arXiv subjects

H. Frederik Nijhout

Publications and source records attributed to H. Frederik Nijhout.

3 recordsLinked to original sources

arXiv2024

Homeostasis Patterns

Homeostasis is a regulatory mechanism that keeps a specific variable close to a set value as other variables fluctuate. The notion of homeostasis can be rigorously formulated when the model of interest is represented as an input-output network, with distinguished input and output nodes, and the dynamics of the network determines the corresponding input-output function of the system. In this context, homeostasis can be defined as an 'infinitesimal' notion, namely, the derivative of the input-output function is zero at an isolated point. Combining this approach with graph-theoretic ideas from combinatorial matrix theory provides a systematic framework for calculating homeostasis points in models and classifying the different homeostasis types in input-output networks. In this paper we extend this theory by introducing the notion of a homeostasis pattern, defined as a set of nodes, in addition to the output node, that are simultaneously infinitesimally homeostatic. We prove that each homeostasis type leads to a distinct homeostasis pattern. Moreover, we describe all homeostasis patterns supported by a given input-output network in terms of a combinatorial structure associated to the input-output network. We call this structure the homeostasis pattern network.

math.DS↗

arXiv2017

The Case for Pyriproxyfen as a Potential Cause for Microcephaly; From Biology to Epidemiology

The Zika virus has been found in individual cases but has not been confirmed as the cause of in the large number of cases of microcephaly in Brazil in 2015-6. Indeed, disparities between the incidence of Zika and microcephaly across geographic locations has led to questions about the virus's role. Here we consider whether the insecticide pyriproxyfen used in Brazilian drinking water might be the primary cause or a cofactor. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog approved as an insecticide in the 1970s has been shown to cause developmental disorders in mammals. Isotretinoin is another retinoid causing microcephaly via activation of the retinoid X receptor in developing fetuses. We review tests of pyriproxyfen by the manufacturer Sumitomo, which actually found some evidence for this effect, including low brain mass and arhinencephaly in exposed rat pups. Pyriproxyfen use in Brazil is unprecedented, never having been applied to a water supply on a large scale. Claims that its geographical pattern of use rule it out as a cause have not been documented or confirmed. On the other hand, the very few microcephaly cases reported in Colombia and the wide discrepancies of incidence in different states across Brazil despite large numbers of Zika cases undermine the claim that Zika is the cause. Given this combination of potential molecular mechanism, toxicological and epidemiological evidence we strongly recommend that the use of pyriproxyfen in Brazil be suspended until the potential causal link to microcephaly is investigated further.

q-bio.TO↗

arXiv2005

Propagation of Fluctuations in Biochemical Systems, I: Linear SSC Networks

We investigate the propagation of random fluctuations through biochemical networks in which the concentrations of species are large enough so that the unperturbed problem is well-described by ordinary differential equation. We characterize the behavior of variance as fluctuations propagate down chains, study the effect of side chains and feedback loops, and investigate the asymptotic behavior as one rate constant gets large. We also describe how the ideas can be applied to the study of methionine metabolism.

math.PR↗