FlyMine is a data warehouse that addresses one of the important challenges of modern biology: how to integrate and make use of the diversity and volume of current biological data. Its main focus is genomic and proteomics data for Drosophila and other insects. It provides web access to integrated data at a number of different levels, from simple browsing to construction of complex queries, which can be executed on either single items or lists. RationaleWith the completion of increasing numbers of genome sequences has come an explosion in the development of both computational and experimental techniques for deciphering the functions of genes, molecules and their interactions. These include theoretical methods for deducing function, such as analysis of protein homologies, structural domain predictions, phylogenetic profiling and analysis of protein domain fusions, as well as experimental techniques, such as microarray-based gene expression and transcription factor binding studies, two-hybrid protein-protein interaction screens, and large-scale RNA interference (RNAi) screens. The result is a huge amount of information and a current challenge is to extract meaningful knowledge and patterns of biological significance that can lead to new experimentally testable hypotheses. Many of these broad datasets, however, are noisy and the data quality can vary significantly. While in some circumstances the data from each of these techniques are useful in their own right, the ability to combine data from different sources facilitates interpretation and potentially allows stronger inferences to be made. Currently, biological data are stored in a wide variety of formats in numerous different places, making their combined analysis difficult: when information from several different databases is required, the assembly of data into a format suitable for querying is a challenge in itself. Sophisticated analysis of diverse data requires that they are available in a form that allows questions to be asked across them and that tools for constructing the questions are available. The development of systems for the integration and combined analysis of diverse data remains a priority in bioinformatics. Avoiding the need to understand and reformat many different data sources is a major benefit for end users of a centralized data access system.A number of studies have illustrated the power of integrating data for cross-validation, functional annotation and generating testable hypotheses (reviewed in [1,2]). These studies have covered a range of data types; some looking at the overlap between two different data sets, for example, protein interaction and expression data [3][4][5][6] Another key component is the use of ontologies that provide a standardized system for naming biological entities and their relationships and this aspect is based on the approach taken by the Chado schema [28]. For example, a large part of the FlyMine data model is based on the Sequence Ontology (a controlled-vocabulary for describing biological sequences) [29...
Bacterial cellulose (BC) serves as a molecular glue to facilitate intra- and inter-domain interactions in nature. Biosynthesis of BC-containing biofilms occurs in a variety of Proteobacteria that inhabit diverse ecological niches. The enzymatic and regulatory systems responsible for the polymerization, exportation, and regulation of BC are equally as diverse. Though the magnitude and environmental consequences of BC production are species-specific, the common role of BC-containing biofilms is to establish close contact with a preferred host to facilitate efficient host–bacteria interactions. Universally, BC aids in attachment, adherence, and subsequent colonization of a substrate. Bi-directional interactions influence host physiology, bacterial physiology, and regulation of BC biosynthesis, primarily through modulation of intracellular bis-(3′→5′)-cyclic diguanylate (c-di-GMP) levels. Depending on the circumstance, BC producers exhibit a pathogenic or symbiotic relationship with plant, animal, or fungal hosts. Rhizobiaceae species colonize plant roots, Pseudomonadaceae inhabit the phyllosphere, Acetobacteriaceae associate with sugar-loving insects and inhabit the carposphere, Enterobacteriaceae use fresh produce as vehicles to infect animal hosts, and Vibrionaceae, particularly Aliivibrio fischeri, colonize the light organ of squid. This review will highlight the diversity of the biosynthesis and regulation of BC in nature by discussing various examples of Proteobacteria that use BC-containing biofilms to facilitate host–bacteria interactions. Through discussion of current data we will establish new directions for the elucidation of BC biosynthesis, its regulation and its ecophysiological roles.
Two unsymmetrical dinucleotide phosphate triesters were synthesized via transesterification from tris(2,2,2trifluoroethyl) phosphate. The protected triesters were phosphytilated to generate phosphoramidites for solid-phase oligonucleotide synthesis. Neutral phenylethyl phosphate-modified short-interfering RNAs (siRNAs) were synthesized and evaluated for their genesilencing ability, siRNA strand selection, and resistance to nucleases. These backbone-modified phosphate triester siRNAs offer many improvements compared to natural unmodified siRNAs.
Short interfering RNAs (siRNAs) show promise as gene-silencing therapeutics, but their cellular uptake remains a challenge. We have recently shown the synthesis of siRNAs bearing a single neutral phenylethyl phosphotriester linkage within the sense strand. Here, we report the synthesis of siRNAs bearing three different hydrophobic phosphate triester linkages at key positions within the sense strand and assess their gene silencing in the absence of a transfection carrier. The best siRNAs bearing hydrophobic phosphate triester tails were not aromatic and exhibited effective gene silencing (IC50 ≈ 56–141 nM), whereas the aromatic derivative with three hydrophobic tails did not exhibit carrier-free gene silencing.
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