7 research outputs found

    Substrate scope for trimethyllysine hydroxylase catalysis

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    Contains fulltext : 161427.pdf (publisher's version ) (Open Access

    Biomolecular Recognition of Methylated Histones

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    Investigating D-lysine stereochemistry for epigenetic methylation, demethylation and recognition

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    Contains fulltext : 181125.pdf (preprint version ) (Open Access

    A critique of injury scoring systems when used for blast injuries: a narrative review with recommendations for future work

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    Injury scoring systems can be used for triaging, predicting morbidity and mortality, and prognosis. Recent conflicts and civilian incidents have highlighted the unique nature of blast injuries, exposing deficiencies in current scoring systems. This review’s aim was to classify and describe the issues with current systems when used in blast, identify deficiencies in the literature, and propose scope for improvements of scoring systems. Strengths of current scoring systems include the ability to highlight survival trends for populations, thus allowing for assessment of medical advances. The review identified the major limitations of current scoring systems as: the inability to accurately and reliably predict mortality outcomes for an individual patient; the saturation effect, where scoring systems are unable to discriminate between high injury score individuals; and underrepresentation of blast injuries by omitting: systemic effects, the effect of the overall injury burden, lack of precision in discriminating between injury mechanism, and lack of data underpinning scoring system coefficients. Other factors influence outcomes, including the level of healthcare, and the delay between injury and presentation. It is an open question whether these should be incorporated in scoring systems. We recommend that a new score adapt the severity of injuries to the blast mechanism. This may include refined and additional codes, and severity scores, being added to the AIS system for high frequency blast-specific injuries; a weighting for body regions of higher risk of fatality; and blast specific trauma coefficients. Finally, the saturation effect (maximum value) be removed enabling classification of more severe injury constellation

    Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins

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    A large number of structurally diverse epigenetic reader proteins specifically recognize methylated lysine residues on histone proteins. Here we describe comparative thermodynamic, structural and computational studies on recognition of the positively charged natural trimethyllysine and its neutral analogues by reader proteins. This work provides experimental and theoretical evidence that reader proteins predominantly recognize trimethyllysine via a combination of favourable cation–π interactions and the release of the high-energy water molecules that occupy the aromatic cage of reader proteins on the association with the trimethyllysine side chain. These results have implications in rational drug design by specifically targeting the aromatic cage of readers of trimethyllysine
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