Their examinations were performed routinely and without bias

g explants. Due to the binominial PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19717844 distribution and the total number of explants, significance was determined using Fisher’s exact test. Western Blot NOP lysates HC030031 web corresponding to one half embryo were separated on an 8% SDS PAGE, transferred to a nitrocellulose membrane, incubated with the primary antibodies anti-alpha tubulin and anti-GFP and an alkaline phosphatase coupled secondary antibody. consisted of four line scans perpendicular to the membrane surface, i.e., scan with 488 nm in focus 1, scan with 488 nm in focus 2, scan with 561 nm in focus 1, scan with 561 nm in focus 2. Each scanned line consisted of 100 pixels with a width of 100 nm each, yielding a 10 mm scan range; the distance between the two scan lines was set to 400 nm. Data Analysis. The analysis was performed with software written in Matlab. The data of the four sequential scans were arranged in four two-dimensional arrays, with the pixels of each individual scan along the x-axis and the scanned lines sequentially along the y axis. To correct for membrane movements within the confocal volume, the membrane position within each line was determined by smoothing the data with a three-pixel averaging filter and identifying the maximum of the intensity. Subsequently, all peaks were shifted to the same column. The average over all scan lines was computed and fitted with a Gaussian function to determine the standard deviation s. An intensity time trace was constructed by adding up, for each line, the pixel intensities within a range of 62.5 s from the center of the Gaussian. The auto- and crosscorrelation curves of the four resulting intensity time traces were computed and globally fitted with model correlation functions by using a nonlinear least-squares fitting algorithm. Alzheimer’s disease is a devastating condition leading to progressive cognitive decline, functional impairment and loss of independence, and is the major cause PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19717794 of dementia in the elderly worldwide. Its prevalence will continue to increase as life expectancy increases. AD therefore represents a major and rising public health concern. However, as none of the medicines currently in use are able to cure this neurodegenerative disorder, understanding its etiology and developing new protective medicines have become the primary research goals in AD research. Many clinicopathological studies have demonstrated that the deposition of beta-amyloid peptides, fragments of the amyloid precursor protein, in brain parenchyma and cerebral blood vessels is one of the hallmarks of AD. Although the molecular mechanism of its involvement in the development and progression of AD is not clear, a critical role for Ab is universally acknowledged. Ab fibrils were once thought to be the main molecular culprit in AD, but recent studies show a more decisive correlation between the levels of soluble, non-fibrillar Ab oligomers and the extent of synaptic loss and cognitive impairment. Compared with Ab fibrils and plaques, Ab oligomers are more potent as neurotoxins that cause disruption of neuronal synaptic plasticity. The relationships between Ab peptides, oligomerisation, cellular dysfunction and AD suggest that inhibition of Ab oligomerisation might lead to novel therapeutics for the treatment of AD. In addition to chemical pharmacological agents, bioactive extracts derived from natural products are attracting increasing attention in the search for new effective agents for the treatment of AD. Examples of such extracts that, when admi