199 research outputs found

    Variation in Tropical Reef Symbiont Metagenomes Defined by Secondary Metabolism

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    The complex evolution of secondary metabolism is important in biology, drug development, and synthetic biology. To examine this problem at a fine scale, we compared the genomes and chemistry of 24 strains of uncultivated cyanobacteria, Prochloron didemni, that live symbiotically with tropical ascidians and that produce natural products isolated from the animals. Although several animal species were obtained along a >5500 km transect of the Pacific Ocean, P. didemni strains are >97% identical across much of their genomes, with only a few exceptions concentrated in secondary metabolism. Secondary metabolic gene clusters were sporadically present or absent in identical genomic locations with no consistent pattern of co-occurrence. Discrete mutations were observed, leading to new chemicals that we isolated from animals. Functional cassettes encoding diverse chemicals are exchanged among a single population of symbiotic P. didemni that spans the tropical Pacific, providing the host animals with a varying arsenal of secondary metabolites

    On minimizing coding operations in network coding based multicast: an evolutionary algorithm

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    In telecommunications networks, to enable a valid data transmission based on network coding, any intermediate node within a given network is allowed, if necessary, to perform coding operations. The more coding operations needed, the more coding resources consumed and thus the more computational overhead and transmission delay incurred. This paper investigates an efficient evolutionary algorithm to minimize the amount of coding operations required in network coding based multicast. Based on genetic algorithms, we adapt two extensions in the proposed evolutionary algorithm, namely a new crossover operator and a neighbourhood search operator, to effectively solve the highly complex problem being concerned. The new crossover is based on logic OR operations to each pair of selected parent individuals, and the resulting offspring are more likely to become feasible. The aim of this operator is to intensify the search in regions with plenty of feasible individuals. The neighbourhood search consists of two moves which are based on greedy link removal and path reconstruction, respectively. Due to the specific problem feature, it is possible that each feasible individual corresponds to a number of, rather than a single, valid network coding based routing subgraphs. The neighbourhood search is applied to each feasible individual to find a better routing subgraph that consumes less coding resource. This operator not only improves solution quality but also accelerates the convergence. Experiments have been carried out on a number of fixed and randomly generated benchmark networks. The results demonstrate that with the two extensions, our evolutionary algorithm is effective and outperforms a number of state-of-the-art algorithms in terms of the ability of finding optimal solutions

    Discovery of microscopic electronic inhomogeneity in the high-Tc superconductor Bi2Sr2CaCu2O8+x

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    The parent compounds of the copper oxide high-Tc superconductors are unusual insulators. Superconductivity arises when they are properly doped away from stoichiometry1. In Bi2Sr2CaCu2O8+x, superconductivity results from doping with excess oxygen atoms, which introduce positive charge carriers (holes) into the CuO2 planes, where superconductivity is believed to originate. The role of these oxygen dopants is not well understood, other than the fact that they provide charge carriers. However, it is not even clear how these charges distribute in the CuO2 planes. Accordingly, many models of high-Tc superconductors simply assume that the charge carriers introduced by doping distribute uniformly, leading to an electronically homogeneous system, as in ordinary metals. Here we report the observation of an electronic inhomogeneity in the high-Tc superconductor Bi2Sr2CaCu2O8+x using scanning tunnelling microscopy/spectroscopy. This inhomogeneity is manifested as spatial variations in both the local density of states spectrum and the superconducting energy gap. These variations are correlated spatially and vary on a surprisingly short length scale of ~ 14 Angs. Analysis suggests that the inhomogeneity observed is a consequence of proximity to a Mott insulator resulting in poor screening of the charge potentials associated with the oxygen ions left behind in the BiO plane after doping. Hence this experiment is a direct probe of the local nature of the superconducting state, which is not easily accessible by macroscopic measurements.Comment: 6 pages, 4 figure

    High-Volume versus Low-Volume for Esophageal Resections for Cancer: The Essential Role of Case-Mix Adjustments based on Clinical Data

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    Background: Most studies addressing the volume-outcome relationship in complex surgical procedures use hospital mortality as the sole outcome measure and are rarely based on detailed clinical data. The lack of reliable information about comorbidities and tumor stages makes the conclusions of these studies debatable. The purpose of this study was to compare outcomes for esophageal resections for cancer in low- versus high-volume hospitals, using an extensive set of variables concerning case-mix and outcome measures, including long-term survival. Methods: Clinical data, from 903 esophageal resections performed between January 1990 and December 1999, were retrieved from the original patients' files. Three hundred and forty-two patients were operated on in 11 low-volume hospitals (<7 resections/year) and 561 in a single high-volume center. Results: Mortality and morbidity rates were significantly lower in the high-volume center, which had an in-hospital mortality of 5 vs 13% (P < .001). On multivariate analysis, hospital volume, but also the presence of comorbidity proved to be strong prognostic factors predicting in-hospital mortality (ORs 3.05 and 2.34). For stage I and II disease, there was a significantly better 5-year survival in the high-volume center. (P = .04). Conclusions: Hospital volume and comorbidity patterns are important determinants of outcome in esophageal cancer surgery. Strong clinical endpoints such as in-hospital mortality and survival can be used as performance indicators, only if they are joined by reliable case-mix information

    Effects of EpCAM overexpression on human breast cancer cell lines

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    <p>Abstract</p> <p>Background</p> <p>Recently, EpCAM has attracted major interest as a target for antibody- and vaccine-based cancer immunotherapies. In breast cancer, the EpCAM antigen is overexpressed in 30-40% of all cases and this increased expression correlates with poor prognosis. The use of EpCAM-specific monoclonal antibodies is a promising treatment approach in these patients.</p> <p>Methods</p> <p>In order to explore molecular changes following EpCAM overexpression, we investigated changes of the transcriptome upon EpCAM gene expression in commercially available human breast cancer cells lines Hs578T and MDA-MB-231. To assess cell proliferation, a tetrazolium salt based assay was performed. A TCF/LEF Reporter Kit was used to measure the transcriptional activity of the Wnt/β-catenin pathway. To evaluate the accumulation of β-catenin in the nucleus, a subcellular fractionation assay was performed.</p> <p>Results</p> <p>For the first time we could show that expression profiling data of EpCAM transfected cell lines Hs578T<sup>EpCAM </sup>and MDA-MB-231<sup>EpCAM </sup>indicate an association of EpCAM overexpression with the downregulation of the Wnt signaling inhibitors SFRP1 and TCF7L2. Confirmation of increased Wnt signaling was provided by a TCF/LEF reporter kit and by the finding of the nuclear accumulation of ß-catenin for MDA-MB-231<sup>EpCAM </sup>but not Hs578T<sup>EpCAM </sup>cells. In Hs578T cells, an increase of proliferation and chemosensitivity to Docetaxel was associated with EpCAM overexpression.</p> <p>Conclusions</p> <p>These data show a cell type dependent modification of Wnt signaling components after EpCAM overexpression in breast cancer cell lines, which results in marginal functional changes. Further investigations on the interaction of EpCAM with SFRP1 and TCF7L2 and on additional factors, which may be causal for changes upon EpCAM overexpression, will help to characterize unique molecular properties of EpCAM-positive breast cancer cells.</p

    Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells

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    e Glasgow and Manchester Experimental Cancer Medicine Centres (ECMC), which are funded by CR-UK and the Chief Scientist’s Office (Scotland). We acknowledge the funders who have contributed to this work: MRC stratified medicine infrastructure award (A.D.W.), CR-UK C11074/A11008 (F.P., L.E.M.H., T.L.H., A.D.W.); LLR08071 (S.A.A., E.C.); LLR11017 (M.C.); SCD/04 (M.C.); LLR13035 (S.A.A., K.D., A.D.W., and A.P.); LLR14005 (M.T.S., D.V.); KKL690 (L.E.P.); KKL698 (P.B.); LLR08004 (A.D.W., A.P. and A.J.W.); MRC CiC (M.E.D.); The Howat Foundation (FACS support); Friends of Paul O’Gorman (K.D. and FACS support); ELF 67954 (S.A.A.); BSH start up fund (S.A.A.); MR/K014854/1 (K.D.)

    The Regulatory Network of Natural Competence and Transformation of Vibrio cholerae

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    The human pathogen Vibrio cholerae is an aquatic bacterium frequently encountered in rivers, lakes, estuaries, and coastal regions. Within these environmental reservoirs, the bacterium is often found associated with zooplankton and more specifically with their chitinous exoskeleton. Upon growth on such chitinous surfaces, V. cholerae initiates a developmental program termed “natural competence for genetic transformation.” Natural competence for transformation is a mode of horizontal gene transfer in bacteria and contributes to the maintenance and evolution of bacterial genomes. In this study, we investigated competence gene expression within this organism at the single cell level. We provide evidence that under homogeneous inducing conditions the majority of the cells express competence genes. A more heterogeneous expression pattern was observable on chitin surfaces. We hypothesize that this was the case due to the heterogeneity around the chitin surface, which might vary extensively with respect to chitin degradation products and autoinducers; these molecules contribute to competence induction based on carbon catabolite repression and quorum-sensing pathways, respectively. Therefore, we investigated the contribution of these two signaling pathways to natural competence in detail using natural transformation assays, transcriptional reporter fusions, quantitative RT–PCR, and immunological detection of protein levels using Western blot analysis. The results illustrate that all tested competence genes are dependent on the transformation regulator TfoX. Furthermore, intracellular cAMP levels play a major role in natural transformation. Finally, we demonstrate that only a minority of genes involved in natural transformation are regulated in a quorum-sensing-dependent manner and that these genes determine the fate of the surrounding DNA. We conclude with a model of the regulatory circuit of chitin-induced natural competence in V. cholerae
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