80 resultados para Risk and loss functions


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Studies suggest that activation of phosphoinositide 3-kinase-Akt may protect against neuronal cell death in Alzheimer's disease (AD). Here, however, we provide evidence of increased Akt activation, and hyperphosphorylation of critical Akt substrates in AD brain, which link to AD pathogenesis, suggesting that treatments aiming to activate the pathway in AD need to be considered carefully. A different distribution of Akt and phospho-Akt was detected in AD temporal cortex neurons compared with control neurons, with increased levels of active phosphorylated-Akt in particulate fractions, and significant decreases in Akt levels in AD cytosolic fractions, causing increased activation of Akt (phosphorylated-Akt/total Akt ratio) in AD. In concordance, significant increases in the levels of phosphorylation of total Akt substrates, including: GSK3ßSer9, tauSer214, mTORSer2448, and decreased levels of the Akt target, p27kip1, were found in AD temporal cortex compared with controls. A significant loss and altered distribution of the major negative regulator of Akt, PTEN (phosphatase and tensin homologue deleted on chromosome 10), was also detected in AD neurons. Loss of phosphorylated-Akt and PTEN-containing neurons were found in hippocampal CA1 at end stages of AD. Taken together, these results support a potential role for aberrant control of Akt and PTEN signalling in AD.

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The role of limpet grazing in preventing the development of algal canopies is a recurrent theme in intertidal ecology. Less is known about interactions of limpets with the long-term dynamics of established canopies. Aerial photographs indicate that intertidal canopy cover has declined over the past 44 yr in Strangford Lough, Northern Ireland. There has been a loss of the previously continuous cover of Ascophyllum nodosum (L.) Le Jolis in the mid-shore. A barnacles dominated assemblage now fills gaps in the A. nodosum canopy. The rates at which barnacle patches become established and grow have increased since 1990. Changes in canopy cover have been accompanied by increases in limpet densities since the 1980s. Measurements between 2003 and 2004 showed no increase in length of A. nodosum fronds when limpets Patella vulgata had access to the algal holdfasts. In contrast, when limpets were experimentally excluded from the holdfasts, there was net frond growth. In the Isle of Man, which is climatically similar to Strangford Lough but has fewer limpets, growth occurred regardless of limpet grazing. The breaking force for A. nodosum declined with increasing local densities of limpets. A. nodosum is a sheltered shore species, potentially vulnerable to changes in wave exposure. There is no evidence, however, that Strangford Lough has become windier over the past 3 decades. Variation in wave exposure among locations within the lough was not related to rates of barnacle patch creation or expansion, Limpet population density has increased following a series of mild winters. Climate change may have a role in causing canopy loss, not by direct effects on the limpet populations.

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