512 research outputs found

    A phosphorylation map of the bovine papillomavirus E1 helicase

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    BACKGROUND: Papillomaviruses undergo a complex life cycle requiring regulated DNA replication. The papillomavirus E1 helicase is essential for viral DNA replication and plays a key role in controlling viral genome copy number. The E1 helicase is regulated at least in part by protein phosphorylation, however no systematic approach to phosphate site mapping has been attempted. We have utilized mass spectrometry of purified bovine papillomavirus E1 protein to identify and characterize new sites of phosphorylation. RESULTS: Mass spectrometry and in silico sequence analysis were used to identify phosphate sites on the BPV E1 protein and kinases that may recognize these sites. Five new and two previously known phosphorylation sites were identified. A phosphate site map was created and used to develop a general model for the role of phosphorylation in E1 function. CONCLUSION: Mass spectrometric analysis identified seven phosphorylated amino acids on the BPV E1 protein. Taken with three previously identified sites, there are at least ten phosphoamino acids on BPV E1. A number of kinases were identified by sequence analysis that could potentially phosphorylate E1 at the identified positions. Several of these kinases have known roles in regulating cell cycle progression. A BPV E1 phosphate map and a discussion of the possible role of phosphorylation in E1 function are presented

    Audit of a clinical guideline for neonatal hypoglycaemia screening

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    NHRMC Early Career Fellowship #511481RMT was supported by NHRMC Grant #63300

    Ab-initio theory of NMR chemical shifts in solids and liquids

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    We present a theory for the ab-initio computation of NMR chemical shifts (sigma) in condensed matter systems, using periodic boundary conditions. Our approach can be applied to periodic systems such as crystals, surfaces, or polymers and, with a super-cell technique, to non-periodic systems such as amorphous materials, liquids, or solids with defects. We have computed the hydrogen sigma for a set of free molecules, for an ionic crystal, LiH, and for a H-bonded crystal, HF, using density functional theory in the local density approximation. The results are in excellent agreement with experimental data.Comment: to appear in Physical Review Letter

    Development of the Guernsey Community Participation and Leisure Assessment – Revised (GCPLA-R).

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    A sufficiently psychometrically robust measure of community and leisure participation of adults with intellectual disabilities was not in existence, despite research identifying this as an important outcome and a key contributor to quality of life. The current study aimed to update the Guernsey Community Participation and Leisure Assessment (GCPLA). Adults with intellectual disabilities, carers and experts were consulted in creating a revised pool of 46 items. These were then tested and data from 326 adults with intellectual disabilities were analysed for their component structure and psychometric properties. Principal Component analysis discovered a stable set of components describing seven different clusters. This revised measure (the GCPLA-R) was demonstrated to have satisfactory reliability, and scores were related to challenging behaviour and adaptive behaviour in theoretically consistent ways and were correlated with scores on comparable measures

    Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses.

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    QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p<0.0001 for both), and no significant differences in antibody concentration between them. Anti-CFP-10 & anti-ESAT-6 antibodies differentiated APTB from LTBI with sensitivities of 88.7% & 71.1% and specificities of 41.4% & 51.7% respectively. Anti-CFP-10 antibody/M.tb specific IFN-γ and anti-ESAT-6 antibody/M.tb specific IFN-γ ratios had sensitivities of 48.5% & 54.6% and specificities of 89.7% and 75.9% respectively. We conclude that QFT-GIT nil supernatants may be used in the place of sera when measuring antibody responses, reducing blood volumes needed for such investigations. Antibodies in QFT-GIT nil supernatants on their own discriminate APTB from LTBI with high sensitivity but have poor specificity, whereas the reverse is true when antibodies are used in combination with M.tb specific cytokines. Further antibody and antibody/cytokine combinations need to be explored to achieve better diagnostic accuracy

    On the biaxiality of smectic C and ferroelectric liquid crystals

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    Ferroelectric liquid crystals (FLCs) were a major topic for research in the 1980s and 1990s, to which George Gray and his research family played a fundamental role in developing the field. The famous symbiotic relationship between the chemists at Hull University and device physicists at the Royal Signals and Radar Establishment (RSRE) continued throughout this period, providing the basis for the τVmin mode of FLC operation. The principal of this mode relies on the dielectric biaxiality inherent to the smectic C and ferroelectric smectic C* liquid crystal phases. As with nematics before, new materials and device physics developed hand-in-hand, allowing materials to be formulated with addressing times of 12μs at voltages below 30 V. After reviewing the material physics behind these devices, new measurements of the biaxial refractive indices and permittivities are presented, from which the biaxial order parameter C is determined

    C-reactive protein is essential for innate resistance to pneumococcal infection

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    Summary: No deficiency of human C-reactive protein (CRP), or even structural polymorphism of the protein, has yet been reported so its physiological role is not known. Here we show for the first time that CRP-deficient mice are remarkably susceptible to Streptococcus pneumoniae infection and are protected by reconstitution with isolated pure human CRP, or by anti-pneumococcal antibodies. Autologous mouse CRP is evidently essential for innate resistance to pneumococcal infection before antibodies are produced. Our findings are consistent with the significant association between clinical pneumococcal infection and non-coding human CRP gene polymorphisms which affect CRP expression. Deficiency or loss of function variation in CRP may therefore be lethal at the first early-life encounter with this ubiquitous virulent pathogen, explaining the invariant presence and structure of CRP in human adults
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