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In contrast, W-12, here considered as the negative counterpart of W-13, induced significantly lower calcium variations in the cytosol. In subsequent experiments, these two compounds were used at a final concentration of 50??m for which the calcium level http://www.selleckchem.com/products/Decitabine.html returned to the basal level within 10?min. In order to investigate the effect of these two drugs either on the calcium response or on the transcriptional response induced by cryptogein, W-13 or W-12 were added to the cell suspension 10?min before cryptogein treatment. Then, cytosolic calcium variations were recorded for 15?min, and the cells were collected after 4?h for transcriptional analysis. The calcium response induced by high concentrations of cryptogein (0.25??m and above) was not modified by either inhibitor, but when cryptogein was added at low concentrations ( http://en.wikipedia.org/wiki/Tryptophan_synthase with the calmodulin inhibitor W-13 than with its negative counterpart W-12. These results confirm the importance of the plateau phase of the calcium signature in the increase of transcript levels induced by cryptogein. Furthermore, the differential effect of anti-CaM compounds, between low and high cryptogein treatments, is consistent with the hypothesis that two calcium decoding modules, one with low affinity and the other with high affinity for calcium, are involved in the regulation of this response. The results presented previously show the existence of correlations between the http://www.selleckchem.com/products/PD-98059.html different phases of the cryptogein-induced calcium signature and the transcriptional response: the calcium-plateau value correlates positively with transcript accumulation, while an increase of the calcium-peak value above a threshold correlates negatively with transcript accumulation. Furthermore, they support the hypothesis of two decoding modules (involving different calcium sensors) able to modulate the response to cryptogein and which could explain the observed correlations. To test this hypothesis and verify its coherence with the experimental data, we used computer modelling and built a model of the non-linear system coupling the cryptogein signal to calcium and transcriptional regulation. The model can be described as follows (see scheme in Fig.?9). The perception of cryptogein triggers opening of calcium channels, which results in an influx of external calcium.