However, upon stimulation with calcium, an additional 18% of the cells reacted , indicating that the treatment did not inactivate the exocytic machinery. A similar percentage of calcium induced exocytosis in permeabilized sperm has been previously reported by us and by other authors. In contrast, sperm from mutated mice did not respond to calcium stimulation, in agreement with the results obtained with A23187 in intact cells. When wild type aSNAP was added to the assay, exocytosis was completely recovered, suggesting that the primary defect in these cells is a deficient amount of functional aSNAP and not an abnormal maturation of sperm in SP mice. However, the previous Western blot analysis and immunofluorescence images showed that these cells have normal levels of aSNAP, suggesting that the M105I mutation affects directly the function of the protein. Since the publication of the human genome sequence, understanding the functional complexity of the genome has become a primary goal of high-throughput experimental research. By definition, AS contributes to proteomic complexity but it has also been suggested that AS is a major driver of phenotypic complexity, though this role remains unproven. By splicing several combinations of exons into different transcripts, AS generates, from a single gene, multiple isoforms of a protein with potentially diverse functions. Not only has AS been invoked as an explanation for our complexity as a species, detection of splice isoforms has been PB 203580 associated with the cause and progression of certain diseases. Alternative splicing is associated with a wide variety of conditions including bipolar disorder, schizophrenia, cancer, diabetes, multiple sclerosis, cystic fibrosis and asthma. Splice isoforms may be functionally relevant in disease or may act as biomarkers indicators of normal or altered biological processes or pharmacological response to a therapeutic intervention. Biomarkers such as disease-specific AS isoforms can serve as indicators of disease susceptibility as well as diagnostic and prognostic markers. If we apply a very restricted definition, which limits the TA to the TMD, our results reveal no effect of the domain on the fission activity. However, the common definition of the TA-domain includes the TMD and the flanking aa concurrently needed for correct targeting. However, heterogeneous phenotype expression has been recently described. It has been shown that Napa -the gene encoding for aSNAP- is mutated in hyh mice. We have used human CpG island microarrays to identify methylated genes in PCa as a whole, as well as differentially methylated in low grade, PP3 and high grade, PP4 PCa. Intermediate Gleason score 7 tumours were not examined as they are composed of both patterns 3 and 4, and we chose to narrow our focus to those tumours that are composed entirely of Gleason pattern 3 or Gleason pattern 4 in order to have enriched cell pattern populations. We found that we were able to identify CpG islands that are both quantitatively more.