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Results for “Spatial heterogeneity”

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PubMed1990

The distribution of blood flow and glucose uptake within single skeletal muscles in the awake rabbit.

We have previously described a substantial regional heterogeneity both in blood flow and in glucose uptake within single skeletal muscles in anaesthetized rabbits. These heterogeneities could be related to effects of anaesthesia. The main goal of the present study was therefore to study regional muscle blood flow and muscle glucose uptake in awake rabbits. We used the microsphere method and the deoxyglucose technique for assessment of regional blood flow and regional glucose uptake respectively. The measurements were performed in 0.25-g regions from hind leg muscles. Some rabbits were first studied while awake and then during anaesthesia. Others were studied while either awake or anaesthetized. The degree of regional heterogeneity in blood flow and in glucose uptake was similar in awake and anaesthetized rabbits. Both temporal and spatial heterogeneity in blood flow were present. Evidence was found for vasomotion with a cycle time exceeding 45 min in awake rabbits. This perfusion pattern was similar in rabbits in which either the motor or sympathetic vasomotor nerves or both had been blocked. We conclude that regional perfusion and glucose uptake within single muscles are also markedly heterogeneous in awake rabbits. Regional, non-synchronized fluctuations in blood flow with a long cycle time seem to be an important part of this perfusion heterogeneity.

Anesthesia↗

PubMed1999

Spatial variation of anthropometric traits in Ireland.

To further elucidate the relationship between geography and genetics in Ireland, we considered variation in anthropometric traits of adult males by town using spatial autocorrelation methods. By describing and distinguishing significant patterns of anthropometric variation, we determined whether the anthropometric traits display a simple pattern of spatial variation, as predicted by the isolation by distance model, or other patterns of spatial variation. Several hypotheses were examined, including (1) whether there was spatial patterning of 20 anthropometric phenotypic distributions and 7 principal components of Irish males and (2) if there was, whether these phenotypic distributions could be explained by a simple isolation by distance model. The results of this study can be summarized by several key findings: (1) There is significant spatial patterning among towns, as detected in correlograms of 14 anthropometric traits and 2 principal component factor scores (values of Moran's I ranging from 0.7510 to -0.3616, p < or = 0.0071); (2) 4 spatial patterns were detected, including clinical patterns, long-distance differentiation, distance distinction, and regional patchiness. These results suggest several likely causes of the observed spatial patterns. First, in Ireland patterns of anthropometric variation could not be explained by a single spatial pattern (i.e., isolation by distance). Second, through an examination of the various combinations of statistical homogeneity or heterogeneity, spatial patterning or nonpatterning, and similarity or dissimilarity of spatial patterns, we conclude that several migrational events structured the genetic landscape of Ireland.

Adult↗

PubMed2003

Spatial variation of metals and acid volatile sulfide in floodplain lake sediment.

In risk assessment of aquatic sediments, much attention is paid to the immobilizing effect of acid volatile sulfide (AVS) on trace metals. The difference of AVS and simultaneously extracted metals (SEM) gives an indication of metal availability. In floodplain sediments, where changing redox conditions occur, AVS may play a major role in determining variation in metal availability. The importance of spatial heterogeneity has been recognized in risk assessment of trace-metal-polluted sediments. However, little is known about spatial variation of available metal fractions. We studied spatial variability of sediment, environmental conditions, total contaminant concentrations, and available metals (as SEM-AVS or SEM-AVS/f(oc)) in a floodplain lake. The top 5 cm of sediment was sampled at 43 locations. Data were analyzed with correlation and principal component analysis as well as with geostatistical methods. Trace metal and SEM concentrations and most sediment characteristics were more or less constant within 10%. In contrast, AVS concentrations were much more variable and showed a strong spatial dependence due to differences in lake depth, total sulfur pools, and redox potential (E(h)), which resulted in crucial differences in trace-metal availability within the lake. The spatial pattern of SEM-AVS deviates from total or normalized trace-metal patterns. This particularly has implications for risk assessment of sediments prone to dynamic hydrological conditions, where AVS concentrations are also variable in time.

Acids↗

PubMed1994

Theoretical studies of the effects of heterogeneity in the parasite population on the transmission dynamics of malaria.

Periodicity in malaria transmission has generally been ascribed to seasonal fluctuations in mosquito population density or spatial heterogeneity with periodic migration. In this paper we demonstrate that simple models of strain heterogeneity can generate periodic behaviour as a consequence of the interaction between parasite strains and host immunological defences. As the degree of cross-immunity between strains increases, the system moves from a régime of independent strain transmission and coexistence, through increasingly coupled behaviour, to the displacement of the strain of lower transmissibility by the strain with a higher basic reproductive rate (R0). Cross-immunity thus serves both to bring the strains into competition, and also to couple the dynamics. We find analytical and numerical results on strain coexistence to show how the range of possible outcomes may be read as an effect of the tension between these two effects of cross-protection.

Animals↗

PubMed2004

Forecasting spatially structured populations: the role of dispersal and scale.

We forecasted spatially structured population models with complex dynamics, focusing on the effect of dispersal and spatial scale on the predictive capability of nonlinear forecasting (NLF). Dispersal influences NLF ability by its influence on population dynamics. For simple 2-cell models, when dispersal is small, our ability to predict abundance in subpopulations decreased and then increased with increasing dispersal. Spatial heterogeneity, dispersal manner, and environmental noise did not qualitatively change this result. But results are not clear for complex spatial configurations because of complicated dispersal interactions across subpopulations. Populations undergoing periodic fluctuations could be forecasted perfectly for all deterministic cases that we studied, but less reliably when environmental noise was incorporated. More importantly, for all models that we have examined, NLF was much worse at larger spatial scales as a consequence of the asynchronous dynamics of subpopulations when the dispersal rate was below some critical value. The only difference among models was the critical value of dispersal rate, which varied with growth rate, carrying capacity, mode of dispersal, and spatial configuration. These results were robust even when environmental noise was incorporated. Intermittency, common in the dynamics of spatially structured populations, lowered the predictive capability of NLF. Forecasting population behaviour is of obvious value in resource exploitation and conservation. We suggest that forecasting at local scales holds promise, whereas forecasting abundance at regional scales may yield poor results. Improved understanding of dispersal can enhance the management and conservation of natural resources, and may help us to understand resource-exploitation strategies employed by local indigenous humans.

Animals↗

PubMed2003

A model of graded calcium release and L-type Ca2+ channel inactivation in cardiac muscle.

We have developed a model of Ca(2+) handling in ferret ventricular myocytes. This model includes a novel L-type Ca(2+) channel, detailed intracellular Ca(2+) movements, and graded Ca(2+)-induced Ca(2+) release (CICR). The model successfully reproduces data from voltage-clamp experiments, including voltage- and time-dependent changes in intracellular Ca(2+) concentration ([Ca(2+)](i)), L-type Ca(2+) channel current (I(CaL)) inactivation and recovery kinetics, and Ca(2+) sparks. The development of graded CICR is critically dependent on spatial heterogeneity and the physical arrangement of calcium channels in opposition to ryanodine-sensitive release channels. The model contains spatially distinct subsystems representing the subsarcolemmal regions where the junctional sarcoplasmic reticulum (SR) abuts the T-tubular membrane and where the L-type Ca(2+) channels and SR ryanodine receptors (RyRs) are localized. There are eight different types of subsystems in our model, with between one and eight L-type Ca(2+) channels distributed binomially. This model exhibits graded CICR and provides a quantitative description of Ca(2+) dynamics not requiring Monte-Carlo simulations. Activation of RyRs and release of Ca(2+) from the SR depend critically on Ca(2+) entry through L-type Ca(2+) channels. In turn, Ca(2+) channel inactivation is critically dependent on the release of stored intracellular Ca(2+). Inactivation of I(CaL) depends on both transmembrane voltage and local [Ca(2+)](i) near the channel, which results in distinctive inactivation properties. The molecular mechanisms underlying many I(CaL) gating properties are unclear, but [Ca(2+)](i) dynamics clearly play a fundamental role.

Animals↗

PubMed2026

Impact of spatial distribution of M2 macrophages on prognosis and neoadjuvant chemotherapy resistance in gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a crucial treatment for locally advanced gastric cancer; however, approximately 30-40% of patients experience primary resistance, the mechanisms of which urgently require elucidation. The tumor microenvironment exhibits a high degree of spatial heterogeneity. M2 macrophages, as critical immune cells within this environment, are typically associated with poor prognosis. Yet, whether their spatial distribution impacts chemotherapy efficacy remains unclear. This study aims to investigate the relationship between the in situ spatial distribution characteristics of M2 macrophages and chemoresistance in gastric cancer. METHODS: Based on The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, the association between M2 markers (CD163, MRC1) and histological grade as well as overall survival (OS) was evaluated. Spearman correlation and functional enrichment analyses were conducted to explore the mechanistic link between M2 macrophages and stromal barrier construction. Multiplex immunofluorescence (mIF) and digital pathology image analysis were utilized to calculate the areal density of M2 macrophages in the intratumoral core and the peritumoral stroma, respectively. The tumor-to-peritumoral ratio (TPR) was constructed, followed by a rank correlation analysis between TPR and the tumor regression grade (TRG). RESULTS: TCGA-STAD results confirmed that patients with high expression of M2 markers had worse OS (P=0.03), and the expression levels of M2 markers increased with histological grade. MRC1 was highly significantly and positively correlated with the pro-fibrotic factor TGFB1 (rho=0.447, P<0.001), with the gene set significantly enriched in pathways such as positive regulation of cytokine production and myeloid leukocyte activation. Histological examination revealed that in chemoresistant patients (TRG 3), M2 macrophages were primarily retained in the peritumoral stroma, with a median TPR of 0.50; in chemosensitive patients (TRG 1-2), a massive influx of M2 macrophages into the tumor core was observed, with a median TPR of 6.67. TPR was negatively correlated with TRG (rs=-0.65, P=0.043). CONCLUSIONS: The clinical impact of M2 macrophages in the gastric cancer microenvironment is highly dependent on their spatial distribution. The peritumoral-enriched pattern (TPR <1) mediates primary chemoresistance, whereas high infiltration in the core objectively reflects the pathological footprint following effective chemotherapy. The TPR serves as a novel tool for assessing neoadjuvant chemosensitivity in gastric cancer.

Gastric cancer (GC)↗

PubMedDate not supplied

[Magnetic sedimentation of protein molecules].

Usage of pondermotive interaction of protein molecules with heterogenous magnetic field for the studies of their physico-chemical properties is considered. Possibility is shown of creating spatial heterogenous concentration of macromolecules whose value is close to the equilibrium one near the slit edge of the magnetic system. Potentialities of magnetic sedimentation of macromolecules are compared with different variants of centrifugation. It is shown that by means of magnetic sedimentation the data on the shape, volume and molecular weight of the molecules, as well as on the change of these parameters, can be obtained. It is also possible to calculate the distribution parameters of macromolecules according to their magnetic sensitivity and partial volumes and to find correlation between these parameters. Conduction of macromolecule sedimentation in the media with different magnetic sensitivity allows to enlarge the scope of the information obtained.

Magnetics↗

PubMed2006

Action potentials induce uniform calcium influx in mammalian myelinated optic nerves.

The myelin sheath enables saltatory conduction by demarcating the axon into a narrow nodal region for excitation and an extended, insulated internodal region for efficient spread of passive current. This anatomical demarcation produces a dramatic heterogeneity in ionic fluxes during excitation, a classical example being the restriction of Na influx at the node. Recent studies have revealed that action potentials also induce calcium influx into myelinated axons of mammalian optic nerves. Does calcium influx in myelinated axons show spatial heterogeneity during nerve excitation? To address this, we analyzed spatial profiles of axonal calcium transients during action potentials by selectively staining axons with calcium indicators and subjected the data to theoretical analysis with parameters for axial calcium diffusion empirically determined using photolysis of caged compounds. The results show surprisingly that during action potentials, calcium influx occurs uniformly along an axon of a fully myelinated mouse optic nerve.

Action Potentials↗

PubMed1996

Cytosolic Ca2+ domain-dependent protective action of adenosine in cardiomyocytes.

Recently, in beating cardiac cells heterogeneous spatiotemporal patterns in cytosolic Ca2+ distribution have been visualized, and associated with cell contraction. In non-beating cardiomyocytes, spatial heterogeneity of intracellular Ca2+ distribution has also been observed, yet its functional implication in resting cardiac cells is not known. Herein, distinct domains of lower versus higher concentrations of cytosolic Ca2+ (0.17 and 0.37 microM, respectively) were observed using epifluorescent digital imaging in single, non-beating, fluo-3-loaded cardiomyocytes. Extracellular K+ (16 mM) induced a uniform increase of cytosolic Ca2+, despite the initial presence of distinct domains of cytosolic Ca2+ (from 0.17 to 1.82 microM in domains with lower, and from 0.37 to 2.03 microM in domains with higher Ca2+ concentration, respectively). In contrast, adenosine (1 mM) prevented exracellular K+ to induce cytosolic Ca2+ loading selectively within domains with lower (from 0.17 to 0.18 microM), but not in domains with higher (from 0.37 to 1.4 microM) basal Ca2+ concentration. Thus, the response of a cardiomyocyte to the protective action of adenosine is heterogeneous within a resting single cell. The domain-distinct cytoprotective action of adenosine appears to be set by the basal Ca2+ concentration within a cytosolic domain.

Adenosine↗

PubMedDate not supplied

Optical coherence tomography speckle reduction by a partially spatially coherent source.

Speckle in optical coherence tomography (OCT) images originates in the high spatial coherence of incident light that enables interference of light backscattered from spatially heterogenous tissue specimens. We report results of a numerical simulation and an experiment to test speckle reduction using a partially spatially coherent source. A Gaussian-Schell model for a partially spatially coherent source is used in the OCT simulation. For the experiment, such a source was generated by a spatially coherent boardband light source and a multimode fiber. The advantage of using a multimode fiber in combination with a broadband source is the large number of photons per coherence volume. To illustrate speckle reduction with a partially spatially coherent source, we record low-coherence interferograms of a scattering surface using single-mode and multimode source fibers. Interferograms recorded using a single-mode source fiber are indicative of those observed using conventional OCT. Speckle in OCT images recorded using a multimode source fiber is substantially reduced.

Algorithms↗

PubMedDate not supplied

The fractal nature of myocardial blood flow emerges from a whole-organ model of arterial network.

Mammalian hearts exhibit a heterogeneous spatial distribution of blood flows, but flows in near-neighbor regions correlate strongly. Also, tracer (15)O-water washout after injection into the inflow shows a straight log-log relationship between outflow concentration and time. To uncover the role of the arterial network in governing these phenomena, morphometric data were used to construct a mathematical model of the coronary arterial network of the pig heart. The model arterial network, built in a simplified three-dimensional representation of tissue geometry, satisfies the statistical morphometric data on segment lengths, diameters and connectivities reported for real arterial networks. The model uses an avoidance algorithm to position successive vascular segments in the network. Assuming flows through the network to be steady, the calculated regional flow distributions showed (1) the degree of heterogeneity observed in normal hearts; (2) spatial self-similarity in local flows; (3) fractal spatial correlations, all with the same fractal dimension found in animal studies; (4) pressure distributions along the model arterial network comparable to those observed in nature, with maximal resistances in small vessels. In addition, the washout of intravascular tracer showed tails with power law slopes that fitted h(t) = at(-alpha-1) with the exponents alpha = 2 for the reconstructed networks compared with those from experimental outflow concentration-time curves with alpha = 2.1+/-0.3. Thus, we concluded that the fractal nature of spatial flow distribution in the heart, and of temporal intravascular washout, are explicable in terms of the morphometry of the coronary network.

Animals↗

PubMed1988

Regional membrane heterogeneity in premyelinated CNS axons: factors influencing the binding of sterol-specific probes.

Binding of the sterol-specific probe filipin to developing optic nerve axonal membrane is spatially heterogeneous prior to association of glial cells with the axons. Experiments were performed using different sterol binding probes (filipin, tomatin, and saponin), at different temperatures (4 degrees C, 23 degrees C, and 37 degrees C), after incubation in different ionic conditions (10 mM Ca2+, 10 mM EGTA, and 20 mM Mg2+), to examine factors that may be responsible for this membrane heterogeneity in rat optic nerve. The patchy pattern of filipin binding is apparent with each sterol-specific probe, even prior to glial ensheathment, and is retained when membrane fluidity is increased at higher temperatures. Increased Ca2+ concentration increased membrane stability, and increased Mg2+ reduced the patchiness of filipin binding. After tannic acid staining, regions of the cytoskeleton are seen associated with the membrane via filaments extending from microtubules to the membrane, preferentially in regions where filipin interaction with the membrane is inhibited. The non-uniform interaction of filipin with the axolemma suggests an underlying heterogeneity in the sterol composition and stability of the membrane. Heterogeneity of premyelinated axonal membrane may provide an important formative influence in the differentiation of axons to their mature morphology and function.

Animals↗

PubMed2006

Effect of scale of Cd heterogeneity and timing of exposure on the Cd uptake and shoot biomass, of plants with a contrasting root morphology.

A pot experiment was conducted to investigate the influence of spatial heterogeneity of Cd distribution in soil on shoot biomass, shoot metal concentration and total shoot Cd uptake by lettuce (Lactuca sativa, variety Tom Thumb) and Indian mustard (Brassica juncea). Five different soil treatments had similar overall concentration of Cd per pot, but different scales of heterogeneity and also timing of plant exposure during the growth cycle. The presence and scale of heterogeneity and timing of exposure were found to have significant effects on shoot biomass for both plants (with one exception). The mean values of Cd mass taken up were significantly affected by the presence of heterogeneity and timing only for lettuce. Only the scale of heterogeneity affected the uptake of Cd by Indian mustard, presumably because of its larger root system (approximately 18 cm, compared with approximately 5 cm for lettuce). These findings have important implications for phytoremediation, and for human health risk assessment where leafy vegetables are grown in situations with highly elevated Cd concentrations.

Analysis of Variance↗

PubMed2000

Breast carcinoma, intratumour heterogeneity and histological grading, using geostatistics.

Tumour progression is currently believed to result from genetic instability. Chromosomal patterns specific of a type of cancer are frequent even though phenotypic spatial heterogeneity is omnipresent. The latter is the usual cause of histological grading imprecision, a well documented problem, without any fully satisfactory solution up to now. The present article addresses this problem in breast carcinoma. The assessment of a genetic marker for human tumours requires quantifiable measures of intratumoral heterogeneity. If any invariance paradigm representing a stochastic or geostatistic function could be discovered, this might help in solving the grading problem. A novel methodological approach using geostatistics to measure heterogeneity is used. Twenty tumours from the three usual (Scarff-Bloom and Richardson) grades were obtained and paraffin sections stained by MIB-1 (Ki-67) and peroxidase staining. Whole two-dimensional sections were sampled. Morphometric grids of variable sizes allowed a simple and fast recording of positions of epithelial nuclei, marked or not by MIB-1. The geostatistical method is based here upon the asymptotic behaviour of dispersion variance. Measure of asymptotic exponent of dispersion variance shows an increase from grade 1 to grade 3. Preliminary results are encouraging: grades 1 and 3 on one hand and 2 and 3 on the other hand are totally separated. The final proof of an improved grading using this measure will of course require a confrontation with the results of survival studies.

Antigens, Nuclear↗

PubMed2001

Three-dimensional visualization of lung blood flow heterogeneity based on fluorescent microsphere technique and fractal dimension: The Blood Flow Analysis System - BFA System.

The heterogeneity of regional pulmonary blood flow (RPBF) can be assessed by fractal analysis. The fractal dimension (FD) is a scale-independent measure of spatial heterogeneity of blood flow. The relative dispersion (RD) is often used to obtain the heterogeneity of RPBF but it is influenced by the resolution of measurement. The Blood Flow Analysis (BFA) System was developed in Delphi to represent the three-dimensional structure of lung blood flow and calculates statistics of FD, RD, spatial correlation of neighbored tissue samples and shows histograms of blood flows at diverse time points during different experiments. The BFA System reads a text file with flows, measured with fluorescent microsphere technique, and constructs the lung anatomy with volumetric pixels showing the flows with a color schema. It is possible to rotate the lungs into two axis (XY) and the statistics are shown with 3D graphics. The System maintains a database with data from various studies at same time. The BFA System was validated with four data sets from previous experiments. The BFA System has shown consistency and it is a new tool to help researchers during lung perfusion studies.

Animals↗

PubMed2001

Ultrasound-mediated disruption of cell membranes. II. Heterogeneous effects on cells.

Ultrasound has been shown to reversibly and irreversibly disrupt membranes of viable cells through a mechanism believed to involve cavitation. Because cavitation is both temporally and spatially heterogeneous, flow cytometry was used to identify and quantify heterogeneity in the effects of ultrasound on molecular uptake and cell viability on a cell-by-cell basis for suspensions of DU145 prostate cancer and aortic smooth muscle cells exposed to varying peak negative acoustic pressures (0.6-3.0 MPa). exposure times (120-2,000 ms), and pulse lengths (0.02-60 ms) in the presence of Optison (1.7% v/v) contrast agent. Cell-to-cell heterogeneity was observed at all conditions studied and was classified into three subpopulations: nominal uptake (NUP), low uptake (LUP), and high uptake (HUP) populations. The average number of molecules within each subpopulation was generally constant: 10(4)-10(5) molecules/cell in NUP, approximately 10(6) molecules/cell in LUP, and approximately 10(7) molecules/cell in HUP. However, the fraction of cells within each subpopulation showed a strong dependence on both acoustic pressure and exposure time. Varying pulse length produced no significant effect. The distribution of cells among the three subpopulations correlated with acoustic energy exposure, which suggests that energy exposure may govern the ability of ultrasound to induce bioeffects by a nonthermal mechanism.

Cell Membrane↗

PubMed1998

Ionic mechanisms of regional action potential heterogeneity in the canine right atrium.

Atrial action potential heterogeneity is a major determinant of atrial reentrant arrhythmias, but the underlying ionic mechanisms are poorly understood. To evaluate the basis of spatial heterogeneity in canine right atrial repolarization, we isolated cells from 4 regions: the crista terminalis (CT), appendage (APG), atrioventricular ring (AVR) area, and pectinate muscles. Systematic action potential (AP) differences were noted: CT cells had a "spike-and-dome" morphology and the longest AP duration (APD; value to 95% repolarization at 1 Hz, 270+/-10 ms [mean+/-SEM]); APG and pectinate muscle cells had intermediate APDs (180+/-3 and 190+/-3 ms, respectively; P<0.001 versus CT for each), with APG cells having a small phase 1; and AVR cells had the shortest APD (160+/-4 ms, P<0.001 versus other regions). The inward rectifier and the slow and ultrarapid delayed rectifier currents were similar in all regions. The transient outward K+ current was significantly smaller in APG cells, explaining their small phase 1 and high plateau. L-type Ca2+ current was greatest in CT cells and least in AVR cells, contributing to their longer and shorter APD, respectively. The E-4031-sensitive rapid delayed rectifier K+ current was larger in AVR cells compared with other regions. Voltage- and time-dependent current properties were constant across regions. We conclude that myocytes from different right atrial regions of the dog show systematic variations in AP properties and ionic currents and that the spatial variation in ionic current density may explain AP differences. Regional variation in atrial ionic currents may play an important role in atrial arrhythmia generation and may present opportunities for improving antiarrhythmic drug therapy.

Action Potentials↗