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Register a new userTemperature effect on the cardiac ryanodine receptor gating and conductance: mathematical modelling
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The temperature effect on the cardiac ryanodine receptor (RyR) function has been studied within the electron-conformational (EC) model. It is shown that simple EC model with the Arrhenius like temperature dependence of internal and external frictions and a specific thermosensitivity of the tunnelling open - close transitions can provide both qualitative and quantitative description of the temperature effects for isolated RyRs. The potential of the model was illustrated by explaining the experimental data on the temperature dependence of sheeps isolated cardiac RyR gating and conductance (R. Sitsapesan et al., J Physiol 434, 469 (1991)).
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We propose four novel mathematical models, describing the microscopic mechanisms of force generation in the cardiac muscle tissue, which are suitable for multiscale numerical simulations of cardiac electromechanics. Such models are based on a biophysically accurate representation of the regulatory and contractile proteins in the sarcomeres. Our models, unlike most of the sarcomere dynamics models that are available in the literature and that feature a comparable richness of detail, do not require the time-consuming Monte Carlo method for their numerical approximation. Conversely, the models that we propose only require the solution of a system of PDEs and/or ODEs (the most reduced of the four only involving 20 ODEs), thus entailing a significant computational efficiency. By focusing on the two models that feature the best trade-off between detail of description and identifiability of parameters, we propose a pipeline to calibrate such parameters starting from experimental measurements available in literature. Thanks to this pipeline, we calibrate these models for room-temperature rat and for body-temperature human cells. We show, by means of numerical simulations, that the proposed models correctly predict the main features of force generation, including the steady-state force-calcium and force-length relationships, the length-dependent prolongation of twitches and increase of peak force, the force-velocity relationship. Moreover, they correctly reproduce the Frank-Starling effect, when employed in multiscale 3D numerical simulation of cardiac electromechanics.
The batch fermentation process, inoculated by pulsed electric field (PEF) treated wine yeasts (S. cerevisiae Actiflore F33), was studied. PEF treatment was applied to the aqueous yeast suspensions (0.12 % wt.) at the electric field strengths of E=100 and 6000 V/cm using the same pulse protocol (number of pulses of n=1000, pulse duration of ti=100 mks, and pulse repetition time of dt=100 ms). Electro-stimulation was confirmed by the observed growth of electrical conductivity of suspensions. The fermentation was running at 30{deg}C for 150 hours in an incubator with synchronic agitation. The obtained results clearly evidence the positive impact of PEF treatment on the batch fermentation process. Electro-stimulation resulted in improvement of such process characteristics as mass losses, consumption of soluble matter content ({deg}Brix) and synthesis of proteins. It also resulted in a noticeable acceleration of consumption of sugars at the initial stage of fermentation in the lag phase. At the end of the lag phase (t=40 hours), consumption of fructose in samples with electrically activated inocula exceeded fructose consumption in samples with control inocula by 2.33 times when it was activated at E=100 V/cm and by 3.98 times after treatment at E=6000 V/cm. At the end of the log phase (120 hours of fermentation), 30% mass reduction was reached in samples with PEF-treated inocula (E=6000 V/cm), whereas the same mass reduction of the control sample required approximately, 20 hours of extra fermentation. The possible mechanisms of electro-stimulation are also discussed in details.
Biological cells sense external chemical stimuli in their environment using cell-surface receptors. To increase the sensitivity of sensing, receptors often cluster, most noticeably in bacterial chemotaxis, a paradigm for signaling and sensing in general. While amplification of weak stimuli is useful in absence of noise, its usefulness is less clear in presence of extrinsic input noise and intrinsic signaling noise. Here, exemplified on bacterial chemotaxis, we combine the allosteric Monod-Wyman- Changeux model for signal amplification by receptor complexes with calculations of noise to study their interconnectedness. Importantly, we calculate the signal-to-noise ratio, describing the balance of beneficial and detrimental effects of clustering for the cell. Interestingly, we find that there is no advantage for the cell to build receptor complexes for noisy input stimuli in absence of intrinsic signaling noise. However, with intrinsic noise, an optimal complex size arises in line with estimates of the sizes of chemoreceptor complexes in bacteria and protein aggregates in lipid rafts of eukaryotic cells.
Complex spatiotemporal patterns of action potential duration have been shown to occur in many mammalian hearts due to a period-doubling bifurcation that develops with increasing frequency of stimulation. Here, through high-resolution optical mapping and numerical simulations, we quantify voltage length scales in canine ventricles via spatiotemporal correlation analysis as a function of stimulation frequency and during fibrillation. We show that i) length scales can vary from 40 to 20 cm during one to one responses, ii) a critical decay length for the onset of the period-doubling bifurcation is present and decreases to less than 3 cm before the transition to fibrillation occurs, iii) fibrillation is characterized by a decay length of about 1 cm. On this evidence, we provide a novel theoretical description of cardiac decay lengths introducing an experimental-based conduction velocity dispersion relation that fits the measured wavelengths with a fractional diffusion exponent of 1.5. We show that an accurate phenomenological mathematical model of the cardiac action potential, fine-tuned upon classical restitution protocols, can provide the correct decay lengths during periodic stimulations but that a domain size scaling via the fractional diffusion exponent of 1.5 is necessary to reproduce experimental fibrillation dynamics. Our study supports the need of generalized reaction-diffusion approaches in characterizing the multiscale features of action potential propagation in cardiac tissue. We propose such an approach as the underlying common basis of synchronization in excitable biological media.
We study kinetic model of Nuclear Receptor Binding to Promoter Regions. This model is written as a system of ordinary differential equations. Model reduction techniques have been used to simplify chemical kinetics.In this case study, the technique of Pseudo-first order approximation is applied to simplify the reaction rates. CellDesigner has been used to draw the structures of chemical reactions of Nuclear Receptor Binding to Promoter Regions. After model reduction, the general analytical solution for reduced model is given and the number of species and reactions are reduced from 9 species and 6 reactions to 6 species and 5 reactions.
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