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Progressive glucose stimulation of islet beta cells reveals a transition from segregated to integrated modular functional connectivity patterns
Rene Markovič, Andraž Stožer, Marko Gosak, Jurij Dolenšek, Marko Marhl, Marjan Rupnik, 2015, original scientific article

Abstract: Collective beta cell activity in islets of Langerhans is critical for the supply of insulin within an organism. Even though individual beta cells are intrinsically heterogeneous, the presence of intercellular coupling mechanisms ensures coordinated activity and a well-regulated exocytosis of insulin. In order to get a detailed insight into the functional organization of the syncytium, we applied advanced analytical tools from the realm of complex network theory to uncover the functional connectivity pattern among cells composing the intact islet. The procedure is based on the determination of correlations between long temporal traces obtained from confocal functional multicellular calcium imaging of beta cells stimulated in a stepwise manner with a range of physiological glucose concentrations. Our results revealed that the extracted connectivity networks are sparse for low glucose concentrations, whereas for higher stimulatory levels they become more densely connected. Most importantly, for all ranges of glucose concentration beta cells within the islets form locally clustered functional sub-compartments, thereby indicating that their collective activity profiles exhibit a modular nature. Moreover, we show that the observed non-linear functional relationship between different network metrics and glucose concentration represents a well-balanced setup that parallels physiological insulin release.
Keywords: endocrinology, computational biophysics, calcium signalling, biological physics
Published: 23.06.2017; Views: 670; Downloads: 227
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Disinhibition-induced transitions between absence and tonic-clonic epileptic seizures
Denggui Fan, Qingyun Wang, Matjaž Perc, 2015, original scientific article

Abstract: Electrophysiological experiments have long revealed the existence of two-way transitions between absence and tonic-clonic epileptic seizures in the cerebral cortex. Based on a modified spatially-extended Taylor & Baier neural field model, we here propose a computational framework to mathematically describe the transition dynamics between these epileptic seizures. We first demonstrate the existence of various transition types that are induced by disinhibitory functions between two inhibitory variables in an isolated Taylor & Baier model. Moreover, we show that these disinhibition-induced transitions can lead to stable tonic-clonic oscillations as well as periodic spike with slow-wave discharges, which are the hallmark of absence seizures. We also observe fascinating dynamical states, such as periodic 2-spike with slow-wave discharges, tonic death, bursting oscillations, as well as saturated firing. Most importantly, we identify paths that represent physiologically plausible transitions between absence and tonic-clonic seizures in the modified spatially-extended Taylor & Baier model.
Keywords: epilepsy, neuronal dynamics, synchronization, biophysics
Published: 23.06.2017; Views: 463; Downloads: 274
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Chimera states in uncoupled neurons induced by a multilayer structure
Soumen Majhi, Matjaž Perc, Dibakar Ghosh, 2016, original scientific article

Abstract: Spatial coexistence of coherent and incoherent dynamics in network of coupled oscillators is called a chimera state. We study such chimera states in a network of neurons without any direct interactions but connected through another medium of neurons, forming a multilayer structure. The upper layer is thus made up of uncoupled neurons and the lower layer plays the role of a medium through which the neurons in the upper layer share information among each other. Hindmarsh-Rose neurons with square wave bursting dynamics are considered as nodes in both layers. In addition, we also discuss the existence of chimera states in presence of inter layer heterogeneity. The neurons in the bottom layer are globally connected through electrical synapses, while across the two layers chemical synapses are formed. According to our research, the competing effects of these two types of synapses can lead to chimera states in the upper layer of uncoupled neurons. Remarkably, we find a density-dependent threshold for the emergence of chimera states in uncoupled neurons, similar to the quorum sensing transition to a synchronized state. Finally, we examine the impact of both homogeneous and heterogeneous inter-layer information transmission delays on the observed chimera states over a wide parameter space.
Keywords: complex networks, computational biophysics, nonlinear phenomena, statistical physics
Published: 23.06.2017; Views: 392; Downloads: 318
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Bacterial chemotaxis and entropy production
Paško Županović, Milan Brumen, Marko Jagodič, Davor Juretić, 2010, original scientific article

Abstract: Entropy production is calculated for bacterial chemotaxis in the case of a migrating band of bacteria in a capillary tube. It is found that the speed of the migrating band is a decreasing function of the starting concentration of the metabolizable attractant. The experimentally found dependence of speed on the starting concentration of galactose, glucose and oxygen is fitted with power-law functions. It is found that the corresponding exponents lie within the theoretically predicted interval. The effect of the reproduction of bacteria on band speed is considered, too. The acceleration of the band is predicted due to the reproduction rate of bacteria. The relationship between chemotaxis, the maximum entropy production principle and the formation of self-organizing structure is discussed.
Keywords: biofizika, bakterijska kemotaksa, hitrost reprodukcije, princip maksimalne produkcije entropije, biophysics, bacterial chemotaxis, reproduction rate, princip maksimalne produkcije entropije
Published: 10.07.2015; Views: 573; Downloads: 69
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Modeling of molecular and cellular mechanisms involved in [Ca sup 2+] signal encoding in airway myocytes
Marko Marhl, Denis Noble, Etienne Roux, 2006, review article

Abstract: In airway myocytes signal transduction via cytosolic calcium plays an important role. In relation with experimental results we review models of basic molecular and cellular mechanisms involved in the signal transduction from the myocyte stimulation to the activation of the contractile apparatus. We concentrate on mechanisms for encoding of input signals into Ca2+ signals and the mechanisms for their decoding. The mechanisms are arranged into a general scheme of cellular signaling, the so-called bow-tie architecture of signaling, in which calcium plays the role of a common media for cellular signals and links the encoding and decoding part. The encoding of calcium signals in airway myocytes is better known and is presented in more detail. Inparticular, we focus on three recent models taking into account the intracellular calcium handling and ion fluxes through the plasma membrane. Themodel of membrane conductances was originally proposed for predicting membrane depolarization and voltage-dependent Ca2+ influx triggered by initialcytosolic Ca2+ increase as observed on cholinergic stimulation. Cellular models of intracellular Ca2+ handling were developed to investigate the role of a mixed population of InsP3 receptor isoforms and the cellular environment in the occurrence of Ca2+ oscillations, and the respective role ofthe sarcoplasmic reticulum, mitochondria, and cytosolic Ca2+-binding proteins in cytosolic Ca2+ clearance. Modeling the mechanisms responsible for the decoding of calcium signals is developed in a lesser extent; however, the most recent theoretical studies are briefly presented in relation with the known experimental results.
Keywords: biophysics, mathematical modelling, modelling, calcium oscillations, contractions, airway smooth muscle cells, muscle cells, smooth muscles, encoding, decoding, bow-tie structures
Published: 07.06.2012; Views: 1282; Downloads: 20
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Theoretical and experimental investigation of calcium-contraction coupling in airway smooth muscle
Prisca Mbikou, Aleš Fajmut, Milan Brumen, Etienne Roux, 2006, original scientific article

Abstract: We investigated theoretically and experimentally the ▫$Ca^{2+}$▫-contraction couplingin rat tracheal smooth muscle. ▫$[Ca^{2+}]_i$▫, isometric contraction and myosin light chain (MLC) phosphorylation were measured in response to 1 mM carbachol. Theoretical modeling consisted in coupling a model of ▫$Ca^{2+}-dependent$▫ MLC kinase (MLCK) activation with a four-state model of smooth muscle contractile apparatus. Stimulation resulted in a short-time contraction obtained within 1 min, followed by a long-time contraction up to the maximal force obtained in 30 min. ML-7 and Wortmannin (MLCK inhibitors) abolished the contraction. Chelerythrine (PKC inhibitor) did not change the short-time, but reduced the long-time contraction. ▫$[Ca^{2+}]_i$▫ responses of isolated myocytes recorded during the first 90 s consisted in a fast peak, followed by a plateau phase and, in 28 % of the cells, superimposed ▫$Ca^{2+}$▫ oscillations. MLC phosphorylation was maximal at 5 s and then decreased, whereas isometric contraction followed a Hill-shaped curve. The model properlypredicts the time course of MLC phosphorylation and force of the short-time response. With oscillating ▫$Ca^{2+}$▫ signal, the predicted force does not oscillate. According to the model, the amplitude of the plateau and the frequency of oscillations encode for the amplitude of force, whereas the peak encodes for force velocity. The long-time phase of the contraction, associated with a second increase in MLC phosphorylation, may be explained, at least partially, by MLC phosphatase (MLCP) inhibition, possibly via PKC inhibition.
Keywords: biophysics, mathematical modelling, modelling, calcium oscillations, contractions, force development, muscle cells, smooth muscles, myosin kinase
Published: 07.06.2012; Views: 1185; Downloads: 71
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Selective regulation of protein activity by complex Ca[sup]2+ oscillations : a theoretical study
Beate Knoke, Marko Marhl, Stefan Schuster, 2007, independent scientific component part or a chapter in a monograph

Abstract: Calcium oscillations play an important role in intracellular signal transduction. As a second messenger, ▫$Ca^{2+}$▫ represents a link between several input signals and several target processes in the cell. Whereas the frequency of simple ▫$Ca^{2+}$▫ oscillations enables a selective activation of a specific protein and herewith a particular process, the question arises of how at the same time two or more classes of proteins can be specifically regulated. The question is general and concerns the problem of how one second messenger can transmit more than one signal simultaneously (bow-tie structure of signalling). To investigate whether a complex ▫$Ca^{2+}$▫ signal like bursting, a succession of low-peak and high-peak oscillatory phases, could selectively activate different proteins, several bursting patterns with simplified square pulses were applied in a theoretical model. The results indicate that bursting ▫$Ca^{2+}$▫ oscillations allow a differential regulation of two different calcium-binding proteins, and hence, perform the desired function.
Keywords: biophysics, calcium oscillations, cellular dynamics, mathematical models, signalling, bow-tie structures, bursting, decoding
Published: 07.06.2012; Views: 1195; Downloads: 13
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Donnan equilibrium and osmotic pressure in hollow polyelectrolyte microcapsules
David Haložan, Gleb B. Sukhorukov, Milan Brumen, Edwin Donath, Helmuth Möhwald, 2007, original scientific article

Abstract: A simple theoretical model of the Donnan equilibrium is applied to studies of distributions of ions between the external and internal volumes of hollow polyelectrolyte capsules as well as of concomitant osmotic pressure load on a capsule wall resulting from these distributions and the presence of polyanion. The model system consist of dispersed polyelectrolyte capsules in an electrolyte solution whereby two cases are considered with respect to the presence of the polyanion, either in the inner or external solution. It is assumed that the capsule wall is impermeable to polyanion, but water and all ions can freely penetrate. The model predictions are summarized by presenting the difference between the external pH, the pH of the inner solution and the osmotic pressure difference across the capsule wall, both in the dependence of sodium chloride concentration.
Keywords: biophysics, polyelectrolytes, polyelectrolyte capsules, Donnan equilibrium, osmotic pressure
Published: 07.06.2012; Views: 1470; Downloads: 80
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