Effects of different per translational kinetics on the dynamics of a core circadian clock model.

Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.

Recent developments on the Kardar-Parisi-Zhang surface-growth equation.

The stochastic nonlinear partial differential equation known as the Kardar-Parisi-Zhang (KPZ) equation is a highly successful phenomenological mesoscopic model of surface and interface growth processes. Its suitability for analytical work, its explicit symmetries and its prediction of an exact dynamic scaling relation for a one-dimensional substratum led people to adopt it as a 'standard' model in the field during the last quarter of a century. At the same time, several conjectures deserving closer scrutiny were established as dogmas throughout the community. Among these, we find the beliefs that 'genuine' non-equilibrium processes are non-variational in essence, and that the exactness of the dynamic scaling relation owes its existence to a Galilean symmetry. Additionally, the equivalence among planar and radial interface profiles has been generally assumed in the literature throughout the years. Here--among other topics--we introduce a variational formulation of the KPZ equation, remark on the importance of consistency in discretization and challenge the mainstream view on the necessity for scaling of both Galilean symmetry and the one-dimensional fluctuation-dissipation theorem. We also derive the KPZ equation on a growing domain as a first approximation to radial growth, and outline the differences with respect to the classical case that arises in this new situation.