2,970 research outputs found

    Solution structure of human MBD1 CXXC1

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    Women post-recession: moving towards insecurity

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    After the recession, the rise in casual and precarious contracts is entrenching gender inequality in the UK

    Solution structure of hMBD1 CXXC1

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    Methylation of CpG dinucleotides is the major epigenetic modification of mammalian DNA which results in the remodelling of transcriptionally active euchromatin to transcriptionally inactive heterochromatin. Recognition of methylated CpG by methylated DNA binding proteins, the MBD family, the Kaiso zinc finger family and the SRA domain proteins results in deacetylation and methylation of histone side chains through the recruitment of HDAC and HMT enzymes. Methylation of DNA is a heritable process ensuring Methylation dependant transcriptional repression is passed from mother to daughter cell during replication. Some of the proteins involved in this chromatin remodelling, MBD1, DNMT1, MLL, and CFP1 contain CXXC domains. hMBD1 contains 2 or 3 CXXC domains depending on the splice variant, with only the third CXXC domain shown to bind CpG dinucleotides. This thesis describes the work done to elucidate the structure of hMBD1 CXXC1 and to investigate hMBD1 CXXC12 di-domain by NMR spectroscopy and biochemical characterisation. The hMBD1 CXXC1 & CXXC12 domains were successfully over expressed in E. coli and purified. Unlabelled and uniformly 15N labelled proteins were produced for nuclear magnetic resonance (NMR) studies. Assignment of NMR spectra was carried out and constraints generated enabling structure determination of hMBD1 CXXC1 and to investigate the relationship between CXXC1 and CXXC2 of hMBD1. The solution structure of hMBD1 CXXC1 determined here was compared to the previously determined solution structure of hMLL CXXC in order to investigate their differences in DNA binding. NOE data from hMBD1 CXXC1 and CXXC12 are compared in order to investigate the domain structure of CXXC12. DNA titration of hMBD1 CXXC1 showed no significant interaction with a single CpG oligo while the loop region of hMBD1 CXXC1 differs significant in both structure and surface charge suggesting the loop region to be important for DNA binding. The recorded NOE data of hMBD CXXC12 suggests the two CXXC domains form a globular rather than a linear structur

    Soluble Fermentable Dietary Fibre (Pectin) Decreases Caloric Intake, Adiposity and Lipidaemia in High-Fat Diet-Induced Obese Rats

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    Funding: This work was funded by the Scottish Government Rural and Environment Science and Analytical Services Division. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Motion of buoyant particles and coarsening of solid-liquid mixtures in a random acceleration field

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    Flow induced by a random acceleration field (g-jitter) is considered in two related situations that are of interest for microgravity fluid experiments: the random motion of an isolated buoyant particle and coarsening of a solid-liquid mixture. We start by analyzing in detail actual accelerometer data gathered during a recent microgravity mission, and obtain the values of the parameters defining a previously introduced stochastic model of this acceleration field. We then study the motion of a solid particle suspended in an incompressible fluid that is subjected to such random accelerations. The displacement of the particle is shown to have a diffusive component if the correlation time of the stochastic acceleration is finite or zero, and mean squared velocities and effective diffusion coefficients are obtained explicitly. Finally, the effect of g-jitter on coarsening of a solid-liquid mixture is considered. Corrections due to the induced fluid motion are calculated, and estimates are given for coarsening of Sn-rich particles in a Sn-Pb eutectic fluid, experiment to be conducted in microgravity in the near future.Comment: 25 pages, 4 figures (included). Also at http://www.scri.fsu.edu/~vinals/ross2.p

    Knowledge of Objective 'Oughts': Monotonicity and the New Miners Puzzle

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    In the classic Miners case, an agent subjectively ought to do what they know is objectively wrong. This case shows that the subjective and objective ‘oughts’ are somewhat independent. But there remains a powerful intuition that the guidance of objective ‘oughts’ is more authoritative—so long as we know what they tell us. We argue that this intuition must be given up in light of a monotonicity principle, which undercuts the rationale for saying that objective ‘oughts’ are an authoritative guide for agents and advisors

    Optimal strategies for regional cultivar testing

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    In undertaking cultivar trials, the variability of the response of the cultivars to the different environments in which they are grown introduces the possibility of release errors and non‐release errors in the decisions made on the basis of the trial results. In this article a model is developed that accounts for the economic costs of those errors as well as the costs of operating the trials, and enables the features of the optimal cultivar testing program to be identified. The model is illustrated by application to wheat cultivar trials in central and southern NSW.Crop Production/Industries,
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