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Both types of AS events have been shown to play decisive roles during development (e.g., sex determination and differentiation in Drosophila melanogaster [ 13] or developmental stage-related changes in the human CFTR gene [ 14]), but also in human disease (e.g. 5'ss mutations in the tau gene [ 15]).

At each location, the tissue analyzed was homogenous, i.e., contained cells of similar developmental stage- this allowed identification of developmental related changes to the transcriptome.

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The stage of NFTs was assessed according to the Braak and Braak neuropathological staging of Alzheimer-related changes [ 7, 8].

The neuropathological diagnoses of AD were made if the postmortem brains revealed the presence of frequent neuritic plaques in the neocortex (Consortium to Establish a Registry for Alzheimer's Disease, CERAD) [ 29], and NFT stage was no less than IV, according to the Braak and Braak neuropathological staging of Alzheimer-related changes [ 7, 8] as assessed with modified Bielschowsky staining.

An individual cancer phenotype is the result of cell-specific, developmental stage-specific, and metabolism-related changes in gene expression selectively occurring at a time and modified by epigenetic interactions [6].

In addition to CERAD criteria, however, diagnosis was confirmed by also rating each case according to the Braak and Braak neuropathological staging criteria for Alzheimer-related changes [ 47] and the recommendations of the National Institute on Aging and Reagan Institute (NIA-RI) [ 48].

The growth advantage of dysplastic cells over their normal neighbours leads to progressive cytological and architectural derangement, and individual cancer phenotypes are the result of cell-specific, developmental stage-specific, and metabolism-related changes in gene expression that occur selectively at specific times and are modified by epigenetic interactions [ 3].

The other related change is demographic.

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In the present study, we were unable to account for sleep parameters; thus, the observed declines in HRV may result from exposure-related changes in sleep stage or quality.

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