108 research outputs found
Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae
Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo
Ab initio molecular dynamics of liquid water using embedded-fragment second-order many-body perturbation theory towards its accurate property prediction
A direct, simultaneous calculation of properties of a liquid using an ab initio electron-correlated theory has long been unthinkable. Here we present structural, dynamical, and response properties of liquid water calculated by ab initio molecular dynamics using the embedded-fragment spin-component-scaled second-order many-body perturbation method with the aug-cc-pVDZ basis set. This level of theory is chosen as it accurately and inexpensively reproduces the water dimer potential energy surface from the coupled-cluster singles, doubles, and noniterative triples with the augcc-pVQZ basis set, which is nearly exact. The calculated radial distribution function, self-diffusion coefficient, coordinate number, and dipole moment, as well as the infrared and Raman spectra are in excellent agreement with experimental results. The shapes and widths of the OH stretching bands in the infrared and Raman spectra and their isotropic-anisotropic Raman noncoincidence, which reflect the diverse local hydrogen-bond environment, are also reproduced computationally. The simulation also reveals intriguing dynamic features of the environment, which are difficult to probe experimentally, such as a surprisingly large fluctuation in the coordination number and the detailed mechanism by which the hydrogen donating water molecules move across the first and second shells, thereby causing this fluctuationopen
Pedigree analysis and epidemiological features of idiopathic congenital talipes equinovarus in the United Kingdom: a case-control study
Anti- Japanese-Encephalitis-Viral Effects of Kaempferol and Daidzin and Their RNA-Binding Characteristics
Background: New therapeutic tools and molecular targets are needed for treatment of Japanese encephalitis virus (JEV) infections. JEV requires an a-1 translational frameshift to synthesize the NS1 ’ protein required for viral neuroinvasiveness. Several flavonoids have been shown to possess antiviral activity in vitro against a wide spectrum of viruses. To date, the antiviral activities of flavonol kaempferol (Kae) and isoflavonoid daidzin (Dai) against JEV have not been described. Methodology/Principal Findings: The 50 % cytotoxic concentration (CC50) and 50 % effective concentration (EC50) against JEV were investigated in BHK21 cells by MTS reduction. Activity against viral genomic RNA and proteins was measured by real-time RT-PCR and western blotting. The frameshift site RNA-binding characterization was also determined by electrospray ionization mass spectrometry, isothermal titration calorimetry and autodocking analysis. EC 50 values of Kae and Dai were 12.6 and 25.9 mM against JEV in cells pretreated before infection, whereas in cells infected before treatment, EC50 was 21.5 and 40.4 mM, respectively. Kae exhibited more potent activity against JEV and RNA binding in cells following internalization through direct inhibition of viral replication and protein expression, indicating that its antiviral activity was principally due to direct virucidal effects. The JEV frameshift site RNA (fsRNA) was selected as a target for assaying Kae and Dai. ITC of fsRNA revealed an apparent Kb value for Kae that was nine fold stronger than that for Dai. This binding was confirmed and localized to the RNA using ESI-MS and autodock analysis. Kae could form non-covalent complexes wit
Does size matter for horny beetles? A geometric morphometric analysis of interspecific and intersexual size and shape variation in Colophon haughtoni Barnard, 1929, and C. kawaii Mizukami, 1997 (Coleoptera: Lucanidae)
Colophon is an understudied, rare and endangered stag beetle genus with all species endemic to isolated mountain peaks in South Africa’s Western Cape. Geometric morphometrics was used to analyse intersexual and interspecific variation of size and shape in the mandibles, heads, pronota and elytra of two sympatric species: Colophon haughtoni and Colophon kawaii. All measured structures showed significant sexual dimorphism, which may result from male-male competition for females. Female mandibles were too small and featureless for analysis, but male Colophon beetles possess large, ornate mandibles for fighting. Males had significantly larger heads and pronota that demonstrated shape changes which may relate to resource diversion to the mandibles and their supporting structures. Females are indistinguishable across species, but males were accurately identified using mandibles, heads and pronota. Male C. kawaii were significantly larger than C. haughtoni for all structures. These results support the species status of C. kawaii, which is currently in doubt due to its hybridisation with C. haughtoni. We also demonstrate the value of geometric morphometrics as a tool which may aid Colophon conservation by providing biological and phylogenetic insights and enabling species identification
Chlorophylls, ligands and assembly of light-harvesting complexes in chloroplasts
Chlorophyll (Chl) b serves an essential function in accumulation of light-harvesting complexes (LHCs) in plants. In this article, this role of Chl b is explored by considering the properties of Chls and the ligands with which they interact in the complexes. The overall properties of the Chls, not only their spectral features, are altered as consequences of chemical modifications on the periphery of the molecules. Important modifications are introduction of oxygen atoms at specific locations and reduction or desaturation of sidechains. These modifications influence formation of coordination bonds by which the central Mg atom, the Lewis acid, of Chl molecules interacts with amino acid sidechains, as the Lewis base, in proteins. Chl a is a versatile Lewis acid and interacts principally with imidazole groups but also with sidechain amides and water. The 7-formyl group on Chl b withdraws electron density toward the periphery of the molecule and consequently the positive Mg is less shielded by the molecular electron cloud than in Chl a. Chl b thus tends to form electrostatic bonds with Lewis bases with a fixed dipole, such as water and, in particular, peptide backbone carbonyl groups. The coordination bonds are enhanced by H-bonds between the protein and the 7-formyl group. These additional strong interactions with Chl b are necessary to achieve assembly of stable LHCs
Phylogenetic Analysis of Pelecaniformes (Aves) Based on Osteological Data: Implications for Waterbird Phylogeny and Fossil Calibration Studies
) were also assessed. The antiquity of these taxa and their purported status as stem members of extant families makes them valuable for studies of higher-level avian diversification. (sister taxon to Phalacrocoracidae). These relationships are invariant when ‘backbone’ constraints based on recent avian phylogenies are imposed.Relationships of extant pelecaniforms inferred from morphology are more congruent with molecular phylogenies than previously assumed, though notable conflicts remain. The phylogenetic position of the Plotopteridae implies that wing-propelled diving evolved independently in plotopterids and penguins, representing a remarkable case of convergent evolution. Despite robust support for the placement of fossil taxa representing key calibration points, the successive outgroup relationships of several “stem fossil + crown family” clades are variable and poorly supported across recent studies of avian phylogeny. Thus, the impact these fossils have on inferred patterns of temporal diversification depends heavily on the resolution of deep nodes in avian phylogeny
Southern Hemisphere climate variability forced by Northern Hemisphere ice-sheet topography
The presence of large Northern Hemisphere ice sheets and reduced greenhouse gas concentrations during the Last Glacial Maximum fundamentally altered global ocean–atmosphere climate dynamics1. Model simulations and palaeoclimate records suggest that glacial boundary conditions affected the El Niño–Southern Oscillation2,3, a dominant source of short-term global climate variability. Yet little is known about changes in short-term climate variability at mid- to high latitudes. Here we use a high-resolution water isotope record from West Antarctica to demonstrate that interannual to decadal climate variability at high southern latitudes was almost twice as large at the Last Glacial Maximum as during the ensuing Holocene epoch (the past 11,700 years). Climate model simulations indicate that this increased variability reflects an increase in the teleconnection strength between the tropical Pacific and West Antarctica, owing to a shift in the mean location of tropical convection. This shift, in turn, can be attributed to the influence of topography and albedo of the North American ice sheets on atmospheric circulation. As the planet deglaciated, the largest and most abrupt decline in teleconnection strength occurred between approximately 16,000 years and 15,000 years ago, followed by a slower decline into the early Holocene
Increased oxidative product formation by peripheral blood polymorphonuclear leukocytes in human periodontal diseases
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