18 research outputs found

    Canine NAPEPLD-associated models of human myelin disorders

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    Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people

    Canine NAPEPLD-associated models of human myelin disorders

    Get PDF
    Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people.</p

    Electric cars and wind energy: Two problems, one solution? A study to combine wind energy and electric cars in 2020 in The Netherlands

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    To limit or, even better, reduce the emission of CO2 and the corresponding global warming effects, measures should be taken in the two most polluting economic sectors: the energy and transport sectors. The Netherlands has set goals to reduce CO2 emissions, in line with global and European initiatives. To reach this target, the electricity production sector should also use more renewables and the transport sector should take measures. In the electricity sector, the Netherlands wants to realize 10 GW of installed wind power in 2020; one of the initiatives for the transport sector is to have one million EVs (electric vehicles) in the same year. When EVs are powered with electricity from renewable sources, both sectors benefit: as such, we can 'kill two birds with one stone'. To study this, we researched the possible effects on the electricity system when introducing a large number of EVs and an increasing amount of wind power. The research presented models this for the 2020 Dutch situation. The study shows that the 2020 electricity system can cope with one million EVs and 10 GW of wind power, provided that EVs are charged using a load management regime that levels the nightly electricity demand. (C) 2012 Elsevier Ltd. All rights reserved

    Spatial aspects affecting acidification factors in European acidification modelling

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    Plain linear models have recently been used in methodologies to model fate and transport for assessing acidification in life cycle impact assessment (LCIA), or in support of air pollution abatement policies. These models originate from a statistical analysis of the relationship between inputs and outputs of physically-based models that reflect the mechanics of a system in detail. Linear models applied to assess acidification use an acidification factor (AF), which relates changes in the magnitude of emissions to changes in the total area that is protected against acidification in Europe. The changes in emission volume refer to changes of one substance, within one country and one sector or one grid cell. This paper evaluates the dependence of AFs on three spatial characteristics, i.e. the spatial emission and deposition resolution, the spatial emission distribution and the actual spatial location of emissions. The applied spatial resolutions of emission and deposition cause non-systematic variations in AFs of up to 60%, relative to the finest resolution. The manner in which the distribution of emissions is modelled, i.e. grid or sector-specific, is shown to affect AFs considerably, as well. We conclude that spatial characteristics of the physically-based acidification model can affect the assessment of acidification by means of plain linear models. (C) 2008 Elsevier Ltd. All rights reserved
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