Biomedical subjects

J Halloy

Publications and source records attributed to J Halloy.

9 recordsLinked to original sources

PubMed2005

Individual discrimination capability and collective decision-making.

Amplification is the main component of many collective phenomena in social and gregarious insects. In a society, individuals face a mixed palette of odours coming from different groups (lines, strains) and individuals present discrimination capabilities. However, often at the collective level, different groups may cooperate and act together. To understand this apparent contradiction, we use a model of food recruitment where each group of foragers have its own blend of pheromone trail that is partly recognized by the others groups. The model shows that a low level of recognition between signals is sufficient to produce a collaborative pattern between groups and that beyond a critical value of recognition, only the aggregation of all the groups around the same food source is observed. The comparison between this model and one describing the site selection by gregarious insects (e.g. cockroach) suggests that such collective response is a generic property of social phenomena governed by amplification processes.

Animals↗

PubMed2003

[Deterministic and stochastic models for circadian rhythms].

Circadian rhythms, characterized by a period of about 24h, are generated in nearly all living organisms by the negative autoregulation of clock gene expression. Deterministic models based on this genetic regulation account for circadian oscillations in constant environmental conditions (e.g., in constant darkness) and for entrainment of these rhythms by light-dark cycles. When the number of clock mRNA and protein molecules is low, it is necessary to resort to stochastic simulations to assess the influence of molecular noise on circadian oscillations. Indeed, it is possible that the autoregulatory mechanism of gene expression might not produce stable rhythms due to fluctuations if the number of molecules involved in the clock mechanism remains too low. We have compared the deterministic and stochastic approaches for a model based on the negative autoregulation of a clock gene. We show by means of stochastic simulations that robust circadian oscillations can already occur when the maximum number of mRNA and protein molecules is of the order of a few tens or hundreds, respectively. Furthermore, the results indicate that the cooperativity characterizing the repression of the transcription process strenghtens the robustness of circadian rhythms and that entrainment by light-dark cycles stabilizes the phase of the oscillations.

Circadian Rhythm↗

PubMed2002

The follicular automaton model: effect of stochasticity and of synchronization of hair cycles.

Human scalp hair consists of a set of about 10(5)follicles which progress independently through developmental cycles. Each hair follicle successively goes through the anagen (A), catagen (C), telogen (T) and latency (L) phases that correspond, respectively, to growth, arrest and hair shedding before a new anagen phase is initiated. Long-term experimental observations in a group of ten male, alopecic and non-alopecic volunteers allowed determination of the characteristics of hair follicle cycles. On the basis of these observations, we previously proposed a follicular automaton model to simulate the dynamics of human hair cycles and the development of different patterns of alopecia [Halloy et al. (2000) Proc. Natl Acad. Sci. U.S.A.97, 8328-8333]. The automaton model is defined by a set of rules that govern the stochastic transitions of each follicle between the successive states A, T, L and the subsequent return to A. These transitions occur independently for each follicle, after time intervals given stochastically by a distribution characterized by a mean and a standard deviation. The follicular automaton model was shown to account both for the dynamical transitions observed in a single follicle, and for the behaviour of an ensemble of independently cycling follicles. Here, we extend these results and investigate additional properties of the model. We present a deterministic version of the follicular automaton. We show that numerical simulations of the stochastic version of the automaton yield steady-state level of follicles in the different phases which approach the levels predicted by the deterministic equations as the number of follicles progressively increases. Only the stochastic version can successfully reproduce the fluctuations of the fractions of follicles in each of the three phases, observed in small follicle populations. When the standard deviation is reduced or when the follicles become otherwise synchronized, e.g. by a periodic external signal inducing the transition of anagen follicles into telogen phase, large-amplitude oscillations occur in the fractions of follicles in the three phases. These oscillations are not observed in humans but are reminiscent of the phenomenon of moulting observed in a number of mammalian species.

Alopecia↗

PubMed2000

Modeling the dynamics of human hair cycles by a follicular automaton.

The hair follicle cycle successively goes through the anagen, catagen, telogen, and latency phases, which correspond, respectively, to hair growth, arrest, shedding, and absence before a new anagen phase is initiated. Experimental observations collected over a period of 14 years in a group of 10 male volunteers, alopecic and nonalopecic, allowed us to determine the characteristics of scalp hair follicle cycles. On the basis of these observations, we propose a follicular automaton model to simulate the dynamics of human hair cycles. The automaton model is defined by a set of rules that govern the stochastic transitions of each follicle between the successive states anagen, telogen, and latency, and the subsequent return to anagen. The transitions occur independently for each follicle, after time intervals given stochastically by a distribution characterized by a mean and a variance. The follicular automaton model accounts both for the dynamical transitions observed in a single follicle and for the behavior of an ensemble of independently cycling follicles. Thus, the model successfully reproduces the evolution of the fractions of follicle populations in each of the three phases, which fluctuate around steady-state or slowly drifting values. We apply the follicular automaton model to the study of spatial patterns of follicular growth that result from a spatially heterogeneous distribution of parameters such as the mean duration of anagen phase. When considering that follicles die or miniaturize after going through a critical number of successive cycles, the model can reproduce the evolution to hair patterns similar to well known types of diffuse or androgenetic alopecia.

Alopecia↗

PubMed2000

The frequency encoding of pulsatility.

Examples of pulsatile signalling abound in intercellular communication, suggesting that this phenomenon represents a major function of biological rhythms. Pulsatile signals can be encoded in terms of their frequency and prove more efficient than monotonous ones whenever constant stimulation induces desensitization of target cells. We address the main examples of frequency encoding of pulsatility, besides those of neuronal nature. Considered in turn are cAMP oscillations in the slime mould Dictyostelium discoideum, the pulsatile secretion of hormones such as gonadotropin-releasing hormone or growth hormone, intracellular Ca2+ oscillations, and circadian rhythms. Models based on receptor desensitization show the possibility of optimizing cellular responses to cAMP signals in Dictyostelium or to pulsatile hormonal stimulation. The models indicate how the optimal duration of the pulsatile signal and the optimal interval between successive pulses vary as a function of the rates or receptor desensitization and resensitization and of the maximum ligand level during stimulation. The frequency encoding of intracellular Ca2+ oscillations appears to rely on another molecular mechanism. Models based on protein phosphorylation by a Ca(2+)-calmodulin activated kinase show that the mean level of phosphorylated protein increases with the frequency of calcium spikes--which itself rises with the degree of stimulation--and that distinct levels of different phosphorylated proteins can be reached for a Ca2+ signal of given frequency.

Animals↗

PubMed1998

Coexistence of multiple propagating wave-fronts in a regulated enzyme reaction model: link with birhythmicity and multi-threshold excitability.

We analyze the spatial propagation of wave-fronts in a biochemical model for a product-activated enzyme reaction with non-linear recycling of product into substrate. This model was previously studied as a prototype for the coexistence of two distinct types of periodic oscillations (birhythmicity). The system is initially in a stable steady state characterized by the property of multi-threshold excitability, by which it is capable of amplifying in a pulsatory manner perturbations exceeding two distinct thresholds. In such conditions, when the effect of diffusion is taken into account, two distinct wave-fronts are shown to propagate in space, with distinct amplitudes and velocities, for the same set of parameter values, depending on the magnitude of the initial perturbation. Such a multiplicity of propagating wave-fronts represents a new type of coexistence of multiple modes of dynamic behavior, besides the coexistence involving, under spatially homogeneous conditions, multiple steady states, multiple periodic regimes, or a combination of steady and periodic regimes.

Journal Article↗

PubMed1998

Modeling oscillations and waves of cAMP in Dictyostelium discoideum cells.

We examine the theoretical aspects of temporal and spatiotemporal organization in the cAMP signaling system of Dictyostelium discoideum amoebae which aggregate in a wavelike manner after starvation, in response to pulses of cAMP emitted with a periodicity of several minutes by cells behaving as aggregation centers. We first extend the model based on receptor desensitization, previously proposed by Martiel and Goldbeter, by incorporating the role of G proteins in signal transduction. The extended model accounts for observations on the response of the signaling system to successive step increases in extracellular cAMP. In the presence of the positive feedback loop in cAMP synthesis, this model generates sustained oscillations in cAMP and in the fraction of active cAMP receptor, similar to those obtained in the simpler model where the role of the G proteins is not taken into account explicitly. We use the latter model to address the formation of concentric and spiral waves of cAMP in the course of D. discoideum aggregation. Previous analyses of the model showed that a progressive increase in the activity of adenylate cyclase and phosphodiesterase can account for the transitions no relay-relay-oscillations-relay observed in the experiments. We show that the degree of cellular synchronization on such a developmental path in parameter space markedly affects the nature of the spatial patterns generated by the model. These patterns range from concentric waves to a small number of large spirals, and finally to a large number of smaller spirals, as the degree of developmental desynchronization between cells increases.

Animals↗

PubMed1997

Desynchronization of cells on the developmental path triggers the formation of spiral waves of cAMP during Dictyostelium aggregation.

Whereas it is relatively easy to account for the formation of concentric (target) waves of cAMP in the course of Dictyostelium discoideum aggregation after starvation, the origin of spiral waves remains obscure. We investigate a physiologically plausible mechanism for the spontaneous formation of spiral waves of cAMP in D. discoideum. The scenario relies on the developmental path associated with the continuous changes in the activity of enzymes such as adenylate cyclase and phosphodiesterase observed during the hours that follow starvation. These changes bring the cells successively from a nonexcitable state to an excitable state in which they relay suprathreshold cAMP pulses, and then to autonomous oscillations of cAMP, before the system returns to an excitable state. By analyzing a model for cAMP signaling based on receptor desensitization, we show that the desynchronization of cells on this developmental path triggers the formation of fully developed spirals of cAMP. Developmental paths that do not correspond to the sequence of dynamic transitions no relay-relay-oscillations-relay are less able or fail to give rise to the formation of spirals.

Animals↗

PubMed1992

Suppression of chaos by periodic oscillations in a model for cyclic AMP signalling in Dictyostelium cells.

We investigate how the introduction of cells oscillating periodically affects the behaviour of a suspension of Dictyostelium discoideum amoebae undergoing chaotic oscillations of cyclic AMP. The analysis of a model indicates that a tiny proportion of periodic cells suffices to transform chaos into periodic oscillations in such suspensions. A similar result is obtained by forcing the aperiodic oscillations by a small-amplitude, periodic input of cyclic AMP. The results provide an explanation for the observation of regular oscillations in suspensions of a putatively chaotic mutant of Dictyostelium discoideum. More generally, the results show how chaos in biological systems may disappear through the coupling with periodic oscillations.

Animals↗