Multistability of bursting rhythms in a half-center oscillator and the protective effects of synaptic inhibition.

For animals to meet environmental challenges, the activity patterns of specialized oscillatory neural circuits, central pattern generators (CPGs), controlling rhythmic movements like breathing and locomotion, are adjusted by neuromodulation. As a representative example, the leech heartbeat is controlled by a CPG driven by two pairs of mutually inhibitory interneurons, heart interneuron (HN) half-center oscillators (HCO). Experiments and modeling indicate that neuromodulation of HCO navigates this CPG between dysfunctional regimes by employing a co-regulating inverted relation; reducing Na+/K+ pump current and increasing hyperpolarization-activated (h-) current. Simply reducing pump activity or increasing h-current leads to either seizure-like bursting or an asymmetric bursting dysfunctional regime, respectively. Here, we demonstrate through modeling that, alongside this coregulation path, a new bursting regime emerges. Both regimes fulfill the criteria for functional bursting activity. Although the cycle periods and burst durations of these patterns are roughly the same, the new one exhibits an intra-burst spike frequency that is twice as high as the other. This finding suggests that neuromodulation could introduce additional functional regimes with higher spike frequency, and thus more effective synaptic transmission to motor neurons. We found that this new regime co-exists with the original bursting. The HCO can be switched between them by a short pulse of excitatory or inhibitory conductance. In this domain of coexisting functional patterns, an isolated cell model exhibits only one regime, a severely dysfunctional plateau-containing, seizure-like activity. This aligns with widely reported notion that deficiency of inhibition can cause seizures and other dysfunctional neural activities. We show that along the coregulation path of neuromodulation, the high excitability of the single HNs induced by myomodulin is harnessed by mutually inhibitory synaptic interactions of the HCO into the functional bursting pattern.

Evaluating dynamic models for rigid-foldable origami: unveiling intricate bistable dynamics of stacked-Miura-origami structures as a case study.

Recent advances in origami science and engineering have particularly focused on the challenges of dynamics. While research has primarily focused on statics and kinematics, the need for effective and processable dynamic models has become apparent. This paper evaluates various dynamic modelling techniques for rigid-foldable origami, particularly focusing on their ability to capture nonlinear dynamic behaviours. Two primary methods, the lumped mass-spring-damper approach and the energy-based method, are examined using a bistable stacked Miura-origami (SMO) structure as a case study. Through systematic dynamic experiments, we analyse the effectiveness of these models in predicting bistable dynamic responses, including intra- and interwell oscillations, in different loading conditions. Our findings reveal that the energy-based approach, which considers the structure's inertia and utilizes dynamic experimental data for parameter identification, outperforms other models in terms of validity and accuracy. This model effectively predicts the dynamic response types, the rich and complex nonlinear characteristics and the critical frequency where interwell oscillations occur. Despite its relatively increased complexity in model derivation, it maintains computational efficiency and shows promise for broader applications in origami dynamics. By comparing model predictions with experimental results, this study enhances our understanding of origami dynamics and contributes valuable insights for future research and applications. This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

Newton's cradle: Cell cycle regulation by two mutually inhibitory oscillators.

The cell division cycle is a fundamental physiological process displaying a great degree of plasticity during the course of multicellular development. This plasticity is evident in the transition from rapid and stringently-timed divisions of the early embryo to subsequent size-controlled mitotic cycles. Later in development, cells may pause and restart proliferation in response to myriads of internal or external signals, or permanently exit the cell cycle following terminal differentiation or senescence. Beyond this, cells can undergo modified cell division variants, such as endoreplication, which increases their ploidy, or meiosis, which reduces their ploidy. This wealth of behaviours has led to numerous conceptual analogies intended as frameworks for understanding the proliferative program. Here, we aim to unify these mechanisms under one dynamical paradigm. To this end, we take a control theoretical approach to frame the cell cycle as a pair of arrestable and mutually-inhibiting, doubly amplified, negative feedback oscillators controlling chromosome replication and segregation events, respectively. Under appropriate conditions, this framework can reproduce fixed-period oscillations, checkpoint arrests of variable duration, and endocycles. Subsequently, we use phase plane and bifurcation analysis to explain the dynamical basis of these properties. Then, using a physiologically realistic, biochemical model, we show that the very same regulatory structure underpins the diverse functions of the cell cycle control network. We conclude that Newton's cradle may be a suitable mechanical analogy of how the cell cycle is regulated.

Modeling virus-stimulated proliferation of CD4+ T-cell, cell-to-cell transmission and viral loss in HIV infection dynamics.

Human immunodeficiency virus (HIV) can persist in infected individuals despite prolonged antiretroviral therapy and it may spread through two modes: virus-to-cell and cell-to-cell transmissions. Understanding viral infection dynamics is pivotal for elucidating HIV pathogenesis. In this study, we incorporate the loss term of virions, and both virus-to-cell and cell-to-cell infection modes into a within-host HIV model, which also takes into consideration the proliferation of healthy target cells stimulated by free viruses. By constructing suitable Lyapunov function and applying geometric methods, we establish global stability results of the infection free equilibrium and the infection persistent equilibrium, respectively. Our findings highlight the crucial role of the basic reproduction number in the threshold dynamics. Moreover, we use the loss rate of virions as the bifurcation parameter to investigate stability switches of the positive equilibrium, local Hopf bifurcation, and its global continuation. Numerical simulations validate our theoretical results, revealing rich viral dynamics including backward bifurcation, saddle-node bifurcation, and bistability phenomenon in the sense that the infection free equilibrium and a limit cycle are both locally asymptotically stable. These insights contribute to a deeper understanding of HIV dynamics and inform the development of effective therapeutic strategies.

Multifunctional Metamaterial with Reconfigurable Electromagnetic Scattering Properties for Advanced Stealth and Adaptive Applications.

The rapid development of radar detection systems has led to an increased sensitivity to the electromagnetic (EM) scattering properties of detected targets. Flexible and adaptable EM scattering properties significantly enhance the survivability of battlefield weapons. This paper presents the design of a novel multifunctional metamaterial with reconfigurable EM scattering properties based on a bistable curved beam. In addition to the cushioning and energy absorption properties of curved beams, the metamaterial achieves more than 90% EM absorption in the frequency range of 2.17-17.31 GHz, with a relative thickness of only 0.09λL. The bistable nature of the metamaterial allows it to switch between different states. Moreover, combined with the digital coding, this metamaterial can continuously adjust the absorbing bandwidth and further enhance the EM absorption rate within a specific frequency band range. If applied to satellite configurations, the developed metamaterial significantly reduces the radar cross section and offers potential applications in reconfiguring EM scattering properties, when applied to satellite configurations. By actively controller and reconstructing the EM scattering properties at certain frequency points, the metamaterial can achieve camouflage, providing innovative solutions for future stealth technology, electronic countermeasures, and deception jamming in radar detection.

Ultralong Bistable, Electrolytic MnO2-Based, Electrochromic Battery Enabled by Porous, Low-Barrier, Hydroxylated TiO2 Interface.

Electrochromic (EC) battery technology shows great potential in future "zero-energy building" by controlling outdoor solar transmission to tune heat gain as well as storing the consumed energy to reuse across other building systems. However, challenges still exist in exploring an electrochemical system to satisfy requirements on both ultra-long optical memory (also called bistability) without continuous power supply and high energy density. Herein, an EC battery is proposed to demonstrate ultra-long bistability (>760 h) based on the reversible deposition and dissolution of manganese oxide (MnO2) without the addition of any mediators. A porous low-barrier hydroxylated titanium dioxide (TiO2) interface is incorporated to synergistically enrich Mn2+-affinity active sites for deposition and effectively reduce the electron transport barrier of MnO2 for dissolution, thereby significantly improving the reversibility, high optical modulation (60.2% at 400 nm), and energy density (352 mAh m-2). The modification strategy is also verified on the cathode-less button cells with a much higher average coulombic efficiency (99.9%) compared to the batteries without the porous hydroxylated TiO2 interface (74.6%). These achievements lay a foundation for advancements in both electrochromism and Zn-Mn aqueous batteries.

Expression of proteins supporting visual function in heterobranch gastropods.

To sense light, animals often utilize mechanisms that rely on visual pigments composed of opsin and retinal. The photon-induced isomerization of 11-cis-retinal to the all-trans configuration triggers phototransduction cascades, resulting in a change in the membrane potential of the photoreceptor. In mollusks, the most abundant opsin in the eye is Gq-coupled rhodopsin (Gq-rhodopsin). The Gq-rhodopsin-based visual pigment is bistable, with the regeneration of 11-cis-retinal occurring in a light-dependent manner without leaving the opsin moiety. 11-cis-retinal is also regenerated by the action of retinochrome in the cell bodies. Retinal binding protein (RALBP) mediates retinal transport between Gq-rhodopsin and retinochrome in the cytoplasm. However, recent studies have identified additional bistable opsins in mollusks, including Opn5 and xenopsin. It is unknown whether these bistable opsins require RALBP and retinochrome for the continuous regeneration of 11-cis-retinal. In the present study, we examined the expression of RALBP and retinochrome in the photoreceptors expressing Opn5 or Xenopsin in the heterobranch gastropods Limax and Peronia. Our findings revealed that retinochrome, but not RALBP, was present in some of the Opn5A-positive brain photosensory neurons of Limax. The ciliary cells in the dorsal eye of Peronia, which express Xenopsin2, lacked both retinochrome and RALBP. Therefore, bistable opsins do not necessarily depend on the RALBP-retinochrome system in a cell. We also examined the expression of other proteins that support visual function, such as ß-arrestin, Gq, and Go, in all types of photoreceptors in these animals, and uncovered differences in the molecular composition among the photoreceptors.

Sustainable scenarios in a plants-rhizobacteria-plant consumers system are in risk when biotic or abiotic factors change.

The ecological relationship among plants, rhizobacteria and plant consumers has attracted the attention of researchers due to its implications in field crops. It is known that, the rhizosphere is occupied not only by rhizobacteria which grant benefits to the plants but also by bacteria which are detrimental for them. In this work, we construct and analyze a plants-rhizobacteria-plant consumers system. In the modeling process, it is assumed that there is a conditioned interaction between plants and bacteria in the rhizosfera such that there is a mutualistic relationship at low densities of rhizobacteria and the relationship is parasitic or competitive at higher densities of them. Benefits granted by rhizobacteria include mechanisms that increase the plant growth and defense mechanisms against plant consumers. From the analysis of the model and its simplified version, we show that scenarios of coexistence of all populations can occur for a wide range of values of the parameters which describe biotic or abiotic factors; however, these scenarios are in risk since scenarios of exclusion of species can occur simultaneously due to the presence of bistability phenomena. The results obtained can be useful for the decision makers to design interventions strategies on field crops when plant growth-promoting rhizobacteria are used.

Reassessing the alternative ecosystem states proposition in the African savanna-forest domain.

Ecologists are being challenged to predict how ecosystems will respond to climate changes. According to the Multi-Colored World (MCW) hypothesis, climate impacts may not manifest because consumers such as fire and herbivory can override the influence of climate on ecosystem state. One MCW interpretation is that climate determinism fails because alternative ecosystem states (AES) are possible at some locations in climate space. We evaluated theoretical and empirical evidence for the proposition that forest and savanna are AES in Africa. We found that maps which infer where AES zones are located were contradictory. Moreover, data from longitudinal and experimental studies provide inconclusive evidence for AES. That is, although the forest-savanna AES proposition is theoretically sound, the existing evidence is not yet convincing. We conclude by making the case that the AES proposition has such fundamental consequences for designing management actions to mitigate and adapt to climate change in the savanna-forest domain that it needs a more robust evidence base before it is used to prescribe management actions.

Dynamics of a network mediated by IL-36 and involved in the pathogenesis of psoriasis.

The pathogenesis of the inflammatory, chronic, and common skin disease psoriasis involves immune cells, skin cells (keratinocytes), and the cytokines they secrete. Hyperproliferation and abnormal differentiation of keratinocytes are hallmarks of the disease. The roles of cytokines such as TNFα, IL-15, IL-17, and IL-23 in psoriasis have been studied through mathematical/computational models as well as experiments. However, the role of proinflammatory cytokine IL-36 in the onset and progression of psoriasis is still elusive. To explore the role of IL-36, we construct a network embodying indirect cell-cell interactions of a few immune and skin cells mediated by IL-36 based on existing knowledge. We also develop a mathematical model for the network and perform a global sensitivity analysis. Our results suggest that the model is most sensitive to a parameter that represents the level of cytokine IL-36. In addition, a steady-state analysis of the model suggests that an increase in the level of IL-36 could lead to the hyperproliferation of keratinocytes and, thus, psoriasis. Our analysis also highlights that the plaque formation and progression of psoriasis could occur through either a gradual or a switch-like increase in the keratinocyte population. We propose that the switch-like increase would be due to a bistable behavior of the network toward either a psoriatic or healthy state and could be used as a novel treatment strategy.

Living in a noisy world-origins of gene expression noise and its impact on cellular decision-making.

The expression level of a gene can vary between genetically identical cells under the same environmental condition-a phenomenon referred to as gene expression noise. Several studies have now elucidated a central role of transcription factors in the generation of expression noise. Transcription factors, as the key components of gene regulatory networks, drive many important cellular decisions in response to cellular and environmental signals. Therefore, a very relevant question is how expression noise impacts gene regulation and influences cellular decision-making. In this Review, we summarize the current understanding of the molecular origins of expression noise, highlighting the role of transcription factors in this process, and discuss the ways in which noise can influence cellular decision-making. As advances in single-cell technologies open new avenues for studying expression noise as well as gene regulatory circuits, a better understanding of the influence of noise on cellular decisions will have important implications for many biological processes.

Consciousness and sleep.

Sleep is a universal, essential biological process. It is also an invaluable window on consciousness. It tells us that consciousness can be lost but also that it can be regained, in all its richness, when we are disconnected from the environment and unable to reflect. By considering the neurophysiological differences between dreaming and dreamless sleep, we can learn about the substrate of consciousness and understand why it vanishes. We also learn that the ongoing state of the substrate of consciousness determines the way each experience feels regardless of how it is triggered-endogenously or exogenously. Dreaming consciousness is also a window on sleep and its functions. Dreams tell us that the sleeping brain is remarkably lively, recombining intrinsic activation patterns from a vast repertoire, freed from the requirements of ongoing behavior and cognitive control.

Neuronal synchrony and critical bistability: Mechanistic biomarkers for localizing the epileptogenic network.

OBJECTIVE: Postsurgical seizure freedom in drug-resistant epilepsy (DRE) patients varies from 30% to 80%, implying that in many cases the current approaches fail to fully map the epileptogenic zone (EZ). We aimed to advance a novel approach to better characterize epileptogenicity and investigate whether the EZ encompasses a broader epileptogenic network (EpiNet) beyond the seizure zone (SZ) that exhibits seizure activity. METHODS: We first used computational modeling to test putative complex systems-driven and systems neuroscience-driven mechanistic biomarkers for epileptogenicity. We then used these biomarkers to extract features from resting-state stereoelectroencephalograms recorded from DRE patients and trained supervised classifiers to localize the SZ against gold standard clinical localization. To further explore the prevalence of pathological features in an extended brain network outside of the clinically identified SZ, we also used unsupervised classification. RESULTS: Supervised SZ classification trained on individual features achieved accuracies of .6-.7 area under the receiver operating characteristic curve (AUC). Combining all criticality and synchrony features further improved the AUC to .85. Unsupervised classification discovered an EpiNet-like cluster of brain regions, in which 51% of brain regions were outside of the SZ. Brain regions in the EpiNet-like cluster engaged in interareal hypersynchrony and locally exhibited high-amplitude bistability and excessive inhibition, which was strikingly similar to the high seizure risk regime revealed by our computational modeling. SIGNIFICANCE: The finding that combining biomarkers improves SZ localization accuracy indicates that the novel mechanistic biomarkers for epileptogenicity employed here yield synergistic information. On the other hand, the discovery of SZ-like brain dynamics outside of the clinically defined SZ provides empirical evidence of an extended pathophysiological EpiNet.

Mechanism of Decision Making between Autophagy and Apoptosis Induction upon Endoplasmic Reticulum Stress.

Dynamic regulation of the cellular proteome is mainly controlled in the endoplasmic reticulum (ER). Accumulation of misfolded proteins due to ER stress leads to the activation of unfolded protein response (UPR). The primary role of UPR is to reduce the bulk of damages and try to drive back the system to the former or a new homeostatic state by autophagy, while an excessive level of stress results in apoptosis. It has already been proven that the proper order and characteristic features of both surviving and self-killing mechanisms are controlled by negative and positive feedback loops, respectively. The new results suggest that these feedback loops are found not only within but also between branches of the UPR, fine-tuning the response to ER stress. In this review, we summarize the recent knowledge of the dynamical characteristic of endoplasmic reticulum stress response mechanism by using both theoretical and molecular biological techniques. In addition, this review pays special attention to describing the mechanism of action of the dynamical features of the feedback loops controlling cellular life-and-death decision upon ER stress. Since ER stress appears in diseases that are common worldwide, a more detailed understanding of the behaviour of the stress response is of medical importance.

Analysis of long transients and detection of early warning signals of extinction in a class of predator-prey models exhibiting bistable behavior.

In this paper, we develop a method of analyzing long transient dynamics in a class of predator-prey models with two species of predators competing explicitly for their common prey, where the prey evolves on a faster timescale than the predators. In a parameter regime near a singular zero-Hopf bifurcation of the coexistence equilibrium state, we assume that the system under study exhibits bistability between a periodic attractor that bifurcates from the singular Hopf point and another attractor, which could be a periodic attractor or a point attractor, such that the invariant manifolds of the coexistence equilibrium point play central roles in organizing the dynamics. To find whether a solution that starts in a vicinity of the coexistence equilibrium approaches the periodic attractor or the other attractor, we reduce the equations to a suitable normal form, and examine the basin boundary near the singular Hopf point. A key component of our study includes an analysis of the long transient dynamics, characterized by their rapid oscillations with a slow variation in amplitude, by applying a moving average technique. We obtain a set of necessary and sufficient conditions on the initial values of a solution near the coexistence equilibrium to determine whether it lies in the basin of attraction of the periodic attractor. As a result of our analysis, we devise a method of identifying early warning signals, significantly in advance, of a future crisis that could lead to extinction of one of the predators. The analysis is applied to the predator-prey model considered in Sadhu (Discrete Contin Dyn Syst B 26:5251-5279, 2021) and we find that our theory is in good agreement with the numerical simulations carried out for this model.

Advantages of Bistable Microwires in Digital Signal Processing.

The advantageous applications of magnetic bistable microwires have emerged during long-lasting research. They have a wide range of applications in the scientific sphere or technical practice. They can be used for various applications, including magnetic memories, biomedicine, and sensors. This manuscript is focused on the last-mentioned application of microwires-sensors-discussing various digital signal processing techniques used in practical applications. Thanks to the highly sensitive properties of microwires and their two stable states of magnetization, it is possible to perform precise measurements with less demanding digital processing. The manuscript presents four practical signal-processing methods of microwire response using three different experiments. These experiments are focused on detecting the signal in a simple environment without an external magnetic background, measuring with the external background of a ferromagnetic core, and measuring in harsh conditions with a strong magnetic background. The experiments aim to propose the best method under various conditions, emphasizing the quality and signal processing speed of the microwire signal.

The Design and Ground Test Verification of an Energy-Efficient Wireless System for the Fatigue Monitoring of Wind Turbine Blades Based on Bistable Piezoelectric Energy Harvesting.

A wireless monitoring system based on piezoelectric energy harvesting (PEH) is presented to provide fatigue data of wind turbine blades in operation. The system comprises three subsystems, each respectively providing the following functions: (i) the conversion of mechanical to electric energy by exploiting the bistable vibration of a composite beam with piezoelectric patches in post-buckling, (ii) harvesting the converted energy by means of a modified, commercial, off-the-shelf (COTS) circuit to feed a LiPo battery and (iii) the battery-powered acquisition and wireless transmission of sensory signals to the cloud to be elaborated upon by the end-user. The system was verified with ground tests under representative operation conditions, which demonstrated the fulfillment of the design requirements. The measurements indicated that the system provided 23% of the required power for fully autonomous operation when subjected to white noise base excitation of 1 g acceleration in the range of 1-20 Hz.

Mathematical modeling of viral infection and the immune response controlled by the circadian clock.

Time of day affects how well the immune system responds to viral or bacterial infections. While it is well known that the immune system is regulated by the circadian clock, the dynamic origin of time-of-day-dependent immunity remains unclear. In this paper, we studied the circadian control of immune response upon infection of influenza A virus through mathematical modeling. Dynamic simulation analyses revealed that the time-of-day-dependent immunity was rooted in the relative phase between the circadian clock and the pulse of viral infection. The relative phase, which depends on the time the infection occurs, plays a crucial role in the immune response. It can drive the immune system to one of two distinct bistable states, a high inflammatory state with a higher mortality rate or a safe state characterized by low inflammation. The mechanism we found here also explained why the same species infected by different viruses has different time-of-day-dependent immunities. Further, the time-of-day-dependent immunity was found to be abolished when the immune system was regulated by an impaired circadian clock with decreased oscillation amplitude or without oscillations.

Tunable optical bistability of two-dimensional tilted Dirac system.

We study the phenomenon of controlling the light by light known as the optical bistability for the two-dimensional tilted Dirac system. Using the Boltzmann approach under relaxation time approximation, we find that the optical bistability can be controlled by the nonlinear response of the system. For the prototype, we consider an inversion symmetry broken system. We find that the optical bistability associated with the nonlinear response is tunable with the strength of the tilt, gap and chemical potential. The resulting features suggest the inputs for the development of future-generation optical devices.