160 research outputs found

    Cisplatin binding sites on human albumin

    Get PDF
    Reactions of cisplatin (cis -[PtCl2(NH3)2]) with albumin are thought to play an important role in the metabolism of this anticancer drug. They are investigated here via (i) labeling of cisplatin with 15N and use of two-dimensional 1H,15N NMR spectroscopy, (ii) comparison of natural human serum albumin with recombinant human albumin (higher homogeneity and SH content), (iii) chemical modification of Cys, Met, and His residues, (iv) reactions of bound platinum with thiourea, and (v) gel filtration chromatography. In contrast to previous reports, it is shown that the major sulfur-containing binding site involves Met and not Cys-34, and also a N ligand, in the form of an S,N macrochelate. Additional monofunctional adducts involving other Met residues and Cys-34 are also observed. During the later stages of reactions of cisplatin with albumin, release of NH3 occurs due to the strong trans influence of Met sulfur, which weakens the Pt-NH3 bonds, and protein cross-linking is observed. The consequences of these findings for the biological activity of cisplatin-albumin complexes are discussed

    The SOFG Anatomy Entry List (SAEL):an annotation tool for functional genomics data

    Get PDF
    A great deal of data in functional genomics studies needs to be annotated with low-resolution anatomical terms. For example, gene expression assays based on manually dissected samples (microarray, SAGE, etc.) need high-level anatomical terms to describe sample origin. First-pass annotation in high-throughput assays (e.g. large-scale in situ gene expression screens or phenotype screens) and bibliographic applications, such as selection of keywords, would also benefit from a minimum set of standard anatomical terms. Although only simple terms are required, the researcher faces serious practical problems of inconsistency and confusion, given the different aims and the range of complexity of existing anatomy ontologies. A Standards and Ontologies for Functional Genomics (SOFG) group therefore initiated discussions between several of the major anatomical ontologies for higher vertebrates. As we report here, one result of these discussions is a simple, accessible, controlled vocabulary of gross anatomical terms, the SOFG Anatomy Entry List (SAEL). The SAEL is available from http://www.sofg.org and is intended as a resource for biologists, curators, bioinformaticians and developers of software supporting functional genomics. It can be used directly for annotation in the contexts described above. Importantly, each term is linked to the corresponding term in each of the major anatomy ontologies. Where the simple list does not provide enough detail or sophistication, therefore, the researcher can use the SAEL to choose the appropriate ontology and move directly to the relevant term as an entry point. The SAEL links will also be used to support computational access to the respective ontologies

    The crafting of an (un)enterprising community: context and the social practice of talk

    Get PDF
    YesThis article examines a ‘deprived’ UK community to identify how (dis)connections between context and enterprise are produced within accounts of a particular locality. We used a discursive psychological approach to examine how the community depicted itself as a context for enterprise. Our analysis identified three discursive repertoires mobilised by a range of voices in the community which combined to portray an unenterprising community and create a conceptual deadlock for enterprise. We suggest it is too deterministic to assume context is fixed and controls the potential for entrepreneurial development. Instead, we should consider social practices, including talk, that help construct the contexts in which entrepreneurship is expected to occur.The research resorted in this article was funded by an Economic and Social Research Council studentship

    Modeling biomedical experimental processes with OBI

    Get PDF
    BACKGROUND: Experimental descriptions are typically stored as free text without using standardized terminology, creating challenges in comparison, reproduction and analysis. These difficulties impose limitations on data exchange and information retrieval. RESULTS: The Ontology for Biomedical Investigations (OBI), developed as a global, cross-community effort, provides a resource that represents biomedical investigations in an explicit and integrative framework. Here we detail three real-world applications of OBI, provide detailed modeling information and explain how to use OBI. CONCLUSION: We demonstrate how OBI can be applied to different biomedical investigations to both facilitate interpretation of the experimental process and increase the computational processing and integration within the Semantic Web. The logical definitions of the entities involved allow computers to unambiguously understand and integrate different biological experimental processes and their relevant components. AVAILABILITY: OBI is available at http://purl.obolibrary.org/obo/obi/2009-11-02/obi.ow

    The impact of dark matter cusps and cores on the satellite galaxy population around spiral galaxies

    Get PDF
    (Abridged) We use N-body simulations to study the effects that a divergent (i.e. "cuspy") dark matter (DM) profile introduces on the tidal evolution of dwarf spheroidal galaxies (dSphs). Our models assume cosmologically-motivated initial conditions where dSphs are DM-dominated systems on eccentric orbits about a host galaxy composed of a dark halo and a baryonic disc. We find that the resilience of dSphs to tidal stripping is extremely sensitive to the halo cuspiness; whereas dwarfs with a cored profile can be easily destroyed by the host disc, those with cusps always retain a bound remnant. For a given halo profile the evolution of the structural parameters as driven by tides is controlled solely by the total amount of mass lost. This information is used to construct a semi-analytic code that simulates the hierarchical build-up of spiral galaxies assuming different halo profiles and disc masses. We find that tidal encounters with discs tend to decrease the average mass of satellites at all galactocentric radii. Interestingly, satellites accreted before re-ionization (z>6), which may be singled out by anomalous metallicity patterns, survive only if haloes are cuspy. We show that the size-mass relation established from Milky Way (MW) dwarfs strongly supports the presence of cusps in the majority of these systems, as cored models systematically underestimate the masses of the known Ultra-Faint dSphs. Our models also indicate that a massive M31 disc may explain why many of its dSphs fall below the size-mass relationship derived from MW dSphs. We use our models to constrain the mass threshold below which star formation is suppressed in DM haloes, finding that luminous satellites must be accreted with masses above 10^8--10^9 M_sol in order to explain the size-mass relation observed in MW dwarfs.Comment: 17 pages, 14 figures, MNRAS accepted after minor revisio
    corecore