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Organisms are equipped with regulatory systems that display a variety of dynamical behaviours ranging from simple stable steady states, to switching and multistability, to oscillations. Earlier work has shown that oscillations in protein concentrations or gene expression levels are related to the presence of at least one negative feedback loop in the regulatory network. Here we study the dynamics of a very general class of negative feedback loops. Our main result is that in these systems the sequence of maxima and minima of the concentrations is uniquely determined by the topology of the loop and the activating/repressing nature of the interaction between pairs of variables. This allows us to devise an algorithm to reconstruct the topology of oscillating negative feedback loops from their time series; this method applies even when some variables are missing from the data set, or if the time series shows transients, like damped oscillations. We illustrate the relevance and the limits of validity of our method with three examples: p53-Mdm2 oscillations, circadian gene expression in cyanobacteria, and cyclic binding of cofactors at the estrogen-sensitive pS2 promoter.
Recently, several studies have investigated the transcription process associated to specific genetic regulatory networks. In this work, we present a stochastic approach for analyzing the dynamics and effect of negative feedback loops (FBL) on the tra
The dynamic behaviors of microRNA and mRNA under external stress are studied with biological experiments and mathematics models. In this study, we developed a mathematic model to describe the biological phenomenon and for the first time reported that
The molecular network in an organism consists of transcription/translation regulation, protein-protein interactions/modifications and a metabolic network, together forming a system that allows the cell to respond sensibly to the multiple signal molec
Genes and proteins regulate cellular functions through complex circuits of biochemical reactions. Fluctuations in the components of these regulatory networks result in noise that invariably corrupts the signal, possibly compromising function. Here, w
Multiple interlinked positive feedback loops shape the stimulus responses of various biochemical systems, such as the cell cycle or intracellular calcium release. Recent studies with simplified models have identified two advantages of coupling fast a