Amplified biochemical oscillations in cellular systems

We describe a mechanism for pronounced biochemical oscillations, relevant to microscopic systems, such as the intracellular environment. This mechanism operates for reaction schemes which, when modeled using deterministic rate equations, fail to exhibit oscillations for any values of rate constants. The mechanism relies on amplification of the underlying stochasticity of reaction kinetics within a narrow window of frequencies. This amplification allows fluctuations to beat the central limit theorem, having a dominant effect even though the number of molecules in the system is relatively large. The mechanism is quantitatively studied within simple models of self-regulatory gene expression, and glycolytic oscillations.Comment: 35 pages, 6 figure

Self-oscillations in glycolysis 1. A simple kinetic model

The paper describes a simple kinetic model of an open monosubstrate enzyme reaction with substrate inhibition and product activation. A comparison between the model and the phospho-fructokinase reaction shows a close resemblance between their dynamical properties. This makes it possible to explain qualitatively most experimental data on single-frequency oscillations in glycolysis. A mathematical analysis of the model has shown the following. 1. I n the model, a t a definite relationship between the parameters, self-oscillations arise. 2. The condition of self-excitation is satisfied more readily with a lower source rate, larger product sink rate constants, lower product-enzyme affinity and higher enzyme activity. 3. Self-oscillations exist only in a certain range of values of the parameter determining the degree of substrate inhibition. This range increases with decreasing source rate. Too strong or, conversely, too weak substrate inhibition leads to damped oscillations. 4. The period of self-oscillations depends on the degree of substrate inhibition, the source rate, the sink rate constant, the enzyme activity, the affinity of the substrate and the product for the enzyme; it decreases with an increase in these values. 5. With an increase in the relative sink rate constant the steady state amplitude of self

EFFECTS OF BACTERIAL LIGANDS OF PATTERN-RECOGNIZING RECEPTORS (PRR) ON MONOCYTE-LIKE THP-1 CELLS UPON THEIR TRANSENDOTHELIAL MIGRATION

Abstract. The aim of study was to compare the influence of lipopolysaccharide (LPS) component from Gram-negative bacteria (E. coli 055:B5), and a lysate of Gram-positive bacterium (Streptococcus pyogenes, type M1, strain 40/58) upon transendothelial migration rates of monocyte-like cells (THP-1 strain). Both LPS and lysate of Streptococcus pyogenes acted as chemoattractants for THP-1 cells. he studied components of Streptococcus pyogenes proved to be more active stimulants of transendothelial THP-1 cell migration, than LPS from E. coli. During spontaneous transmigration of THP-1 cells through a monolayer of endothelial cells, augmented levels of chemokines (RANTES, MCP-1, IL-8, IP-10) were noticed, that were more pronounced in presence of LPS. Upon spontaneous transmigration of THP-1 cells through endothelial monolayer, the levels of proinflammatory cytokines (TNFα, IL-1β and IL-6) in cultural medium were found to be rather low. The transmigration-associated secretion of these cytokines increased in presence of LPS and Streptococcus pyogenes lysate. Incubation with these bacterial constituents did increase cytokine levels both in monoculture of THP-1 cells and in transmigration model. Our results suggest that the levels of THP-1 transendothelial migration depend mainly on activation of monocyte-like cells influenced by PRR-ligands from Streptococcus pyogenes lysate. (Med. Immunol., vol. 10, N 6, pp 571-576)

Lactobacillus gasseri OLL2809 inhibits development of ectopic endometrial cell in peritoneal cavity via activation of NK cells in a murine endometriosis model

We have previously reported that peritoneal administration of interleukin-12 (IL-12) suppresses development of ectopic endometriotic lesions via activation of natural killer (NK) cells in a mouse endometriosis model. Lactobacillus gasseri OLL2809 is one of a probiotic lactobacillus that has been selected on an ability to stimulate production of IL-12 from murine splenocytes. In this study, we examined whether the oral administration of heat-killed L. gasseri OLL2809 suppressed development of endometriosis. Administration of L. gasseri OLL2809 for 21 consecutive days resulted in reduction of the development of ectopic endometriotic lesions in an extent similar to IL-12. Although obvious effects of L. gasseri OLL2809 on the peritoneal cytokine levels, population of peritoneal cells as well as cytotoxicity of splenic NK cells, gene expression analysis of the peritoneal cells revealed enhancement in the transcription of IL-2 and natural killer cell triggering receptor 1 genes. Therefore, it was suggested that L. gasseri OLL2809 suppressed development of endometriosis via activation of NK cells

The existence and non-existence of travelling front in high order auto-catalysis chemical reaction

This article studies propagating wave fronts in an isothermal chemical reaction A+nB → (n+1)B involving two chemical species, a reactant A and an auto-catalyst B whose diffusion coefficients, D A and D B, are unequal due to different molecular weights and/or sizes. More accurate bounds v * and v * that depend on D B/D A, when the ratio is less than 1, are derived such that there is a unique travelling wave of every speed v ≥ v * and there does not exist any travelling wave of speed v \u3c v *. The refined bounds for D B/D A \u3c 1 case is compatible to what has been shown in earlier work for D B/D A \u3e 1 when n ≥ 3. © 2012 Science China Press and Springer-Verlag Berlin Heidelberg