High-dimensional switches and the modeling of cellular differentiation

Many genes have been identified as driving cellular differentiation, but because of their complex interactions, the understanding of their collective behaviour requires mathematical modelling. Intriguingly, it has been observed in numerous developmental contexts, and particularly hematopoiesis, that genes regulating differentiation are initially co-expressed in progenitors despite their antagonism, before one is upregulated and others downregulated. We characterise conditions under which 3 classes of generic "master regulatory networks", modelled at the molecular level after experimentally-observed interactions (including bHLH protein dimerisation), and including an arbitrary number of antagonistic components, can behave as a "multi-switch", directing differentiation in an all-or-none fashion to a specific cell-type chosen among more than 2 possible outcomes. bHLH dimerisation networks can readily display coexistence of many antagonistic factors when competition is low (a simple characterisation is derived). Decision-making can be forced by a transient increase in competition, which could correspond to some unexplained experimental observations related to Id proteins; the speed of response varies with the initial conditions the network is subjected to, which could explain some aspects of cell behaviour upon reprogramming.The coexistence of antagonistic factors at low levels, early in the differentiation process or in pluripotent stem cells, could be an intrinsic property of the interaction between those factors, not requiring a specific regulatory system

Tongue-placed tactile biofeedback suppresses the deleterious effects of muscle fatigue on joint position sense at the ankle

Whereas the acuity of the position sense at the ankle can be disturbed by muscle fatigue, it recently also has been shown to be improved, under normal ankle neuromuscular state, through the use of an artificial tongue-placed tactile biofeedback. The underlying principle of this biofeedback consisted of supplying individuals with supplementary information about the position of their matching ankle position relative to their reference ankle position through electrotactile stimulation of the tongue. Within this context, the purpose of the present experiment was to investigate whether this biofeedback could mitigate the deleterious effect of muscle fatigue on joint position sense at the ankle. To address this objective, sixteen young healthy university students were asked to perform an active ankle-matching task in two conditions of No-fatigue and Fatigue of the ankle muscles and two conditions of No-biofeedback and Biofeedback. Measures of the overall accuracy and the variability of the positioning were determined using the absolute error and the variable error, respectively. Results showed that the availability of the biofeedback allowed the subjects to suppress the deleterious effects of muscle fatigue on joint position sense at the ankle. In the context of sensory re-weighting process, these findings suggested that the central nervous system was able to integrate and increase the relative contribution of the artificial tongue-placed tactile biofeedback to compensate for a proprioceptive degradation at the ankle

Optimizing the Use of an Artificial Tongue-Placed Tactile Biofeedback for Improving Ankle Joint Position Sense in Humans

The performance of an artificial tongue-placed tactile biofeedback device for improving ankle joint position sense was assessed in 12 young healthy adults using an active matching task. The underlying principle of this system consists of supplying individuals with supplementary information about the position of the matching ankle relative to the reference ankle position through a tongue-placed tactile output device generating electrotactile stimulation on a 36-point (6 X 6) matrix held against the surface of the tongue dorsum. Precisely, (1) no electrodes were activated when both ankles were in a similar angular position within a predetermined "angular dead zone" (ADZ); (2) 12 electrodes (2 X 6) of the anterior and posterior zones of the matrix were activated (corresponding to the stimulation of the front and rear portion of the tongue) when the matching ankle was in a too plantarflexed and dorsiflexed position relative to the reference ankle, respectively. Two ADZ values of 0.5 degrees and 1.5 degrees were evaluated. Results showed (1) more accurate and more consistent matching performances with than without biofeedback and (2) more accurate and more consistent ankle joint matching performances when using the biofeedback device with the smaller ADZ valu

Linear And Nonlinear Arabesques: A Study Of Closed Chains Of Negative 2-Element Circuits

In this paper we consider a family of dynamical systems that we call "arabesques", defined as closed chains of 2-element negative circuits. An $n$-dimensional arabesque system has $n$ 2-element circuits, but in addition, it displays by construction, two $n$-element circuits which are both positive vs one positive and one negative, depending on the parity (even or odd) of the dimension $n$. In view of the absence of diagonal terms in their Jacobian matrices, all these dynamical systems are conservative and consequently, they can not possess any attractor. First, we analyze a linear variant of them which we call "arabesque 0" or for short "A0". For increasing dimensions, the trajectories are increasingly complex open tori. Next, we inserted a single cubic nonlinearity that does not affect the signs of its circuits (that we call "arabesque 1" or for short "A1"). These systems have three steady states, whatever the dimension is, in agreement with the order of the nonlinearity. All three are unstable, as there can not be any attractor in their state-space. The 3D variant (that we call for short "A1\_3D") has been analyzed in some detail and found to display a complex mixed set of quasi-periodic and chaotic trajectories. Inserting $n$ cubic nonlinearities (one per equation) in the same way as above, we generate systems "A2\_$n$D". A2\_3D behaves essentially as A1\_3D, in agreement with the fact that the signs of the circuits remain identical. A2\_4D, as well as other arabesque systems with even dimension, has two positive $n$-circuits and nine steady states. Finally, we investigate and compare the complex dynamics of this family of systems in terms of their symmetries.Comment: 22 pages, 12 figures, accepted for publication at Int. J. Bif. Chao

Guiding the surgical gesture using an electro-tactile stimulus array on the tongue: A feasibility study

Under conventional "open-" surgery, the physician has to take care of the patient, interact with other clinicians and check several monitoring devices. Nowadays, the Computer Assisted Surgery proposes to integrate 3D cameras in the operating theatre in order to assist the surgeon in performing minimal-invasive surgical punctures. The cameras localize the needle and the computer guides the surgeon towards an intracorporeal clinically-defined target. A visualization system (screen) is employed to provide the surgeon with indirect visual spatial information about the intracorporeal positions of the needle. The present work proposes to use another sensory modality to guide the surgeon thus keeping the visual modality fully dedicated to the surgical gesture. For this, the sensory substitution paradigm using the Bach-y-Rita's "Tongue Display Unit" (TDU) is exploited to provide to the surgeon information of the position tool. The TDU device is composed of a 6x6 matrix of electrodes transmitting electrotactile information on the tongue surface. The underlying idea consists in transmitting information about the deviation of the needle movement with regard to a pre-planned "optimal" trajectory. We present an experiment assessing the guidance effectiveness of an intracorporeal puncture under TDU guidance with respect to the performance evidenced under a usual visual guidance system

Artificial Tongue-Placed Tactile Biofeedback for perceptual supplementation: application to human disability and biomedical engineering

The present paper aims at introducing the innovative technologies, based on the concept of "sensory substitution" or "perceptual supplementation", we are developing in the fields of human disability and biomedical engineering. Precisely, our goal is to design, develop and validate practical assistive biomedical and/technical devices and/or rehabilitating procedures for persons with disabilities, using artificial tongue-placed tactile biofeedback systems. Proposed applications are dealing with: (1) pressure sores prevention in case of spinal cord injuries (persons with paraplegia, or tetraplegia); (2) ankle proprioceptive acuity improvement for driving assistance in older and/or disabled adults; and (3) balance control improvement to prevent fall in older and/or disabled adults. This paper presents results of three feasibility studies performed on young healthy adults

Postural destabilization induced by trunk extensor muscles fatigue is suppressed by use of a plantar pressure-based electro-tactile biofeedback

Separate studies have reported that postural control during quiet standing could be (1) impaired with muscle fatigue localized at the lower back, and (2) improved through the use of plantar pressure-based electro-tactile biofeedback, under normal neuromuscular state. The aim of this experiment was to investigate whether this biofeedback could reduce postural destabilization induced by trunk extensor muscles. Ten healthy adults were asked to stand as immobile as possible in four experimental conditions: (1) no fatigue/no biofeedback, (2) no fatigue/biofeedback, (3) fatigue/no biofeedback and (4) fatigue/biofeedback. Muscular fatigue was achieved by performing trunk repetitive extensions until maximal exhaustion. The underlying principle of the biofeedback consisted of providing supplementary information related to foot sole pressure distribution through electro-tactile stimulation of the tongue. Centre of foot pressure (CoP) displacements were recorded using a force platform. Results showed (1) increased CoP displacements along the antero-posterior axis in the fatigue than no fatigue condition in the absence of biofeedback and (2) no significant difference between the no fatigue and fatigue conditions in the presence of biofeedback. This suggests that subjects were able to efficiently integrate an artificial plantar pressure information delivered through electro-tactile stimulation of the tongue that allowed them to suppress the destabilizing effect induced by trunk extensor muscles fatigue

SARS-CoV-2 and miRNA-like inhibition power

(1) Background: RNA viruses and especially coronaviruses could act inside host cells not only by building their own proteins, but also by perturbing the cell metabolism. We show the possibility of miRNA-like inhibitions by the SARS-CoV-2 concerning for example the hemoglobin and type I interferons syntheses, hence highly perturbing oxygen distribution in vital organs and immune response as described by clinicians; (2) Methods: We compare RNA subsequences of SARS-CoV-2 protein S and RNA-dependent RNA polymerase genes to mRNA sequences of beta-globin and type I interferons; (3) Results: RNA subsequences longer than eight nucleotides from SARS-CoV-2 genome could hybridize subsequences of the mRNA of beta-globin and of type I interferons; (4) Conclusions: Beyond viral protein production, Covid-19 might affect vital processes like host oxygen transport and immune response.Comment: 14 pages, 12 figure

Dynamical system model of decision making and propagation

International audienceIndividual decision making is described as a bistable dynamical system. It can be influenced by the environment represented by other individuals, public opinion, all kinds of visual, oral and other information. We will study how the interaction of the individual decision making with the environment results in various patterns of decision making in the society

Structural Sensitivity of Neural and Genetic Networks

International audienceThis paper aims at giving new results on the structural sensitivity of biological networks represented by threshold Boolean networks and ruled by Hopfield-like evolution laws classically used in the context of neural and genetic networks. Indeed, the objective is to present how certain changes and/or perturbations in such networks can modify signicantly their asymptotic behaviour. More precisely, this work has been focused on three diferent kinds of what we think to be relevant in the biological area of robustness (in both theoretical and applied frameworks): the boundary sensitivity (external fields, hormone flows, ...), the state sensitivity (axonal or somatic modulations, microRNAs actions, ...) and the updating sensitivity