrane protein PQ-loop repeat protein (PQ-LRP) gene,so as to investigate the roles of PQ-LRP in the pathogenesis of tinea capitis.Methods A Microsporum canis strain (A518) from a patient with tinea capitis served as the experimental strain.Rapid cDNA end amplification (RACE) was performed to clone the full length cDNA sequence of PQLRP gene.Bioinformatics methods were used to make a preliminary functional analysis of the gene.Results The cDNA of PQ-LRP gene was obtained with a full length of 1522 bp,including the 5' untranslated region (49 bp),coding region (1080 bp) and 3' untranslated region (393 bp).The coding region encoded a protein precursor including 359 amino acid residues.The cloned cDNA of PQ-LRP gene shared an 81% nucleotide identity with that of Trichophyton tonsurans and a 79% nucleotide identity with that of Trichophyton rubrum.Conclusions The full-length cDNA of Microsporum canis membrane protein PQ-LRP gene has been successfully cloned,which will provide an important basis for further researches into the roles of PQ-LRP in Microsporum canis-associated diseases.%目的 克隆犬小孢子菌膜蛋白PQ-LRP(PQ-loop repeat protein)基因全长cDNA,探讨在头癣发病机制中的作用.方法 选用犬小孢子菌头癣株(A518)为实验株,采用cDNA快速末端扩增法(RACE),克隆PQ-LRP基因的全长序列.结合生物信息学方法对获得的序列进行初步功能分析.结果 获得犬小孢子菌PQ-LRP全长序列为1522 bp,拥有一个1080 bp的开放阅读框,编码359个氨基酸,5 '非编码区为49 bp,3 '非编码区为393 bp;同源性比对与断发毛癣菌的PQ-LRP同源性达到81%,与红色毛癣菌PQ-LRP同源性达到79%.结论 克隆出犬小孢子菌膜蛋白PQ-LRP cDNA全长序列,为研究膜蛋白PQ-LRP基因在犬小孢子菌病中的功能奠定基础.

  10. The Shark Strikes Twice: Hypervariable Loop 2 of Shark IgNAR Antibody Variable Domains and Its Potential to Function as an Autonomous Paratope.

    Science.gov (United States)

    Zielonka, Stefan; Empting, Martin; Könning, Doreen; Grzeschik, Julius; Krah, Simon; Becker, Stefan; Dickgießer, Stephan; Kolmar, Harald

    2015-08-01

    In this present study, we engineered hypervariable loop 2 (HV2) of the IgNAR variable domain in a way that it solely facilitates antigen binding, potentially functioning as an autonomous paratope. For this, the surface-exposed loop corresponding to HV2 was diversified and antigen-specific variable domain of IgNAR antibody (vNAR) molecules were isolated by library screening using yeast surface display (YSD) as platform technology. An epithelial cell adhesion molecule (EpCAM)-specific vNAR was used as starting material, and nine residues in HV2 were randomized. Target-specific clones comprising a new HV2-mediated paratope were isolated against cluster of differentiation 3ε (CD3ε) and human Fcγ while retaining high affinity for EpCAM. Essentially, we demonstrate that a new paratope comprising moderate affinities against a given target molecule can be engineered into the vNAR scaffold that acts independent of the original antigen-binding site, composed of complementarity-determining region 3 (CDR3) and CDR1.

  11. Loop-loop interaction in an adenine-sensing riboswitch: a molecular dynamics study.

    Science.gov (United States)

    Allnér, Olof; Nilsson, Lennart; Villa, Alessandra

    2013-07-01

    Riboswitches are mRNA-based molecules capable of controlling the expression of genes. They undergo conformational changes upon ligand binding, and as a result, they inhibit or promote the expression of the associated gene. The close connection between structural rearrangement and function makes a detailed knowledge of the molecular interactions an important step to understand the riboswitch mechanism and efficiency. We have performed all-atom molecular dynamics simulations of the adenine-sensing add A-riboswitch to study the breaking of the kissing loop, one key tertiary element in the aptamer structure. We investigated the aptamer domain of the add A-riboswitch in complex with its cognate ligand and in the absence of the ligand. The opening of the hairpins was simulated using umbrella sampling using the distance between two loops as the reaction coordinate. A two-step process was observed in all the simulated systems. First, a general loss of stacking and hydrogen bond interactions is seen. The last interactions that break are the two base pairs G37-C61 and G38-C60, but the break does not affect the energy profile, indicating their pivotal role in the tertiary structure formation but not in the structure stabilization. The junction area is partially organized before the kissing loop formation and residue A24 anchors together the loop helices. Moreover, when the distance between the loops is increased, one of the hairpins showed more flexibility by changing its orientation in the structure, while the other conserved its coaxial arrangement with the rest of the structure.

  12. 副溶血弧菌tdh基因LAMP检测技术的建立%Establishment of Loop-Mediated Isothermal Amplification for Detecting Vibrio Parahaemolyticus tdh Gene

    Institute of Scientific and Technical Information of China (English)

    程晓艳; 刘庆慧; 黄倢

    2012-01-01

    Loop-mediated isothermal amplification (LAMP) is a novel DNA amplification technology which amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. In this paper, LAMP was applied for rapid detection of Vibrio parahaemolyticus. According to the sequence of the specific tdh gene of Vibrio parahaemolyticus, a set of primers was designed to amplify the specifial DNA sequences by LAMP. Moreover, the reaction conditions were optimized. The results showed the optimum LAMP assay for the rapid detection of Vibrio paiakaemolyticus was performed at 60.8 ℃ for 45 min. No crossreaction was found with other common bacteria which showed a good specificity. The LAMP assay had an detection limit of 35.5 fg/tube, which was 10 times lower than that of PCR assay. The LAMP assay could be finished within an hour requiring only a regular laboratory water bath for reaction. The detection of the strains isolated from scallop also proved the LAMP assay reliability.%环等温扩增技术(Loop-mediated isothermal amplification,LAMP)是一种在等温条件下高特异性、高效、快速地扩增靶基因的DNA扩增技术.根据副溶血弧菌特异性的毒力基因tdh保守序列,本文设计1套特异性引物对该基因进行环等温扩增,同时对反应条件进行优化,建立携带tdh基因的致病性副溶血弧菌的LAMP快速检测技术.结果表明,LAMP最适反应在60.8℃恒温、45 min内完成,与其它常见的细菌无交叉反应.LAMP方法的细菌DNA最低检出限为35.5 fg/反应管,灵敏度较PCR方法高10倍.对扇贝样品中分离的菌株的检测表明,LAMP方法对检测致病性副溶血弧菌具有良好的可靠性.

  13. Gene-environment interaction and male reproductive function

    DEFF Research Database (Denmark)

    Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L;

    2010-01-01

    As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between...... that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism...... of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity...

  14. An efficient RNA interference screening strategy for gene functional analysis

    Directory of Open Access Journals (Sweden)

    Chang Chih-Hung

    2012-09-01

    Full Text Available Abstract Background RNA interference (RNAi is commonly applied in genome-scale gene functional screens. However, a one-on-one RNAi analysis that targets each gene is cost-ineffective and laborious. Previous studies have indicated that siRNAs can also affect RNAs that are near-perfectly complementary, and this phenomenon has been termed an off-target effect. This phenomenon implies that it is possible to silence several genes simultaneously with a carefully designed siRNA. Results We propose a strategy that is combined with a heuristic algorithm to design suitable siRNAs that can target multiple genes and a group testing method that would reduce the number of required RNAi experiments in a large-scale RNAi analysis. To verify the efficacy of our strategy, we used the Orchid expressed sequence tag data as a case study to screen the putative transcription factors that are involved in plant disease responses. According to our computation, 94 qualified siRNAs were sufficient to examine all of the predicated 229 transcription factors. In addition, among the 94 computer-designed siRNAs, an siRNA that targets both TF15 (a previously identified transcription factor that is involved in the plant disease-response pathway and TF21 was introduced into orchids. The experimental results showed that this siRNA can simultaneously silence TF15 and TF21, and application of our strategy successfully confirmed that TF15 is involved in plant defense responses. Interestingly, our second-round analysis, which used an siRNA specific to TF21, indicated that TF21 is a previously unidentified transcription factor that is related to plant defense responses. Conclusions Our computational results showed that it is possible to screen all genes with fewer experiments than would be required for the traditional one-on-one RNAi screening. We also verified that our strategy is capable of identifying genes that are involved in a specific phenotype.

  15. Functions of coenzyme Q10 in inflammation and gene expression.

    Science.gov (United States)

    Schmelzer, Constance; Lindner, Inka; Rimbach, Gerald; Niklowitz, Petra; Menke, Thomas; Döring, Frank

    2008-01-01

    Clinical studies demonstrated the efficacy of Coenzyme Q10 (CoQ10) as an adjuvant therapeutic in cardiovascular diseases, mitochondrial myopathies and neurodegenerative diseases. More recently, expression profiling revealed that Coenzyme Q10 (CoQ10) influences the expression of several hundred genes. To unravel the functional connections of these genes, we performed a text mining approach using the Genomatix BiblioSphere. We identified signalling pathways of G-protein coupled receptors, JAK/STAT, and Integrin which contain a number of CoQ10 sensitive genes. Further analysis suggested that IL5, thrombin, vitronectin, vitronectin receptor, and C-reactive protein are regulated by CoQ10 via the transcription factor NFkappaB1. To test this hypothesis, we studied the effect of CoQ10 on the NFkappaB1-dependent pro-inflammatory cytokine TNF-alpha. As a model, we utilized the murine macrophage cell lines RAW264.7 transfected with human apolipoprotein E3 (apoE3, control) or pro-inflammatory apoE4. In the presence of 2.5 microM or 75 microM CoQ10 the LPS-induced TNF-alpha response was significantly reduced to 73.3 +/- 2.8% and 74.7 +/- 8.9% in apoE3 or apoE4 cells, respectively. Therefore, the in silico analysis as well as the cell culture experiments suggested that CoQ10 exerts anti-inflammatory properties via NFkappaB1-dependent gene expression.

  16. Functional analysis of NLP genes from Botrytis elliptica.

    Science.gov (United States)

    Staats, Martijn; VAN Baarlen, Peter; Schouten, Alexander; VAN Kan, Jan A L

    2007-03-01

    SUMMARY We functionally analysed two Nep1-like protein (NLP) genes from Botrytis elliptica (a specialized pathogen of lily), encoding proteins homologous to the necrosis and ethylene-inducing protein (NEP1) from Fusarium oxysporum. Single gene replacement mutants were made for BeNEP1 and BeNEP2, providing the first example of transformation and successful targeted mutagenesis in this fungus. The virulence of both mutants on lily leaves was not affected. BeNEP1 and BeNEP2 were individually expressed in the yeast Pichia pastoris, and the necrosis-inducing activity was tested by infiltration of both proteins into leaves of several monocots and eudicots. Necrotic symptoms developed on the eudicots tobacco, Nicotiana benthamiana and Arabidopsis thaliana, and cell death was induced in tomato cell suspensions. No necrotic symptoms developed on leaves of the monocots rice, maize and lily. These results support the hypothesis that the necrosis-inducing activity of NLPs is limited to eudicots. We conclude that NLPs are not essential virulence factors and they do not function as host-selective toxins for B. elliptica.

  17. Interrogating the function of metazoan histones using engineered gene clusters.

    Science.gov (United States)

    McKay, Daniel J; Klusza, Stephen; Penke, Taylor J R; Meers, Michael P; Curry, Kaitlin P; McDaniel, Stephen L; Malek, Pamela Y; Cooper, Stephen W; Tatomer, Deirdre C; Lieb, Jason D; Strahl, Brian D; Duronio, Robert J; Matera, A Gregory

    2015-02-09

    Histones and their posttranslational modifications influence the regulation of many DNA-dependent processes. Although an essential role for histone-modifying enzymes in these processes is well established, defining the specific contribution of individual histone residues remains a challenge because many histone-modifying enzymes have nonhistone targets. This challenge is exacerbated by the paucity of suitable approaches to genetically engineer histone genes in metazoans. Here, we describe a platform in Drosophila for generating and analyzing any desired histone genotype, and we use it to test the in vivo function of three histone residues. We demonstrate that H4K20 is neither essential for DNA replication nor for completion of development, unlike inferences drawn from analyses of H4K20 methyltransferases. We also show that H3K36 is required for viability and H3K27 is essential for maintenance of cellular identity but not for gene activation. These findings highlight the power of engineering histones to interrogate genome structure and function in animals. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Hardware-in-the-loop simulation for the virtual application of control functions for a coordination of the interaction between a gasoline engine and the 14V-power electrical system; Hardware-in-the-Loop-Simulation fuer die virtuelle Applikation von Steuerungsfunktionen zur Motor-Energiebordnetz-Koordination

    Energy Technology Data Exchange (ETDEWEB)

    Schiele, Thomas

    2010-07-01

    The development of advanced engine management systems increasingly is supported by model-based development tools. Thereby the hardware-in-the-loop simulation is one of these tools. The author of the contribution under consideration reports on an extension of the capabilities of the hardware-in-the-loop simulation from the classic functional testing and safety tests up to the model-based application. Using the control functions for the coordination of the interaction between a gasoline engine and the 14V-power electrical system as an example, the practical application of hardware-in-the-loop systems is presented. Here, the author reviews on the state of technology for the real-time modeling of internal combustion engines and wiring systems.

  19. Effect of transverse aortic constriction on cardiac structure, function and gene expression in pregnant rats.

    Directory of Open Access Journals (Sweden)

    Nils Thomas Songstad

    Full Text Available BACKGROUND: There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload. METHODS: Pregnant (gestational day 5.5-8.5 and non-pregnant Wistar rats were randomized to transverse aortic constriction (TAC or sham surgery. After 14.2 ± 0.14 days echocardiography was performed. Aortic blood pressure and left ventricular (LV pressure-volume loops were obtained using a conductance catheter. LV collagen content and cardiomyocyte circumference were measured. Myocardial gene expression was assessed by real-time polymerase chain reaction. RESULTS: Heart weight was increased by TAC (p<0.001 but not by pregnancy. Cardiac myocyte circumference was larger in pregnant compared to non-pregnant rats independent of TAC (p = 0.01, however TAC per se did not affect this parameter. Collagen content in LV myocardium was not affected by pregnancy or TAC. TAC increased stroke work more in pregnant rats (34.1 ± 2.4 vs 17.5 ± 2.4 mmHg/mL, p<0.001 than in non-pregnant (28.2 ± 1.7 vs 20.9 ± 1.5 mmHg/mL, p = 0.06. However, it did not lead to overt heart failure in any group. In pregnant rats, α-MHC gene expression was reduced by TAC. Increased in the expression of β-MHC gene was higher in pregnant (5-fold compared to non-pregnant rats (2-fold after TAC (p = 0.001. Nine out of the 19 genes related to cardiac remodeling were affected by pregnancy independent of TAC. CONCLUSIONS: This study did not support the hypothesis that pregnancy is cardioprotective against the negative effects of increased afterload. Some differences in cardiac structure, function and gene expression between pregnant and non-pregnant rats following TAC indicated that

  20. A phosphatase-independent gain-of-function mutation in PTEN triggers aberrant cell growth in astrocytes through an autocrine IGF-1 loop.

    Science.gov (United States)

    Fernández, S; Genis, L; Torres-Alemán, I

    2014-08-07

    Loss-of-function mutations in the phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome10) contribute to aberrant cell growth in part through upregulation of the mitogenic IGF-1/PI3K/Akt pathway. In turn, this pathway exerts a homeostatic feedback over PTEN. Using mutagenesis analysis to explore a possible impact of this mutual control on astrocyte growth, we found that truncation of the C-terminal region of PTEN (Δ51) associates with a marked increase in NFκB activity, a transcription factor overactivated in astrocyte tumors. Whereas mutations of PTEN are considered to lead to a loss-of-function, PTENΔ51, a truncation that comprises a region frequently mutated in human gliomas, displayed a neomorphic (gain-of-function) activity that was independent of its phosphatase activity. This gain-of-function of PTENΔ51 includes stimulation of IGF-1 synthesis through protein kinase A activation of the IGF-1 promoter. Increased IGF-1 originates an autocrine loop that activates Akt and NFκB. Constitutive activation of NFκB in PTENΔ51-expressing astrocytes leads to aberrant cell growth; astrocytes expressing this mutant PTEN generate colonies in vitro and tumors in vivo. Mutations converting a tumor suppressor such as PTEN into a tumor promoter through a gain-of-function involving IGF-1 production may further our understanding of the role played by this growth factor in glioma growth and help us define druggable targets for personalized therapy.

  1. DNA Topoisomerase 1 Prevents R-loop Accumulation to Modulate Auxin-Regulated Root Development in Rice.

    Science.gov (United States)

    Shafiq, Sarfraz; Chen, Chunli; Yang, Jing; Cheng, Lingling; Ma, Fei; Widemann, Emilie; Sun, Qianwen

    2017-06-05

    R-loop structures (RNA:DNA hybrids) have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA topoisomerase 1 (TOP1), an essential manipulator of DNA topology during RNA transcription and DNA replication processes, can prevent R-loop accumulation by removing the positive and negative DNA supercoiling that is made by RNA polymerases during transcription. TOP1 is required for plant development, but little is known about its function in preventing co-transcriptional R-loop accumulation in various biological processes in plants. Here we show that knockdown of OsTOP1 strongly affects rice development, causing defects in root architecture and gravitropism, which are the consequences of misregulation of auxin signaling and transporter genes. We found that R-loops are naturally formed at rice auxin-related gene loci, and overaccumulate when OsTOP1 is knocked down or OsTOP1 protein activity is inhibited. OsTOP1 therefore sets the accurate expression levels of auxin-related genes by preventing the overaccumulation of inherent R-loops. Our data reveal R-loops as important factors in polar auxin transport and plant root development, and highlight that OsTOP1 functions as a key to link transcriptional R-loops with plant hormone signaling, provide new insights into transcriptional regulation of hormone signaling in plants. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  2. Functional and evolutionary correlates of gene constellations in the Drosophila melanogaster genome that deviate from the stereotypical gene architecture

    Directory of Open Access Journals (Sweden)

    Kohn Michael H

    2010-05-01

    Full Text Available Abstract Background The biological dimensions of genes are manifold. These include genomic properties, (e.g., X/autosomal linkage, recombination and functional properties (e.g., expression level, tissue specificity. Multiple properties, each generally of subtle influence individually, may affect the evolution of genes or merely be (auto-correlates. Results of multidimensional analyses may reveal the relative importance of these properties on the evolution of genes, and therefore help evaluate whether these properties should be considered during analyses. While numerous properties are now considered during studies, most work still assumes the stereotypical solitary gene as commonly depicted in textbooks. Here, we investigate the Drosophila melanogaster genome to determine whether deviations from the stereotypical gene architecture correlate with other properties of genes. Results Deviations from the stereotypical gene architecture were classified as the following gene constellations: Overlapping genes were defined as those that overlap in the 5-prime, exonic, or intronic regions. Chromatin co-clustering genes were defined as genes that co-clustered within 20 kb of transcriptional territories. If this scheme is applied the stereotypical gene emerges as a rare occurrence (7.5%, slightly varied schemes yielded between ~1%-50%. Moreover, when following our scheme, paired-overlapping genes and chromatin co-clustering genes accounted for 50.1 and 42.4% of the genes analyzed, respectively. Gene constellation was a correlate of a number of functional and evolutionary properties of genes, but its statistical effect was ~1-2 orders of magnitude lower than the effects of recombination, chromosome linkage and protein function. Analysis of datasets on male reproductive proteins showed these were biased in their representation of gene constellations and evolutionary rate Ka/Ks estimates, but these biases did not overwhelm the biologically meaningful

  3. The importance of hinge sequence for loop function and catalytic activity in the reaction catalyzed by triosephosphate isomerase.

    Science.gov (United States)

    Xiang, J; Sun, J; Sampson, N S

    2001-04-01

    We have determined the sequence requirements for the N-terminal protein hinge of the active-site lid of triosephosphate isomerase. The codons for the hinge (PVW) were replaced with a genetic library of all possible 8000 amino acid combinations. The most active of these 8000 mutants were selected using in vivo complementation of a triosephosphate isomerase-deficient strain of Escherichia coli, DF502. Approximately 0.3 % of the mutants complement DF502 with an activity that is between 10 and 70 % of wild-type activity. They all contain Pro at the first position. Furthermore, the sequences of these hinge mutants reveal that hydrophobic packing is very important for efficient formation of the enediol intermediate. However, the reduced catalytic activities observed are not due to increased rates of loop opening. To explore the relationship between the N-terminal and C-terminal hinges, three semi-active mutants from the N-terminal hinge selection experiment (PLH, PHS and PTF), and six active C-terminal hinge mutants from previous work (NSS, LWA, YSL, KTK, NPN, KVA) were combined to form 18 "double-hinge" mutants. The activities of these mutants suggest that the N-terminal and C-terminal hinge structures affect one another. It appears that specific side-chain interactions are important for forming a catalytically active enzyme, but not for preventing release of the unstable enediol intermediate from the active site of the enzyme. The independence of intermediate release on amino acid sequence is consistent with the absence of a "universal" hinge sequence in structurally related enzymes.

  4. Alternative loop rings

    CERN Document Server

    Goodaire, EG; Polcino Milies, C

    1996-01-01

    For the past ten years, alternative loop rings have intrigued mathematicians from a wide cross-section of modern algebra. As a consequence, the theory of alternative loop rings has grown tremendously. One of the main developments is the complete characterization of loops which have an alternative but not associative, loop ring. Furthermore, there is a very close relationship between the algebraic structures of loop rings and of group rings over 2-groups. Another major topic of research is the study of the unit loop of the integral loop ring. Here the interaction between loop rings and group ri

  5. Hyd5 gene-based detection of the major gushing-inducing Fusarium spp. in a loop-mediated isothermal amplification (LAMP) assay.

    Science.gov (United States)

    Denschlag, Carla; Vogel, Rudi F; Niessen, Ludwig

    2012-06-01

    Fusarium graminearum and the closely related F. culmorum were found to be associated with over foaming of bottled beer (gushing) when contaminated brewing malt is used. The presence of highly surface active hydrophobins produced by these fungi upon growth on wheat or barley in the field or during malting may affect bubble formation and stability in gushing beers and other carbonated beverages. Aiming for a method for the rapid and user friendly analysis of unmalted and malted cereals during quality control in the brewing industry, a loop-mediated isothermal amplification (LAMP) assay for the detection of Fusarium spp. capable of producing the gushing inducing hydrophobin Hyd5p was set up. A set of primers was designed towards a 221 bp region within the hyd5 gene of F. culmorum. The LAMP product was verified by sequencing a 150 bp portion. Testing specificity with purified DNA from 99 different fungal species as well as barley and wheat showed that DNA synthesis only occurred during LAMP when DNA of the closely related species F. graminearum, F. culmorum, F. cerealis and F. lunulosporum were used as template. In-tube indirect detection of DNA amplification was applied using manganese-quenched calcein as fluorescence indicator for pyrophosphate produced during DNA synthesis. The assay had a detection limit of 0.74 pg of purified target DNA which corresponds 20 copy numbers per reaction within 30 minutes using a simple heating block. Analysis of Fusarium infected cereals revealed that the assay was able to detect F. graminearum at a level of 0.5% of infected grains in uninfected barley by analysis of surface washings without further sample preparation. Results show that the hyd5 based LAMP assay can be a rapid, useful and sensitive tool for quality control in the brewing and malting industry.

  6. Wilson Loops in Open String Theory

    Science.gov (United States)

    Shiraishi, Kiyoshi

    Wilson loop elements on torus are introduced into the partition function of open strings as Polyakov’s path integral at one-loop level. Mass spectra from compactification and expected symmetry breaking are illustrated by choosing the correct weight for the contributions from annulus and Möbius strip. We show that Jacobi’s imaginary transformation connects the mass spectra with the Wilson loops. The application to thermopartition function and cosmological implications are briefly discussed.

  7. Wilson Loops in Open String Theory

    CERN Document Server

    Shiraishi, Kiyoshi

    2012-01-01

    Wilson loop elements on torus are introduced into the partition function of open strings as Polyakov's path integral at one-loop level. Mass spectra from compactification and expected symmetry breaking are illustrated by choosing the correct weight for the contributions from annulus and M\\"obius strip. We show that Jacobi's imaginary transformation connects the mass spectra with the Wilson loops. The application to thermopartition function and cosmological implications are briefly discussed.

  8. Expression and function of Dlx genes in the osteoblast lineage.

    Science.gov (United States)

    Li, Haitao; Marijanovic, Inga; Kronenberg, Mark S; Erceg, Ivana; Stover, Mary Louise; Velonis, Dimitrios; Mina, Mina; Heinrich, Jelica Gluhak; Harris, Stephen E; Upholt, William B; Kalajzic, Ivo; Lichtler, Alexander C

    2008-04-15

    Our laboratory and others have shown that overexpression of Dlx5 stimulates osteoblast differentiation. Dlx5(-/-)/Dlx6(-/-) mice have more severe craniofacial and limb defects than Dlx5(-/-), some of which are potentially due to defects in osteoblast maturation. We wished to investigate the degree to which other Dlx genes compensate for the lack of Dlx5, thus allowing normal development of the majority of skeletal elements in Dlx5(-/-) mice. Dlx gene expression in cells from different stages of the osteoblast lineage isolated by FACS sorting showed that Dlx2, Dlx5 and Dlx6 are expressed most strongly in less mature osteoblasts, whereas Dlx3 is very highly expressed in differentiated osteoblasts and osteocytes. In situ hybridization and Northern blot analysis demonstrated the presence of endogenous Dlx3 mRNA within osteoblasts and osteocytes. Dlx3 strongly upregulates osteoblastic markers with a potency comparable to Dlx5. Cloned chick or mouse Dlx6 showed stimulatory effects on osteoblast differentiation. Our results suggest that Dlx2 and Dlx6 have the potential to stimulate osteoblastic differentiation and may compensate for the absence of Dlx5 to produce relatively normal osteoblastic differentiation in Dlx5 knockout mice, while Dlx3 may play a distinct role in late stage osteoblast differentiation and osteocyte function.

  9. Expression and function of FERMT genes in colon carcinoma cells.

    Science.gov (United States)

    Kiriyama, Kenji; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Kubo, Terufumi; Tamura, Yasuaki; Kanaseki, Takayuki; Takahashi, Akari; Nakazawa, Emiri; Saka, Eri; Ragnarsson, Charlotte; Nakatsugawa, Munehide; Inoda, Satoko; Asanuma, Hiroko; Takasu, Hideo; Hasegawa, Tadashi; Yasoshima, Takahiro; Hirata, Koichi; Sato, Noriyuki

    2013-01-01

    Invasion into the matrix is one of hallmarks of malignant diseases and is the first step for tumor metastasis. Thus, analysis of the molecular mechanisms of invasion is essential to overcome tumor cell invasion. In the present study, we screened for colon carcinoma-specific genes using a cDNA microarray database of colon carcinoma tissues and normal colon tissues, and we found that fermitin family member-1 (FERMT1) is overexpressed in colon carcinoma cells. FRRMT1, FERMT2 and FERMT3 expression was investigated in colon carcinoma cells. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that only FERMT1 had cancer cell-specific expression. Protein expression of FERMT1 was confirmed by western blotting and immunohistochemical staining. To address the molecular functions of FERMT genes in colon carcinoma cells, we established FERMT1-, FERMT2- and FERMT3-overexpressing colon carcinoma cells. FERMT1-overexpressing cells exhibited greater invasive ability than did FERMT2- and FERMT3-overexpressing cells. On the other hand, FERMT1-, FERMT2- and FERMT3-overexpressing cells exhibited enhancement of cell growth. Taken together, the results of this study indicate that FERMT1 is expressed specifically in colon carcinoma cells, and has roles in matrix invasion and cell growth. These findings indicate that FERMT1 is a potential molecular target for cancer therapy.

  10. From Gene Regulation to Gene Function: Regulatory Networks in Bacillus Subtilis

    Directory of Open Access Journals (Sweden)

    Ivan Moszer

    2006-04-01

    Full Text Available Bacillus subtilis is a sporulating Gram-positive bacterium that lives primarily in the soil and associated water sources. The publication of the B. subtilis genome sequence and subsequent systematic functional analysis and gene regulation programmes, together with an extensive understanding of its biochemistry and physiology, makes this micro-organism a prime candidate in which to model regulatory networks in silico. In this paper we discuss combined molecular biological and bioinformatical approaches that are being developed to model this organism’s responses to changes in its environment.

  11. fabp4 is central to eight obesity associated genes: a functional gene network-based polymorphic study.

    Science.gov (United States)

    Bag, Susmita; Ramaiah, Sudha; Anbarasu, Anand

    2015-01-07

    Network study on genes and proteins offers functional basics of the complexity of gene and protein, and its interacting partners. The gene fatty acid-binding protein 4 (fabp4) is found to be highly expressed in adipose tissue, and is one of the most abundant proteins in mature adipocytes. Our investigations on functional modules of fabp4 provide useful information on the functional genes interacting with fabp4, their biochemical properties and their regulatory functions. The present study shows that there are eight set of candidate genes: acp1, ext2, insr, lipe, ostf1, sncg, usp15, and vim that are strongly and functionally linked up with fabp4. Gene ontological analysis of network modules of fabp4 provides an explicit idea on the functional aspect of fabp4 and its interacting nodes. The hierarchal mapping on gene ontology indicates gene specific processes and functions as well as their compartmentalization in tissues. The fabp4 along with its interacting genes are involved in lipid metabolic activity and are integrated in multi-cellular processes of tissues and organs. They also have important protein/enzyme binding activity. Our study elucidated disease-associated nsSNP prediction for fabp4 and it is interesting to note that there are four rsID׳s (rs1051231, rs3204631, rs140925685 and rs141169989) with disease allelic variation (T104P, T126P, G27D and G90V respectively). On the whole, our gene network analysis presents a clear insight about the interactions and functions associated with fabp4 gene network. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Rapid, simple, and sensitive detection of the ompB gene of spotted fever group rickettsiae by loop-mediated isothermal amplification

    Directory of Open Access Journals (Sweden)

    Pan Lei

    2012-10-01

    Full Text Available Abstract Background Spotted fever caused spotted fever group rickettsiae (SFGR is prevalent throughout China. In this study, we describe a rapid, simple, and sensitive loop-mediated isothermal amplification (LAMP assay targeting the ompB gene of spotted fever group rickettsiae ideal for application in China. The LAMP assay has the potential to detect spotted fever group rickettsiae early in infection and could therefore serve as an alternative to existing methods. Methods A set of universal primers which are specific 7 common species of spotted fever group rickettsiae in China were designed using PrimerExplorer V4 software based on conserved sequences of ompB gene. The sensitivity, specificity and reproducibility of the LAMP were evaluated. The LAMP assay for detecting SFGR was compared with conventional PCR assays for sensitivity and specificity in early phase blood samples obtained from 11 infected human subjects. Results The sensitivity of the LAMP assay was five copies per reaction (25 μL total volume, and the assay did not detect false-positive amplification across 42 strains of 27 members of the order Rickettsiales and 17 common clinical pathogens. The LAMP assay was negative to typhus group rickettsiae including R. prowazekii and R. typhi for no available conserved sequences of ompB was obtained for designing primers. To evaluate the clinical applicability of the LAMP assay, a total of 11 clinical samples, 10 samples confirmed serologically (3 cases, ecologically (1 case, by real-time polymerase chain reaction (PCR; 2 cases, ecologically and by real-time PCR (1 case, and serologically and by real-time PCR (3 cases were analyzed by the ompB LAMP assay. Data were validated using a previously established nested PCR protocol and real-time PCR. A positive LAMP result was obtained for 8 of the 10 confirmed cases (sensitivity, 73%; specificity, 100%, while none of these samples were positive by nested PCR (sensitivity, 0%; specificity, 100

  13. Loop-mediated isothermal amplification assay targeting the blaCTX-M9 gene for detection of extended spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

    Science.gov (United States)

    Thirapanmethee, Krit; Pothisamutyothin, Kanokporn; Nathisuwan, Surakit; Chomnawang, Mullika T; Wiwat, Chanpen

    2014-12-01

    Extended-spectrum β-lactamases (ESBLs) produced by Enterobacteriaceae are one of the resistance mechanisms to most β-lactam antibiotics. ESBLs are currently a major problem in both hospitals and community settings worldwide. Rapid and reliable means of detecting ESBL-producing bacteria is necessary for identification, prevention and treatment. Loop-mediated isothermal amplification (LAMP) is a technique that rapidly amplifies DNA with high specificity and sensitivity under isothermal conditions. This study was aimed to develop a convenient, accurate and inexpensive method for detecting ESBL-producing bacteria by a LAMP technique. ESBLs-producing Escherichia coli and Klebsiella pneumoniae were isolated from a tertiary hospital in Bangkok, Thailand and reconfirmed by double-disk synergy test. A set of four specific oligonucleotide primers of LAMP for detection of bla(CTX-M9) gene was designed based on bla(CTX-M9) from E. coli (GenBank Accession No. AJ416345). The LAMP reaction was amplified under isothermal temperature at 63°C for 60 min. Ladder-like patterns of band sizes from 226 bp of the bla(CTX-M9) DNA target was observed. The LAMP product was further analyzed by restriction digestion with MboI and TaqI endonucleases. The fragments generated were approximately 168, 177 and 250 bp in size for MboI digestion and 165, 193, 229, 281 and 314 bp for TaqI digestion, which is in agreement with the predicted sizes. The sensitivity of the LAMP technique to bla(CTX-M9) was greater than that of the PCR method by at least 10,000-fold. These results showed that the LAMP primers specifically amplified only the bla(CTX-M9) gene. Moreover, the presence of LAMP amplicon was simply determined by adding SYBR Green I in the reaction. In conclusion, this technique for detection of ESBLs is convenient, reliable and easy to perform routinely in hospitals or laboratory units in developing countries.

  14. Data Integration and Applications of Functional Gene Networks in Drosophila Melanogaster

    Science.gov (United States)

    Costello, James Christopher

    2009-01-01

    Understanding the function of every gene in the genome is a central goal in the biological sciences. This includes full characterization of a genes phenotypic effects, molecular interactions, the evolutionary forces that shape its function(s), and how these functions interrelate. Despite a long history and considerable effort to understand all…

  15. Data Integration and Applications of Functional Gene Networks in Drosophila Melanogaster

    Science.gov (United States)

    Costello, James Christopher

    2009-01-01

    Understanding the function of every gene in the genome is a central goal in the biological sciences. This includes full characterization of a genes phenotypic effects, molecular interactions, the evolutionary forces that shape its function(s), and how these functions interrelate. Despite a long history and considerable effort to understand all…

  16. Xenobiotic transporters: ascribing function from gene knockout and mutation studies.

    Science.gov (United States)

    Klaassen, Curtis D; Lu, Hong

    2008-02-01

    Transporter-mediated absorption, secretion, and reabsorption of chemicals are increasingly recognized as important determinants in the biological activities of many xenobiotics. In recent years, the rapid progress in generating and characterizing mice with targeted deletion of transporters has greatly increased our knowledge of the functions of transporters in the pharmacokinetics/toxicokinetics of xenobiotics. In this introduction, we focus on functions of transporters learned from experiments on knockout mice as well as humans and rodents with natural mutations of these transporters. We limit our discussion to transporters that either directly transport xenobiotics or are important in biliary excretion or cellular defenses, namely multidrug resistance, multidrug resistance-associated proteins, breast cancer resistance protein, organic anion transporting polypeptides, organic anion transporters, organic cation transporters, nucleoside transporters, peptide transporters, bile acid transporters, cholesterol transporters, and phospholipid transporters, as well as metal transporters. Efflux transporters in intestine, liver, kidney, brain, testes, and placenta can efflux xenobiotics out of cells and serve as barriers against the entrance of xenobiotics into cells, whereas many xenobiotics enter the biological system via uptake transporters. The functional importance of a given transporter in each tissue depends on its substrate specificity, expression level, and the presence/absence of other transporters with overlapping substrate preferences. Nevertheless, a transporter may affect a tissue independent of its local expression by altering systemic metabolism. Further studies on the gene regulation and function of transporters, as well as the interrelationship between transporters and phase I/II xenobiotic-metabolizing enzymes, will provide a complete framework for developing novel strategies to protect us from xenobiotic insults.

  17. A transforming ras gene can provide an essential function ordinarily supplied by an endogenous ras gene

    DEFF Research Database (Denmark)

    Papageorge, A G; Willumsen, B M; Johnsen, M;

    1986-01-01

    Microinjection of monoclonal antibody Y13-259, which reacts with all known mammalian and yeast ras-encoded proteins, has previously been shown to prevent NIH 3T3 cells from entering the S phase (L. S. Mulcahy, M. R. Smith, and D. W. Stacey, Nature [London] 313:241-243, 1985). We have now found...... several transformation-competent mutant v-rasH genes whose protein products in transformed NIH 3T3 cells are not immunoprecipitated by this monoclonal antibody. These mutant proteins are, however, precipitated by a different anti-ras antibody. Each of these mutants lacks Met-72 of v-rasH. In contrast...... to the result for cells transformed by wild-type v-rasH, Y13-259 microinjection of NIH 3T3 cells transformed by these mutant ras genes did not prevent the cells from entering the S phase. These results imply that a transformation-competent ras gene can supply a normal essential function for NIH 3T3 cells. When...

  18. Functional evolution of ADAMTS genes: Evidence from analyses of phylogeny and gene organization

    Directory of Open Access Journals (Sweden)

    Van Meir Erwin G

    2005-02-01

    Full Text Available Abstract Background The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndromes Weill-Marchesani syndrome (ADAMTS10, thrombotic thrombocytopenic purpura (ADAMTS13, and Ehlers-Danlos syndrome type VIIC (ADAMTS2 in humans and belted white-spotting mutation in mice (ADAMTS20. Results Phylogenetic analysis and comparison of the exon/intron organization of vertebrate (Homo, Mus, Fugu, chordate (Ciona and invertebrate (Drosophila and Caenorhabditis ADAMTS homologs has elucidated the evolutionary relationships of this important gene family, which comprises 19 members in humans. Conclusions The evolutionary history of ADAMTS genes in vertebrate genomes has been marked by rampant gene duplication, including a retrotransposition that gave rise to a distinct ADAMTS subfamily (ADAMTS1, -4, -5, -8, -15 that may have distinct aggrecanase and angiogenesis functions.

  19. Verification of Loop Diagnostics

    Science.gov (United States)

    Winebarger, A.; Lionello, R.; Mok, Y.; Linker, J.; Mikic, Z.

    2014-01-01

    Many different techniques have been used to characterize the plasma in the solar corona: density-sensitive spectral line ratios are used to infer the density, the evolution of coronal structures in different passbands is used to infer the temperature evolution, and the simultaneous intensities measured in multiple passbands are used to determine the emission measure. All these analysis techniques assume that the intensity of the structures can be isolated through background subtraction. In this paper, we use simulated observations from a 3D hydrodynamic simulation of a coronal active region to verify these diagnostics. The density and temperature from the simulation are used to generate images in several passbands and spectral lines. We identify loop structures in the simulated images and calculate the loop background. We then determine the density, temperature and emission measure distribution as a function of time from the observations and compare with the true temperature and density of the loop. We find that the overall characteristics of the temperature, density, and emission measure are recovered by the analysis methods, but the details of the true temperature and density are not. For instance, the emission measure curves calculated from the simulated observations are much broader than the true emission measure distribution, though the average temperature evolution is similar. These differences are due, in part, to inadequate background subtraction, but also indicate a limitation of the analysis methods.

  20. Hox in frogs : xenopus reveals novel functions for vertebrate hoz genes

    NARCIS (Netherlands)

    Bardine, Nabila

    2008-01-01

    Hox genes are a very important family of transcription factors during development of vertebrate and invertebrates. This family of genes contains up to 39 Hox gene members organized in 4 clusters in the genome. The main function of Hox genes is the establishment of the anteroposterior axis of the emb

  1. A Network Partition Algorithm for Mining Gene Functional Modules of Colon Cancer from DNA Microarray Data

    Institute of Scientific and Technical Information of China (English)

    Xiao-Gang Ruan; Jin-Lian Wang; Jian-Geng Li

    2006-01-01

    Computational analysis is essential for transforming the masses of microarray data into a mechanistic understanding of cancer. Here we present a method for finding gene functional modules of cancer from microarray data and have applied it to colon cancer. First, a colon cancer gene network and a normal colon tissue gene network were constructed using correlations between the genes. Then the modules that tended to have a homogeneous functional composition were identified by splitting up the network. Analysis of both networks revealed that they are scale-free.Comparison of the gene functional modules for colon cancer and normal tissues showed that the modules' functions changed with their structures.

  2. Loop Quantum Cosmology

    Directory of Open Access Journals (Sweden)

    Bojowald Martin

    2008-07-01

    Full Text Available Quantum gravity is expected to be necessary in order to understand situations in which classical general relativity breaks down. In particular in cosmology one has to deal with initial singularities, i.e., the fact that the backward evolution of a classical spacetime inevitably comes to an end after a finite amount of proper time. This presents a breakdown of the classical picture and requires an extended theory for a meaningful description. Since small length scales and high curvatures are involved, quantum effects must play a role. Not only the singularity itself but also the surrounding spacetime is then modified. One particular theory is loop quantum cosmology, an application of loop quantum gravity to homogeneous systems, which removes classical singularities. Its implications can be studied at different levels. The main effects are introduced into effective classical equations, which allow one to avoid the interpretational problems of quantum theory. They give rise to new kinds of early-universe phenomenology with applications to inflation and cyclic models. To resolve classical singularities and to understand the structure of geometry around them, the quantum description is necessary. Classical evolution is then replaced by a difference equation for a wave function, which allows an extension of quantum spacetime beyond classical singularities. One main question is how these homogeneous scenarios are related to full loop quantum gravity, which can be dealt with at the level of distributional symmetric states. Finally, the new structure of spacetime arising in loop quantum gravity and its application to cosmology sheds light on more general issues, such as the nature of time.

  3. Loop Quantum Cosmology

    Directory of Open Access Journals (Sweden)

    Bojowald Martin

    2005-12-01

    Full Text Available Quantum gravity is expected to be necessary in order to understand situations where classical general relativity breaks down. In particular in cosmology one has to deal with initial singularities, i.e., the fact that the backward evolution of a classical space-time inevitably comes to an end after a finite amount of proper time. This presents a breakdown of the classical picture and requires an extended theory for a meaningful description. Since small length scales and high curvatures are involved, quantum effects must play a role. Not only the singularity itself but also the surrounding space-time is then modified. One particular realization is loop quantum cosmology, an application of loop quantum gravity to homogeneous systems, which removes classical singularities. Its implications can be studied at different levels. Main effects are introduced into effective classical equations which allow to avoid interpretational problems of quantum theory. They give rise to new kinds of early universe phenomenology with applications to inflation and cyclic models. To resolve classical singularities and to understand the structure of geometry around them, the quantum description is necessary. Classical evolution is then replaced by a difference equation for a wave function which allows to extend space-time beyond classical singularities. One main question is how these homogeneous scenarios are related to full loop quantum gravity, which can be dealt with at the level of distributional symmetric states. Finally, the new structure of space-time arising in loop quantum gravity and its application to cosmology sheds new light on more general issues such as time.

  4. Molecular characterization and gene functional analysis of Dicer-2 gene from Nilaparvata lugens(Hemiptera:Geometroidea)

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yi Zhang; Kai Lu; Jia-Liang Zhou; Qiang Zhou

    2013-01-01

    Nilaparvata lugens(St((A)l)(Hemiptera: Geometroidea),a serious rice pest in many countries of Asia,causes a great loss in rice production every year.RNA interference (RNAi)is a powerful technology for gene function study in insects and a potential tool for pest control.As a core component of RNAi pathway,Dicer-2(Dcr-2)protein determines the production of small interfering RNA(siRNA)and is crucial for the efficiency of RNAi.In this study,the full-length complementary DNA(cDNA)ofN.lugens Dcr-2(NlDcr-2)was first cloned and analyzed,and then the RNAi experiment was conducted to explore the function of NIDcr-2 gene.The complete Dcr-2 cDNA ofN.lugens was 4971 bp in length with an open reading frame(ORF)of 1,656 amino acids.Phylogenetic and protein domain analysis showed that the predicted NlDcr-2 protein was similar to Tribolium castaneum.In the RNAi experiment,the messenger RNA level of NIDcr-2 was significantly reduced by NlDcr-2double-stranded RNA(dsRNA)(dsDcr-2).Fifty-five per cent decrease of NlDcr-2 was found after 4 days of unremitting feeding.No significant effect was observed on the development ofN.lugens after dsRNA ingestion.

  5. GeneViTo: Visualizing gene-product functional and structural features in genomic datasets

    Directory of Open Access Journals (Sweden)

    Promponas Vasilis J

    2003-10-01

    Full Text Available Abstract Background The availability of increasing amounts of sequence data from completely sequenced genomes boosts the development of new computational methods for automated genome annotation and comparative genomics. Therefore, there is a need for tools that facilitate the visualization of raw data and results produced by bioinformatics analysis, providing new means for interactive genome exploration. Visual inspection can be used as a basis to assess the quality of various analysis algorithms and to aid in-depth genomic studies. Results GeneViTo is a JAVA-based computer application that serves as a workbench for genome-wide analysis through visual interaction. The application deals with various experimental information concerning both DNA and protein sequences (derived from public sequence databases or proprietary data sources and meta-data obtained by various prediction algorithms, classification schemes or user-defined features. Interaction with a Graphical User Interface (GUI allows easy extraction of genomic and proteomic data referring to the sequence itself, sequence features, or general structural and functional features. Emphasis is laid on the potential comparison between annotation and prediction data in order to offer a supplement to the provided information, especially in cases of "poor" annotation, or an evaluation of available predictions. Moreover, desired information can be output in high quality JPEG image files for further elaboration and scientific use. A compilation of properly formatted GeneViTo input data for demonstration is available to interested readers for two completely sequenced prokaryotes, Chlamydia trachomatis and Methanococcus jannaschii. Conclusions GeneViTo offers an inspectional view of genomic functional elements, concerning data stemming both from database annotation and analysis tools for an overall analysis of existing genomes. The application is compatible with Linux or Windows ME-2000-XP operating

  6. The extended loop representation of quantum gravity

    CERN Document Server

    Di Bartolo, C; Griego, J R

    1995-01-01

    A new representation of Quantum Gravity is developed. This formulation is based on an extension of the group of loops. The enlarged group, that we call the Extended Loop Group, behaves locally as an infinite dimensional Lie group. Quantum Gravity can be realized on the state space of extended loop dependent wavefunctions. The extended representation generalizes the loop representation and contains this representation as a particular case. The resulting diffeomorphism and hamiltonian constraints take a very simple form and allow to apply functional methods and simplify the loop calculus. In particular we show that the constraints are linear in the momenta. The nondegenerate solutions known in the loop representation are also solutions of the constraints in the new representation. The practical calculation advantages allows to find a new solution to the Wheeler-DeWitt equation. Moreover, the extended representation puts in a precise framework some of the regularization problems of the loop representation. We sh...

  7. DELLA genes restrict inflorescence meristem function independently of plant height.

    Science.gov (United States)

    Serrano-Mislata, Antonio; Bencivenga, Stefano; Bush, Max; Schiessl, Katharina; Boden, Scott; Sablowski, Robert

    2017-08-21

    DELLA proteins associate with transcription factors to control plant growth in response to gibberellin (1) . Semi-dwarf DELLA mutants with improved harvest index and decreased lodging greatly improved global food security during the 'green revolution' in the 1960-1970s (2) . However, DELLA mutants are pleiotropic and the developmental basis for their effects on plant architecture remains poorly understood. Here, we show that DELLA proteins have genetically separable roles in controlling stem growth and the size of the inflorescence meristem, where flowers initiate. Quantitative three-dimensional image analysis, combined with a genome-wide screen for DELLA-bound loci in the inflorescence tip, revealed that DELLAs limit meristem size in Arabidopsis by directly upregulating the cell-cycle inhibitor KRP2 in the underlying rib meristem, without affecting the canonical WUSCHEL-CLAVATA meristem size regulators (3) . Mutation of KRP2 in a DELLA semi-dwarf background restored meristem size, but not stem growth, and accelerated flower production. In barley, secondary mutations in the DELLA gain-of-function mutant Sln1d (4) also uncoupled meristem and inflorescence size from plant height. Our work reveals an unexpected and conserved role for DELLA genes in controlling shoot meristem function and suggests how dissection of pleiotropic DELLA functions could unlock further yield gains in semi-dwarf mutants.During gibberellic acid signalling, DELLAs restrict the size of the shoot apical meristem by targeting the cell cycle regulator KRP2. The roles of DELLAs in the shoot apical meristem and stem growth can be genetically uncoupled in Arabidopsis and barley.

  8. Rationale for developing new virus vectors to analyze gene function in grasses through virus-induced gene silencing.

    Science.gov (United States)

    Ramanna, Hema; Ding, Xin Shun; Nelson, Richard S

    2013-01-01

    The exploding availability of genome and EST-based sequences from grasses requires a technology that allows rapid functional analysis of the multitude of genes that these resources provide. There are several techniques available to determine a gene's function. For gene knockdown studies, silencing through RNAi is a powerful tool. Gene silencing can be accomplished through stable transformation or transient expression of a fragment of a target gene sequence. Stable transformation in rice, maize, and a few other species, although routine, remains a relatively low-throughput process. Transformation in other grass species is difficult and labor-intensive. Therefore, transient gene silencing methods including Agrobacterium-mediated and virus-induced gene silencing (VIGS) have great potential for researchers studying gene function in grasses. VIGS in grasses already has been used to determine the function of genes during pathogen challenge and plant development. It also can be used in moderate-throughput reverse genetics screens to determine gene function. However, the number of viruses modified to serve as silencing vectors in grasses is limited, and the silencing phenotype induced by these vectors is not optimal: the phenotype being transient and with moderate penetration throughout the tissue. Here, we review the most recent information available for VIGS in grasses and summarize the strengths and weaknesses in current virus-grass host systems. We describe ways to improve current virus vectors and the potential of other grass-infecting viruses for VIGS studies. This work is necessary because VIGS for the foreseeable future remains a higher throughput and more rapid system to evaluate gene function than stable transformation.

  9. (TG/CAn repeats in human gene families: abundance and selective patterns of distribution according to function and gene length

    Directory of Open Access Journals (Sweden)

    Ramachandran Srinivasan

    2005-06-01

    Full Text Available Abstract Background Creation of human gene families was facilitated significantly by gene duplication and diversification. The (TG/CAn repeats exhibit length variability, display genome-wide distribution, and are abundant in the human genome. Accumulation of evidences for their multiple functional roles including regulation of transcription and stimulation of recombination and splicing elect them as functional elements. Here, we report analysis of the distribution of (TG/CAn repeats in human gene families. Results The 1,317 human gene families were classified into six functional classes. Distribution of (TG/CAn repeats were analyzed both from a global perspective and from a stratified perspective based on their biological properties. The number of genes with repeats decreased with increasing repeat length and several genes (53% had repeats of multiple types in various combinations. Repeats were positively associated with the class of Signaling and communication whereas, they were negatively associated with the classes of Immune and related functions and of Information. The proportion of genes with (TG/CAn repeats in each class was proportional to the corresponding average gene length. The repeat distribution pattern in large gene families generally mirrored the global distribution pattern but differed particularly for Collagen gene family, which was rich in repeats. The position and flanking sequences of the repeats of Collagen genes showed high conservation in the Chimpanzee genome. However the majority of these repeats displayed length polymorphism. Conclusion Positive association of repeats with genes of Signaling and communication points to their role in modulation of transcription. Negative association of repeats in genes of Information relates to the smaller gene length, higher expression and fundamental role in cellular physiology. In genes of Immune and related functions negative association of repeats perhaps relates to the smaller gene

  10. Functional gene composition, diversity and redundancy in microbial stream biofilm communities.

    Directory of Open Access Journals (Sweden)

    Andrew Dopheide

    Full Text Available We surveyed the functional gene composition and diversity of microbial biofilm communities in 18 New Zealand streams affected by different types of catchment land use, using a comprehensive functional gene array, GeoChip 3.0. A total of 5,371 nutrient cycling and energy metabolism genes within 65 gene families were detected among all samples (342 to 2,666 genes per stream. Carbon cycling genes were most common, followed by nitrogen cycling genes, with smaller proportions of sulphur, phosphorus cycling and energy metabolism genes. Samples from urban and native forest streams had the most similar functional gene composition, while samples from exotic forest and rural streams exhibited the most variation. There were significant differences between nitrogen and sulphur cycling genes detected in native forest and urban samples compared to exotic forest and rural samples, attributed to contrasting proportions of nitrogen fixation, denitrification, and sulphur reduction genes. Most genes were detected only in one or a few samples, with only a small minority occurring in all samples. Nonetheless, 42 of 65 gene families occurred in every sample and overall proportions of gene families were similar among samples from contrasting streams. This suggests the existence of functional gene redundancy among different stream biofilm communities despite contrasting taxonomic composition.

  11. Functional gene composition, diversity and redundancy in microbial stream biofilm communities.

    Science.gov (United States)

    Dopheide, Andrew; Lear, Gavin; He, Zhili; Zhou, Jizhong; Lewis, Gillian D

    2015-01-01

    We surveyed the functional gene composition and diversity of microbial biofilm communities in 18 New Zealand streams affected by different types of catchment land use, using a comprehensive functional gene array, GeoChip 3.0. A total of 5,371 nutrient cycling and energy metabolism genes within 65 gene families were detected among all samples (342 to 2,666 genes per stream). Carbon cycling genes were most common, followed by nitrogen cycling genes, with smaller proportions of sulphur, phosphorus cycling and energy metabolism genes. Samples from urban and native forest streams had the most similar functional gene composition, while samples from exotic forest and rural streams exhibited the most variation. There were significant differences between nitrogen and sulphur cycling genes detected in native forest and urban samples compared to exotic forest and rural samples, attributed to contrasting proportions of nitrogen fixation, denitrification, and sulphur reduction genes. Most genes were detected only in one or a few samples, with only a small minority occurring in all samples. Nonetheless, 42 of 65 gene families occurred in every sample and overall proportions of gene families were similar among samples from contrasting streams. This suggests the existence of functional gene redundancy among different stream biofilm communities despite contrasting taxonomic composition.

  12. Functional Haplotypes in Interleukin 4 Gene Associated with Periodontitis

    Science.gov (United States)

    Mayer, Marcia Pinto Alves; Rossa, Carlos

    2017-01-01

    Chronic periodontitis (CP) is an infectious inflammatory disease that affects tooth-supporting structures and in which dental plaque bacteria, immune mechanisms and genetic predisposition play important roles. Interleukin 4 (IL-4) is a key anti-inflammatory cytokine with relevant action in imbalances in inflamed periodontal tissue. Individuals carrying the TCI/CCI genotype (S-haplotype) of the IL-4 gene are 5 times more susceptible to CP, whereas the CTI/TTD genotype (P-haplotype) confers protection against CP. Compared with the S-haplotype, subjects with the P-haplotype produce higher levels of the IL-4 protein after non-surgical periodontal therapy. The present in vitro study aimed to investigate the functionality of IL-4 haplotypes in immune cells to obtain insight into the influence of these genetic variations in regulating immune responses to CP-associated bacteria. Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens to compare responses of the different haplotypes with regard to gene expression, protein secretion and the immunophenotype of T helper responses. We found higher IL-4 mRNA and protein levels in the P-haplotype, which also presented higher levels of anti-inflammatory cytokines. In contrast, cells from S-haplotype subjects responded with higher levels of pro-inflammatory cytokines. S-haplotype individuals exhibited significantly greater polarization toward the Th1 phenotype, whereas the P-haplotype was associated with an attenuated response to periodontopathogens, with suggestive skewing toward Th2/M2 phenotypes. In conclusion, IL-4 genetic variations associated with susceptibility to or protection against chronic periodontitis are directly associated with influencing the response of immune cells to periodontopathogens. PMID:28114408

  13. Cut and Paste: restoring cellular function by gene correction

    Institute of Scientific and Technical Information of China (English)

    Guang-Hui Liu; Ignacio Sancho-Martinez; Juan Carlos Izpisua Belmonte

    2012-01-01

    Gene-editing technologies and patient-specific induced pluripotent stem cells (iPSCs) may represent an unprecedented opportunity for merging the stem cell and traditional gene therapy fields to fulfill the promises of regenerative medicine.

  14. Phylogenetic analysis, structural evolution and functional divergence of the 12-oxo-phytodienoate acid reductase gene family in plants

    Directory of Open Access Journals (Sweden)

    Wang Hongbin

    2009-05-01

    . Most notably, significant functional divergence was also found in all pairs, except for the II/IV, II/V and V/VI pairs. Strikingly, analysis of the site-specific profiles established by posterior probability revealed that the positive-selection sites and/or critical amino acid residues for functional divergence are mainly distributed in α-helices and substrate binding loop (SBL, indicating the functional importance of these regions for this protein family. Conclusion This study highlights the molecular evolution of the OPR gene family in all plant lineages and indicates critical amino acid residues likely relevant for the distinct functional properties of the paralogues. Further experimental verification of these findings may provide valuable information on the OPRs' biochemical and physiological functions.

  15. Evolution and Functional Classification of Vertebrate Gene Deserts

    Energy Technology Data Exchange (ETDEWEB)

    Ovcharenko, I; Loots, G; Nobrega, M; Hardison, R; Miller, W; Stubbs, L

    2004-07-14

    Gene deserts, long stretches of DNA sequence devoid of protein coding genes, span approximately one quarter of the human genome. Through human-chicken genome comparisons we were able to characterized one third of human gene deserts as evolutionarily stable - they are highly conserved in vertebrates, resist chromosomal rearrangements, and contain multiple conserved non-coding elements physically linked to their neighboring genes. A linear relationship was observed between human and chicken orthologous stable gene deserts, where the human deserts appear to have expanded homogeneously by a uniform accumulation of repetitive elements. Stable gene deserts are associated with key vertebrate genes that construct the framework of vertebrate development; many of which encode transcription factors. We show that the regulatory machinery governing genes associated with stable gene deserts operates differently from other regions in the human genome and relies heavily on distant regulatory elements. The regulation guided by these elements is independent of the distance between the gene and its distant regulatory element, or the distance between two distant regulatory cassettes. The location of gene deserts and their associated genes in the genome is independent of chromosomal length or content presenting these regions as well-bounded regions evolving separately from the rest of the genome.

  16. Modulating gene function with peptide nucleic acids (PNA)

    DEFF Research Database (Denmark)

    Nielsen, Peter E.; Crooke, Stanley T.

    2008-01-01

    A review on peptide nucleic acid (PNA) oligomers as modulators of gene expression ranging from gene silencing at the mRNAor the dsDNA (antigene) level, and redirection of mRNA splicing to gene activation through transcription bubble mimicking. PNA chem., anti-infective agents, cellular delivery, ...

  17. Ultrasound and Microbubbles: Their Functions in Gene Transfer In Vitro

    Institute of Scientific and Technical Information of China (English)

    CHEN Yunchao; HUANG Daozhong; LI Kaiyan; WANG Zhihui; HONG Kai; WANG Fen; ZANG Qingping

    2007-01-01

    To examine the role of ultrasound in gene delivery in vitro, three cells lines were exposed to the low-frequency ultrasound of varying intensities and for different durations to evaluate their effect on gene transfection and cell viability of the cells. Microbubble (MB), Optison (10%), was also used to observe the role of the microbubbles in gene transfection. The results demonstrated that as the ultrasound intensity and the exposure time increased, the gene transfer rate increased and the cell viability decreased, but at high energy intensities, the cell viability decreased dramatically, which caused the transfer rate to decrease. The most efficient ultrasound intensity for inducing gene transfer was 1 W/cm2 with duration being 20 s. At the same energy intensity, higher ultrasound intensity could achieve maximal gene transfer rate earlier. Microbubbles could increase ultrasound-induced cell gene transfer rate by about 2 to 3 times mainly at lower energy intensities. Moreover, microbubbles could raise the maximum gene transfer rate mediated by ultrasound. It is concluded that the low-frequency ultrasound can induce cell gene transfer and the cell gene transfer rate and viability are correlated with not only the ultrasound energy intensity but also the ultrasound intensity, the higher ultrasound intensity achieves its maximal transfer rate more quickly and the ultrasound intensity that can induce optimal gene transfer is 1 W/cm2 with duration being 20 s, and microbubbles can significantly increase the maximal gene transfer rate in vitro.

  18. Multilevel deconstruction of the In vivo behavior of looped DNA-protein complexes.

    Directory of Open Access Journals (Sweden)

    Leonor Saiz

    Full Text Available Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.

  19. Retinal structure and function in achromatopsia: implications for gene therapy.

    Science.gov (United States)

    Sundaram, Venki; Wilde, Caroline; Aboshiha, Jonathan; Cowing, Jill; Han, Colin; Langlo, Christopher S; Chana, Ravinder; Davidson, Alice E; Sergouniotis, Panagiotis I; Bainbridge, James W; Ali, Robin R; Dubra, Alfredo; Rubin, Gary; Webster, Andrew R; Moore, Anthony T; Nardini, Marko; Carroll, Joseph; Michaelides, Michel

    2014-01-01

    To characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical trials of gene therapy. Cross-sectional study. Forty subjects with ACHM. All subjects underwent spectral domain optical coherence tomography (SD-OCT), microperimetry, and molecular genetic testing. Foveal structure on SD-OCT was graded into 5 distinct categories: (1) continuous inner segment ellipsoid (ISe), (2) ISe disruption, (3) ISe absence, (4) presence of a hyporeflective zone (HRZ), and (5) outer retinal atrophy including retinal pigment epithelial loss. Foveal and outer nuclear layer (ONL) thickness was measured and presence of hypoplasia determined. Photoreceptor appearance on SD-OCT imaging, foveal and ONL thickness, presence of foveal hypoplasia, retinal sensitivity and fixation stability, and association of these parameters with age and genotype. Forty subjects with a mean age of 24.9 years (range, 6-52 years) were included. Disease-causing variants were found in CNGA3 (n = 18), CNGB3 (n = 15), GNAT2 (n = 4), and PDE6C (n = 1). No variants were found in 2 individuals. In all, 22.5% of subjects had a continuous ISe layer at the fovea, 27.5% had ISe disruption, 20% had an absent ISe layer, 22.5% had an HRZ, and 7.5% had outer retinal atrophy. No significant differences in age (P = 0.77), mean retinal sensitivity (P = 0.21), or fixation stability (P = 0.34) across the 5 SD-OCT categories were evident. No correlation was found between age and foveal thickness (P = 0.84) or between age and foveal ONL thickness (P = 0.12). The lack of a clear association of disruption of retinal structure or function in ACHM with age suggests that the window of opportunity for intervention by gene therapy is wider in some individuals than previously indicated. Therefore, the potential benefit for a given subject is likely to be better predicted by specific measurement of photoreceptor structure rather than simply by age. The ability to directly assess cone photoreceptor

  20. Functional Associations by Response Overlap (FARO), a functional genomics approach matching gene expression phenotypes

    DEFF Research Database (Denmark)

    Nielsen, Henrik Bjørn; Mundy, J.; Willenbrock, Hanni

    2007-01-01

    The systematic comparison of transcriptional responses of organisms is a powerful tool in functional genomics. For example, mutants may be characterized by comparing their transcript profiles to those obtained in other experiments querying the effects on gene expression of many experimental factors...... including treatments, mutations and pathogen infections. Similarly, drugs may be discovered by the relationship between the transcript profiles effectuated or impacted by a candidate drug and by the target disease. The integration of such data enables systems biology to predict the interplay between...

  1. Gene-gene interaction and functional impact of polymorphisms on innate immune genes in controlling Plasmodium falciparum blood infection level.

    Directory of Open Access Journals (Sweden)

    Madhumita Basu

    Full Text Available Genetic variations in toll-like receptors and cytokine genes of the innate immune pathways have been implicated in controlling parasite growth and the pathogenesis of Plasmodium falciparum mediated malaria. We previously published genetic association of TLR4 non-synonymous and TNF-α promoter polymorphisms with P.falciparum blood infection level and here we extend the study considerably by (i investigating genetic dependence of parasite-load on interleukin-12B polymorphisms, (ii reconstructing gene-gene interactions among candidate TLRs and cytokine loci, (iii exploring genetic and functional impact of epistatic models and (iv providing mechanistic insights into functionality of disease-associated regulatory polymorphisms. Our data revealed that carriage of AA (P = 0.0001 and AC (P = 0.01 genotypes of IL12B 3'UTR polymorphism was associated with a significant increase of mean log-parasitemia relative to rare homozygous genotype CC. Presence of IL12B+1188 polymorphism in five of six multifactor models reinforced its strong genetic impact on malaria phenotype. Elevation of genetic risk in two-component models compared to the corresponding single locus and reduction of IL12B (2.2 fold and lymphotoxin-α (1.7 fold expressions in patients'peripheral-blood-mononuclear-cells under TLR4Thr399Ile risk genotype background substantiated the role of Multifactor Dimensionality Reduction derived models. Marked reduction of promoter activity of TNF-α risk haplotype (C-C-G-G compared to wild-type haplotype (T-C-G-G with (84% and without (78% LPS stimulation and the loss of binding of transcription factors detected in-silico supported a causal role of TNF-1031. Significantly lower expression of IL12B+1188 AA (5 fold and AC (9 fold genotypes compared to CC and under-representation (P = 0.0048 of allele A in transcripts of patients' PBMCs suggested an Allele-Expression-Imbalance. Allele (A+1188C dependent differential stability (2 fold of IL12B-transcripts upon

  2. Functional cohesion of gene sets determined by latent semantic indexing of PubMed abstracts.

    Directory of Open Access Journals (Sweden)

    Lijing Xu

    Full Text Available High-throughput genomic technologies enable researchers to identify genes that are co-regulated with respect to specific experimental conditions. Numerous statistical approaches have been developed to identify differentially expressed genes. Because each approach can produce distinct gene sets, it is difficult for biologists to determine which statistical approach yields biologically relevant gene sets and is appropriate for their study. To address this issue, we implemented Latent Semantic Indexing (LSI to determine the functional coherence of gene sets. An LSI model was built using over 1 million Medline abstracts for over 20,000 mouse and human genes annotated in Entrez Gene. The gene-to-gene LSI-derived similarities were used to calculate a literature cohesion p-value (LPv for a given gene set using a Fisher's exact test. We tested this method against genes in more than 6,000 functional pathways annotated in Gene Ontology (GO and found that approximately 75% of gene sets in GO biological process category and 90% of the gene sets in GO molecular function and cellular component categories were functionally cohesive (LPv<0.05. These results indicate that the LPv methodology is both robust and accurate. Application of this method to previously published microarray datasets demonstrated that LPv can be helpful in selecting the appropriate feature extraction methods. To enable real-time calculation of LPv for mouse or human gene sets, we developed a web tool called Gene-set Cohesion Analysis Tool (GCAT. GCAT can complement other gene set enrichment approaches by determining the overall functional cohesion of data sets, taking into account both explicit and implicit gene interactions reported in the biomedical literature.GCAT is freely available at http://binf1.memphis.edu/gcat.

  3. Functional Expression of an Orchid Fragrance Gene in Lactococcus lactis

    Directory of Open Access Journals (Sweden)

    Adelene Ai Lian Song

    2012-02-01

    Full Text Available Vanda Mimi Palmer (VMP, an orchid hybrid of Vanda tesselata and Vanda Tan Chay Yan is a highly scented tropical orchid which blooms all year round. Previous studies revealed that VMP produces a variety of isoprenoid volatiles during daylight. Isoprenoids are well known to contribute significantly to the scent of most fragrant plants. They are a large group of secondary metabolites which may possess valuable characteristics such as flavor, fragrance and toxicity and are produced via two pathways, the mevalonate (MVA pathway or/and the 2-C-methyl-D-erythritol-4-phosphate (MEP pathway. In this study, a sesquiterpene synthase gene denoted VMPSTS, previously isolated from a floral cDNA library of VMP was cloned and expressed in Lactococcus lactis to characterize the functionality of the protein. L. lactis, a food grade bacterium which utilizes the mevalonate pathway for isoprenoid production was found to be a suitable host for the characterization of plant terpene synthases. Through recombinant expression of VMPSTS, it was revealed that VMPSTS produced multiple sesquiterpenes and germacrene D dominates its profile.

  4. Performance of free-space laser communication systems as a function of the sampling rate in the tracking loop

    Science.gov (United States)

    Nikulin, V.; Sofka, J.; Khandekar, R.

    2005-08-01

    Laser technology plays an ever-increasing role in aerospace and communication systems and is often viewed as a technology that has the potential for providing the material base for high-bandwidth applications. Laser provides the most logical connectivity channel for mobile systems requiring high data rates, low power consumption, covert operation, and high resistance to jamming. While advancements in modern opto-electronics have resulted in small size, reliable and power efficient lasers and modulators, successful operation of any communication technology hinges upon the ability to develop an equally advanced beam steering/positioning system. In many aerospace applications, when the transmitting optical platform is placed on board of an airplane, the ability to track the target is affected by the complex high-speed maneuvers performed by the aircraft and the resident vibration of the airframe. The tracking system must assure that in spite of the relative motion of both the transmitting and receiving stations and adverse environments, such as vibration, mutual alignment of two systems will be maintained to minimize communication errors. The work presented in this paper concentrates on the development of agile beam steering systems for laser communication terminals. Acousto-optic Bragg cells are used as deflectors while feedback information is generated by a quadrant detector. The control system is synthesized using a relatively simple constant-gain controller augmented with an adaptive Kalman filter to mitigate the effects of measurement noise in the tracking system. Laboratory experiments are conducted to investigate communication performance as a function of the sampling rate in the beam position feedback.

  5. Abstract Acceleration of General Linear Loops

    OpenAIRE

    2014-01-01

    International audience; We present abstract acceleration techniques for computing loop invariants for numerical programs with linear assignments and conditionals. Whereas abstract interpretation techniques typically over-approximate the set of reachable states iteratively, abstract acceleration captures the effect of the loop with a single, non-iterative transfer function applied to the initial states at the loop head. In contrast to previous acceleration techniques, our approach applies to a...

  6. Magnetic Monopole in the Loop Representation

    CERN Document Server

    Leal, L; Leal, Lorenzo; Lopez, Alexander

    2004-01-01

    We quantize the electromagnetic field in the presence of a static magnetic monopole, within the loop-representation formalism. We find that the loop-dependent wave functional becomes multivalued, in the sense that it acquires a dependence on the surfaces bounded by the loop. This generalizes what occurs in quantum mechanics in multiply connected spaces. When Dirac's quantization condition holds, this surface-dependence disappears, together with the effect of the monopole on the electromagnetic field.

  7. EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions

    DEFF Research Database (Denmark)

    Luo, Yonglun; Friis, Jenny Blechingberg; Fernandes, Ana Miguel;

    2015-01-01

    IP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression...... at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. Conclusions The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes...

  8. Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

    Science.gov (United States)

    Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

    2016-10-03

    FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

  9. Discovering cancer genes by integrating network and functional properties

    Directory of Open Access Journals (Sweden)

    Davis David P

    2009-09-01

    Full Text Available Abstract Background Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO annotations, to facilitate the identification of cancer genes. Methods Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1. Results Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1. Conclusion Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.

  10. Insights into the Function of Long Noncoding RNAs in Sepsis Revealed by Gene Co-Expression Network Analysis

    Directory of Open Access Journals (Sweden)

    Diogo Vieira da Silva Pellegrina

    2017-01-01

    Full Text Available Sepsis is a major cause of death and its incidence and mortality increase exponentially with age. Most gene expression studies in sepsis have focused in protein-coding genes and the expression patterns, and potential roles of long noncoding RNAs (lncRNAs have not been investigated yet. In this study, we performed co-expression network analysis of protein-coding and lncRNAs measured in neutrophil granulocytes from adult and elderly septic patients, along with age-matched healthy controls. We found that the genes displaying highest network similarity are predominantly differently expressed in sepsis and are enriched in loci encoding proteins with structural or regulatory functions related to protein translation and mitochondrial energetic metabolism. A number of lncRNAs are strongly connected to genes from these pathways and may take part in regulatory loops that are perturbed in sepsis. Among those, the ribosomal pseudogenes RP11-302F12.1 and RPL13AP7 are differentially expressed and appear to have a regulatory role on protein translation in both the elderly and adults, and lncRNAs MALAT1, LINC00355, MYCNOS, and AC010970.2 display variable connection strength and inverted expression patterns between adult and elderly networks, suggesting that they are the best candidates to be further studied to understand the mechanisms by which the immune response is impaired by age. In summary, we report the expression of lncRNAs that are deregulated in patients with sepsis, including subsets that display hub properties in molecular pathways relevant to the disease pathogenesis and that may participate in gene expression regulatory circuits related to the poorer disease outcome observed in elderly subjects.

  11. Annotating the Function of the Human Genome with Gene Ontology and Disease Ontology.

    Science.gov (United States)

    Hu, Yang; Zhou, Wenyang; Ren, Jun; Dong, Lixiang; Wang, Yadong; Jin, Shuilin; Cheng, Liang

    2016-01-01

    Increasing evidences indicated that function annotation of human genome in molecular level and phenotype level is very important for systematic analysis of genes. In this study, we presented a framework named Gene2Function to annotate Gene Reference into Functions (GeneRIFs), in which each functional description of GeneRIFs could be annotated by a text mining tool Open Biomedical Annotator (OBA), and each Entrez gene could be mapped to Human Genome Organisation Gene Nomenclature Committee (HGNC) gene symbol. After annotating all the records about human genes of GeneRIFs, 288,869 associations between 13,148 mRNAs and 7,182 terms, 9,496 associations between 948 microRNAs and 533 terms, and 901 associations between 139 long noncoding RNAs (lncRNAs) and 297 terms were obtained as a comprehensive annotation resource of human genome. High consistency of term frequency of individual gene (Pearson correlation = 0.6401, p = 2.2e - 16) and gene frequency of individual term (Pearson correlation = 0.1298, p = 3.686e - 14) in GeneRIFs and GOA shows our annotation resource is very reliable.

  12. Functional clustering of time series gene expression data by Granger causality

    Science.gov (United States)

    2012-01-01

    Background A common approach for time series gene expression data analysis includes the clustering of genes with similar expression patterns throughout time. Clustered gene expression profiles point to the joint contribution of groups of genes to a particular cellular process. However, since genes belong to intricate networks, other features, besides comparable expression patterns, should provide additional information for the identification of functionally similar genes. Results In this study we perform gene clustering through the identification of Granger causality between and within sets of time series gene expression data. Granger causality is based on the idea that the cause of an event cannot come after its consequence. Conclusions This kind of analysis can be used as a complementary approach for functional clustering, wherein genes would be clustered not solely based on their expression similarity but on their topological proximity built according to the intensity of Granger causality among them. PMID:23107425

  13. Functional clustering of time series gene expression data by Granger causality

    Directory of Open Access Journals (Sweden)

    Fujita André

    2012-10-01

    Full Text Available Abstract Background A common approach for time series gene expression data analysis includes the clustering of genes with similar expression patterns throughout time. Clustered gene expression profiles point to the joint contribution of groups of genes to a particular cellular process. However, since genes belong to intricate networks, other features, besides comparable expression patterns, should provide additional information for the identification of functionally similar genes. Results In this study we perform gene clustering through the identification of Granger causality between and within sets of time series gene expression data. Granger causality is based on the idea that the cause of an event cannot come after its consequence. Conclusions This kind of analysis can be used as a complementary approach for functional clustering, wherein genes would be clustered not solely based on their expression similarity but on their topological proximity built according to the intensity of Granger causality among them.

  14. The finite Bruck Loops

    CERN Document Server

    Baumeister, Barbara

    2009-01-01

    We continue the work by Aschbacher, Kinyon and Phillips [AKP] as well as of Glauberman [Glaub1,2] by describing the structure of the finite Bruck loops. We show essentially that a finite Bruck loop $X$ is the direct product of a Bruck loop of odd order with either a soluble Bruck loop of 2-power order or a product of loops related to the groups $PSL_2(q)$, $q= 9$ or $q \\geq 5$ a Fermat prime. The latter possibillity does occur as is shown in [Nag1, BS]. As corollaries we obtain versions of Sylow's, Lagrange's and Hall's Theorems for loops.

  15. Phylogenetic and functional gene structure shifts of the oral microbiomes in periodontitis patients

    Science.gov (United States)

    Li, Yan; He, Jinzhi; He, Zhili; Zhou, Yuan; Yuan, Mengting; Xu, Xin; Sun, Feifei; Liu, Chengcheng; Li, Jiyao; Xie, Wenbo; Deng, Ye; Qin, Yujia; VanNostrand, Joy D; Xiao, Liying; Wu, Liyou; Zhou, Jizhong; Shi, Wenyuan; Zhou, Xuedong

    2014-01-01

    Determining the composition and function of subgingival dental plaque is crucial to understanding human periodontal health and disease, but it is challenging because of the complexity of the interactions between human microbiomes and human body. Here, we examined the phylogenetic and functional gene differences between periodontal and healthy individuals using MiSeq sequencing of 16S rRNA gene amplicons and a specific functional gene array (a combination of GeoChip 4.0 for biogeochemical processes and HuMiChip 1.0 for human microbiomes). Our analyses indicated that the phylogenetic and functional gene structure of the oral microbiomes were distinctly different between periodontal and healthy groups. Also, 16S rRNA gene sequencing analysis indicated that 39 genera were significantly different between healthy and periodontitis groups, and Fusobacterium, Porphyromonas, Treponema, Filifactor, Eubacterium, Tannerella, Hallella, Parvimonas, Peptostreptococcus and Catonella showed higher relative abundances in the periodontitis group. In addition, functional gene array data showed that a lower gene number but higher signal intensity of major genes existed in periodontitis, and a variety of genes involved in virulence factors, amino acid metabolism and glycosaminoglycan and pyrimidine degradation were enriched in periodontitis, suggesting their potential importance in periodontal pathogenesis. However, the genes involved in amino acid synthesis and pyrimidine synthesis exhibited a significantly lower relative abundance compared with healthy group. Overall, this study provides new insights into our understanding of phylogenetic and functional gene structure of subgingival microbial communities of periodontal patients and their importance in pathogenesis of periodontitis. PMID:24671083

  16. A 3800 gene microarray for cattle functional genomics: comparison of gene expression in spleen, placenta, and brain.

    Science.gov (United States)

    Band, Mark R; Olmstead, Colleen; Everts, Robin E; Liu, Zonglin L; Lewin, Harris A

    2002-05-01

    A cDNA microarray representing approximately 3800 cattle genes was created for functional genomic studies. The array elements were selected from > 7000 cDNA clones identified in a large-scale expressed sequence tag (EST) project that utilized spleen and normalized and subtracted placenta cDNA libraries. Sequence similarity searches of the 3820 ESTs represented on the array using BLASTN identified 3290 (86.1%) as putative human orthologs, with the remainder consisting of "novel" genes or highly divergent orthologs. Experiments were conducted with a prototype 768 gene microarray created from spleen cDNAs and with the 3800 gene array that included genes from spleen and placenta. The 768 gene array was used to profile RNA transcripts expressed by adult and fetal spleen. The 3800 gene array was used to profile transcripts expressed by adult brain and placenta. Microarray analysis of RNA extracted from fetal and adult spleen identified 29 genes that were differentially expressed two-fold or more. Transcriptional differences of two of these genes, IGJ and CTSS, were confirmed using TaqMan technology. The comparison of brain and placenta revealed 400 genes expressed at higher levels in brain and 72 genes expressed at higher levels in placenta. These results demonstrate the potential power of microarrays for understanding the molecular mechanisms of cattle development, disease resistance, nutrition, fertility and production traits.

  17. Analysis of TIR- and non-TIR-NBS-LRR disease resistance gene analogous in pepper: characterization, genetic variation, functional divergence and expression patterns

    Directory of Open Access Journals (Sweden)

    Wan Hongjian

    2012-09-01

    Full Text Available Abstract Background Pepper (Capsicum annuum L. is one of the most important vegetable crops worldwide. However, its yield and fruit quality can be severely threatened by several pathogens. The plant nucleotide-binding site (NBS-leucine-rich repeat (LRR gene family is the largest class of known disease resistance genes (R genes effective against such pathogens. Therefore, the isolation and identification of such R gene homologues from pepper will provide a critical foundation for improving disease resistance breeding programs. Results A total of 78 R gene analogues (CaRGAs were identified in pepper by degenerate PCR amplification and database mining. Phylogenetic tree analysis of the deduced amino acid sequences for 51 of these CaRGAs with typically conserved motifs ( P-loop, kinase-2 and GLPL along with some known R genes from Arabidopsis and tomato grouped these CaRGAs into the non-Toll interleukin-1 receptor (TIR-NBS-LRR (CaRGAs I to IV and TIR-NBS-LRR (CaRGAs V to VII subfamilies. The presence of consensus motifs (i.e. P-loop, kinase-2 and hydrophobic domain is typical of the non-TIR- and TIR-NBS-LRR gene subfamilies. This finding further supports the view that both subfamilies are widely distributed in dicot species. Functional divergence analysis provided strong statistical evidence of altered selective constraints during protein evolution between the two subfamilies. Thirteen critical amino acid sites involved in this divergence were also identified using DIVERGE version 2 software. Analyses of non-synonymous and synonymous substitutions per site showed that purifying selection can play a critical role in the evolutionary processes of non-TIR- and TIR-NBS-LRR RGAs in pepper. In addition, four specificity-determining positions were predicted to be responsible for functional specificity. qRT-PCR analysis showed that both salicylic and abscisic acids induce the expression of CaRGA genes, suggesting that they may primarily be involved in

  18. Closed-loop afferent electrical stimulation for recovery of hand function in individuals with motor incomplete spinal injury: early clinical results.

    Science.gov (United States)

    Schildt, Christopher J; Thomas, Sarah H; Powell, Elizabeth S; Sawaki, Lumy; Sunderam, Sridhar

    2016-08-01

    Afferent electrical stimulation is known to augment the effect of rehabilitative therapy through use-dependent cortical plasticity. Experiments pairing transcranial magnetic stimulation (TMS) with peripheral nerve stimulation (PNS) have shown a timing-dependent effect on motor evoked potential (MEP) amplitude suggesting that PNS applied in closed-loop (CL) mode could augment this effect through positive reinforcement. We present early results from a clinical trial in which an EEG brain-machine interface (BMI) was used to apply PNS to two subjects in response to motor intent detected from sensorimotor cortex in a cue-driven hand grip task. Both subjects had stable incomplete cervical spinal cord injury (SCI) with impaired upper limb function commensurate with the injury level. Twelve sessions of CL-PNS applied over a 4-6 week period yielded results suggesting improved hand grip strength and increased task-related modulation of the EEG in one hand of both subjects, and increased TMS-measured motor map area in one. These observations suggest that rehabilitation using such interactive therapies could benefit affected individuals.

  19. Genetic structure of African buffalo herds based on variation at the mitochondrial D-loop and autosomal microsatellite loci: Evidence for male-biased gene flow

    NARCIS (Netherlands)

    Hooft, van W.F.; Groen, A.F.; Prins, H.H.T.

    2003-01-01

    Sexual differences in herding behaviour of African buffalo (Syncerus caffer) were studied by analysing at the herd level mitochondrial D-loop hypervariable region I and fourteen autosomal microsatellites. Three herds from Arusha National Park in Tanzania were analysed with mtDNA and five herds from

  20. Expression of RNA-interference/antisense transgenes by the cognate promoters of target genes is a better gene-silencing strategy to study gene functions in rice.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available Antisense and RNA interference (RNAi-mediated gene silencing systems are powerful reverse genetic methods for studying gene function. Most RNAi and antisense experiments used constitutive promoters to drive the expression of RNAi/antisense transgenes; however, several reports showed that constitutive promoters were not expressed in all cell types in cereal plants, suggesting that the constitutive promoter systems are not effective for silencing gene expression in certain tissues/organs. To develop an alternative method that complements the constitutive promoter systems, we constructed RNAi and/or antisense transgenes for four rice genes using a constitutive promoter or a cognate promoter of a selected rice target gene and generated many independent transgenic lines. Genetic, molecular, and phenotypic analyses of these RNAi/antisense transgenic rice plants, in comparison to previously-reported transgenic lines that silenced similar genes, revealed that expression of the cognate promoter-driven RNAi/antisense transgenes resulted in novel growth/developmental defects that were not observed in transgenic lines expressing constitutive promoter-driven gene-silencing transgenes of the same target genes. Our results strongly suggested that expression of RNAi/antisense transgenes by cognate promoters of target genes is a better gene-silencing approach to discovery gene function in rice.

  1. Expression of RNA-interference/antisense transgenes by the cognate promoters of target genes is a better gene-silencing strategy to study gene functions in rice.

    Science.gov (United States)

    Li, Jing; Jiang, Dagang; Zhou, Hai; Li, Feng; Yang, Jiawei; Hong, Laifa; Fu, Xiao; Li, Zhibin; Liu, Zhenlan; Li, Jianming; Zhuang, Chuxiong

    2011-03-03

    Antisense and RNA interference (RNAi)-mediated gene silencing systems are powerful reverse genetic methods for studying gene function. Most RNAi and antisense experiments used constitutive promoters to drive the expression of RNAi/antisense transgenes; however, several reports showed that constitutive promoters were not expressed in all cell types in cereal plants, suggesting that the constitutive promoter systems are not effective for silencing gene expression in certain tissues/organs. To develop an alternative method that complements the constitutive promoter systems, we constructed RNAi and/or antisense transgenes for four rice genes using a constitutive promoter or a cognate promoter of a selected rice target gene and generated many independent transgenic lines. Genetic, molecular, and phenotypic analyses of these RNAi/antisense transgenic rice plants, in comparison to previously-reported transgenic lines that silenced similar genes, revealed that expression of the cognate promoter-driven RNAi/antisense transgenes resulted in novel growth/developmental defects that were not observed in transgenic lines expressing constitutive promoter-driven gene-silencing transgenes of the same target genes. Our results strongly suggested that expression of RNAi/antisense transgenes by cognate promoters of target genes is a better gene-silencing approach to discovery gene function in rice.

  2. Gene Network Analysis and Functional Studies of Senescence-associated Genes Reveal Novel Regulators of Arabidopsis Leaf Senescence

    Institute of Scientific and Technical Information of China (English)

    Zhonghai Li; Jinying Peng; Xing Wen; Hongwei Guo

    2012-01-01

    Plant leaf senescence has been recognized as the last phase of plant development,a highly ordered process regulated by genes known as senescence associated genes (SAGs).However,the function of most of SAGs in regulating leaf senescence as well as regulators of those functionally known SAGs are still unclear.We have previously developed a curated database of genes potentially associated with leaf senescence,the Leaf Senescence Database (LSD).In this study,we built gene networks to identify common regulators of leaf senescence in Arabidopsis thaliana using promoting or delaying senescence genes in LSD.Our results demonstrated that plant hormones cytokinin,auxin,nitric oxide as well as small molecules,such as Ca2+,delay leaf senescence.By contrast,ethylene,ABA,SA and JA as well as small molecules,such as oxygen,promote leaf senescence,altogether supporting the idea that phytohormones play a critical role in regulating leaf senescence.Functional analysis of candidate SAGs in LSD revealed that a WRKY transcription factor WRKY75 and a Cys2/His2-type transcription factor AZF2 are positive regulators of leaf senescence and loss-of-function of WRKY75 or AZF2 delayed leaf senescence.We also found that silencing of a protein phosphatase,AtMKP2,promoted early senescence.Collectively,LSD can serve as a comprehensive resource for systematic study of the molecular mechanism of leaf senescence as well as offer candidate genes for functional analyses.

  3. Gauge theory loop operators and Liouville theory

    Energy Technology Data Exchange (ETDEWEB)

    Drukker, Nadav [Humboldt Univ. Berlin (Germany). Inst. fuer Physik; Gomis, Jaume; Okuda, Takuda [Perimeter Inst. for Theoretical Physics, Waterloo, ON (Canada); Teschner, Joerg [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2009-10-15

    We propose a correspondence between loop operators in a family of four dimensional N=2 gauge theories on S{sup 4} - including Wilson, 't Hooft and dyonic operators - and Liouville theory loop operators on a Riemann surface. This extends the beautiful relation between the partition function of these N=2 gauge theories and Liouville correlators found by Alday, Gaiotto and Tachikawa. We show that the computation of these Liouville correlators with the insertion of a Liouville loop operator reproduces Pestun's formula capturing the expectation value of a Wilson loop operator in the corresponding gauge theory. We prove that our definition of Liouville loop operators is invariant under modular transformations, which given our correspondence, implies the conjectured action of S-duality on the gauge theory loop operators. Our computations in Liouville theory make an explicit prediction for the exact expectation value of 't Hooft and dyonic loop operators in these N=2 gauge theories. The Liouville loop operators are also found to admit a simple geometric interpretation within quantum Teichmueller theory as the quantum operators representing the length of geodesics. We study the algebra of Liouville loop operators and show that it gives evidence for our proposal as well as providing definite predictions for the operator product expansion of loop operators in gauge theory. (orig.)

  4. Efficient Loop Navigation for Symbolic Execution

    CERN Document Server

    Obdrzalek, Jan

    2011-01-01

    Symbolic execution is a successful and very popular technique used in software verification and testing. A key limitation of symbolic execution is in dealing with code containing loops. The problem is that even a single loop can generate a huge number of different symbolic execution paths, corresponding to different number of loop iterations and taking various paths through the loop. We introduce a technique which, given a start location above some loops and a target location anywhere below these loops, returns a feasible path between these two locations, if such a path exists. The technique infers a collection of constraint systems from the program and uses them to steer the symbolic execution towards the target. On reaching a loop it iteratively solves the appropriate constraint system to find out which path through this loop to take, or, alternatively, whether to continue below the loop. To construct the constraint systems we express the values of variables modified in a loop as functions of the number of ...

  5. An Overview of Hox Genes in Lophotrochozoa: Evolution and Functionality

    Directory of Open Access Journals (Sweden)

    Marco Barucca

    2016-03-01

    Full Text Available Hox genes are regulators of animal embryonic development. Changes in the number and sequence of Hox genes as well as in their expression patterns have been related to the evolution of the body plan. Lophotrochozoa is a clade of Protostomia characterized by several phyla which show a wide morphological diversity. Despite that the works summarized in this review emphasize the fragmentary nature of the data available regarding the presence and expression of Hox genes, they also offer interesting insight into the evolution of the Hox cluster and the role played by Hox genes in several phyla. However, the number of genes involved in the cluster of the lophotrochozoan ancestor is still a question of debate. The data presented here suggest that at least nine genes were present while two other genes, Lox4 and Post-2, may either have been present in the ancestor or may have arisen as a result of duplication in the Brachiopoda-Mollusca-Annelida lineage. Spatial and temporal collinearity is a feature of Hox gene expression which was probably present in the ancestor of deuterostomes and protostomes. However, in Lophotrochozoa, it has been detected in only a few species belonging to Annelida and Mollusca.

  6. The mammalian gene function resource: The International Knockout Mouse Consortium

    NARCIS (Netherlands)

    A. Bradley (Allan); K. Anastassiadis (Konstantinos); A. Ayadi (Abdelkader); J.F. Battey (James); C. Bell (Cindy); M.-C. Birling (Marie-Christine); J. Bottomley (Joanna); S.D.M. Brown (Steve); F. Bürger (Friederike); C.J. Bult (Carol); W. Bushell (Wendy); F.S. Collins (Francis); C. Desaintes (Christian); B. Doe (Brendan); E. Aris (Economides); J.T. Eppig (Janan); R.H. Finnell (Richard); C. Fletcher (Colin); M. Fray (Martin); D. Frendewey (David); R.H. Friedel (Roland); F.G. Grosveld (Frank); J. Hansen; Y. Hérault (Yann); G. Hicks (Geoffrey); A. Hörlein (Andreas); C. Houghton (Catherine); M. Hrabé De Angelis (Martin); D. Huylebroeck (Danny); V. Iyer (Vivek); P.J. de Jong (Pieter); J.A. Kadin (James); C. Kaloff (Cornelia); K. Kennedy (Karen); M. Koutsourakis (Manousos); K.C. Kent Lloyd (K.); S. Marschall (Susan); J. Mason (Jeremy); C. McKerlie (Colin); M.P. McLeod (Michael); H. von Melchner (Harald); M. Moore (Matt); A.O. Mujica (Alejandro); A. Nagy (Andras); M. Nefedov (Mikhail); L.M. Nutter (Lauryl); G. Pavlovic (Guillaume); J.L. Peterson (Jane); I. Pollock; R. Ramirez-Solis (Ramiro); D.E. Rancourt (Derrick); M. Raspa (Marcello); J.E. Remacle (Jacques); M. Ringwald (Martin); B. Rosen (Barry); N. Rosenthal (Nadia); J. Rossant (Janet); P. Ruiz Noppinger (Patricia); S. Ryder; J.Z. Schick (Joel Zupicich); F. Schnütgen (Frank); C.J. Schofield (Christopher); C. Seisenberger (Claudia); M. Selloum (Mohammed); E.M. Simpson (Elizabeth); W.C. Skarnes (William); D. Smedley (Damian); W.L. Stanford (William); A. Francis Stewart (A.); K. Stone (Kevin); K. Swan (Kate); H. Tadepally (Hamsa); J.L. Teboul (Jean Louis); G.P. Tocchini-Valentini (Glauco); D. Valenzuela (David); A.P. West (Anthony); K.-I. Yamamura (Ken-Ichi); Y. Yoshinaga (Yuko); M. Wurst (Martin)

    2012-01-01

    textabstractIn 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed highthroughput gene trapping and, i

  7. The mammalian gene function resource: The International Knockout Mouse Consortium

    NARCIS (Netherlands)

    A. Bradley (Allan); K. Anastassiadis (Konstantinos); A. Ayadi (Abdelkader); J.F. Battey (James); C. Bell (Cindy); M.-C. Birling (Marie-Christine); J. Bottomley (Joanna); S.D.M. Brown (Steve); F. Bürger (Friederike); C.J. Bult (Carol); W. Bushell (Wendy); F.S. Collins (Francis); C. Desaintes (Christian); B. Doe (Brendan); E. Aris (Economides); J.T. Eppig (Janan); R.H. Finnell (Richard); C. Fletcher (Colin); M. Fray (Martin); D. Frendewey (David); R.H. Friedel (Roland); F.G. Grosveld (Frank); J. Hansen; Y. Hérault (Yann); G. Hicks (Geoffrey); A. Hörlein (Andreas); C. Houghton (Catherine); M. Hrabé De Angelis (Martin); D. Huylebroeck (Danny); V. Iyer (Vivek); P.J. de Jong (Pieter); J.A. Kadin (James); C. Kaloff (Cornelia); K. Kennedy (Karen); M. Koutsourakis (Manousos); K.C. Kent Lloyd (K.); S. Marschall (Susan); J. Mason (Jeremy); C. McKerlie (Colin); M.P. McLeod (Michael); H. von Melchner (Harald); M. Moore (Matt); A.O. Mujica (Alejandro); A. Nagy (Andras); M. Nefedov (Mikhail); L.M. Nutter (Lauryl); G. Pavlovic (Guillaume); J.L. Peterson (Jane); I. Pollock; R. Ramirez-Solis (Ramiro); D.E. Rancourt (Derrick); M. Raspa (Marcello); J.E. Remacle (Jacques); M. Ringwald (Martin); B. Rosen (Barry); N. Rosenthal (Nadia); J. Rossant (Janet); P. Ruiz Noppinger (Patricia); S. Ryder; J.Z. Schick (Joel Zupicich); F. Schnütgen (Frank); C.J. Schofield (Christopher); C. Seisenberger (Claudia); M. Selloum (Mohammed); E.M. Simpson (Elizabeth); W.C. Skarnes (William); D. Smedley (Damian); W.L. Stanford (William); A. Francis Stewart (A.); K. Stone (Kevin); K. Swan (Kate); H. Tadepally (Hamsa); J.L. Teboul (Jean Louis); G.P. Tocchini-Valentini (Glauco); D. Valenzuela (David); A.P. West (Anthony); K.-I. Yamamura (Ken-Ichi); Y. Yoshinaga (Yuko); M. Wurst (Martin)

    2012-01-01

    textabstractIn 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed highthroughput gene trapping and,

  8. NaviGO: interactive tool for visualization and functional similarity and coherence analysis with gene ontology.

    Science.gov (United States)

    Wei, Qing; Khan, Ishita K; Ding, Ziyun; Yerneni, Satwica; Kihara, Daisuke

    2017-03-20

    The number of genomics and proteomics experiments is growing rapidly, producing an ever-increasing amount of data that are awaiting functional interpretation. A number of function prediction algorithms were developed and improved to enable fast and automatic function annotation. With the well-defined structure and manual curation, Gene Ontology (GO) is the most frequently used vocabulary for representing gene functions. To understand relationship and similarity between GO annotations of genes, it is important to have a convenient pipeline that quantifies and visualizes the GO function analyses in a systematic fashion. NaviGO is a web-based tool for interactive visualization, retrieval, and computation of functional similarity and associations of GO terms and genes. Similarity of GO terms and gene functions is quantified with six different scores including protein-protein interaction and context based association scores we have developed in our previous works. Interactive navigation of the GO function space provides intuitive and effective real-time visualization of functional groupings of GO terms and genes as well as statistical analysis of enriched functions. We developed NaviGO, which visualizes and analyses functional similarity and associations of GO terms and genes. The NaviGO webserver is freely available at: http://kiharalab.org/web/navigo .

  9. Isolation and preliminary function analysis of a Na /H antiporter gene ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

    Oct 5, 2009 ... Key words: Malus zumi, Na+/H+ antiporter gene, gene cloning, gene function. INTRODUCTION ... Malus species (apple) is grown worldwide, and is an important fruit .... VvNHX1 (AAV36562), Vitis vinifera; CNHX1, RhNHX1.

  10. Effects of percutaneous transluminal septal myocardial ablation for obstructive hypertrophic cardiomyopathy on systolic and diastolic left ventricular function assessed by pressure-volume loops.

    Science.gov (United States)

    Meliga, Emanuele; Steendijk, Paul; Valgimigli, Marco; Ten Cate, Folkert J; Serruys, Patrick W

    2008-04-15

    The aim of the present study was to determine the long-term effects of percutaneous transluminal septal myocardial ablation (PTSMA) on systolic and diastolic left ventricular (LV) functions in patients with obstructive hypertrophic cardiomyopathy (HC). Ten consecutive patients with symptomatic HC despite optimal medical treatment were referred for PTSMA at our center. LV systolic and diastolic functions were assessed by online LV pressure-volume loops obtained by conductance catheter at baseline and at 6 months after the procedure. At follow-up, the mean gradients at rest and after extrasystole were significantly decreased compared with baseline (88 +/- 29 to 21 +/- 11 mm Hg and 130 +/- 50 to 35 +/- 22 mm Hg, respectively, p <0.01 for the 2 comparisons). End-systolic and end-diastolic pressures significantly decreased (p <0.01), whereas end-systolic and end-diastolic LV volumes significantly increased (p <0.01 for the 2 comparisons). Cardiac output and stroke volume were unchanged, as were ejection fraction (p = 0.25) and maximum dP/dt (p = 0.13). The slope of the end-systolic pressure-volume relation was not decreased, indicating a preserved contractility. The relaxation constant time, end-diastolic stiffness, projected volume of the end-diastolic pressure-volume relation at 30 mm Hg, and diastolic stiffness constant showed a significant improvement of active and passive myocardial diastolic properties. In conclusion, PTSMA is an effective method in the treatment of symptomatic patients with HC. At 6-month follow-up, the LV-aortic gradient was decreased and active and passive LV diastolic properties were increased. Myocardial contractility was not decreased and general hemodynamics was maintained.

  11. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  12. Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS transcription factor complex NPAS4/ARNT2 disrupt function.

    Directory of Open Access Journals (Sweden)

    David C Bersten

    Full Text Available Neuronal Per-Arnt-Sim homology (PAS Factor 4 (NPAS4 is a neuronal activity-dependent transcription factor which heterodimerises with ARNT2 to regulate genes involved in inhibitory synapse formation. NPAS4 functions to maintain excitatory/inhibitory balance in neurons, while mouse models have shown it to play roles in memory formation, social interaction and neurodegeneration. NPAS4 has therefore been implicated in a number of neuropsychiatric or neurodegenerative diseases which are underpinned by defects in excitatory/inhibitory balance. Here we have explored a broad set of non-synonymous human variants in NPAS4 and ARNT2 for disruption of NPAS4 function. We found two variants in NPAS4 (F147S and E257K and two variants in ARNT2 (R46W and R107H which significantly reduced transcriptional activity of the heterodimer on a luciferase reporter gene. Furthermore, we found that NPAS4.F147S was unable to activate expression of the NPAS4 target gene BDNF due to reduced dimerisation with ARNT2. Homology modelling predicts F147 in NPAS4 to lie at the dimer interface, where it appears to directly contribute to protein/protein interaction. We also found that reduced transcriptional activation by ARNT2 R46W was due to disruption of nuclear localisation. These results provide insight into the mechanisms of NPAS4/ARNT dimerisation and transcriptional activation and have potential implications for cognitive phenotypic variation and diseases such as autism, schizophrenia and dementia.

  13. Gene fusions and gene duplications: relevance to genomic annotation and functional analysis

    Directory of Open Access Journals (Sweden)

    Riley Monica

    2005-03-01

    Full Text Available Abstract Background Escherichia coli a model organism provides information for annotation of other genomes. Our analysis of its genome has shown that proteins encoded by fused genes need special attention. Such composite (multimodular proteins consist of two or more components (modules encoding distinct functions. Multimodular proteins have been found to complicate both annotation and generation of sequence similar groups. Previous work overstated the number of multimodular proteins in E. coli. This work corrects the identification of modules by including sequence information from proteins in 50 sequenced microbial genomes. Results Multimodular E. coli K-12 proteins were identified from sequence similarities between their component modules and non-fused proteins in 50 genomes and from the literature. We found 109 multimodular proteins in E. coli containing either two or three modules. Most modules had standalone sequence relatives in other genomes. The separated modules together with all the single (un-fused proteins constitute the sum of all unimodular proteins of E. coli. Pairwise sequence relationships among all E. coli unimodular proteins generated 490 sequence similar, paralogous groups. Groups ranged in size from 92 to 2 members and had varying degrees of relatedness among their members. Some E. coli enzyme groups were compared to homologs in other bacterial genomes. Conclusion The deleterious effects of multimodular proteins on annotation and on the formation of groups of paralogs are emphasized. To improve annotation results, all multimodular proteins in an organism should be detected and when known each function should be connected with its location in the sequence of the protein. When transferring functions by sequence similarity, alignment locations must be noted, particularly when alignments cover only part of the sequences, in order to enable transfer of the correct function. Separating multimodular proteins into module units makes

  14. Effective potential for Polyakov loops in lattice QCD

    Science.gov (United States)

    Nemoto, Y.; RBC Collaboration

    2003-05-01

    Toward the derivation of an effective theory for Polyakov loops in lattice QCD, we examine Polyakov loop correlation functions using the multi-level algorithm which was recently developed by Luscher and Weisz.

  15. Complete renormalization of QCD at five loops

    Science.gov (United States)

    Luthe, Thomas; Maier, Andreas; Marquard, Peter; Schröder, York

    2017-03-01

    We present new analytical five-loop Feynman-gauge results for the anomalous dimensions of ghost field and -vertex, generalizing the known values for SU(3) to a general gauge group. Together with previously published results on the quark mass and -field anomalous dimensions and the Beta function, this completes the 5-loop renormalization program of gauge theories in that gauge.

  16. EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions

    DEFF Research Database (Denmark)

    Luo, Yonglun; Friis, Jenny Blechingberg; Fernandes, Ana Miguel

    2015-01-01

    at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. Conclusions The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes...... and involved in the human neurological diseases amyotrophic lateral sclerosis and fronto-temporal lobar degeneration. Results To determine the gene regulatory functions of FUS and EWS at the level of chromatin, we have performed chromatin immunoprecipitation followed by next generation sequencing (Ch......IP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression...

  17. Pseudonoise code tracking loop

    Science.gov (United States)

    Laflame, D. T. (Inventor)

    1980-01-01

    A delay-locked loop is presented for tracking a pseudonoise (PN) reference code in an incoming communication signal. The loop is less sensitive to gain imbalances, which can otherwise introduce timing errors in the PN reference code formed by the loop.

  18. Gene expression, signal transduction pathways and functional networks associated with growth of sporadic vestibular schwannomas

    DEFF Research Database (Denmark)

    Sass, Hjalte Christian Reeberg; Borup, Rehannah; Alanin, Mikkel

    2017-01-01

    The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined...... of signal transduction pathways and functional molecular networks associated with tumor growth. In total 109 genes were deregulated in relation to tumor growth rate. Genes associated with apoptosis, growth and cell proliferation were deregulated. Gene ontology included regulation of the cell cycle, cell...... differentiation an