3,445 research outputs found

    Prevention of the disrupted enamel phenotype in Slc4a4-null mice using explant organ culture maintained in a living host kidney capsule.

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    Slc4a4-null mice are a model of proximal renal tubular acidosis (pRTA). Slc4a4 encodes the electrogenic sodium base transporter NBCe1 that is involved in transcellular base transport and pH regulation during amelogenesis. Patients with mutations in the SLC4A4 gene and Slc4a4-null mice present with dysplastic enamel, amongst other pathologies. Loss of NBCe1 function leads to local abnormalities in enamel matrix pH regulation. Loss of NBCe1 function also results in systemic acidemic blood pH. Whether local changes in enamel pH and/or a decrease in systemic pH are the cause of the abnormal enamel phenotype is currently unknown. In the present study we addressed this question by explanting fetal wild-type and Slc4a4-null mandibles into healthy host kidney capsules to study enamel formation in the absence of systemic acidemia. Mandibular E11.5 explants from NBCe1-/- mice, maintained in host kidney capsules for 70 days, resulted in teeth with enamel and dentin with morphological and mineralization properties similar to cultured NBCe1+/+ mandibles grown under identical conditions. Ameloblasts express a number of proteins involved in dynamic changes in H+/base transport during amelogenesis. Despite the capacity of ameloblasts to dynamically modulate the local pH of the enamel matrix, at least in the NBCe1-/- mice, the systemic pH also appears to contribute to the enamel phenotype. Extrapolating these data to humans, our findings suggest that in patients with NBCe1 mutations, correction of the systemic metabolic acidosis at a sufficiently early time point may lead to amelioration of enamel abnormalities

    Development of a severe local storm prediction system: A 60-day test of a mesoscale primitive equation model

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    The progress and problems associated with the dynamical forecast system which was developed to predict severe storms are examined. The meteorological problem of severe convective storm forecasting is reviewed. The cascade hypothesis which forms the theoretical core of the nested grid dynamical numerical modelling system is described. The dynamical and numerical structure of the model used during the 1978 test period is presented and a preliminary description of a proposed multigrid system for future experiments and tests is provided. Six cases from the spring of 1978 are discussed to illustrate the model's performance and its problems. Potential solutions to the problems are examined

    Development of the health and economic consequences of smoking interactive model

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    Objective-To describe the health and economic consequences of smoking model, a user friendly, web based tool, designed to estimate the health and economic outcomes associated with smoking and the benefits of smoking cessation. Results-An overview of the development of the model equations and user interface is given, and data from the UK are presented as an example of the model outputs. These results show that a typical smoking cessation strategy costs approximately pound 1200 per life year saved and pound 22 000 per death averted. Conclusions-The model successfully captures the complexity required to model smoking behaviour and associated mortality, morbidity, and health care costs. Furthermore, the interface provides the results in a simple and flexible way so as to be useful to a variety of audiences and to simulate a variety of smoking cessation methods

    Hair Whorls and Monozygosity

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    X-ray rocking curve study of Si-implanted GaAs, Si, and Ge

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    Crystalline properties of Si-implanted GaAs, Si, and Ge have been studied by Bragg case double-crystal x-ray diffraction. Sharp qualitative and quantitative differences were found between the damage in GaAs on one hand and Si and Ge on the other. In Si and Ge the number of defects and the strain increase linearly with dose up to the amorphous threshold. In GaAs the increase in these quantities is neither linear nor monotonic with dose. At a moderate damage level the GaAs crystal undergoes a transition from elastic to plastic behavior. This transition is accompanied by the creation of extended defects, which are not detected in Si or Ge

    TFIP11 Interacts with mDEAH9, an RNA Helicase Involved in Spliceosome Disassembly

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    Yeast proteins Ntr1, Ntr2 and Prp43 function in spliceosome disassembly. An Ntr1-Ntr2 protein complex recruits Prp43 to allow the removal of the lariat-intron in late-stage RNA splicing activity. Based on amino-acid sequence similarities across species, TFIP11 and mDEAH9/Dhx15 have been identified as homologues of yeast Ntr1 and Prp43, respectively. The N-terminal region of TFIP11 contains a G-patch, which is a highly conserved domain of many RNA-processing proteins. TFIP11 displays a unique and characteristic subnuclear localization pattern, in close proximity to SC35 nuclear speckles. Transfected GFP-tagged mDEAH9 displays an evenly distributed nuclear localization and is excluded from the nucleoli; however when TFIP11 and mDEAH9 are co-transfected, both proteins colocalize to distinct nuclear speckles. These data show that TFIP11 recruits mDEAH9 suggesting that these two proteins have similar biological activities to their yeast counterparts
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