Novel generic models for differentiating stem cells reveal oscillatory mechanisms

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington’s epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario, gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario, two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

On the edge of criticality: strength-dependent perturbation unveils delicate balance between fluctuation and oscillation in brain dynamics

Going beyond previous research, we use strength-dependent perturbation to obtain a deeper understanding of the mechanisms underlying the emergence of large-scale brain activity. Despite decades of research, we still have a shallow understanding of the role and generating mechanisms of the ubiquitous fluctuations and oscillations found in recordings of brain dynamics. Here, we used global strength-dependent perturbation to give a causal mechanistic description of human brain function providing a delicate balance between fluctuation and oscillation on the edge of criticality. After application of precise local strength-dependent perturbations and measuring the well-known perturbative complexity index, we demonstrated that the overall balance is shifted towards a fluctuating regime which is superior in terms of enhancing different functional networks compared to the oscillatory regime. This framework can generate specific, testable empirical predictions to be tested in human stimulation studies with strength-dependent rather than constant perturbation. Overall, our novel strength-dependent perturbation framework demonstrates that the human brain is poised on the edge of criticality, between fluctuations to oscillations, allowing for maximal flexibility.

The oscillatory longwave Marangoni convection in a thin film heated from below

A novel type of Marangoni convection was predicted theoretically a decade ago. The thin liquid film atop a substrate of low thermal conductivity was considered. In the case of heating from below, the Marangoni convection emerges not only in a conventional stationary regime, but also as oscillatory flows. Specifically, the oscillatory Marangoni convection emerges if (1) the heat flux from the free surface is small, and (2) the large-scale deformation of the free surface is allowed. During the past decade, this novel Marangoni convection was detected and investigated in several other theoretical works. The review discusses the recent achievements in studying the oscillatory Marangoni convection in a thin film heated from below. The guiding data for observation of the oscillatory regime are also provided.

Novel Generic Models for Differentiating Stem Cells Reveal Oscillatory Mechanisms

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically-motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington's epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

Systematic Approach to Find the Global Minimum of Relaxation Dispersion Data for Protein-Induced B–Z Transition of DNA

Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion spectroscopy is commonly used for quantifying conformational changes of protein in μs-to-ms timescale transitions. To elucidate the dynamics and mechanism of protein binding, parameters implementing CPMG relaxation dispersion results must be appropriately determined. Building an analytical model for multi-state transitions is particularly complex. In this study, we developed a new global search algorithm that incorporates a random search approach combined with a field-dependent global parameterization method. The robust inter-dependence of the parameters carrying out the global search for individual residues (GSIR) or the global search for total residues (GSTR) provides information on the global minimum of the conformational transition process of the Zα domain of human ADAR1 (hZαADAR1)–DNA complex. The global search results indicated that a α-helical segment of hZαADAR1 provided the main contribution to the three-state conformational changes of a hZαADAR1—DNA complex with a slow B–Z exchange process. The two global exchange rate constants, kex and kZB, were found to be 844 and 9.8 s−1, respectively, in agreement with two regimes of residue-dependent chemical shift differences—the “dominant oscillatory regime” and “semi-oscillatory regime”. We anticipate that our global search approach will lead to the development of quantification methods for conformational changes not only in Z-DNA binding protein (ZBP) binding interactions but also in various protein binding processes.

An Explanation to the Nusselt–Rayleigh Discrepancy in Naturally Convected Porous Media

We model hydrothermal convection using a partial differential equation formed by Darcy velocity and temperature—the velocity formulation. Using the Elder problem as a benchmark, we found that the velocity formulation is a valid model of hydrothermal convection. By performing simulations with Rayleigh numbers in the non-oscillatory regime, we show that multiple quasi-steady-state solutions can be one of the reasons that caused the Nusselt–Rayleigh discrepancy found in previous experiments. The results reveal more understandings about the nature of uncertainty of convection modes in porous media.

Up and Down States During Slow Oscillations in Slow-Wave Sleep and Different Levels of Anesthesia

Slow oscillations are a pattern of synchronized network activity generated by the cerebral cortex. They consist of Up and Down states, which are periods of activity interspersed with periods of silence, respectively. However, even when this is a unique dynamic regime of transitions between Up and Down states, this pattern is not constant: there is a range of oscillatory frequencies (0.1–4 Hz), and the duration of Up vs. Down states during the cycles is variable. This opens many questions. Is there a constant relationship between the duration of Up and Down states? How much do they vary across conditions and oscillatory frequencies? Are there different sub regimes within the slow oscillations? To answer these questions, we aimed to explore a concrete aspect of slow oscillations, Up and Down state durations, across three conditions: deep anesthesia, light anesthesia, and slow-wave sleep (SWS), in the same chronically implanted rats. We found that light anesthesia and SWS have rather similar properties, occupying a small area of the Up and Down state duration space. Deeper levels of anesthesia occupy a larger region of this space, revealing that a large variety of Up and Down state durations can emerge within the slow oscillatory regime. In a network model, we investigated the network parameters that can explain the different points within our bifurcation diagram in which slow oscillations are expressed.

Electrocatalytic Efficiency of the Oxidation of Ethylene glycol, Glycerol, and Glucose under Oscillatory Regime

There is an increasingly interest in the use of small organic molecules in the interconversion between chemical and electrical energies. Among the strategies to improve the processes of yielding electrical energy in fuel cells and the production of clear hydrogen in electrochemical reform is the use of kinetic instabilities to improve the conversion and selectivity. Herein we report on the electrocatalytic efficiency of the oxidation of ethylene glycol, glycerol, and glucose, under regular and oscillatory regimes, on polycrystalline platinum, in sulfuric acid aqueous solution, and at 25 oC. Despite the high overpotentials for the electro-oxidation of these molecules, the electrochemical activity along quasi-stationary potentio/gavanostatic experiments evidenced that, in all cases, relatively lower potential values, and thus higher activity, are reached during oscillations. Noticeably higher power densities for the electrooxidation of ethylene glycol and glycerol under oscillatory regime in a hypothetical direct liquid fuel cell. The use of identical experimental conditions of that of our previous study[J. Phys. Chem. C 120 (2016) 22365] allowed at discussing some universal trends for seven small organic molecules. We compile the results in terms of the peak current, the maximum poisoning rate found along the oscillations, and the oscillation frequency. The three parameters were found to decrease in the order: formaldehyde > formic acid > methanol > ethanol > ethylene glycol > glycerol > glucose. In addition, we discussed the increase of the voltammetric current with the self-organized poisoning rate and reinforce the trend that high electrocatalytic activity implies high susceptibility to surface poisoning for this set of species. Finally, the analysis done for all species (formic acid, formaldehyde, methanol, ethylene glycol, ethanol, glycerol, and glucose) adds to the available thermodynamic data and is a benchmark against which the activities under oscillatory regime at 25 oC may be compared or assessed. This point of reference permits to explore further experimental conditions that are relevant for energy-related devices, including the conversion of chemical into electrical energy and the electrochemical reform to produce clean hydrogen in electrolyzers.