306 research outputs found

    Novel genomic island modifies DNA with 7-deazaguanine derivatives

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    The discovery of ∌20-kb gene clusters containing a family of paralogs of tRNA guanosine transglycosylase genes, called tgtA5, alongside 7-cyano-7-deazaguanine (preQ[subscript 0]) synthesis and DNA metabolism genes, led to the hypothesis that 7-deazaguanine derivatives are inserted in DNA. This was established by detecting 2’-deoxy-preQ[subscript 0] and 2’-deoxy-7-amido-7-deazaguanosine in enzymatic hydrolysates of DNA extracted from the pathogenic, Gram-negative bacteria Salmonella enterica serovar Montevideo. These modifications were absent in the closely related S. enterica serovar Typhimurium LT2 and from a mutant of S. Montevideo, each lacking the gene cluster. This led us to rename the genes of the S. Montevideo cluster as dpdA-K for 7-deazapurine in DNA. Similar gene clusters were analyzed in ∌150 phylogenetically diverse bacteria, and the modifications were detected in DNA from other organisms containing these clusters, including Kineococcus radiotolerans, Comamonas testosteroni, and Sphingopyxis alaskensis. Comparative genomic analysis shows that, in Enterobacteriaceae, the cluster is a genomic island integrated at the leuX locus, and the phylogenetic analysis of the TgtA5 family is consistent with widespread horizontal gene transfer. Comparison of transformation efficiencies of modified or unmodified plasmids into isogenic S. Montevideo strains containing or lacking the cluster strongly suggests a restriction–modification role for the cluster in Enterobacteriaceae. Another preQ[subscript 0] derivative, 2’-deoxy-7-formamidino-7-deazaguanosine, was found in the Escherichia coli bacteriophage 9g, as predicted from the presence of homologs of genes involved in the synthesis of the archaeosine tRNA modification. These results illustrate a deep and unexpected evolutionary connection between DNA and tRNA metabolism.Deutsche ForschungsgemeinschaftSingapore-MIT Alliance in Research and Technology (SMART

    Helical Chirality: a Link between Local Interactions and Global Topology in DNA

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    DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

    Quantum character varieties and braided module categories

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    We compute quantum character varieties of arbitrary closed surfaces with boundaries and marked points. These are categorical invariants ∫SA\int_S\mathcal A of a surface SS, determined by the choice of a braided tensor category A\mathcal A, and computed via factorization homology. We identify the algebraic data governing marked points and boundary components with the notion of a {\em braided module category} for A\mathcal A, and we describe braided module categories with a generator in terms of certain explicit algebra homomorphisms called {\em quantum moment maps}. We then show that the quantum character variety of a decorated surface is obtained from that of the corresponding punctured surface as a quantum Hamiltonian reduction. Characters of braided A\mathcal A-modules are objects of the torus category ∫T2A\int_{T^2}\mathcal A. We initiate a theory of character sheaves for quantum groups by identifying the torus integral of A=Repq⁥G\mathcal A=\operatorname{Rep_q} G with the category Dq(G/G)−mod⁥\mathcal D_q(G/G)-\operatorname{mod} of equivariant quantum D\mathcal D-modules. When G=GLnG=GL_n, we relate the mirabolic version of this category to the representations of the spherical double affine Hecke algebra (DAHA) SHq,t\mathbb{SH}_{q,t}.Comment: 33 pages, 5 figures. Final version, to appear in Sel. Math. New Se

    Cyclotomic Gaudin models: construction and Bethe ansatz

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    This is a pre-copyedited author produced PDF of an article accepted for publication in Communications in Mathematical Physics, Benoit, V and Young, C, 'Cyclotomic Gaudin models: construction and Bethe ansatz', Commun. Math. Phys. (2016) 343:971, first published on line March 24, 2016. The final publication is available at Springer via http://dx.doi.org/10.1007/s00220-016-2601-3 © Springer-Verlag Berlin Heidelberg 2016To any simple Lie algebra g\mathfrak g and automorphism σ:g→g\sigma:\mathfrak g\to \mathfrak g we associate a cyclotomic Gaudin algebra. This is a large commutative subalgebra of U(g)⊗NU(\mathfrak g)^{\otimes N} generated by a hierarchy of cyclotomic Gaudin Hamiltonians. It reduces to the Gaudin algebra in the special case σ=id\sigma = \text{id}. We go on to construct joint eigenvectors and their eigenvalues for this hierarchy of cyclotomic Gaudin Hamiltonians, in the case of a spin chain consisting of a tensor product of Verma modules. To do so we generalize an approach to the Bethe ansatz due to Feigin, Frenkel and Reshetikhin involving vertex algebras and the Wakimoto construction. As part of this construction, we make use of a theorem concerning cyclotomic coinvariants, which we prove in a companion paper. As a byproduct, we obtain a cyclotomic generalization of the Schechtman-Varchenko formula for the weight function.Peer reviewe

    Computerized general practice based networks yield comparable performance with sentinel data in monitoring epidemiological time-course of influenza-like illness and acute respiratory illness

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    <p>Abstract</p> <p>Background</p> <p>Computerized morbidity registration networks might serve as early warning systems in a time where natural epidemics such as the H<sub>1</sub>N<sub>1 </sub>flu can easily spread from one region to another.</p> <p>Methods</p> <p>In this contribution we examine whether general practice based broad-spectrum computerized morbidity registration networks have the potential to act as a valid surveillance instrument of frequently occurring diseases. We compare general practice based computerized data assessing the frequency of influenza-like illness (ILI) and acute respiratory infections (ARI) with data from a well established case-specific sentinel network, the European Influenza Surveillance Scheme (EISS). The overall frequency and trends of weekly ILI and ARI data are compared using both networks.</p> <p>Results</p> <p>Detection of influenza-like illness and acute respiratory illness occurs equally fast in EISS and the computerized network. The overall frequency data for ARI are the same for both networks, the overall trends are similar, but the increases and decreases in frequency do not occur in exactly the same weeks. For ILI, the overall rate was slightly higher for the computerized network population, especially before the increase of ILI, the overall trend was almost identical and the increases and decreases occur in the same weeks for both networks.</p> <p>Conclusions</p> <p>Computerized morbidity registration networks are a valid tool for monitoring frequent occurring respiratory diseases and the detection of sudden outbreaks.</p
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