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Dynamic changes in nerve growth factor and substance P in the murine hair cycle induced by depilation.

Increasing evidence suggests that various neurotrophins and neuropeptides play an important role in the progression of hair follicle cycling. Among them, nerve growth factor (NGF) and substance P (SP) have attracted special interest recently. However, the interaction between these factors during hair cycling has not yet been systematically studied. We therefore investigated the mutual relationships between NGF and SP and the mechanism by which the anagen stage of the hair cycle is initiated. Fluctuations in numbers of SP-positive nerve fibers and variations in amounts of SP, NGF, and another neurotrophic factor, glial cell-derived neurotrophic factor, in skin in the C57BL/6 mouse depilation-induced hair cycle model, together with the spatiotemporal expression patterns of each of these factors, were followed simultaneously by enzyme-linked immunosorbent assay and immunohistochemistry. The main finding was that a surge in NGF expression and a rapid increase in NGF content in skin is an initial event within 1 day after depilation, followed by elevation of SP content and numbers of SP-containing fibers 2 days after the increase in NGF. Our findings suggest that a rapid and abundant increase in NGF plays a key role in the induction and progression of anagen hair cycling through keratinocyte growth promotion. NGF may also induce plastic changes such as sprouting and hyperplasia in dermal nerve fibers and enhance their SP production. Elevated levels of SP in skin may additionally contribute to the progression of consecutive anagen hair cycles.

Adipose Tissue↗

The accuracy of interceptive action in time and space.

Hitting a moving target demands that movement is both spatially and temporally accurate. Recent experiments have begun to reveal how performance of such actions depends on the spatial and temporal accuracy requirements of the task. The results suggest a simple strategy for achieving spatiotemporal accuracy using brief, high-speed movements.

Central Nervous System↗

Variations on the vertical jump: individual adaptations to changing task demands.

Here we explored the coordination of joint behaviors exhibited during the vertical jump and variations of that jump. By manipulating the take-off angle, we required an adjustment to changing task demands. It was hypothesized that kinematic features of the jump would change but that spatiotemporal relationships essential to propulsion would remain invariant across all conditions. To test this hypothesis, six adult male subjects performed jumps at six different take-off angles. An analysis of cinematographic data revealed that individual subjects changed the sequence and timing of lower-extremity joint reversals. In contrast, the covariation of joint behaviors during the propulsive phase and the timing of maximum intersegmental extension velocities were extremely stable within each individual across changes in task. We argue that the flexibility to alter sequence and timing is part of a strategy that permits adaptation to the context and facilitates a continued coordination among variables associated with propulsion.

Journal Article↗

Spatiotemporal effects of syncytial heterogeneities on cardiac far-field excitations during monophasic and biphasic shocks.

INTRODUCTION: It has recently been postulated that syncytial (anatomic) heterogeneities inherent within cardiac tissue might represent a significant mechanism underlying field-induced polarization of the bulk myocardium. This simulation study examines and characterizes the spatiotemporal excitatory dynamics associated with this newly hypothesized mechanism. METHODS AND RESULTS: Two-dimensional regions of syncytially heterogeneous cardiac tissue were simulated with active membrane kinetics. Heterogeneities were manifested via random spatial variations of intracellular volume fractions over multiple length scales. Excitation thresholds were determined for uniform rectangular monophasic (M) and symmetric biphasic (B) far-field stimuli, from which strength-duration and strength-interval relationships were constructed. For regions measuring 5.4 x 5.4 mm, baseline diastolic thresholds for longitudinal (L) and transverse (T) shocks of 5-msec total duration averaged (in V/cm, n = 10) M-L = 2.87+/-0.26, M-T = 6.71+/-0.83, B-L = 3.22+/-0.25, and B-T = 7.93+/-0.51. These thresholds decreased by 15% to 25% when the region sizes were increased to 10.8 x 10.8 mm. Strength-duration relationships correlated strongly with the Weiss-Lapicque hyperbolic relationship, with rheobases and chronaxies of 2.33 V/cm and 1.15 msec for M-L stimuli, and 2.28 V/cm and 2.04 msec for B-L stimuli. Strength-interval relationships for M-L and B-L stimuli decreased monotonically with increasing coupling intervals, with similar minimum coupling intervals at absolute refractoriness. However, the B-L thresholds were substantially less sensitive to changes in coupling intervals than their M-L counterparts. CONCLUSION: This study provides strong additional support for and understanding of the syncytial heterogeneity hypothesis and its manifested properties. Furthermore, these results predict that syncytial heterogeneities of even modest proportions could represent a significant mechanism contributing to the far-field excitation process.

Cell Membrane↗

Modeling of transcellular Ca transport in rat duodenum points to coexistence of two mechanisms of apical entry.

Employing realistic parameters, we have demonstrated that a relatively simple mathematical model can reproduce key features of steady-state Ca2+ transport with the assumption of two mechanisms of Ca2+ entry: a channel-like flux and a carrier-mediated transport. At low luminal [Ca2+] (1-5 mM), facilitated entry dominates and saturates with Km = 0.4 mM. At luminal [Ca2+] of tens of millimolar, apical permeability is dominated by the channel flux that in turn is regulated by cytosolic Ca2+. The model reproduces the linear relationship between maximum Ca2+ transport rate and intestinal calbindin D9K (CaBP) content. At luminal [Ca2+] > 50 mM, local sensitivity analysis shows transcellular transport to be most sensitive to variations in CaBP. At low luminal [Ca2+], transport becomes sensitive to apical entry regulation. The simulations have been run within the Virtual Cell modeling environment, yielding the time course of external Ca2+ and spatiotemporal distributions of both intracellular Ca2+ and CaBP. Coexistence of two apical entry mechanisms accords with the properties of the duodenal Ca2+ transport protein CaT1 and the epithelial Ca2+ channel ECaC.

Animals↗

Directional selectivity in a nonspiking interneuron of the crayfish optic lobe: evaluation of a linear model.

1. Intracellular recordings, sine wave gratings, and paired flashes were used to characterize the directional selectivity (DS) of the peripheral neurons of the crayfish visual pathway. DS was observed in nonspiking tangential (Tan1) neurons of the distal medulla externa and it is expressed by the amplitude of the modulated synaptic potential elicited with drifting gratings. 2. The directional mechanism was characterized by variations in the grating contrast, spatial frequency, and temporal frequency. DS is both contrast and velocity dependent. 3. The velocity dependence of DS for fixed stimulus contrast can be described by a linear model including a delay and subtractive compare operation. This mechanism operates over the entire useful range of spatial and temporal frequencies. 4. The parameters of the linear model can be estimated from the spatiotemporal structure of the Tan1 cell receptive field. The receptive field exhibits a spatially asymmetric inhibitory subfield that is offset from the excitatory subfield by 3-5 degrees (1-2 ommatidia). The inhibition is delayed relative to excitation by 50-100 ms. 5. The contrast dependence of DS reflects an apparent nonlinearity in the mechanism that determines the null response amplitude. The preferred response magnitude is approximately linear with variations in contrast. 6. The nonlinearity observed in the null direction can in principle be attributed to either a tonic excitation at 0 contrast or a threshold for inhibition. There is evidence for both processes in the Tan1 cell visual response.

Acetylcholine↗

Critical behavior of crisis-induced transition to spatiotemporal chaos in parameter space.

In previous works we reported a transition mechanism from a temporal chaos (TC) to spatiotemporal chaos (STC) through a crisis due to a collision to a saddle steady wave (SSW). However, the transition also displays as a critical phenomenon in parameter space. In the present work the time variations of mode interaction energy, deltaE(I)(k)(t), of the perturbation wave (PW) with its carrier SSW are calculated. In the TC state in all the dimensions the motion is dominated by negative deltaE(I)(k)(t). With variation of the parameter in one dimension deltaE(I)(k=1)(t) becomes smaller and smaller while statistically more balanced in its negative and positive values. The critical parameter point for the crisis is right at the place where the time-averaged negative and positive deltaE(I)(k=1)(t) are equal. A power-law behavior is observed when approaching to the point. After the crisis in the STC state the motion with positive deltaE(I)(k=1)(t) suddenly becomes much stronger than that with negative ones. In addition, it is shown that stable orbit of the SSW is a boundary of the PW motion, it behaves like a potential well that constrains the PW motion.

Journal Article↗

A new tactile illusion: temporal limits on the processing of spatiotemporal patterns.

A novel illusion was observed when 12 tactile point-stimulators arranged in a circle were sequentially activated so that each quadrant was first traced in a clockwise manner, then counterclockwise, and again in a clockwise manner, after which the next quadrant was similarly traced. Under certain temporal conditions this stimulus pattern was experienced as a point moving through an overall circular path but looping inwardly about once per quandrant. The effects of variations in rate of presentation of such stimuli were investigated by having subjects make drawings of their perceptual experiences. Three skin surfaces were used (palm, fingers, and forearm), and all produced similar results except for lower confidence and reliability of drawings made from forearm stimulation. Pattern presentation rate, however, had a consistent and powerful effect, with the looping illusion most frequently observed at rates around 25 pattern points per s and with different perceptual organizations dominating as rates departed widely from this optimum. The illusory perceptual organizations were interpreted as compromises between past and present stimulation necessitated by the relative slowness of tactile processing of spatiotemporal patterns.

Humans↗

Spatiotemporal complexity of patchy invasion in a predator-prey system with the Allee effect.

Invasion of an exotic species initiated by its local introduction is considered subject to predator-prey interactions and the Allee effect when the prey growth becomes negative for small values of the prey density. Mathematically, the system dynamics is described by two nonlinear diffusion-reaction equations in two spatial dimensions. Regimes of invasion are studied by means of extensive numerical simulations. We show that, in this system, along with well-known scenarios of species spread via propagation of continuous population fronts, there exists an essentially different invasion regime which we call a patchy invasion. In this regime, the species spreads over space via irregular motion and interaction of separate population patches without formation of any continuous front, the population density between the patches being nearly zero. We show that this type of the system dynamics corresponds to spatiotemporal chaos and calculate the dominant Lyapunov exponent. We then show that, surprisingly, in the regime of patchy invasion the spatially average prey density appears to be below the survival threshold. We also show that a variation of parameters can destroy this regime and either restore the usual invasion scenario via propagation of continuous fronts or brings the species to extinction; thus, the patchy spread can be qualified as the invasion at the edge of extinction. Finally, we discuss the implications of this phenomenon for invasive species management and control.

Animals↗

A comparison of signal instability in 2D and 3D EPI resting-state fMRI.

Spatiotemporally structured noise, such as physiological noise, is a potential source of artifacts in functional magnetic resonance imaging (fMRI) and is the main limiting factor for the detection of small blood oxygen level-dependent (BOLD) signal variations. fMRI was employed to detect low-frequency BOLD signal fluctuations, which are thought to be related to spontaneous neuronal activity in the resting human brain. The sensitivity to noise, that is, signal variations of non-BOLD origin, was investigated for two- (2D) and three-dimensional (3D) imaging techniques. Incomplete relaxation between subsequent scans increases the level of temporally and spatially correlated signal variations originating from physiological and/or systemic noise. Although inflow effects are suspected to be reduced in 3D echo-planar imaging (EPI) compared with multi-slice 2D EPI, the noise level was higher in the 3D technique. The noise level in 3D fMRI experiments was significantly increased by instabilities of the transverse steady-state magnetization as the repetition time was of the order of T(2). By implementing radiofrequency spoiling, temporal signal fluctuations and erroneous inter-regional correlation in connectivity maps were diminished to a level present in data sets acquired with 2D EPI.

Adult↗

Spatial forcing of spontaneous optical patterns.

A nonlinear optical system, which spontaneously forms hexagonal patterns, is exposed to a weak, spatially modulated forcing. As forcing, stationary hexagonal patterns are used under variation of their transverse wave number. In the experiment, we observe a locking when the forcing wave number is close to one of the critical wave numbers of the unforced system. Outside the locking regimes, forcing provokes spatiotemporal disorder. The system response is characterized quantitatively with respect to its dynamics and to its spatial order.

Journal Article↗

Variability in initial spray deposit in apple trees in space and time.

Variation in pesticide residues in space and time has not been investigated systematically in spite of the large variability found at single scales (e.g. between trees or orchards). Information on variability at different scales will support the development of sampling methods and more reliable prediction of residues. Experiments were conducted to quantify the spatiotemporal variability in initial spray deposit on apple leaves and fruit using a substitute tracer (zinc EDTA chelate). Five hierarchical spatial scales were defined as (1) between orchards, (2) between plots within an orchard, (3) between trees within a plot, (4) between zones within a tree and (5) between leaves/fruit within a zone. Similarly, two temporal scales were defined as (1) between applications within a single year and (2) between years. The initial zinc concentration was approximately log-normally distributed; the variability in initial deposit concentration was greater on leaves than on fruit. The average initial zinc deposition was significantly greater in the top and outside zones than in the middle zones within individual trees. The most important scale for driving residue variability is the within-zone unit-to-unit variation, contributing to 71 and 49% of the observed variability for leaf and fruit samples respectively. Variability at other scales was related to the variation in the tree architecture. The results indicated that stratified sampling on the basis of within-tree zone structures, with the effort focused on within-zone sampling, should be used for the determination of pesticide residues.

Chelating Agents↗

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution.

Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages.

Animals↗

Immediate and simultaneous sensory reorganization at cortical and subcortical levels of the somatosensory system.

The occurrence of cortical plasticity during adulthood has been demonstrated using many experimental paradigms. Whether this phenomenon is generated exclusively by changes in intrinsic cortical circuitry, or whether it involves concomitant cortical and subcortical reorganization, remains controversial. Here, we addressed this issue by simultaneously recording the extracellular activity of up to 135 neurons in the primary somatosensory cortex, ventral posterior medial nucleus of the thalamus, and trigeminal brainstem complex of adult rats, before and after a reversible sensory deactivation was produced by subcutaneous injections of lidocaine. Following the onset of the deactivation, immediate and simultaneous sensory reorganization was observed at all levels of the somatosensory system. No statistical difference was observed when the overall spatial extent of the cortical (9.1 +/- 1.2 whiskers, mean +/- SE) and the thalamic (6.1 +/- 1.6 whiskers) reorganization was compared. Likewise, no significant difference was found in the percentage of cortical (71.1 +/- 5.2%) and thalamic (66. 4 +/- 10.7%) neurons exhibiting unmasked sensory responses. Although unmasked cortical responses occurred at significantly higher latencies (19.6 +/- 0.3 ms, mean +/- SE) than thalamic responses (13. 1 +/- 0.6 ms), variations in neuronal latency induced by the sensory deafferentation occurred as often in the thalamus as in the cortex. These data clearly demonstrate that peripheral sensory deafferentation triggers a system-wide reorganization, and strongly suggest that the spatiotemporal attributes of cortical plasticity are paralleled by subcortical reorganization.

Animals↗

Statistical parametric mapping for event-related potentials (II): a hierarchical temporal model.

In this paper, we describe a temporal model for event-related potentials (ERP) in the context of statistical parametric mapping (SPM). In brief, we project channel data onto a two-dimensional scalp surface or into three-dimensional brain space using some appropriate inverse solution. We then treat the spatiotemporal data in a mass-univariate fashion. This implicitly factorises the model into spatial and temporal components. The key contribution of this paper is the use of observation models that afford an explicit distinction between observation error and variation in the expression of ERPs. This distinction is created by employing a two-level hierarchical model, in which the first level models the ERP effects within-subject and trial type, while the second models differences in ERP expression among trial types and subjects. By bringing the analysis of ERP data into a classical hierarchical (i.e., mixed effects) framework, many apparently disparate approaches (e.g., conventional P300 analyses and time-frequency analyses of stimulus-locked oscillations) can be reconciled within the same estimation and inference procedure. Inference proceeds in the normal way using t or F statistics to test for effects that are localised in peristimulus time or in some time-frequency window. The use of F statistics is an important generalisation of classical approaches, because it allows one to test for effects that lie in a multidimensional subspace (i.e., of unknown but constrained form). We describe the analysis procedures, the underlying theory and compare its performance to established techniques.

Analysis of Variance↗

Transmission intensity and impact of control policies on the foot and mouth epidemic in Great Britain.

The foot and mouth disease (FMD) epidemic in British livestock remains an ongoing cause for concern, with new cases still arising in previously unaffected areas. Epidemiological analyses have been vital in delivering scientific advice to government on effective control measures. Using disease, culling and census data on all livestock farms in Great Britain, we analysed the risk factors determining the spatiotemporal evolution of the epidemic and of the impact of control policies on FMD incidence. Here we show that the species mix, animal numbers and the number of distinct land parcels in a farm are central to explaining regional variation in transmission intensity. We use the parameter estimates thus obtained in a dynamical model of disease spread to show that extended culling programmes were essential for controlling the epidemic to the extent achieved, but demonstrate that the epidemic could have been substantially reduced in scale had the most efficient control measures been rigorously applied earlier.

Animals↗

Analysis of a "phase transition" from tumor growth to latency.

A mathematical model, based on the local interaction simulation approach, is developed in order to allow simulations of the spatiotemporal evolution of neoplasies. The model consists of a set of rules, which govern the interaction of cancerous cells among themselves and in competition with other cell populations for the acquisition of essential nutrients. As a result of small variations in the basic parameters, it leads to four different outcomes: indefinite growth, metastasis, latency, and complete regression. In the present contribution a detailed analysis of the dormant phase is carried on and the critical parameters for the transition to other phases are computed. Interesting chaotic behaviors can also be observed, with different attractors in the parameters space. Interest in the latency phase has been aroused by therapeutical strategies aiming to reduce a growing tumor to dormancy. The effect of such strategies may be simulated with our approach.

Cell Division↗

Cortically-induced coherence of a thalamic-generated oscillation.

Oscillatory patterns in neocortical electrical activity show various degrees of large-scale synchrony depending on experimental conditions, but the exact mechanisms underlying these variations of coherence are not known. Analysis of multisite local field potentials revealed that the coherence of spindle oscillations varied during different states. During natural sleep, the coherence was remarkably high over cortical distances of several millimeters, but could be disrupted by artificial cortical depression, similar to the effect of barbiturates. Possible mechanisms for these variations of coherence were investigated by computational models of interacting cortical and thalamic neurons, including their intrinsic firing patterns and various synaptic receptors present in the circuitry. The model indicates that modulation of the excitability of the cortex can affect spatiotemporal coherence with no change in the thalamus. The highest level of coherence was obtained by enhancing the excitability of cortical pyramidal cells, simulating the action of neuromodulators such as acetylcholine and noradrenaline. The underlying mechanism was due to cortex-thalamus-cortex loops in which a more excitable cortical network generated a more powerful and coherent feedback onto the thalamus, resulting in highly coherent oscillations, similar to the properties measured during natural sleep. In conclusion, these experiments and models are compatible with a powerful role for the cortex in triggering and synchronizing oscillations generated in the thalamus, through corticothalamic feedback projections. The model suggests that intracortical mechanisms may be responsible for synchronizing oscillations over cortical distances of several millimeters through cortex-thalamus-cortex loops, thus providing a possible cellular mechanism to explain the genesis of large-scale coherent oscillations in the thalamocortical system.

Anesthesia↗