204 research outputs found

    Assessing the potential impact of environmental land management schemes on emergent infection disease risks

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    Financial incentives are provided by governments to encourage the plantation of new woodland to increase habitat, biodiversity, carbon sequestration, and other economic benefits for landowners. Whilst these are largely positive effects, it is worth considering that greater biodiversity and presence of wildlife species in proximity to agricultural holdings may pose a risk of disease transmission between wildlife and livestock. Wildlife transmission and the provision of a reservoir for infectious disease is particularly important in the transmission dynamics of bovine tuberculosis. In this paper we develop an economic model for changing land use due to forestry subsidies. We use this asses the impact on wild deer populations in the newly created woodland areas and the emergent infectious disease risk arising from the proximity of new and existing wild deer populations and existing cattle holdings. We consider an area in the South-West of Scotland, having existing woodland, deer populations, and extensive and diverse cattle farm holdings. In this area we find that, with a varying level of subsidy and plausible new woodland creation, the contact risk between areas of wild deer and cattle increases between 26% and 35% over the contact risk present with zero subsidy. This model provides a foundation for extending to larger regions and for examining potential risk mitigation strategies, for example the targeting of subsidy in low risk areas or provisioning for buffer zones between woodland and agricultural holdings

    Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition

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    Alzheimer’s disease (AD) is characterised by the aggregation and deposition of amyloid-β (Aβ) peptides in the human brain. In age-related late-onset AD, deficient degradation and clearance, rather than enhanced production, of Aβ contributes to disease pathology. In the present study, we assessed the contribution of the two key Aβ-degrading zinc metalloproteases, insulin-degrading enzyme (IDE) and neprilysin (NEP), to Aβ degradation in human induced pluripotent stem cell (iPSC)-derived cortical neurons. Using an Aβ fluorescence polarisation assay, inhibition of IDE but not of NEP, blocked the degradation of Aβ by human neurons. When the neurons were grown in a 3D extracellular matrix to visualise Aβ deposition, inhibition of IDE but not NEP, increased the number of Aβ deposits. The resulting Aβ deposits were stained with the conformation-dependent, anti-amyloid antibodies A11 and OC that recognise Aβ aggregates in the human AD brain. Inhibition of the Aβ-forming β-secretase prevented the formation of the IDE-inhibited Aβ deposits. These data indicate that inhibition of IDE in live human neurons grown in a 3D matrix increased the deposition of Aβ derived from the proteolytic cleavage of the amyloid precursor protein. This work has implications for strategies aimed at enhancing IDE activity to promote Aβ degradation in AD
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