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At least 991 records · Page 55Linked to original sources

Laminar cortical dynamics of 3D surface perception: stratification, transparency, and neon color spreading.

The 3D LAMINART neural model is developed to explain how the visual cortex gives rise to 3D percepts of stratification, transparency, and neon color spreading in response to 2D pictures and 3D scenes. Such percepts are sensitive to whether contiguous image regions have the same contrast polarity and ocularity. The model predicts how like-polarity competition at V1 simple cells in layer 4 may cause these percepts when it interacts with other boundary and surface processes in V1, V2, and V4. The model also explains how: the Metelli Rules cause transparent percepts, bistable transparency percepts arise, and attention influences transparency reversal.

Color Perception↗

Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations.

Transcriptional regulation is an inherently noisy process. The origins of this stochastic behavior can be traced to the random transitions among the discrete chemical states of operators that control the transcription rate and to finite number fluctuations in the biochemical reactions for the synthesis and degradation of transcripts. We develop stochastic models to which these random reactions are intrinsic and a series of simpler models derived explicitly from the first as approximations in different parameter regimes. This innate stochasticity can have both a quantitative and qualitative impact on the behavior of gene-regulatory networks. We introduce a natural generalization of deterministic bifurcations for classification of stochastic systems and show that simple noisy genetic switches have rich bifurcation structures; among them, bifurcations driven solely by changing the rate of operator fluctuations even as the underlying deterministic system remains unchanged. We find stochastic bistability where the deterministic equations predict monostability and vice-versa. We derive and solve equations for the mean waiting times for spontaneous transitions between quasistable states in these switches.

Feedback, Physiological↗

Unzipping DNA with optical tweezers: high sequence sensitivity and force flips.

Force measurements are performed on single DNA molecules with an optical trapping interferometer that combines subpiconewton force resolution and millisecond time resolution. A molecular construction is prepared for mechanically unzipping several thousand-basepair DNA sequences in an in vitro configuration. The force signals corresponding to opening and closing the double helix at low velocity are studied experimentally and are compared to calculations assuming thermal equilibrium. We address the effect of the stiffness on the basepair sensitivity and consider fluctuations in the force signal. With respect to earlier work performed with soft microneedles, we obtain a very significant increase in basepair sensitivity: presently, sequence features appearing at a scale of 10 basepairs are observed. When measured with the optical trap the unzipping force exhibits characteristic flips between different values at specific positions that are determined by the base sequence. This behavior is attributed to bistabilities in the position of the opening fork; the force flips directly reflect transitions between different states involved in the time-averaging of the molecular system.

Calibration↗

Feedback regulation in the lactose operon: a mathematical modeling study and comparison with experimental data.

A mathematical model for the regulation of induction in the lac operon in Escherichia coli is presented. This model takes into account the dynamics of the permease facilitating the internalization of external lactose; internal lactose; beta-galactosidase, which is involved in the conversion of lactose to allolactose, glucose and galactose; the allolactose interactions with the lac repressor; and mRNA. The final model consists of five nonlinear differential delay equations with delays due to the transcription and translation process. We have paid particular attention to the estimation of the parameters in the model. We have tested our model against two sets of beta-galactosidase activity versus time data, as well as a set of data on beta-galactosidase activity during periodic phosphate feeding. In all three cases we find excellent agreement between the data and the model predictions. Analytical and numerical studies also indicate that for physiologically realistic values of the external lactose and the bacterial growth rate, a regime exists where there may be bistable steady-state behavior, and that this corresponds to a cusp bifurcation in the model dynamics.

Computer Simulation↗

A physical model of potassium channel activation: from energy landscape to gating kinetics.

We have developed a method for rapidly computing gating currents from a multiparticle ion channel model. Our approach is appropriate for energy landscapes that can be characterized by a network of well-defined activation pathways with barriers. To illustrate, we represented the gating apparatus of a channel subunit by an interacting pair of charged gating particles. Each particle underwent spatial diffusion along a bistable potential of mean force, with electrostatic forces coupling the two trajectories. After a step in membrane potential, relaxation of the smaller barrier charge led to a time-dependent reduction in the activation barrier of the principal gate charge. The resulting gating current exhibited a rising phase similar to that measured in voltage-dependent ion channels. Reduction of the two-dimensional diffusion landscape to a circular Markov model with four states accurately preserved the time course of gating currents on the slow timescale. A composite system containing four subunits leading to a concerted opening transition was used to fit a series of gating currents from the Shaker potassium channel. We end with a critique of the model with regard to current views on potassium channel structure.

Adaptation, Physiological↗

Voltage oscillations in the barnacle giant muscle fiber.

Barnacle muscle fibers subjected to constant current stimulation produce a variety of types of oscillatory behavior when the internal medium contains the Ca++ chelator EGTA. Oscillations are abolished if Ca++ is removed from the external medium, or if the K+ conductance is blocked. Available voltage-clamp data indicate that the cell's active conductance systems are exceptionally simple. Given the complexity of barnacle fiber voltage behavior, this seems paradoxical. This paper presents an analysis of the possible modes of behavior available to a system of two noninactivating conductance mechanisms, and indicates a good correspondence to the types of behavior exhibited by barnacle fiber. The differential equations of a simple equivalent circuit for the fiber are dealt with by means of some of the mathematical techniques of nonlinear mechanics. General features of the system are (a) a propensity to produce damped or sustained oscillations over a rather broad parameter range, and (b) considerable latitude in the shape of the oscillatory potentials. It is concluded that for cells subject to changeable parameters (either from cell to cell or with time during cellular activity), a system dominated by two noninactivating conductances can exhibit varied oscillatory and bistable behavior.

Action Potentials↗

Model of the Ca2+ oscillator for shuttle streaming in Physarum polycephalum.

We propose a mechanism for the cytoplasmic Ca++ oscillator which is thought to power shuttle streaming in strands of the slime-mold Physarum polycephalum. The mechanism uses a phosphorylation-dephosphorylation cycle of myosin light chain kinase. This kinase is bistable if the kinase phosphorylation chain, through adenylate cyclase and cAMP, is activated by calcium. Relaxation oscillations can then occur if calcium is exchanged between the cytoplasm and internal vacuoles known to exist in physarum. As contractile activity in physarum myosin is inhibited by calcium, this model can give calcium oscillations 180 degrees out of phase with actin filament tension as observed. Oscillations of ATP concentration are correctly predicted to be in phase with the tension, provided the actomyosin cycling rate is comparable with ATPase rates for phosphorylation of the myosin light chain and its kinase.

Adenosine Triphosphatases↗

Spontaneous action potentials due to channel fluctuations.

A theoretical and numerical analysis of the Hodgkin-Huxley equations with the inclusion of stochastic channel dynamics is presented. It is shown that the system can be approximated by a one-dimensional bistable Langevin equation. Spontaneous action potentials can arise from the channel fluctuations and are analogous to escape by a particle over a potential barrier. The mean firing rate can be calculated using Kramers' classic result for barrier escape. The probability density function of the interspike intervals can also be estimated. The analytical results compare favorably with numerical simulations of the complete stochastic system.

Action Potentials↗

Quasi- and nonequivalence in the structure of bacterial flagellar filament.

In supercoiled forms of flagellar filaments, which are thought to be produced by combinations of two distinct subunit lattices, the lattices are elastically deformed in 11 different ways, depending on their azimuthal positions on the circumference of a tube with 11 protofilaments. Those two interactions are nonequivalent as opposed to quasiequivalent ones in elastically deformed lattices of otherwise identical interactions. The term nonequivalence is defined to represent different bonding interactions, and quasiequivalent is used to describe deformed but conserved bonding interactions. By using two distinct lattices that were accurately determined by x-ray fiber diffraction, 10 possible supercoiled forms of flagellar filaments were simulated, based on a bistable-subunit packing model. Comparison to the observed forms showed good agreement, indicating that the model and determined lattice parameters effectively represent realistic features of the structure. The simulated quasiequivalent lattices have been compared to the two nonequivalent lattices, revealing an interesting feature: the maximum deviation in the intersubunit distance by elastic deformation is almost three-quarters of the difference between the two distinct lattices, demonstrating a balanced coexistence of a well-defined conformational distinction and extensive adaptability in the molecular structure of flagellin and its packing interactions.

Bacteria↗

Impact of mitochondrial Ca2+ cycling on pattern formation and stability.

Energization of mitochondria significantly alters the pattern of Ca2+ wave activity mediated by activation of the inositol (1,4,5) trisphosphate (IP3) receptor (IP3R) in Xenopus oocytes. The number of pulsatile foci is reduced and spiral Ca2+ waves are no longer observed. Rather, target patterns of Ca2+ release predominate, and when fragmented, fail to form spirals. Ca2+ wave velocity, amplitude, decay time, and periodicity are also increased. We have simulated these experimental findings by supplementing an existing mathematical model with a differential equation for mitochondrial Ca2+ uptake and release. Our calculations show that mitochondrial Ca2+ efflux plays a critical role in pattern formation by prolonging the recovery time of IP3Rs from a refractory state. We also show that under conditions of high energization of mitochondria, the Ca2+ dynamics can become bistable with a second stable stationary state of high resting Ca2+ concentration.

Animals↗

Time and temperature dependent aggregation behaviour of the ganglioside GM1 in aqueous solution.

Gangliosides are marked amphiphiles with several ramified sugar rings and a ceramide moiety. Therefore they form micelles in aqueous solution. This aggregation behavior is studied with static and dynamic light scattering and small angle X-ray scattering. The shape and the size of the GM1 micelles in dependence of time and temperature are investigated. Some data have been published recently where two stable states for the micelles are found. This bistability is said to be achieved by temperature rise from room temperature up to 55 degrees C. The authors did not find such an internal structural change of the micelle in the experiments. Instead the authors found some large aggregates of the ganglioside in parallel to the micelle caused by the low solubility of this system at room temperature. These aggregates are dissolved quickly with increasing temperature or slowly with time at room temperature. So the variation of the scattering intensity is explainable by dissolving the large particles, meanwhile the structure of the GM1 micelles is the same all the time.

Calorimetry, Differential Scanning↗

Perceptual interaction between real and synesthetic colors.

People with color-graphemic synesthesia experience vivid, reliable color upon viewing achromatic alphanumeric characters. Recent evidence indicates that synesthetic color experiences are as perceptually real as actual colors are for non-synesthetic observers. To investigate possible interactions between real and synesthetic colors, we tested two adult color-graphemic synesthetes on a pair of perceptual grouping tasks. In Experiment 1, we employed a well-known phenomenon of motion perception, bistable apparent motion, to explore whether synesthetic colors interact with real colors in grouping over time. Two-frame apparent motion sequences were presented with both path lengths and colors systematically manipulated. Results showed that synesthetic colors of motion tokens interacted with matching real colors of the corresponding motion tokens, which could subsequently bias perceived direction of motion. In Experiment 2, we exploited binocular rivalry, a condition under which two dissimilar monocular images compete with each other and result in perceptual switches, to explore whether synesthetic colors interact with real colors in grouping over space. Pairs of rival images with two different characters were presented dichoptically with colors of characters manipulated. Results showed that synesthetic and real colors of characters tended to group together, which, in turn, promoted the perceived global dominance during binocular rivalry. Therefore, the present results identify substantial interaction between synesthetic colors and real colors in perceptual grouping.

Adult↗

The photoreceptor protein of Euglena gracilis.

We isolated the photoactive protein Erh, isolated from the photoreceptor of the unicellular photosynthetic flagellate Euglena gracilis. It is a 27 kDa protein with a photocycle resembling that of sensory rhodopsin, but with at least one stable intermediate. We recorded the absorption spectrum of the parent form of this protein both under native form and in the presence of hydroxylamine and sodium borohydride, and the fluorescence spectra of both the parent and intermediate forms. We suggest that Erh is a rhodopsin-like protein and propose a simple photocycle. This protein shows optical bistability, without thermal deactivation.

Animals↗

Autocatalytic processes in cooperative mechanisms of prion diseases.

According to the leading theory, the agent responsible for prion diseases would be the conformational isomer PrP(Sc) of a cellular protein PrP(C), the pathogenic form PrP(Sc) multiplying by converting the normal protein into a likeness of itself. The pathogenic isoform could catalyze the conformational transition so that the process, taken as a whole, is autocatalytic. However, in this simple but atypic model, unrealistic values of rate parameters are needed in order to account for the kinetics of the propagation of prion diseases. In this paper, I show that these limits can be overcome by assuming that catalysis proceeds through a multimeric assembly of the pathogenic isoform of the prion protein. Such a structure would indeed be able to provide cooperativity both at the assembly and conformational change levels, strongly reinforcing the autocatalytic character of the activated process. Moreover, such a property is a prerequisite to endow the metabolic system with dynamic bistability. Together with a good agreement regarding experimental data, this analysis is closely akin to Griffith's original idea concerning the thermodynamic conditions required for autocatalyzed modifications of any protein.

Allosteric Regulation↗

Neural adaptations with chronic physical activity.

Chronic activity patterns, such as strength training, limb immobilization, and aging, produce marked adaptations in both the muscular and nervous systems. In this brief review, some of the involved mechanisms are examined as they are revealed through studies on the maximality, specificity, and pattern of the neural drive to muscle. The studies on maximality indicate that it is difficult to activate maximally a muscle by voluntary command, the capacity varies across muscles, tasks, and training, and the maximum discharge rates of motor neurons decreases with immobilization and increases with strength training. The data on specificity demonstrate that: strength can be increased by training with imagined contractions; the velocity specificity of isokinetic training is evident with intended contractions; the strength training influences the untrained homologous muscle in the contralateral limb; the bilatral deficit can become a bilateral facilitation with appropriate training; and that eccentric contractions appear to involve a different activation scheme compared to isometric and concentric contractions. Finally, the literature on the pattern of the neural drive suggests that: coactivation varies with training and often decreases as skill level increases; measures of motor-unit synchronization reveal changes in neuronal connectivity with physical training; the reflex potentiation varies across muscles, individuals, and activity patterns; the modulation of the H-reflex amplitude with training involves changes in the motor neuron; and the motor neurons exhibit a bistable, excitability property that may be influenced by exercise. Despite the breadth of this evidence, there remain substantial gaps in our knowledge, particularly regarding the symmetry of adaptations with increased and decreased chronic physical activity.

Adaptation, Physiological↗

Theoretical computation of phase locking in embryonic atrial heart cell aggregates.

The effects of periodic stimulation of spontaneously beating aggregates of chick atrial heart cells are considered. Provided the effects of a single stimulus do not change the properties of the oscillation, and that the oscillation is re-established rapidly following a stimulus, this system can be modeled by one-dimensional finite difference equations. These equations employ experimentally generated phase resetting data that describe the effects of a single isolated stimulus at different phases of the oscillation. A complete analysis of the predicted dynamics is given over a broad range of stimulation frequencies and amplitudes. Prominent features of the dynamics include phase locking, bistability, chaos, and disappearance of Arnold tongues at large stimulation amplitudes. The fine details of the bifurcations are sensitive to properties of the phase resetting curves, and consequently, the observed bifurcations are not expected to be "universal" for larger stimulation amplitudes. Experimental traces show many correspondences with theoretical computations.

Animals↗

Stochastic resonance in a single neuron model: theory and analog simulation.

Here, we consider a noisy, bistable, single neuron model in the presence of periodic external modulation. The modulation induces a correlated switching between states driven by the noise. The information flow through the system, from the modulation, or signal, to the output switching events, leads to a succession of strong peaks in the power spectrum. The signal-to-noise ratio (SNR) obtained from this power spectrum is a measure of the information content in the neuron response. With increasing noise intensity, the SNR passes through a maximum: an effect which has been called stochastic resonance, and which was first advanced as a possible explanation of the observed periodicity in the recurrences of the Earth's ice ages. We treat the problem within the framework of a recently developed approximate theory, valid in the limits of weak noise intensity, weak periodic forcing and low forcing frequency, for both additive and multiplicative noise. Moreover, we have constructed an analog simulator of the neuron which demonstrates the stochastic resonance effect, and with which we have measured the SNRs for comparison with the theoretical results. Our model should be of interest in situations where a single inherently noisy neuron is the receptor of a periodic signal, which is itself noisy, either from the network or from an external source.

Animals↗

Selectivity and sensitivity improvement in co-operative systems with a threshold in the presence of noise.

High selectivity (specificity) and sensitivity to natural or artificial stimuli which are normally observed for biological systems can be realized in an ensemble composed of many co-operatively connected primary receptors. The co-operative interaction results in the formation of several stable states and a switching from one state to another is performed in a threshold manner. When any noise is absent the ensemble with a threshold can secure as high a selectivity and sensitivity as is desired. The presence of noise sets limits on the possible informational quality of a system because spontaneous switchings will occur. The question: What advantage as regards selectivity and sensitivity can a co-operative system with a threshold have is considered quantitatively as an example for a bistable chemical system. As a result it is established that a co-operative system may have much higher selectivity and sensitivity than its individual primary receptors.

Mathematics↗