Changes in insulin like growth factors, myostatin and vascular endothelial growth factor in rat musculus latissimus dorsi by poly 3-hydroxybutyrate implants

The present study aimed at researching the synergistic effect between an ectopic bone substitute and surrounding muscle tissue. To describe this effect, changes of insulin like growth factors (IGF1, IGF2), myostatin (GDF8) and vascular endothelial growth factor (VEGF) mRNA content of 12 Wistar-King rats musculus latissimus dorsi with implanted poly-3-hydroxybutyrate (PHB) scaffold were examined after 6 and 12 weeks. At each time interval six rats were killed and implants and surrounding tissues prepared for genetic evaluation. Eight rats without any implants served as controls. RNAwas extracted from homogenized muscle tissue and reverse transcribed. Changes in mRNA content were measured by Real-Time PCR using specific primers for IGF1, IGF2, GDF8 and VEGF. Comparing the level of VEGF mRNA in muscle after 6 and 12 weeks to the controls, we could assess a significant increase of VEGF gene expression (

Popular history and the desire for knowledge : an examination of James A. Michener’s The Source as a popular history of Israel

This thesis explores the issues that arise when we consider James A. Michener’s number 1 best-seller The Source (1965) as a popular history of Israel. It examines the educational desires of middlebrow audiences that led to Michener’s popularity, and discusses the benefits and concerns of presenting history in a fictionalised popular form. It then explores how these issues arise within The Source, examining the novel in-depth, arguing that popular history should be cause of greater concern as it has the ability to express particular historical narratives to a wide-reaching audience

Expanding the parameters of academia

This paper draws on qualitative data gathered from two studies funded by the UK Leadership Foundation for Higher Education to examine the expansion of academic identities in higher education. It builds on Whitchurch’s earlier work, which focused primarily on professional staff, to suggest that the emergence of broadly based projects such as widening participation, learning support and community partnership is also impacting on academic identities. Thus, academic as well as professional staff are increasingly likely to work in multi-professional teams across a variety of constituencies, as well as with external partners, and the binary distinction between ‘academic’ and ‘non-academic’ roles and activities is no longer clear-cut. Moreover, there is evidence from the studies of an intentionality about deviations from mainstream academic career routes among respondents who could have gone either way. Consideration is therefore given to factors that influence individuals to work in more project-oriented areas, as well as to variables that affect ways in which these roles and identities develop. Finally, three models of academically oriented project activity are identified, and the implications of an expansion of academic identities are reviewed

Of “sluts” and “arseholes”: Antagonistic desire and the production of sexual vigilance

This article examines a contemporary antagonism in gendered safety discourses—the imperative to be free in public space against the obligation to be safe and “properly” feminine. We argue that this produces (and is produced by) contemporary rape culture, which might be contested through recourse to an agonistic ethic. Using qualitative interview data, we examine how participants contest victim-blaming discourses, while limiting how far they will accept the female body’s right to occupy public space. This article has significant implications for approaching social justice, in particular justice for women and their right to occupy public space

The Crystal Structure of PPIL1 Bound to Cyclosporine A Suggests a Binding Mode for a Linear Epitope of the SKIP Protein

BACKGROUND: The removal of introns from pre-mRNA is carried out by a large macromolecular machine called the spliceosome. The peptidyl-prolyl cis/trans isomerase PPIL1 is a component of the human spliceosome and binds to the spliceosomal SKIP protein via a binding site distinct from its active site. PRINCIPAL FINDINGS: Here, we have studied the PPIL1 protein and its interaction with SKIP biochemically and by X-ray crystallography. A minimal linear binding epitope derived from the SKIP protein could be determined using a peptide array. A 36-residue region of SKIP centred on an eight-residue epitope suffices to bind PPIL1 in pull-down experiments. The crystal structure of PPIL1 in complex with the inhibitor cyclosporine A (CsA) was obtained at a resolution of 1.15 A and exhibited two bound Cd(2+) ions that enabled SAD phasing. PPIL1 residues that have previously been implicated in binding of SKIP are involved in the coordination of Cd(2+) ions in the present crystal structure. Employing the present crystal structure, the determined minimal binding epitope and previously published NMR data, a molecular docking study was performed. In the docked model of the PPIL1.SKIP interaction, a proline residue of SKIP is buried in a hydrophobic pocket of PPIL1. This hydrophobic contact is encircled by several hydrogen bonds between the SKIP peptide and PPIL1. CONCLUSION: We characterized a short, linear epitope of SKIP that is sufficient to bind the PPIL1 protein. Our data indicate that this SKIP peptide could function in recruiting PPIL1 into the core of the spliceosome. We present a molecular model for the binding mode of SKIP to PPIL1 which emphasizes the versatility of cyclophilin-type PPIases to engage in additional interactions with other proteins apart from active site contacts despite their limited surface area

Optimizing accuracy and efficacy in data-driven materials discovery for the solar production of hydrogen

The production of hydrogen fuels, via water splitting, is of practical relevance for meeting global energy needs and mitigating the environmental consequences of fossil-fuel-based transportation. Water photoelectrolysis has been proposed as a viable approach for generating hydrogen, provided that stable and inexpensive photocatalysts with conversion efficiencies over 10% can be discovered, synthesized at scale, and successfully deployed (Pinaud et al., Energy Environ. Sci., 2013, 6, 1983). While a number of first-principles studies have focused on the data-driven discovery of photocatalysts, in the absence of systematic experimental validation, the success rate of these predictions may be limited. We address this problem by developing a screening procedure with co-validation between experiment and theory to expedite the synthesis, characterization, and testing of the computationally predicted, most desirable materials. Starting with 70 150 compounds in the Materials Project database, the proposed protocol yielded 71 candidate photocatalysts, 11 of which were synthesized as single-phase materials. Experiments confirmed hydrogen generation and favorable band alignment for 6 of the 11 compounds, with the most promising ones belonging to the families of alkali and alkaline-earth indates and orthoplumbates. This study shows the accuracy of a nonempirical, Hubbard-corrected density-functional theory method to predict band gaps and band offsets at a fraction of the computational cost of hybrid functionals, and outlines an effective strategy to identify photocatalysts for solar hydrogen generation

Antamanide, a Derivative of Amanita phalloides, Is a Novel Inhibitor of the Mitochondrial Permeability Transition Pore

Antamanide is a cyclic decapeptide derived from the fungus Amanita phalloides. Here we show that antamanide inhibits the mitochondrial permeability transition pore, a central effector of cell death induction, by targeting the pore regulator cyclophilin D. Indeed, (i) permeability transition pore inhibition by antamanide is not additive with the cyclophilin D-binding drug cyclosporin A, (ii) the inhibitory action of antamanide on the pore requires phosphate, as previously shown for cyclosporin A; (iii) antamanide is ineffective in mitochondria or cells derived from cyclophilin D null animals, and (iv) abolishes CyP-D peptidyl-prolyl cis-trans isomerase activity. Permeability transition pore inhibition by antamanide needs two critical residues in the peptide ring, Phe6 and Phe9, and is additive with ubiquinone 0, which acts on the pore in a cyclophilin D-independent fashion. Antamanide also abrogates mitochondrial depolarization and the ensuing cell death caused by two well-characterized pore inducers, clotrimazole and a hexokinase II N-terminal peptide. Our findings have implications for the comprehension of cyclophilin D activity on the permeability transition pore and for the development of novel pore-targeting drugs exploitable as cell death inhibitors

Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design