A qualitative method for analysis of prey-predator systems under enrichment

A new qualitative method of analysis suitable for dynamic systems of the prey-predator type is presented. An application of the method to a specific ecosystem is given and the model's behaviour under conditions of enrichment is examined. It is shown that the existence of limit cycle oscillations, as well as the location of these cycles, can be positively established. The critical value of enrichment at which globally stable oscillations occur is found using the method, and the results are shown to be in agreement with those of previous research.     

Coupling oscillations and switches in genetic networks

Switches (bistability) and oscillations (limit cycle) are omnipresent in biological networks. Synthetic genetic networks producing bistability and oscillations have been designed and constructed experimentally. However, in real biological systems, regulatory circuits are usually interconnected and the dynamics of those complex networks is often richer than the dynamics of simple modules. Here we couple the genetic Toggle switch and the Repressilator, two prototypic systems exhibiting bistability and oscillations, respectively. We study two types of coupling. In the first type, the bistable switch is under the control of the oscillator. Numerical simulation of this system allows us to determine the conditions under which a periodic switch between the two stable steady states of the Toggle switch occurs. In addition we show how birhythmicity characterized by the coexistence of two stable small-amplitude limit cycles, can easily be obtained in the system. In the second type of coupling, the oscillator is placed under the control of the Toggleswitch. Numerical simulation of this system shows that this construction could for example be exploited to generate a permanent transition from a stable steady state to self-sustained oscillations (and vice versa) after a transient external perturbation. Those results thus describe qualitative dynamical behaviors that can be generated through the coupling of two simple network modules. These results differ from the dynamical properties resulting from interlocked feedback loops systems in which a given variable is involved at the same time in both positive and negative feedbacks. Finally the models described here may be of interest in synthetic biology, as they give hints on how the coupling should be designed to get the required properties.     

Local and global bifurcations at infinity in models of glycolytic oscillations

 We investigate two models of glycolytic oscillations. Each model consists of two coupled nonlinear ordinary differential equations. Both models are found to have a saddle point at infinity and to exhibit a saddle-node bifurcation at infinity, giving rise to a second saddle and a stable node at infinity. Depending on model parameters, a stable limit cycle may blow up to infinite period and amplitude and disappear in the bifurcation, and after the bifurcation, the stable node at infinity then attracts all trajectories. Alternatively, the stable node at infinity may coexist with either a stable sink (not at infinity) or a stable limit cycle. This limit cycle may then disappear in a heteroclinic bifurcation at infinity in which the unstable manifold from one saddle at infinity joins the stable manifold of the other saddle at infinity. These results explain prior reports for one of the models concerning parameter values for which the system does not admit any physical (bounded) behavior. Analytic results on the scaling of amplitude and period close to the bifurcations are obtained and confirmed by numerical computations. Finally, we consider more realistic modified models where all solutions are bounded and show that some of the features stemming from the bifurcations at infinity are still present. Received 4 September 1995; received in revised form 18 September 1996     

Metastability in a temperature-dependent model system for predator-prey mite outbreak interactions on fruit trees

The nonlinear behavior of a particular Kolmogorov-type exploitation differential equation system assembled by May (1973,Stability and Complexity in Model Ecosystems, Princeton University Press) from predator and prey components developed by Leslie (1948,Biometrica 35, 213–245) and Holling (1973,Mem. Entomol. Soc. Can. 45, 1–60), respectively, is re-examined by means of the numerical bifurcation code AUTO 86 with model parameters chosen appropriately for a temperature dependent mite interaction on fruit trees. The most significant result of this analysis is that, in addition to the temperature ranges over which the single community equilibrium point of the system iseither globally stableor gives rise to a globally stable limit cycle, there can also exist a range wherein multiple stable states occur. These stable states consist of a focus (spiral point) and a limit cycle, separated from each other in the phase plane by an unstable limit cycle. The ecological implications of such metastability, hysteresis and threshold behavior for the occurrence of outbreaks, the persistence of oscillations, the resiliency of the system and the biological control of mite populations are discussed. It is further suggested that a model of this sort which possesses a single community equilibrium point may be more useful for representing outbreak phenomena, especially in the presence of oscillations, than the non-Kolmogorov predator-prey systems possessing three community equilibrium points, two of which are stable and the other a saddle point, traditionally employed for this purpose.     

Modeling experimental time series with ordinary differential equations

Recently some methods have been presented to extract ordinary differential equations (ODE) directly from an experimental time series. Here, we introduce a new method to find an ODE which models both the short time and the long time dynamics. The experimental data are represented in a state space and the corresponding flow vectors are approximated by polynomials of the state vector components. We apply these methods both to simulated data and experimental data from human limb movements, which like many other biological systems can exhibit limit cycle dynamics. In systems with only one oscillator there is excellent agreement between the limit cycling displayed by the experimental system and the reconstructed model, even if the data are very noisy. Furthermore, we study systems of two coupled limit cycle oscillators. There, a reconstruction was only successful for data with a sufficiently long transient trajectory and relatively low noise level.     

A Simple Unforced Oscillatory Growth Model in the Chemostat

In a chemostat, transient oscillations in cell number density are often experimentally observed during cell growth. The aim of this paper is to propose a simple autonomous model which is able to generate these oscillations, and to investigate it analytically. Our point of view is based on a simplification of the cell cycle in which there are two states (mature and immature) with the transfer between the two dependent on the available resources. We use the mathematical global properties of competitive differential systems to prove the existence of a limit cycle. A comparison between our model and a more complex model consisting of partial differential equations is made with the help of numerical simulations, giving qualitatively similar results.     

Oscillatory dynamics in rock-paper-scissors games with mutations

We study the oscillatory dynamics in the generic three-species rock-paper-scissors games with mutations. In the mean-field limit, different behaviors are found: (a) for high mutation rate, there is a stable interior fixed point with coexistence of all species; (b) for low mutation rates, there is a region of the parameter space characterized by a limit cycle resulting from a Hopf bifurcation; (c) in the absence of mutations, there is a region where heteroclinic cycles yield oscillations of large amplitude (not robust against noise). After a discussion on the main properties of the mean-field dynamics, we investigate the stochastic version of the model within an individual-based formulation. Demographic fluctuations are therefore naturally accounted and their effects are studied using a diffusion theory complemented by numerical simulations. It is thus shown that persistent erratic oscillations (quasi-cycles) of large amplitude emerge from a noise-induced resonance phenomenon. We also analytically and numerically compute the average escape time necessary to reach a (quasi-)cycle on which the system oscillates at a given amplitude.     

Temperature-mediated stability of the interaction between spider mites and predatory mites in orchards

The nonlinear behavior of the Holling-Tanner predatory-prey differential equation system, employed by R.M. May to illustrate the apparent robustness of Kolmogorov’s Theorem when applied to such exploitation systems, is re-examined by means of the numerical bifurcation code AUTO 86 with model parameters chosen appropriately for a temperature-dependent mite interaction on fruit trees. The most significant result of this analysis is that there exists a temperature range wherein multiple stable states can occur, in direct violation of May’s interpretation of this system’s satisfaction of Kolmogorov’s Theorem: namely, that linear stability predictions have global consequences. In particular these stable states consist of a focus (spiral point) and a limit cycle separated from each other in the phase plane by an unstable limit cycle, all of which are associated with the single community equilibrium point of the system. The ecological implications of such metastability, hysteresis, and threshold behavior for the occurrence of outbreaks, the persistence of oscillations, the resiliency of the system, and the biological control of mite populations are discussed.     

Deconstructing the role of myosin contractility in force fluctuations within focal adhesions

Force fluctuations exhibited in focal adhesions that connect a cell to its extracellular environment point to the complex role of the underlying machinery that controls cell migration. To elucidate the explicit role of myosin motors in the temporal traction force oscillations, we vary the contractility of these motors in a dynamical model based on the molecular clutch hypothesis. As the contractility is lowered, effected both by changing the motor velocity and the rate of attachment/detachment, we show analytically in an experimentally relevant parameter space, that the system goes from decaying oscillations to stable limit cycle oscillations through a supercritical Hopf bifurcation. As a function of the motor activity and the number of clutches, the system exhibits a rich array of dynamical states. We corroborate our analytical results with stochastic simulations of the motor-clutch system. We obtain limit cycle oscillations in the parameter regime as predicted by our model. The frequency range of oscillations in the average clutch and motor deformation compares well with experimental results.     

Are circadian oscillators structurally unstable?

The common belief is that all biological oscillations are of limit cycle type. It is shown in this article that the phase response curves simulated on a two-species Lotka-Volterra linear (i.e. non-limit cycle type) oscillator, do look similar to those obtained by experimental methods by different workers. The form of the phase response curves, the existence of singularities and the mirror-image symmetry of opposite perturbations are modelled on the Lotka-Volterra system. The study, which is strongly indicative of the possibility that the underlying oscillator (or oscillators) is (are) not structurally stable, also indicates the necessity of designing critical experiments, capable of distinguishing between limit cycle and non-limit cycle oscillators, since the single-pulse phase resetting does nothing to distinguish between them.     

Landscape and global stability of nonadiabatic and adiabatic oscillations in a gene network

We quantify the potential landscape to determine the global stability and coherence of biological oscillations. We explore a gene network motif in our experimental synthetic biology studies of two genes that mutually repress and activate each other with self-activation and self-repression. We find that in addition to intrinsic molecular number fluctuations, there is another type of fluctuation crucial for biological function: the fluctuation due to the slow binding/unbinding of protein regulators to gene promoters. We find that coherent limit cycle oscillations emerge in two regimes: an adiabatic regime with fast binding/unbinding and a nonadiabatic regime with slow binding/unbinding relative to protein synthesis/degradation. This leads to two mechanisms of producing the stable oscillations: the effective interactions from averaging the gene states in the adiabatic regime; and the time delays due to slow binding/unbinding to promoters in the nonadiabatic regime, which can be tested by forthcoming experiments. In both regimes, the landscape has a topological shape of the Mexican hat in protein concentrations that quantitatively determines the global stability of limit cycle dynamics. The oscillation coherence is shown to be correlated with the shape of the Mexican hat characterized by the height from the oscillation ring to the central top. The oscillation period can be tuned in a wide range by changing the binding/unbinding rate without changing the amplitude much, which is important for the functionality of a biological clock. A negative feedback loop with time delays due to slow binding/unbinding can also generate oscillations. Although positive feedback is not necessary for generating oscillations, it can make the oscillations more robust.     

Limit cycle oscillations of the human eye

The altered feedback technique is very suited to display nonlinearities of the human smooth pursuit system. In fact, when the gain of the retinal feedback path is raised, for the horizontal channel, above its normal unitary negative value, a threshold is met beyond which sustained horizontal self-excited smooth oscillations of the eye can be observed, which point out the existence of a stable limit cycle. Furthermore, the characterizing features of both the transient and steady state show a well defined dependence on the total feedback factor K. In particular, the analytical dependence on K of the amplitude and frequency of limit cycle oscillations can be derived. Implications of the experiment with respect to the mathematical modelling of the system are discussed.     

Stable oscillations in mathematical models of biological control systems

Summary Oscillations in a class of piecewise linear (PL) equations which have been proposed to model biological control systems are considered. The flows in phase space determined by the PL equations can be classified by a directed graph, called a state transition diagram, on anN-cube. Each vertex of theN-cube corresponds to an orthant in phase space and each edge corresponds to an open boundary between neighboring orthants. If the state transition diagram contains a certain configuration called a cyclic attractor, then we prove that for the associated PL equation, all trajectories in the regions of phase space corresponding to the cyclic attractor either (i) approach a unique stable limit cycle attractor, or (ii) approach the origin, in the limitt→∞. An algebraic criterion is given to distinguish the two cases. Equations which can be used to model feedback inhibition are introduced to illustrate the techniques.     

Method for constructing the boundary of the bursting oscillations region in the neuron model

We examine the problem of constructing the boundary of bursting oscillations on a parameter plane for the system of equations describing the electrical behaviour of the membrane neuron arising from the interaction of fast oscillations of the cytoplasma membrane potential and slow oscillations of the intracellular calcium concentration. As the boundary point on the parameter plane we consider the values at which the limit cycle of the slow subsystem is tangent to the Hopf bifurcation curve of the fast subsystem. The method suggested for determining the boundary is based on the dissection of the system variables into slow and fast. The strong point of the method is that it requires the integration of the slow subsystem only. An example of the application of the method for the stomatogastric neuron model [Guckenheimer J, Gueron S, Harris-Warrick RM (1993) Philos Trans R Soc Lond B 341: 345–359] is given. Received: 31 May 1999 / Accepted in revised form: 19 November 1999     

Models of cell cycle control in eukaryotes.

The molecular mechanisms of cell cycle control are now known in enough detail to warrant mathematical modeling by kinetic equations. Despite the repetitive nature of the cell division cycle, the most appropriate models emphasize steady-state solutions rather than limit cycle oscillations, because cells progress toward division by passing a series of checkpoints (steady states).