178 research outputs found

    A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP.

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    Clues to Alzheimer disease (AD) pathogenesis come from a variety of different sources including studies of clinical and neuropathological features, biomarkers, genomics and animal and cellular models. An important role for amyloid precursor protein (APP) and its processing has emerged and considerable interest has been directed at the hypothesis that Aβ peptides induce changes central to pathogenesis. Accordingly, molecules that reduce the levels of Aβ peptides have been discovered such as γ-secretase inhibitors (GSIs) and modulators (GSMs). GSIs and GSMs reduce Aβ levels through very different mechanisms. However, GSIs, but not GSMs, markedly increase the levels of APP CTFs that are increasingly viewed as disrupting neuronal function. Here, we evaluated the effects of GSIs and GSMs on a number of neuronal phenotypes possibly relevant to their use in treatment of AD. We report that GSI disrupted retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF), suppressed BDNF-induced downstream signaling pathways and induced changes in the distribution within neuronal processes of mitochondria and synaptic vesicles. In contrast, treatment with a novel class of GSMs had no significant effect on these measures. Since knockdown of APP by specific siRNA prevented GSI-induced changes in BDNF axonal trafficking and signaling, we concluded that GSI effects on APP processing were responsible, at least in part, for BDNF trafficking and signaling deficits. Our findings argue that with respect to anti-amyloid treatments, even an APP-specific GSI may have deleterious effects and GSMs may serve as a better alternative

    Decomposition and nitrogen mineralisation of two wild lupins (Leguminosae) species with potential as green manures

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    The amount of biomass produced by various native species of genus Lupinus (L.) growing in Mexico ranges from 2.9- 8.2 Mg/ha of dry matter, which can add up to 200 kg/ha of N to soil as green manure. However, information is scarce on the decomposition and mineralisation this biomass in the soil. The above-ground decomposition and N mineralisation of Lupinus mexicanus Cerv. ex Lag. and Lupinus rotundiflorus M.E. Jones species from Mexico using fine-mesh litter bags was evaluated. Litter bags containing 5 g of above-ground air-dried biomass at the vegetative and flowering stages were buried at a depth of 20 cm. Were dug up every 3 weeks over the course of 4 months, dried and re-weighed to determine the lost mass and total N by the Kjeldahl method. The largest decrease in residue mass occurred during the first 3 weeks of incubation. However, the lost mass was higher in younger green manure (75 days old) than in older plants (85 days old) after 18 weeks of exposure in the field. It was found that 60-75% of the total N in the plant material was released in the first 6 weeks. In L. rotundiflorus green manure, it was found that 79.14% of the initial N in the vegetative stage and 77.6% of N in the flowering stage was released 18 weeks after litter bag installation, whereas L. mexicanus were 74.6% and 74.7%, respectively. It was found that both decomposition and N mineralisation occurred quickly in the green manures evaluated

    Karyotypic Assymmetries observed in two species of Gossypium L.

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    Karyotypic Assymmetries observed in two species  of  Asimetrías cariotípicas observadas en dos especies de Gossypium L. </htm

    The use of activity diaries for understanding the daily lives of farmers and their livelihood choices

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    This paper reviews the use of activity diaries in two Australian Centre for International Agricultural Research (ACIAR) projects in PNG: a smallholder cocoa project in the East New Britain province (ASEM/2006/127) and a smallholder coffee project in Eastern Highlands province (ASEM/2008/036). Both projects were similarly concerned with identifying the production constraints on cocoa- and coffee-farming households and to better understand the range of socioeconomic and cultural factors influencing farmer decision-making and the allocation of household labour among various livelihood activities. In PNG, the household is the principal production unit underpinning livelihood activities such as commodity production. It is at the household level that decisions and negotiations are made regarding the organisation, mobilisation and management of family and extended family labour. Thus, examining in detail the daily economic and social livelihood activities of household members, through time-allocation studies, helps researchers to understand more comprehensively the factors influencing smallholder decision-making regarding livelihood choices, agricultural practices and the adoption of agricultural innovations. This paper outlines two different techniques using activity diaries employed in the projects, and discusses the methodological advantages and challenges of these techniques in smallholder studies in PNG
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