DISTINCT,VERY HIGH FREQUENCY OSCILLATIONS IN THE ACTIVITY AND AMOUNT OF ACTIVE ISOZYME OF LACTATE DEHYDROGENASE IN MURINE ERYTHROLEUKAEMIC CELLS AND A CELL-FREE SYSTEM

Electrophoretic and kinetic determinations of the activity of lactate dehydrogenase in murine erythroleukaemic (MEL) cells, sampled at 1min intervals, reveal distinct oscillations in the activity and amount of active isozyme. Both oscillations have periods in the range of 2–6min (probably less) and both appear to be rhythmically modulated with respect to period, amplitude and mean. The oscillations also occur in cell-free systems, a fact which throws doubt on the value of studies where it is assumed that such preparations have constant composition.     

Mechanical and biochemical modeling of cortical oscillations in spreading cells

Actomyosin-based cortical contractility is a common feature of eukaryotic cells and is involved in cell motility, cell division, and apoptosis. In nonmuscle cells, oscillations in contractility are induced by microtubule depolymerization during cell spreading. We developed an ordinary differential equation model to describe this behavior. The computational model includes 36 parameters. The values for all but two of the model parameters were taken from experimental measurements found in the literature. Using these values, we demonstrate that the model generates oscillatory behavior consistent with current experimental observations. The rhythmic behavior occurs because of the antagonistic effects of calcium-induced contractility and stretch-activated calcium channels. The model makes several experimentally testable predictions: 1), buffering intracellular calcium increases the period and decreases the amplitude of cortical oscillations; 2), increasing the number or activity of stretch activated channels leads to an increase in period and amplitude of cortical oscillations; 3), inhibiting Ca²⁺ pump activity increases the period and amplitude of oscillations; and 4), a threshold exists for the calcium concentration below which oscillations cease.     

UNDAMPED OSCILLATIONS OF PYRIDINE NUCLEOTIDE AND OXYGEN TENSION IN CHEMOSTAT CULTURES OF KLEBSIELLA AEROGENES

Klebsiella aerogenes was grown in chemostat culture with the pH controlled to ±0.01 and temperature to ±0.1°C. The oxygen tension of the culture was regulated by changing the partial pressure of oxygen in the gas phase and recorded by means of an oxygen electrode. Reduced pyridine nucleotide was monitored continuously in the culture by means of direct fluorimetry. On applying an anaerobic shock to the culture, damped oscillations in pyridine nucleotide fluorescence were obtained. Further anaerobic shocks decreased the damping and eventually gave rise to undamped oscillations of a 2–3 min period which continued for several days. These oscillations were paralleled by oscillations of the same frequency in respiration rate. The amplitude of the oscillations in the respiration rate was equivalent to only 1% of the total steady-state respiration, whereas that of pyridine nucleotide oscillations was equivalent to 10% of the total aerobic/anaerobic fluorescence response. The oscillations ceased on interrupting the glucose feed but restarted on adding excess glucose to the culture. Addition of succinate also restarted the oscillations so that they appear not to be of glycolytic origin. The frequency of oscillations varied with growth rate and conditions. Oscillations of much lower frequency were obtained under limited-oxygen and anaerobic conditions than under fully aerobic conditions. Under glucose-limited conditions, fluctuations were found in adenosine triphosphate (ATP) content which were in phase with the pyridine nucleotide oscillations, but under nitrogen-limited growth conditions no such fluctuations in ATP were observed. The primary oscillating pathway could not be identified but the mechanism would appear to be quite different from that involved in oscillations observed in yeast cells. The synchronization of oscillations and observations of negative damping could be explained by a syntalysis effect.     

描述肝细胞中两类不同特性钙离子浓度振荡

细胞内第二信使钙离子通常以浓度振荡的方式转导多种生理学信息,影响细胞分化、成熟和凋亡等各种生理过程。肝细胞实验中看到在一定浓度范围的激动剂刺激下,细胞质钙离子浓度的变化可呈现出很不相同的图像。例如顺脱羟肾上腺素刺激下,可出现简单的周期振荡,振荡频率随激动剂浓度的不同有变化;在腺苷三磷酸刺激下,随激动剂浓度从低到高,胞质钙离子浓度的变化可以从开始出现简单振荡,到形成复杂的多峰间歇振荡。肝细胞中钙离子浓度振荡的峰值多在500nmol/L到800nmol/L范围。给出一个四为量数学模型的改进形式,可以模拟肝细胞中钙离子浓度从简单振荡向复杂振荡的变化。数值计算给出与实验结果比较一致的振荡波形和振幅。     

Amplitude of circadian oscillations entrained by 24-h light-dark cycles

An intriguing property of circadian clocks is that their free-running period is not exactly 24h. Using models for circadian rhythms in Neurospora and Drosophila, we determine how the entrainment of these rhythms is affected by the free-running period and by the amplitude of the external light-dark cycle. We first consider the model for Neurospora, in which light acts by inducing the expression of a clock gene. We show that the amplitude of the oscillations of the clock protein entrained by light-dark cycles is maximized when the free-running period is smaller than 24h. Moreover, if the amplitude of the light-dark cycle is very strong, complex oscillations occur when the free-running period is close to 24h. In the model for circadian rhythms in Drosophila, light acts by enhancing the degradation of a clock protein. We show that while the amplitude of circadian oscillations entrained by light-dark cycles is also maximized if the free-running period is smaller than 24h, the range of entrainment is centered around 24h in this model. We discuss the physiological relevance of these results in regard to the setting of the free-running period of the circadian clock.     

Interferon-gamma and sinusoidal electric fields signal by modulating NAD(P)H oscillations in polarized neutrophils

Metabolic activity in eukaryotic cells is known to naturally oscillate. We have recently observed a 20-s period NAD(P)H oscillation in neutrophils and other polarized cells. Here we show that when polarized human neutrophils are exposed to interferon-gamma or to ultra-low-frequency electric fields with periods double that of the NAD(P)H oscillation, the amplitude of the NAD(P)H oscillations increases. Furthermore, increases in NAD(P)H amplitude, whether mediated by interferon-gamma or by an oscillating electric field, signals increased production of reactive oxygen metabolites. Hence, amplitude modulation of NAD(P)H oscillations suggests a novel signaling mechanism in polarized cells.     

Characteristics of intracellular on - off responses of amacrine cells of the dark-adapted carp retina

The dependence of the amplitude and latent period of intracellular on and off responses of the amacrine cells of the isolated, dark-adapted carp retina on the intensity and diameter of the light spot was investigated. On and off responses of amacrine cells to light were shown to consist of fast depolarization responses with oscillations and spikes superposed upon them. With an increase in the intensity and area of the stimulus the latent period of the on response decreases but that of the off response increases. A near-linear relationship was found between the amplitude of the on response and the logarithm of the diameter of the spot up to 3 mm during changes in stimulus intensity of not more than 4 logarithmic units. With an increase in stimulus intensity the amplitude and zone of summation of the off response are reduced; it is suggested that under these circumstances this decrease may be connected with the different amplitude and temporal characteristics of off processes in the bipolar cells converging on the amacrine cells.     

A mathematical model of oxygen transport in intact muscle with imposed surface oscillations

A one-dimensional (1D) reaction-diffusion equation is presented to model oxygen delivery by the microcirculation and oxygen diffusion and consumption in intact muscle. This model is motivated by in vivo experiments in which oscillatory boundary conditions are used to study the mechanisms of local blood flow regulation in response to changes in the tissue oxygen environment. An exact periodic solution is presented for the 1D 'in vivo' model and shown to agree with experimental data for the case where the blood flow regulation system is not activated. Approximate low- and high-frequency solutions are presented, and the latter is shown to agree with the pure diffusion solution in the absence of sources or sinks. For the low frequencies considered experimentally, the 1D in vivo model shows that as depth increases: (i) the mean of tissue O(2) oscillations changes exponentially, (ii) the amplitude of oscillations decreases very rapidly, and (iii) the phase of oscillations remains nearly the same as that of the imposed surface oscillations. The 1D in vivo model also shows that the dependence on depth of the mean, amplitude, and phase of tissue O(2) oscillations is nearly the same for all stimulation periods >30s, implying that experimentally varying the forcing period in this range will not change the spatial distribution of the O(2) stimulation.     

Persistent cell-autonomous circadian oscillations in fibroblasts revealed by six-week single-cell imaging of PER2::LUC bioluminescence

Biological oscillators naturally exhibit stochastic fluctuations in period and amplitude due to the random nature of molecular reactions. Accurately measuring the precision of noisy oscillators and the heterogeneity in period and strength of rhythmicity across a population of cells requires single-cell recordings of sufficient length to fully represent the variability of oscillations. We found persistent, independent circadian oscillations of clock gene expression in 6-week-long bioluminescence recordings of 80 primary fibroblast cells dissociated from PER2::LUC mice and kept in vitro for 6 months. Due to the stochastic nature of rhythmicity, the proportion of cells appearing rhythmic increases with the length of interval examined, with 100% of cells found to be rhythmic when using 3-week windows. Mean period and amplitude are remarkably stable throughout the 6-week recordings, with precision improving over time. For individual cells, precision of period and amplitude are correlated with cell size and rhythm amplitude, but not with period, and period exhibits much less cycle-to-cycle variability (CV 7.3%) than does amplitude (CV 37%). The time series are long enough to distinguish stochastic fluctuations within each cell from differences among cells, and we conclude that the cells do exhibit significant heterogeneity in period and strength of rhythmicity, which we measure using a novel statistical metric. Furthermore, stochastic modeling suggests that these single-cell clocks operate near a Hopf bifurcation, such that intrinsic noise enhances the oscillations by minimizing period variability and sustaining amplitude.     

DIEL OSCILLATIONS IN THE PHOTOSYNTHESIS-IRRADIANCE RELATIONSHIP OF A PLANKTONIC MARINE DIATOM1

The amplitude of diel oscillations in photosynthesis as a function of irradiance varied with the growth phase in a marine phytoplankton species. The common centric diatom (Bacillariophyta), Ditylum brightwellii (West) Grun., showed strong periodicity in the photosynthesis-irradiance (P-I) relationship, which damped progressively from early to late exponential and stationary phase. These findings suggest that short-term temporal characteristics of phytoplankton production depend on factors which affect growth, and that the amplitude is most enhanced at maximal growth rates likely to be encountered in the natural environment.     

Glucose modulates [Ca2+]i oscillations in pancreatic islets via ionic and glycolytic mechanisms

Pancreatic islets of Langerhans display complex intracellular calcium changes in response to glucose that include fast (seconds), slow ( approximately 5 min), and mixed fast/slow oscillations; the slow and mixed oscillations are likely responsible for the pulses of plasma insulin observed in vivo. To better understand the mechanisms underlying these diverse patterns, we systematically analyzed the effects of glucose on period, amplitude, and plateau fraction (the fraction of time spent in the active phase) of the various regimes of calcium oscillations. We found that in both fast and slow islets, increasing glucose had limited effects on amplitude and period, but increased plateau fraction. In some islets, however, glucose caused a major shift in the amplitude and period of oscillations, which we attribute to a conversion between ionic and glycolytic modes (i.e., regime change). Raising glucose increased the plateau fraction equally in fast, slow, and regime-changing islets. A mathematical model of the pancreatic islet consisting of an ionic subsystem interacting with a slower metabolic oscillatory subsystem can account for these complex islet calcium oscillations by modifying the relative contributions of oscillatory metabolism and oscillatory ionic mechanisms to electrical activity, with coupling occurring via K(ATP) channels.     

Dynamic aspects of insulin action: synchronization of oscillatory glycolysis in isolated perifused rat fat cells by insulin and hydrogen peroxide

Glucose oxidation to CO2 was investigated in isolated perifused rat epididymal fat cells. Insulin stimulated rates of oxidation up to 30-fold. Multiple pulses of insulin or prolonged perifusion with the hormone led to a time-dependent desensitization of the cells. The action of insulin could be mimicked by H2O2. Reversal of H2O2 effects was associated with a damped oscillation of large initial amplitude. Initiation of perifusion with insulin induced rates of glucose oxidation that oscillated around a mean elevated rate with an amplitude of about +/- 4% of the mean, significantly larger than the measurement error. Basal rates did not show clear oscillations. The oscillations after insulin had a statistically significant period of around 14 min. The results were the same with C1- or C6-labeled glucose and occurred in the presence of both 0.275 and 5.5 mM glucose in the perifusion medium. The oscillations were interpreted as the result of insulin- or H2O2-induced synchronization of oscillatory glycolysis by individual fat cells. The similarity of the observed oscillatory period with the period of oscillatory insulin secretion by pancreatic beta cells suggests that oscillatory glycolysis may constitute the internal pacemaker for the latter process.     

Dynamic Interaction of Spindles and Gamma Activity during Cortical Slow Oscillations and Its Modulation by Subcortical Afferents

Slow oscillations are a hallmark of slow wave sleep. They provide a temporal framework for a variety of phasic events to occur and interact during sleep, including the expression of high-frequency oscillations and the discharge of neurons across the entire brain. Evidence shows that the emergence of distinct high-frequency oscillations during slow oscillations facilitates the communication among brain regions whose activity was correlated during the preceding waking period. While the frequencies of oscillations involved in such interactions have been identified, their dynamics and the correlations between them require further investigation. Here we analyzed the structure and dynamics of these signals in anesthetized rats. We show that spindles and gamma oscillations coexist but have distinct temporal dynamics across the slow oscillation cycle. Furthermore, we observed that spindles and gamma are functionally coupled to the slow oscillations and between each other. Following the activation of ascending pathways from the brainstem by means of a carbachol injection in the pedunculopontine nucleus, we were able to modify the gain in the gamma oscillations that are independent of the spindles while the spindle amplitude was reduced. Furthermore, carbachol produced a decoupling of the gamma oscillations that are dependent on the spindles but with no effect on their amplitude. None of the changes in the high-frequency oscillations affected the onset or shape of the slow oscillations, suggesting that slow oscillations occur independently of the phasic events that coexist with them. Our results provide novel insights into the regulation, dynamics and homeostasis of cortical slow oscillations.     

STABILIZATION MECHANISM IN SWIMMING ODONTOCETE CETACEANS BY PHASED MOVEMENTS

Propulsive movements of the caudal oscillating flukes produce large forces that could induce equally large recoil forces at the cranial end of the animal, and, thus, affect stability. To examine these vertical oscillations, video analysis was used to measure the motions of the rostrum, pectoral flipper, caudal peduncle, and fluke tip for seven odontocete cetaceans: Delphinapterus leucas, Globicephala melaena, Lagenorhynchus obliquidens, Orcinus orca, Pseudorca crassidens, Stenella plagiodon , and Tursiops truncatus. Animals swam over a range of speeds of 1.4–7.30 m/sec. For each species, oscillatory frequency of the fluke tip increased linearly with swimming speed. Peak-to-peak amplitude at each body position remained constant with respect to swimming speed for all species. Mean peak-to-peak amplitude ranged from 0.02 to 0.06 body length at the rostrum and from 0.17 to 0.25 body length at the fluke tip. The phase relationships between the various body components remain constant with respect to swimming speed. Oscillations of the rostrum were nearly in phase with the fluke tip with phase differences out of—9.4°-33.0° of a cycle period of 360°. Pectoral flipper oscillations trailed fluke oscillations by 60.9°-123.4°. The lower range in amplitude at the rostrum compared to the fluke tip reflects increased resistance to vertical oscillation at the cranial end, which enhances the animal's stability. This resistance is likely due to both active and passive increased body stiffness, resistance on the flippers, phased movements of body components, and use of a lift-based propulsion. Collectively, these mechanisms stabilize the body of cetaceans during active swimming, which can reduce locomotor energy expenditure and reduce excessive motions of the head affecting sensory capabilities.     

INDEPENDENT HIGH-FREQUENCY OSCILLATIONS IN THE AMOUNTS OF INDIVIDUAL ISOZYMES OF LACTATE DEHYDROGENASE IN HL60 CELLS

Early studies, using kinetic methods, suggested that the isozyme pattern of lactate dehydrogenase in various cells oscillated with time. More recent electrophoretic studies on murine erythroleukaemic cells (which exhibit only one isozyme) indicated very high frequency variations (period 2min or less) in the amount of the lone active isozyme. We now show that in HL60 cells, the activity stain intensities of the two major isozyme bands both oscillate but the temporal variations are distinct. As with other cellular rhythms, each of the two periodicities seem to be modulated in cyclic fashion with respect to period, amplitude and mean levels, the periods of both the primary and modulating rhythms being of the order of 10–15min or probably much less.     

Oscillatory Transpiration and Water Uptake of Avena Plants

The action of D₂O on oscillatory transpiration of Avena plants was investigated. D₂O affects the amplitude and the period of the oscillations when given as a root medium to intact plants. The period is then dependent on the amplitude. From such experiments it is not possible to conclude whether the period change is simply due to the changed amplitude or to a change in the stomatal parameters. When given to xylem compressed, excised plants without roots, the D₂O hardly affects the amplitude of the oscillations but the period is increased. Thus, the period of the self-sustained transpiratory oscillations is lengthened by D₂O action on the stomatal parameters. Phase and amplitude changes of the oscillatory transpiration caused by short D₂O pulses given both to intact and excised plants, are discussed. The following conclusion is emphasized: a substance which affects the root system can also cause profound changes in the stomatal water regulation.     

Bloch Oscillations of Surface Plasmon-Like Modes in Waveguide Arrays That Comprise Perforated Perfect Conductor Layers and Dielectric Layers

This study investigates the optical Bloch oscillations (OBOs) in waveguide arrays that consist of alternative perfect electric conductor (PEC) layers and dielectric layers by performing both numerical simulations and theoretical analyses. In PEC dielectric waveguide arrays (PDWAs), the PEC layers are perforated with square holes to support the surface plasmon-like (SPL) modes. The relative permittivities of the dielectric layers have a constant gradient across the waveguide arrays. The OBOs in the PDWAs arise because of the excitation and coupling of the SPL modes. The ray trajectories that are predicted using Hamiltonian optics are consistent with the simulated results. When the position of incidence is fixed, the period of oscillation varies as the reciprocal of the incident frequency. However, the amplitude of oscillation is almost independent of the frequency. For a fixed incident frequency, the amplitude and period of oscillation increases and decreases, respectively as the position of incidence moves toward the dielectric layers with higher relative permittivities.     

Recording of spontaneous oscillations in the procerebrum of terrestrial mollusk Helix in free behavior

Procerebrum is the central part of the olfactory system in terrestrial snails. Spontaneous rhythmic oscillations were described in this structure. The role of these oscillations in the mechanisms of odor perception and discrimination is unknown yet. Electrical activity of the Helix procerebrum was recorded in vivo. Changes in spontaneous rhythmic oscillations in response to olfactory stimulation were observed. Within the first 10 s after odor application (cineole) in low concentration, a statistically significant decrease in the frequency and increase in the amplitude of procerebrum oscillations were revealed in freely behaving animals. Timing of those changes corresponded to the time of defensive reaction realization of the tentacle withdrawal. The increase in the amplitude and a tendency to a decrease in the frequency of oscillations in response to odor application in high concentration were observed in time period 11-20 s, which corresponded to an increased duration of tentacle withdrawal. The results suggest an implicit relation of the amplitude and frequency of oscillations in odor perception and discrimination.     

Effects of caffeine, tetracaine, and ryanodine on calcium-dependent oscillations in sheep cardiac Purkinje fibers

Membrane current and tension were measured in voltage-clamped sheep cardiac Purkinje fibers. Elevating the intracellular calcium concentration ([Ca2+]i) results in oscillations of membrane current and tension both at rest and during stimulation. During stimulation, an oscillatory transient inward current and an after contraction follow repolarization. We have examined the effects on the oscillations of changing the extracellular calcium concentration ([Ca2+]o) and of adding various drugs. In agreement with previous work, high concentrations of drugs that affect the sarcoplasmic reticulum, namely caffeine (10-20 mM), tetracaine (1 mM), and ryanodine (10 microM), abolish the oscillations. However, at lower concentrations, these three drugs have different effects on the oscillations. Caffeine (1-2 mM) decreases the oscillation amplitude but increases the frequency. Tetracaine (100-500 microM) has little effect on the magnitude of the oscillations but decreases their frequency. Ryanodine, at all concentrations used (0.1-10 microM), eventually abolishes the oscillations but, in doing so, decreases the magnitude, leaving the frequency unaffected. When [Ca2+]o was changed in order to vary [Ca2+]i, both the frequency and the magnitude of the oscillations always changed in the same direction. This suggests that these three drugs have effects in addition to just changing [Ca2+]i.     

Epidemiological effects of seasonal oscillations in birth rates

Seasonal oscillations in birth rates are ubiquitous in human populations. These oscillations might play an important role in infectious disease dynamics because they induce seasonal variation in the number of susceptible individuals that enter populations. We incorporate seasonality of birth rate into the standard, deterministic susceptible-infectious-recovered (SIR) and susceptible-exposed-infectious-recovered (SEIR) epidemic models and identify parameter regions in which birth seasonality can be expected to have observable epidemiological effects. The SIR and SEIR models yield similar results if the infectious period in the SIR model is compared with the "infected period" (the sum of the latent and infectious periods) in the SEIR model. For extremely transmissible pathogens, large amplitude birth seasonality can induce resonant oscillations in disease incidence, bifurcations to stable multi-year epidemic cycles, and hysteresis. Typical childhood infectious diseases are not sufficiently transmissible for their asymptotic dynamics to be likely to exhibit such behaviour. However, we show that fold and period-doubling bifurcations generically occur within regions of parameter space where transients are phase-locked onto cycles resembling the limit cycles beyond the bifurcations, and that these phase-locking regions extend to arbitrarily small amplitude of seasonality of birth rates. Consequently, significant epidemiological effects of birth seasonality may occur in practice in the form of transient dynamics that are sustained by demographic stochasticity.