29 research outputs found

    A cellular disease model system of ARB: The creation of iPS-RPE from a patient with a premature stop mutation (p.R200X)

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    The Experiment Data Depot: A Web-Based Software Tool for Biological Experimental Data Storage, Sharing, and Visualization

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    Although recent advances in synthetic biology allow us to produce biological designs more efficiently than ever, our ability to predict the end result of these designs is still nascent. Predictive models require large amounts of high-quality data to be parametrized and tested, which are not generally available. Here, we present the Experiment Data Depot (EDD), an online tool designed as a repository of experimental data and metadata. EDD provides a convenient way to upload a variety of data types, visualize these data, and export them in a standardized fashion for use with predictive algorithms. In this paper, we describe EDD and showcase its utility for three different use cases: storage of characterized synthetic biology parts, leveraging proteomics data to improve biofuel yield, and the use of extracellular metabolite concentrations to predict intracellular metabolic fluxes

    Simultaneous Mutations in Multi-Viral Proteins Are Required for Soybean mosaic virus to Gain Virulence on Soybean Genotypes Carrying Different R Genes

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    BACKGROUND: Genetic resistance is the most effective and sustainable approach to the control of plant pathogens that are a major constraint to agriculture worldwide. In soybean, three dominant R genes, i.e., Rsv1, Rsv3 and Rsv4, have been identified and deployed against Soybean mosaic virus (SMV) with strain-specificities. Molecular identification of virulent determinants of SMV on these resistance genes will provide essential information for the proper utilization of these resistance genes to protect soybean against SMV, and advance knowledge of virus-host interactions in general. METHODOLOGY/PRINCIPAL FINDINGS: To study the gain and loss of SMV virulence on all the three resistance loci, SMV strains G7 and two G2 isolates L and LRB were used as parental viruses. SMV chimeras and mutants were created by partial genome swapping and point mutagenesis and then assessed for virulence on soybean cultivars PI96983 (Rsv1), L-29 (Rsv3), V94-5152 (Rsv4) and Williams 82 (rsv). It was found that P3 played an essential role in virulence determination on all three resistance loci and CI was required for virulence on Rsv1- and Rsv3-genotype soybeans. In addition, essential mutations in HC-Pro were also required for the gain of virulence on Rsv1-genotype soybean. To our best knowledge, this is the first report that CI and P3 are involved in virulence on Rsv1- and Rsv3-mediated resistance, respectively. CONCLUSIONS/SIGNIFICANCE: Multiple viral proteins, i.e., HC-Pro, P3 and CI, are involved in virulence on the three resistance loci and simultaneous mutations at essential positions of different viral proteins are required for an avirulent SMV strain to gain virulence on all three resistance loci. The likelihood of such mutations occurring naturally and concurrently on multiple viral proteins is low. Thus, incorporation of all three resistance genes in a soybean cultivar through gene pyramiding may provide durable resistance to SMV

    Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies

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    The characterization of a new class of hydrophilic liver-targeted agents for gamma-scintigraphy and MRI, consisting, respectively, of [153Sm]3+ or Gd3+ complexes of DOTA monoamide or bisamide linked glycoconjugates (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), is reported. In vitro studies show high uptake of radiolabeled [153Sm]-DOTAGal2 by the human hepatocyte carcinoma cell line Hep G2 containing the asialoglycoprotein receptor (ASGP-R), which is decreased to less than 50% by the presence of its high-affinity ligand asialofetuin (ASF). In vivo biodistribution, gamma-imaging and pharmacokinetic studies on Wistar rats using the [153Sm]3+-labeled glycoconjugates show a high uptake in the receptor-rich organ liver of the radiolabeled compounds containing terminal galactosyl groups, but very little uptake for those compounds with terminal glycosyl groups. Blocking the receptor in vivo reduced liver uptake by 90%, strongly suggesting that the liver uptake of these compounds is mediated by their binding to the asyaloglycoprotein receptor (ASGP-R). This study also demonstrated that the valency increase improves the targeting capability of the glycoconjugates, which is also affected by their topology. However despite the specific liver uptake of the radiolabeled galactose-bearing multivalent compounds, the animal MRI assessment of the corresponding Gd3+ chelates shows liver-to-kidney contrast effects which are not significantly better than those shown by GdDTPA. This probably results from the quick wash-out from the liver of these highly hydrophilic complexes, before they can be sufficiently concentrated within the hepatocytes via receptor-mediated endocytosis. Copyright © 2006 John Wiley & Sons, Ltd
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