184 research outputs found

    Analysis of the hippocampal proteome in ME7 prion disease reveals a predominant astrocytic signature and highlights the brain-restricted production of clusterin in chronic neurodegeneration

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    Prion diseases are characterized by accumulation of misfolded protein, gliosis, synaptic dysfunction, and ultimately neuronal loss. This sequence, mirroring key features of Alzheimer disease, is modeled well in ME7 prion disease. We used iTRAQ(TM)/mass spectrometry to compare the hippocampal proteome in control and late-stage ME7 animals. The observed changes associated with reactive glia highlighted some specific proteins that dominate the proteome in late-stage disease. Four of the up-regulated proteins (GFAP, high affinity glutamate transporter (EAAT-2), apo-J (Clusterin), and peroxiredoxin-6) are selectively expressed in astrocytes, but astrocyte proliferation does not contribute to their up-regulation. The known functional role of these proteins suggests this response acts against protein misfolding, excitotoxicity, and neurotoxic reactive oxygen species. A recent convergence of genome-wide association studies and the peripheral measurement of circulating levels of acute phase proteins have focused attention on Clusterin as a modifier of late-stage Alzheimer disease and a biomarker for advanced neurodegeneration. Since ME7 animals allow independent measurement of acute phase proteins in the brain and circulation, we extended our investigation to address whether changes in the brain proteome are detectable in blood. We found no difference in the circulating levels of Clusterin in late-stage prion disease when animals will show behavioral decline, accumulation of misfolded protein, and dramatic synaptic and neuronal loss. This does not preclude an important role of Clusterin in late-stage disease, but it cautions against the assumption that brain levels provide a surrogate peripheral measure for the progression of brain degeneration

    Indicators of Pathogen Potential of Pasture Soils

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    A simple pot test was used to indicate the combined effects of several pathogens common in pasture soils (plant parasitic nematodes and pathogenic fungi e.g. Pythium spp.) by comparing the dry weight yields of clover seedlings grown in untreated soil with those from soil treated in a microwave oven. Response to microwave treatment, expressed as a Soil Pathogenicity Index , was greater with soil from old pasture or from areas in 2 year old pasture plots showing poor regrowth after grazing of white clover (Trifolium repens L) or Caucasian clover (T. ambiguum Bieb.), than from soil from new pasture or areas in the 2 year old plots with vigorous clover regrowth

    Effect of Management and Cultivar on Nodal Root Development of White Clover

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    Nodal root development of white clover (Trifolium repens L.) swards was monitored by harvesting marked nodes from late autumn to spring and by taking tiller plugs over 15 months. At a hill country site Grasslands Huia and a large-leaved French eultivar, Crau, had greater nodal root development, in terms of root length, than a small­leaved hill country ecotype. Compadson of the effects of rotational sheep and cattle grazing at both lowland and hill country sites showed greater nodal root development root length and lateral root production under cattle grazing. Percentage of nodes with roots was greater under rotational than set-stocked grazing in winter and early spring but differences were not apparent in late spring, summer or autumn. In late spring percentage of nodes with roots was greater under set­stocked than rotational sheep grazing, Numbers of nodal roots per m2 were 75-140% greater under rotational grazing than set-stocked grazing in autumn and winter but similar in summer and spring. Reduced nodal development during winter under set-stocked sheep grazing was associated with reduced carbon export to young nodal roots developed on shaded stolons (simulating stolon burial) which were severely defoliated. Under more lenient defoliation which occurs under rotational grazing, carbon export to young nodal roots is greater on shaded compared with unshaded stolons

    Loess origin, transport, and deposition over the past 10,000 years, Wrangell-St. Elias National Park, Alaska

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    Contemporary glaciogenic dust has not received much attention, because most research has been on glaciogenic dust of the last glacial period or non-glaciogenic dust of the present interglacial period. Nevertheless, dust from modern glaciogenic sources may be important for Fe inputs to primary producers in the ocean. Adjacent to the subarctic Pacific Ocean, we studied a loess section near Chitina, Alaska along the Copper River in Wrangell-St. Elias National Park, where dust has been accumulating over the past ~10,000 years. Mass accumulation rates for the fine-grained (\u3c20 \u3eµm) fraction of this loess section are among the highest reported for the Holocene of high-latitude regions of the Northern Hemisphere. Based on mineralogy and geochemistry, loess at Chitina is derived from glacial sources in the Wrangell Mountains, the Chugach Mountains, and probably the Alaska Range. Concentrations of Fe in the silt-plus-clay fraction of the loess at Chitina are much higher than in all other loess bodies in North America and higher than most loess bodies on other continents. The very fine-grained (\u3c2 \u3eµm) portion of this sediment, capable of long-range transport, is dominated by Fe-rich chlorite, which can yield Fe readily to primary producers in the ocean. Examination of satellite imagery shows that dust from the Copper River is transported by wind on a regular basis to the North Pacific Ocean. This Alaskan example shows that high-latitude glaciogenic dust needs to be considered as a significant Fe source to primary producers in the open ocean

    Creative Futures: Act, Sing, Play. Evaluation report and executive summary

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    Act, Sing, Play (ASP) offered music and drama tuition to Year 2 pupils. The aim of the programme was to evaluate whether music workshops had a bigger impact than drama workshops in terms of pupils’ maths and literacy attainment. The evaluation was based on the hypothesis that participation in high-quality music instruction promotes educational attainment over and above instruction in other artistic pursuits. The ASP programme was developed specifically for this trial and ran from September 2013 to June 2014: 909 pupils participated in 19 schools across London, Essex, Sussex and Coventry. In each participating Year 2 class, pupils were randomly allocated to one of three groups: violin or cello workshops (ASPstrings), singing lessons (ASP-singing), or drama workshops (ASP-drama). The two music groups (strings and singing) represented the treatment arms of the trial. Students in the ASP-drama workshops represented the control. Each workshop had around 10 students. Workshops were held once a week over 32 weeks. This evaluation provides no evidence that ASP-music workshops had a greater impact on maths or literacy attainment than ASP-drama workshops. Analysis of students receiving free school meals similarly found no evidence that ASP-music workshops had a greater impact on maths or literacy than ASP-drama workshops
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