314 research outputs found

    Smad7:β-catenin Complex Regulates Myogenic Gene Transcription

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    Recent reports indicate that Smad7 promotes skeletal muscle differentiation and growth. We previously documented a non-canonical role of nuclear Smad7 during myogenesis, independent of its role in TGF-β signaling. Here further characterization of the myogenic function of Smad7 revealed β-catenin as a Smad7 interacting protein. Biochemical analysis identified a Smad7 interaction domain (SID) between aa575 and aa683 of β-catenin. Reporter gene analysis and chromatin immunoprecipitation demonstrated that Smad7 and β-catenin are cooperatively recruited to the extensively characterized ckm promoter proximal region to facilitate its muscle restricted transcriptional activation in myogenic cells. Depletion of endogenous Smad7 and β-catenin in muscle cells reduced ckm promoter activity indicating their role during myogenesis. Deletion of the β-catenin SID substantially reduced the effect of Smad7 on the ckm promoter and exogenous expression of SID abolished β-catenin function, indicating that SID functions as a trans dominant-negative regulator of β-catenin activity. β-catenin interaction with the Mediator kinase complex through its Med12 subunit led us to identify MED13 as an additional Smad7-binding partner. Collectively, these studies document a novel function of a Smad7-MED12/13-β-catenin complex at the ckm locus, indicating a key role of this complex in the program of myogenic gene expression underlying skeletal muscle development and regeneration.York University Librarie

    Corporate Privacy Trend: The “Value” of Personally Identifiable Information (“PII”) Equals the “Value” of Financial Assets

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    Corporate America’s increasing dependence on the electronic use of personally identifiable information (“PII”) necessitates a reexamination and expansion of the traditional conception of corporate assets. PII is now a commodity that companies trade and sell. As technological development increases, aspects of day-to-day business involving PII are performed electronically in a more cost effective and efficient manner. PII, which companies obtain at little cost, has quantifiable value that is rapidly reaching a level comparable to the value of traditional financial assets

    Application of laccase enzymes in organic synthesis

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    A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of requirements for the degree of Master of Science. Johannesburg, 2018.The use of enzymes as catalysts in various synthetic procedures appears to be an economical and profound way of providing selective processes in synthetic organic chemistry. Enzymes provide alternative and sustainable processes and have helped to avoid limitations encountered when using traditional heterogeneous and homogeneous catalysts; this includes the use of toxic substances, use of expensive heavy metals, extensive use of harmful organic solvents, harsh reaction conditions, and also poor selectivity of many catalysts. Laccases are oxidoreductase enzymes capable of catalysing oxidation reactions of several low molecular weight organic compounds such as polyphenols, aminophenols, methoxyphenols, polyamines, and lignin-related molecules. The catalytic process of these enzymes occurs though a one-electron oxidation and water is released as the only by-product. In this project we investigated the range and limitations of applications of laccase enzymes in organic synthesis. The project focus was on method development for cross-coupling reactions of Carbon, Nitrogen, Oxygen, and Sulphur substituted aromatic compounds. The laccase facilitated synthesis of five classes of compounds; biaryl compounds, benzoxazoles, benzimidazoles, benzothiazoles, and aminobenzoquinones, was investigated. The research explored the synthesis of biaryl compounds from simple substituted phenol substrates. The optimal reaction conditions for the synthesis of biaryl compounds from simple phenols were investigated. A condensation reaction between 2-aminophenol and aryl aldehyde derivatives was performed with the aim of synthesising 2-arylbenzoxazole derivatives; however various aminophenol derivatives were formed as the phenolic Schiff base failed to cyclise. Alternatively, when including the laccase-mediator ABTS, dimerization of 2-aminophenol to 2-amino-3H-phenoxazin-3-one (4) occurred. A chemo-selective method for the synthesis of 2-aryl-1H-benzimidazoles from condensation of 2-phenelynediamine and aryl aldehydes was developed using laccase as an oxidising catalyst. Optimal conditions for synthesising 2-aryl-1H-benzimidazoles were identified while using acetate buffer (0.1 M, pH 4.5), acetonitrile as a co-solvent and the commercial laccase preparation Novoprime base 268. A modern and practical laccase-catalysed route suitable for the synthesis of 2-arylbenzothiazoles was developed. To the best of our knowledge, the laccase catalysed method for preparation of 2-arylbenzothiazole derivatives derived from condensation–dehydration reaction of 2-aminothiophenol with aryl-aldehydes has not been reported before. The method described is green, effective and simply requires a facile work-up routine, utilising solvents such as acetonitrile and DMF as co-solvents. Finally, factors limiting yields for the synthesis of aminobenzoquinones were investigated by varying the reaction conditions. The laccase catalysed nuclear diamination of aromatic hydrobenzoquinones with aliphatic and aromatic amine molecules was investigated under mild reaction conditions using commercial laccases from Novozymes (Suberase®, Denilite® II Base, and Novoprime Base 268). Conducting the reactions under dilute conditions, sequential addition of enzyme and substrate over time and using Novoprime Base 268 as our laccase increased the yields to up to 100%.LG201

    LEGAL ANALYSIS OF ELECTRONIC BULLETIN BOARD ACTIVITIES

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