21,840 research outputs found

    G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy

    Get PDF
    G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guanine-rich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed

    Highly Improved Electrospray Ionization-Mass Spectrometry Detection of G-Quadruplex-Folded Oligonucleotides and Their Complexes with Small Molecules

    Get PDF
    G-quadruplexes are nucleic acids structures stabilized by physiological concentration of potassium ions. Because low stability G-quadruplexes are hardly detectable by mass spectrometry, we optimized solvent conditions: isopropanol in a triethylamine/hexafluoroisopropanol mixture highly increased G-quadruplex sensitivity with no modification of the physiological G-quadruplex conformation. G-quadruplexes/G-quadruplex-ligand complexes were also correctly detected at concentration as low as 40 nM. Detection of the physiological conformation of G4s and their complexes opens up the possibility to perform high-throughput screening of G-quadruplex ligands for the development of drug molecules effective against critical human diseases

    Discrete symmetries from hidden sectors

    Get PDF
    We study the presence of abelian discrete symmetries in globally consistent orientifold compactifications based on rational conformal field theory. We extend previous work [1] by allowing the discrete symmetries to be a linear combination of U(1) gauge factors of the visible as well as the hidden sector. This more general ansatz significantly increases the probability of finding a discrete symmetry in the low energy effective action. Applied to globally consistent MSSM-like Gepner constructions we find multiple models that allow for matter parity or Baryon triality.Comment: 20 page

    Frustrated spin ladder with alternating spin-1 and spin-1/2 rungs

    Full text link
    We study the impact of the diagonal frustrating couplings on the quantum phase diagram of a two-leg ladder composed of alternating spin-1 and spin-1/2 rungs. As the coupling strength is increased the system successively exhibits two gapped paramagnetic phases (a rung-singlet and a Haldane-like non-degenerate states) and two ferrimagnetic phases with different ferromagnetic moments per rung. The first two states are similar to the phases studied in the frustrated spin-1/2 ladder, whereas the magnetic phases appear as a result of the mixed-spin structure of the model. A detailed characterization of these phases is presented using density-matrix renormalization-group calculations, exact diagonalizations of periodic clusters, and an effective Hamiltonian approach inspired by the analysis of numerical data. The present theoretical study was motivated by the recent synthesis of the quasi-one-dimensional ferrimagnetic material FeII^{II}FeIII^{III} (trans-1,4-cyclohexanedicarboxylate) exhibiting a similar ladder structure.Comment: 10 pages, 8 figure

    Preparation and photoemission investigation of bulk-like a-Mn films on W(110)

    Get PDF
    We report the successful stabilization of a thick bulk-like, distorted α\alpha-Mn film with (110) orientation on a W(110) substrate. The observed (3×3)(3\times3) overstructure for the Mn film with respect to the original W(110) low-energy electron diffraction pattern is consistent with the presented structure model. The possibility to stabilize such a pseudomorphic Mn film is supported by density functional total energy calculations. Angle-resolved photoemission spectra of the stabilized α\alpha-Mn(110) film show weak dispersions of the valence band electronic states in accordance with the large unit cell.Comment: 11 pages; 5 figure

    CaII and NaI absorption signatures from the circumgalactic gas of the Milky Way

    Full text link
    We combine CaII/NaI absorption and HI 21 cm emission line measurements to analyse the metal abundances, the distribution, the small-scale structure, and the physical conditions of intermediate- and high-velocity gas in the Galactic halo.Comment: 2 pages, 1 figure, to appear in proceeding of "Galaxies in the Local Volume" Sydney 8-13 July 200

    Surface Plasmon Resonance kinetic analysis of the interaction between G-quadruplex nucleic acids and an anti-G-quadruplex monoclonal antibody

    Get PDF
    Background G-quadruplexes (G4s) are nucleic acids secondary structures formed in guanine-rich sequences. Anti-G4 antibodies represent a tool for the direct investigation of G4s in cells. Surface Plasmon Resonance (SPR) is a highly sensitive technology, suitable for assessing the affinity between biomolecules. We here aimed at improving the orientation of an anti-G4 antibody on the SPR sensor chip to optimize detection of binding antigens. Methods SPR was employed to characterize the anti-G4 antibody interaction with G4 and non-G4 oligonucleotides. Dextran-functionalized sensor chips were used both in covalent coupling and capturing procedures. Results The use of two leading molecule for orienting the antibody of interest allowed to improve its activity from completely non-functional to 65% active. The specificity of the anti-G4 antobody for G4 structures could thus be assessed with high sensitivity and reliability. Conclusions Optimization of the immobilization protocol for SPR biosensing, allowed us to determine the anti-G4 antibody affinity and specificity for G4 antigens with higher sensitivity with respect to other in vitro assays such as ELISA. Anti-G4 antibody specificity is a fundamental assumption for the future utilization of this kind of antibodies for monitoring G4s directly in cells. General significance The heterogeneous orientation of amine-coupling immobilized ligands is a general problem that often leads to partial or complete inactivation of the molecules. Here we describe a new strategy for improving ligand orientation: driving it from two sides. This principle can be virtually applied to every molecule that loses its activity or is poorly immobilized after standard coupling to the SPR chip surface

    Magnetic phase diagram of a frustrated ferrimagnetic ladder: Relation to the one-dimensional boson Hubbard model

    Full text link
    We study the magnetic phase diagram of two coupled mixed-spin (1,1/2)(1,{1/2}) Heisenberg chains as a function of the frustration parameter related to diagonal exchange couplings. The analysis is performed by using spin-wave series and exact numerical diagonalization techniques. The obtained phase diagram--containing the Luttinger liquid phase, the plateau phase with a magnetization per rung M=1/2M=1/2, and the fully polarized phase--is closely related to the generic (J/U,ÎĽ/U)(J/U,\mu/U) phase diagram of the one-dimensional boson Hubbard model.Comment: 4 pages, 2 figure
    • …
    corecore