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Results for “spatiotemporal coupling”

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PubMedDate not supplied

Spatiotemporal dynamics of epidemics: synchrony in metapopulation models.

Multi-patch models - also known as metapopulation models - provide a simple framework within which the role of spatial processes in disease transmission can be examined. An n-patch model which distinguishes between k different classes of individuals is considered. The linear stability of spatially homogeneous solutions of such models is studied using an extension of an analysis technique previously described for a population setting in which individuals migrate between patches according to a simple linear term. The technique considerably simplifies the analysis as it decouples the nk dimensional linearized system into n distinct k-dimensional systems. An important feature of the spatial epidemiological model is that the spatial coupling may involve non-linear terms. As an example of the use of this technique, the dynamical behavior in the vicinity of the endemic equilibrium of a symmetric SIR model is decomposed into spatial modes. For parameter values appropriate for childhood diseases, expressions for the eigenvalues corresponding to in-phase and out-of-phase modes are obtained, and it is shown that the dominant mode of the system is an in-phase mode. Furthermore, the out-of-phase modes are shown to decay much more rapidly than the in-phase mode for a broad range of coupling strengths.

Communicable Diseases↗

PubMed2000

Influence of walkoff on pattern formation in nondegenerate optical parametric oscillators.

Convective and absolute nature of instabilities in nondegenerate optical parametric oscillators with large transverse section, for negative detunings and in the presence of walkoff, is examined. The asymptotic response of the signal and idler fields to a transverse localized two-dimensional perturbation is evaluated. The presence of walkoff breaks the rotational symmetry in the transverse plane, and the system, at the absolute instability threshold, selects traveling waves propagating in the walkoff direction among an infinity of unstable spatiotemporal modes. We show that in optical parametric oscillators (OPO's) with negative detunings, contrary to the case of positive detunings, the walkoff shrinks the region of convective instabilities, and even may suppress the convective/absolute transition. Hence, in a certain range of parameters, signal field envelopes in the form of wave packets of zero group velocity are found where the instability is absolute at the onset, although the walkoff is present. We also show that nonlinear pattern selection is ruled by the cross-coupling terms appearing in the asymmetric coupled Ginzburg-Landau equations derived near-threshold of the signal and idler generation. The numerical solutions of the original OPO equations confirm the analytical predictions for the values of the instability thresholds and the corresponding selected patterns.

Journal Article↗

PubMed2004

Rate-dependent propagation of cardiac action potentials in a one-dimensional fiber.

Action potential duration (APD) restitution, which relates APD to the preceding diastolic interval (DI), is a useful tool for predicting the onset of abnormal cardiac rhythms. However, it is known that different pacing protocols lead to different APD restitution curves (RCs). This phenomenon, known as APD rate dependence, is a consequence of memory in the tissue. In addition to APD restitution, conduction velocity restitution also plays an important role in the spatiotemporal dynamics of cardiac tissue. We present results concerning rate-dependent restitution in the velocity of propagating action potentials in a one-dimensional fiber. Our numerical simulations show that, independent of the amount of memory in the tissue, the wave-back velocity exhibits pronounced rate dependence and the wave-front velocity does not. Moreover, the discrepancy between wave-back velocity RCs is most significant for a small DI. We provide an analytical explanation of these results, using a system of coupled maps to relate the wave-front and wave-back velocities. Our calculations show that rate-dependent wave-back velocity can be present even if neither APD nor wave-front velocity exhibits rate dependence.

Action Potentials↗

PubMed2002

Disturbed jaw behavior in whiplash-associated disorders during rhythmic jaw movements.

As shown previously, "functional jaw movements" are the result of coordinated activation of jaw as well as neck muscles, leading to simultaneous movements in the temporomandibular, atlanto-occipital, and cervical spine joints. In this study, the effect of neck trauma on natural jaw function was evaluated in 12 individuals suffering from whiplash-associated disorders (WAD). Spatiotemporal characteristics of mandibular and concomitant head movements were evaluated for three different modes of rhythmic jaw activities: self-paced continuous maximal jaw-opening/-closing movements, paced continuous maximal jaw-opening/-closing movements at 50 cycles/minute, and unilateral chewing. Compared with healthy subjects, the WAD group showed smaller magnitude and altered coordination pattern (a change in temporal relations) of mandibular and head movements. In conclusion, these results show that neck trauma can derange integrated jaw and neck behavior, and underline the functional coupling between the jaw and head-neck motor systems.

Adult↗

PubMed2006

Gene expression and gene therapy imaging.

The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters.

Animals↗

PubMedDate not supplied

Control of apoptosis by IP(3) and ryanodine receptor driven calcium signals.

Intracellular calcium signals mediated by IP(3)and ryanodine receptors (IP(3)R/RyR) play a central role in cell survival, but emerging evidence suggests that IP(3)R/RyR are also important in apoptotic cell death. Switch from the life program to the death program may involve coincident detection of proapoptotic stimuli and calcium signals or changes in the spatiotemporal pattern of the calcium signal or changes at the level of effectors activated by the calcium signal (e.g. calpain, calcineurin). The fate of the cell is often determined in the mitochondria, where calcium spikes may support cell survival through stimulation of ATP production or initiate apoptosis v ia opening of the permeability transition pore and release of apoptotic factors such as cytochrome c. The functional importance of these mitochondrial calcium signalling pathways has been underscored by the elucidation of a highly effective, local Ca(2+)coupling between IP(3)R/RyR and mitochondrial Ca(2+)uptake sites. This article will focus on the IP(3)R/RyR-dependent pathways to apoptosis, particularly on the mitochondrial phase of the death cascade.

Apoptosis↗

PubMed1994

Insulin and insulin-like growth factor system components gene expression in the chicken retina from early neurogenesis until late development and their effect on neuroepithelial cells.

To better understand the role of insulin-related growth factors in neural development, we have characterized by in situ hybridization in chicken embryonic retina the patterns of gene expression for insulin, insulin-like growth factor I (IGF-I), their respective receptors and the IGF binding protein 5 (IGFBP5) from early stages (E6) until late stages (E18)--an analysis not performed yet in any species. In addition, we studied the effect of insulin and IGF-I on cultured neuroepithelial cells. Insulin receptor mRNA and IGF-I receptor mRNA were both present and showed a similar, widespread pattern throughout retina development. Insulin mRNA could be detected only by reverse transcription coupled to polymerase chain reaction. IGF-I mRNA was concentrated in the ciliary processes and extraocular muscles early in development (embryonic day 6; E6) and in maturing retinal ganglion cells subsequently (E9-15). IGFBP5 mRNA was preferentially localized in the more differentiated central retinal zone and was maximally concentrated in the inner nuclear and ganglion cell layers at E9. These findings suggest a near constitutive expression of insulin receptor and IGF-I receptor genes, while IGF-I and IGFBP5 showed a highly focal spatiotemporal regulation of gene expression. Insulin and IGF-I, already at 10(-8) M, increased the proportion of PM1-positive neuroepithelial cells found in E5 retinal cultures without affecting significantly the total number of proliferating cells. Together, these data support the finding that, during early neurogenesis in chicken retina, insulin and IGF-I have a specific paracrine/autocrine action. This action, as well as possible effects elicited subsequently, may be dictated by restricted-local synthesis of the ligands and limited access to the factors contained in the vitreous humour. In the case of IGF's role, local IGFBPs expression can contribute to the fine modulation.

Animals↗

PubMed2002

Neuropeptides as growth factors for normal and cancerous cells.

Neuropeptides are molecular messengers that regulate multiple functions in the central nervous system and in the periphery via G-protein-coupled receptors. These signaling peptides have also been identified as potent cellular growth factors for normal cells and they participate in autocrine/paracrine stimulation of tumor cell proliferation and migration. Recent studies on the signaling pathways activated by mitogenic neuropeptides revealed previously unsuspected connections and complexities, including the realization that these receptors not only stimulate the synthesis of conventional second messengers but also induce tyrosine phosphorylation cascades. A major task for the future will be to identify all the contributing molecules, define their functional importance and elucidate the spatiotemporal relationships of this complicated signaling network. As our understanding of the role of neuropeptides in cancer increases, novel possibilities for translational research are emerging for improving the diagnosis and treatment of the disease.

Animals↗

PubMed2003

Rac regulates cardiovascular superoxide through diverse molecular interactions: more than a binary GTP switch.

The small G protein Rac has been implicated in multiple cardiovascular processes. Rac has two major functions: 1) it regulates the organization of the actin cytoskeleton, and 2) it controls the activity of the key enzyme complex NADPH oxidase to control superoxide production in both phagocytes and nonphagocytic cells. In phagocytes, superoxide derived from NADPH has a bactericidal function, whereas Rac-derived superoxide in the cardiovascular system has a diverse array of functions that have recently been a subject of intense interest. Rac is differentially activated by cellular receptors coupled to distinct Rac-activating adapter molecules, with each leading to pathway-specific arrays of downstream effects. Thus it may be important to investigate not just whether Rac is activated but also where, how, and for what effector. An understanding of the biochemical functions of Rac and its effectors lays the groundwork for a dissection of the exact array of effects produced by Rac in common cardiovascular processes, including cardiac and vascular hypertrophy, hypertension, leukocyte migration, platelet biology, and atherosclerosis. In addition, investigation of the spatiotemporal regulation of both Rac activation and consequent superoxide generation may produce new insights into the development of targeted antioxidant therapies for cardiovascular disease and enhance our understanding of important cardiovascular drugs, including angiotensin II antagonists and statins, that may depend on Rac modulation for their effect.

Angiotensin II↗

PubMed2004

Self-organizing dual coding based on spike-time-dependent plasticity.

It has been a matter of debate how firing rates or spatiotemporal spike patterns carry information in the brain. Recent experimental and theoretical work in part showed that these codes, especially a population rate code and a synchronous code, can be dually used in a single architecture. However, we are not yet able to relate the role of firing rates and synchrony to the spatiotemporal structure of inputs and the architecture of neural networks. In this article, we examine how feedforward neural networks encode multiple input sources in the firing patterns. We apply spike-time-dependent plasticity as a fundamental mechanism to yield synaptic competition and the associated input filtering. We use the Fokker-Planck formalism to analyze the mechanism for synaptic competition in the case of multiple inputs, which underlies the formation of functional clusters in downstream layers in a self-organizing manner. Depending on the types of feedback coupling and shared connectivity, clusters are independently engaged in population rate coding or synchronous coding, or they interact to serve as input filters. Classes of dual codings and functional roles of spike-time-dependent plasticity are also discussed.

Action Potentials↗

PubMed1991

Selective perturbation of visual input during prehension movements. 1. The effects of changing object position.

Prehension involves processing information in two hypothesized visuomotor channels: one for extrinsic object properties (e.g., the spatial location of objects) and one for intrinsic objects properties (e.g., shape and size). The present study asked how the two motor components that correspond to these channels (transport and grasp, respectively) are related. One way to address this question is to create a situation where unexpected changes occur at the input level of one of the visuomotor channels, and to observe how the movement reorganizes. If transport and grasp are independent components, then changing the object location, for example, should affect only the transport, not the grasp component. Subjects were requested to reach, grasp and lift as accurately as possible one of three dowels using the distal pads of the thumb and index finger. On certain trials, upon movement initiation towards the middle dowel, the dowel was made to instantaneously change its location to one of the two other positions, requiring the subject to reorient the hand to the new dowel location. Results consisted of comparing the movement characteristics of the transport and grasp components of these perturbed movements with appropriate control movements. Kinematics of the wrist trajectory showed fast adjustments, within 100 ms, to the change of dowel position. This duration seems to correspond to the minimum delay required within the visuomotor system for visual and/or proprioceptive reafferents to influence the ongoing movement. In addition, these delays are much shorter than has been found for conditions where object location changes before movement initiation (approximately 300 ms). The faster times may relate to the dynamic character of the deviant limb position signals, with the only constraint being the physiological delays for visual and kinaesthetic signals to influence the movement. A spatiotemporal variability analysis of the movement trajectories for non-perturbed trials showed variability to be greatest during the acceleration part of the movement, interpreted as due to control by a relatively inaccurate directional coding mechanism. Control during the deceleration phase, marked by low trajectory variability, was seen to be due to a sensorimotor process, using motor output signals, and resulting in an optimized trajectory supporting a successful grasp. Analysis of the grasp component of prehension showed that perturbing object location influenced the movement of the fingers suggesting a kinematic coupling of the two components. However, forthcoming work shows that, when object size changes, and location remains constant, there is a clear temporal dissociation of the two components of prehension.(ABSTRACT TRUNCATED AT 400 WORDS)

Fingers↗

PubMed1995

Inositol trisphosphate receptor mediated spatiotemporal calcium signalling.

Spatiotemporal Ca2+ signalling in the cytoplasm is currently understood as an excitation phenomenon by analogy with electrical excitation in the plasma membrane. In many cell types, Ca2+ waves and Ca2+ oscillations are mediated by inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ channels in the endoplasmic reticulum membrane, with positive feedback between cytosolic Ca2+ and IP3-induced Ca2+ release creating a regenerative process. Remarkable advances have been made in the past year in the analysis of subcellular Ca2+ microdomains using confocal microscopy and of Ca2+ influx pathways that are functionally coupled to IP3-induced Ca2+ release. Ca2+ signals can be conveyed into the nucleus and mitochondria. Ca2+ entry from outside the cell allows repetitive Ca2+ release by providing Ca2+ to refill the endoplasmic reticulum stores, thus giving rise to frequency-encoded Ca2+ signals.

Animals↗

PubMed2001

Higher-order transverse modes of ultrashort isodiffracting pulses.

We present a family of space-time nonseparable analytic solutions describing spatiotemporal dynamics of isodiffracting single-cycle and few-cycle pulses with Hermite-Gaussian and Laguerre-Gaussian transverse profiles. These solutions are space-time localized wave packets propagating in free space. The transverse field profile acts as a spatially dependent filter, modifying the pulse spectrum and removing certain frequencies. The consequences of those effects in the time domain are the distortions of pulse envelope and temporal wave form and the creation of "dark pulses" at certain transverse positions. In addition, due to the space-time coupling, the instantaneous transverse field pattern changes inside the pulse, as well as with propagation distance. These higher-order mode solutions can be used to analyze reflected or scattered terahertz pulses, and to understand the wave-form distortions of terahertz signals in applications. They are also capable of modeling pulsed fields of phase locking of both transverse and longitudinal modes in total mode-locked lasers.

Journal Article↗

PubMed1995

Articulatory organization of mandibular, labial, and velar movements during speech.

It has been shown that articulator movements during speech are adjusted along a number of spatiotemporal dimensions. For example, variations in the extent of lip, jaw, or tongue motion are associated with proportional changes in the respective articulators' peak velocity. Modifications in the timing of lip and jaw actions are apparently constrained, exhibiting relative timing covariation. Syllable prominence systematically affects some combination of the articular motion parameters, i.e., extent, speed, and duration. The present investigation is an attempt to extend observations of the spatiotemporal properties of articulator movement to include the velum. Lip, jaw, and velar kinematics were recorded optoelectronically and simultaneously with the acoustic signal during productions of the utterance/mabnab/. The spatial and temporal relations between the lips, the jaw, and the velum were examined and compared across articulators. For movements associated with each syllable, the velum displayed scaling pattern qualitatively similar to those of the lips and jaw. Moreover, velocity-displacement relations were more robust for the lowering than for the raising movements of the velum. There was evidence of interarticulator coupling between the velum and the jaw, and between the velum and the upper lip, although this coupling was not as strong as that observed among the oral articulators. Articulator specific differences in velocity-displacement correlations and degree of interarticulator cohesion for the various movement phases may be related to a combination of aerodynamic and phonetic factors, such as the phonologically noncontrastive nature of nasalization in English.

Adult↗

PubMed2006

Mitochondria and neuronal activity.

Mitochondria are central for various cellular processes that include ATP production, intracellular Ca(2+) signaling, and generation of reactive oxygen species. Neurons critically depend on mitochondrial function to establish membrane excitability and to execute the complex processes of neurotransmission and plasticity. While much information about mitochondrial properties is available from studies on isolated mitochondria and dissociated cell cultures, less is known about mitochondrial function in intact neurons in brain tissue. However, a detailed description of the interactions between mitochondrial function, energy metabolism, and neuronal activity is crucial for the understanding of the complex physiological behavior of neurons, as well as the pathophysiology of various neurological diseases. The combination of new fluorescence imaging techniques, electrophysiology, and brain slice preparations provides a powerful tool to study mitochondrial function during neuronal activity, with high spatiotemporal resolution. This review summarizes recent findings on mitochondrial Ca(2+) transport, mitochondrial membrane potential (DeltaPsi(m)), and energy metabolism during neuronal activity. We will first discuss interactions of these parameters for experimental stimulation conditions that can be related to the physiological range. We will then describe how mitochondrial and metabolic dysfunction develops during pathological neuronal activity, focusing on temporal lobe epilepsy and its experimental models. The aim is to illustrate that 1) the structure of the mitochondrial compartment is highly dynamic in neurons, 2) there is a fine-tuned coupling between neuronal activity and mitochondrial function, and 3) mitochondria are of central importance for the complex behavior of neurons.

Animals↗

PubMed2026

Spatiotemporal mapping of tertiary lymphoid structure heterogeneity shapes immune niches and clinical outcomes in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy with limited therapeutic options. The spatial architecture and functional diversity of tertiary lymphoid structures (TLSs) in iCCA remain unclear. Here, we present a multimodal spatial atlas of TLSs and identified intratumoral TLSs (iTLSs) as independent prognostic markers. Bulk proteomic profiling of 214 discovery and 155 validation cases identified a four-tier TLS-based tumor microenvironment classification system and supported development of a TLS-predictive random forest classifier. Imaging mass cytometry revealed that iTLS+ tumors harbor structured immune architectures, where M1-like tissue-resident macrophages (RTMs), dendritic cells, and CXCL13+ CD4+ T cells colocalize to form antigen-presenting neighborhoods (apc-CNs) spatially coupled to TLS core regions (TLScore-CNs). Single-cell spatial transcriptomics further resolved 61 TLSs into 14 spatial niches and defined a pseudotemporal maturation continuum: aggregated, activated, and postactivated. Intraniche communication, primarily mediated by ifnCAFs, iCAFs, and CXCL12+ macrophages, evolved dynamically with maturation. Single-nucleus RNA sequencing combined with Tangram-based spatial mapping revealed CXCL12+ macrophages and iCAFs forming a peripheral band in aggregated TLSs, whereas ifnCAFs infiltrated TLS interiors during activation. These findings define TLS heterogeneity and provide insights for stroma-directed immunotherapy.

Cholangiocarcinoma↗

PubMed2003

The digestive food vacuole of the malaria parasite is a dynamic intracellular Ca2+ store.

The acidic food vacuole of Plasmodium falciparum has been the subject of intense scientific investigation in the 40 years since its role in the digestion of host hemoglobin was first suggested. This proposed role has important implications for the complex host-parasite inter-relationship and also for the mode of action of several of the most effective antimalarial drugs. In addition, adaptive changes in the physiology of this organelle are implicated in drug resistance. Here we show that in addition to these functions, the digestive food vacuole of the malaria parasite is a dynamic internal store for free Ca2+, a role hitherto unsuspected. With the aid of live-cell laser scanning confocal imaging, spatiotemporal studies revealed that maintenance of elevated free Ca2+ in the digestive food vacuole (relative to cytosolic levels) is achieved by a thapsigargin (and cyclopiazonic acid)-sensitive Ca2+-pump in cooperation with a H+-dependent Ca2+ transporter. Redistribution of free cytosolic and vacuolar Ca2+ during parasite growth also suggests that vacuolar Ca2+ plays an essential role in parasite morphogenesis. These data imply that the digestive food vacuole of the malaria parasite is functionally akin to the vacuole of plants (tonoplast) and the small electron-dense granules of some parasites (acidocalcisomes) whereby H+-coupled Ca2+ transport is involved in ion transport, Ca2+ homeostasis, and signal transduction. These findings have significant implications for parasite development, antimalarial drug action, and mechanisms of drug resistance.

Animals↗

PubMed2003

Pattern selection in a cooperative biochemical in vitro amplification system: the role of parasites.

Previously, numerical simulations have shown that evolving systems can be stabilized against emerging parasites by pattern formation in spatially extended flow reactors. Hence, it can be argued that pattern formation is a prerequisite for any experimental investigation of the biochemical evolution of cooperative function. Here, we study a model of an experimental biochemical system for the cooperative in vitro amplification of DNA strands and show that emerging parasites can induce a complex pattern formation even when no pattern formation occurs without parasites. In an adiabatic approximation where the cooperative amplification reaction is assumed to adapt fast to slowly emerging parasites, the parasite concentration itself acts as a Steuer parameter for the selection of various complex patterns. Without such an adiabatic approximation only transient patterns emerge. As any species can grow for very low concentrations, the parasite is able to infect the entire reactor and the system is finally diluted out. In the experimental biochemical system, however, the species are individual molecules and the growth of spatially separated, non-infected regions becomes feasible. Hence a cutoff threshold for the minimal concentration is applied. In these simulations the otherwise lethal infection by parasites induces the formation of spatiotemporal spirals, and this spatial structure help the host and parasitoid species to survive together. These theoretical results describe an inherent property of cooperative reactions and have an important impact on experimental investigations on the molecular evolution and complex function in spatially extended reactors. Since the formation of the complex pattern is restricted either to a rather large cutoff value or a special choice of the kinetic parameters, we, however, conclude that the persistence of evolving cooperative amplification is not possible in a simple reaction-diffusion reactor. Experimental set-ups with patchy environments, e.g. biomolecular amplification in coupled microstructured flow chambers or in microemulsion, are eligible candidates for the observation of such a self-organized pattern selection.

Animals↗