Journal
CHRONOBIOLOGY INTERNATIONAL
Volume 17, Issue 1, Pages 1-14Publisher
MARCEL DEKKER INC
DOI: 10.1081/CBI-100101027
Keywords
control theory; chronotherapy; entrainment; oscillations; periodic intermittent stimulation
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PER protein circadian oscillations in Drosophila have been described by Goldbeter according to a five-dimensional model that includes the possibility of genetic mutation described by changing one parameter, the maximum degradation rate of the PER protein. Assuming that, in a mutant Drosophila this parameter is unreachable, we modify another parameter, the translation rate between the mRNA and the nonphosphorylated form of PER protein, by periodic intermittent activation or inhibition. We show how such a modification, simulated in the model by a periodic, on/off, piecewise constant stimulation (which increases or decreases this parameter) allows the entrainment of oscillations exactly at, or close to, a desired period. In a different context, this suggests that some diseases may be corrected using pharmacological agents according to specific periodic delivery schedules.
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