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[The rule of "one migrant per generation" and genetic differentiation in subdivided populations].

The genetic differentiation in population with migration according island and two-dimensional stepping stone models was studied with simulation methods. It is shown that migration of one or few individuals per generation is insufficient for leveling differences between subpopulations in allele frequencies. Even if migration is estimated as m = 0.5 (exchange of 50 and 500 individuals per generation) statistically significant differences remain at least in the half of populations with insular structure. Spatial heterogeneity disappears completely only if m = 0.7-0.8. In case of two-dimensional step model the level of genetic differentiation is higher and statistically significant heterogeneity remains at all levels of genetic exchange including that which was estimated as m = 1.

Animal Migration↗

[QT rate dependence in norm and myocardial infarction].

AIM: To assess QT/RR relationship in healthy subjects and in patients with acute myocardial infarction (AMI) using long term 12-lead ECG monitoring. MATERIAL AND METHODS: We studied separately diurnal and nocturnal QT interval rate-dependence using a linear model "QT=beta+alphaxRR" in 42 patients with AMI on 2-nd week of the disease and in 14 healthy volunteers. All necessary parameters were automatically calculated from 24-hour 12 lead ECG recordings using special programs. Myocardial perfusion and infarct size were assessed using 99mTc-MIBI gated SPECT. RESULTS: Long-term ECG monitoring permitted: 1) to detect the ECG lead with most pronounced QT/RR relationship delineated by alpha(max); 2) to determine value of "deltaalpha=alpha(max)-alpha(min)", that characterized spatial heterogeneity of QT/RR relationship. In norm diurnal values of alpha(max) were significantly higher than nocturnal ones (0.207+/-0.037 vs. 0.151+/-0.035, respectively; p<0.01). The alpha(max) values correlated with the size of MI (r=0.42-0.43, p<0.01). Therefore in patients with anterior AMI who demonstrated significantly larger defects of 99mTc-MIBI uptake than patients with inferior AMI, diurnal mean value of amax remained high despite therapy with b-blockers (0.225+/-0.037), and nocturnal alpha(max) value significantly exceeded respective amax value in healthy subjects (0.216+/-0.097 vs 0.151+/-0.035, respectively; p<0.01). Patients with AMI demonstrated an increased mean Da value when compared to normal subjects (in anterior AMI 0.098+/-0.057 vs. 0.039+/-0.014, respectively; p<0.001--diurnal period; 0.104+/-0,042 vs. 0.039+/-0.022, respectively; p<0.001--nocturnal period). In anterior AMI Da values correlated with infarct size (r=0.62, p=0.001). CONCLUSIONS: A new approach to the assessment of QT rate dependence with the use of 12-lead Holter monitoring widens possibilities of the method, firstly, because of selection of most informative ECG lead that shows maximal QT/RR relationship dynamic, and, secondly due, to discovery of the new field of ventricular repolarization research by assessment of space dispersion of QT/RR relationship. In patients with AMI when compared with healthy subjects we observed a decrease of QT/RR circadian modulation, increase of the slope and space dispersion of QT/RR rate dependence.

Electrocardiography, Ambulatory↗

Metabolic imaging of patients with cardiomyopathy.

The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies.

Carbon Radioisotopes↗

In vivo lectin-binding of photoreceptors and interphotoreceptor matrix in rat.

The in vivo distribution of lectin receptors in the photoreceptors and interphotoreceptor matrix (IPM) was studied by histochemistry and light microscopy. Horseradish peroxidase-conjugated lectins (peanut agglutinin, PNA; Ricinus communis agglutinin-1, RCA-1; or wheat germ agglutinin, WGA) were administered into the subretinal space of living rats, and 1 and 6 hours later eyeballs were enucleated to examine retinal tissues with a light microscope. The surfaces of cone photoreceptor outer segments and inner segments, and/or cone-associated IPM were labeled preferentially with PNA at 1 and 6 hours after its subretinal administration. One hour after subretinal injection, RCA-1 labeling appeared in the distal surface of the outer segments, the basal region of the inner segments, and the surface of the retinal pigment epithelium (RPE). At 6 hours the basal portion of the outer segments showed RCA-1 labeling as well. The distribution of labeling by WGA was uniform throughout the outer segments and/or the IPM domain except for the most distal portion of the outer segments. These observations conform for the most part to previous in vitro experiments, and indicate, together with previously not explicitly described observations, that a spatial heterogeneity in the vertical and horizontal directions exists in the IPM domain.

Animals↗

[Spike transmission in statistical neuronal ensembles. Induced epileptic focus in a model of hippocampal field CA3].

In a spatially heterogeneous model the transition to supercritical phase was investigated as to the parameter characterizing the activation level of the pyramidal cells related to one another assuming the nonuniformity radius to be R0 = const. This is a transition from spontaneous activity to epileptoid bursts. Before the onset of epileptoid bursts the region of stochastic nonequilibrium of solutions is developed likely to produce pathologic dynamic patterns. With further increase of the activation parameter the system comes to epileptoid state. This synchronized firing of pyramidal cells is accompanied with phases of inhibition. A decrease in the nonuniformity radius leads to the formation of an epileptic focus. It is a dissipative structure. The evolution of it is not further followed, since the transport equations do not include its dynamics.

Hippocampus↗

Temperature dependent factors influencing nutrient uptake: an analysis of responses at different levels of organization.

Ion fluxes show a characteristically biochemical dependence on temperature when observed at the membrane level and over short periods after a perturbation of temperature. The primary active transport systems are enzymic and are dependent both on substrate supply and on changes in protein conformation. The hydrophobic parts of the proteins are surrounded by lipid molecules whose physical state may crucially affect conformation changes. These lipids may undergo transitions from a fluid to a gel state at temperatures occurring in the natural environment. It will be noted that the concepts developed in model systems of pure phospholipid/protein interactions cannot be very readily applied to the spatially heterogeneous assemblies of lipid molecules and transport proteins in real cell membranes. While it is obvious that ion transport rates are responsive to temperature changes in a given cell, it is difficult to explain exactly which components of the transport process become limiting. We will show that, on cooling, the membrane potential can initially be greatly disturbed when temperature is changed and that this may be related to ATP supply to H+-translocating ATPase. This affects the driving force for all other solutes. When temperature is lowered the permeability coefficients for most ions are reduced and yet it is commonly found that diffusive efflux of ions increases in the cold. We attempt to explain this paradox on the basis of driving forces and metabolic regulation of ion transport. Acclimatory changes occur on extended exposure of a cell or an organism to a reduced growth temperature. Some of these changes occur at the membrane level and relate to lipid composition and modulation of carrier activity. Others involve changes in the relative size and sometimes the morphology of the root system. We will show that these processes lessen the temperature dependence of ion transport and ensure that the intake of nutrients does not limit growth at low temperatures. These acclimatory changes are seen as part of the general process of regulation of nutrient uptake.

Acclimatization↗

Nature and properties of cardiovascular deposits.

Mineral deposits from human aortas and bioprosthetic devices implanted in experimental animals show close similarities in chemical composition, solubility and structural characteristics. Chemical analyses show compositions corresponding to a Na, Mg, CO3 substituted apatitic calcium phosphate. Synergistic XRD, FT-IR and Raman microprobe spectroscopic data provided coherent indication of Type-B CO3(2-) incorporation. Microscopic and electron microprobe microanalyses, however, indicate substantial morphological and spatial heterogeneity in the deposits. Solubility and kinetic dissolution data of the mineral fraction of deposits can be compared with the corresponding data of octacalcium phosphate (OCP). This may indicate that OCP is a possible precursor phase which initiates formation of the mineral deposit. Our data indicate that the deposits can be represented by a series of carbonate-substituted products, arising from OCP that has hydrolyzed to varying degrees. Dissolution of deposits can be described kinetically as a surface controlled rate process. The similarities in the two types of deposits suggest that they form by a common mechanism (e.g., OCP could be the precursor for both deposits).

Animals↗

Cardiac positron emission tomography.

Positron emission tomography (PET) is a new technique for noninvasively assessing myocardial metabolism and perfusion. It has provided new insight into the dynamics of myocardial fatty acid and glucose metabolism in normal subjects, patients with ischemic heart disease and those with cardiomyopathies, documenting regionally depressed fatty acid metabolism during myocardial ischemia and infarction and spatial heterogeneity of fatty acid metabolism in patients with cardiomyopathy. Regional myocardial perfusion has been studied with PET using water, ammonia and rubidium labeled with positron emitters, permitting the noninvasive detection of hypoperfused zones at rest and during vasodilator stress. With these techniques the relationship between perfusion and the metabolism of a variety of substrates has been studied. The great strides that have been made in developing faster high-resolution instruments and producing new labeled intermediates indicate the promise of this technique for facilitating an increase in the understanding of regional metabolism and blood flow under normal and pathophysiologic conditions.

Coronary Circulation↗

Novel growth systems.

Most laboratory growth systems are based on homogeneous culture techniques. This review article discusses model systems which incorporate spatial heterogeneity. The latter include linked homogeneous growth vessels such as the multistage chemostat and the bidirectionally connected gradostat, gel stabilized models including one and two dimensional variants, microbial film fermenters, percolating columns and fluidized bed reactors.

Bacteria↗

[Evaluation of the professional qualities of operators working with computer displays].

The influence of spatio-temporal factors (spatial heterogeneity of distribution of the numbers sought for in the matrix of data, processes of learning and development of fatigue, periodic attention oscillations) of the character of solving the task of searching the numbers in a matrix of 176 three-figure numbers (16 lines, 11 columns) was studied in 39 operators. The possibility was shown to use the characteristics obtained for evaluation of professionally important abilities of an operator working at the display.

Adult↗

Sampling schemes for estimating nerve fibre size. II. Methods for unifascicular nerve trunks.

The total number of myelinated fibres in four unifascicular tibial nerves from diabetic rats has been counted and measured in order to assess the merits of various schemes for estimating group mean fibre diameter. The average nerve trunk contained some 2960 fibres which were measured in just under five hours. With different sampling designs, the average measurement time per nerve was reduced to between 17 and 69 minutes, with little consequent loss of reliability or precision of estimated mean fibre size. The most efficient schemes were those taking systematic samples of squares or sectors. A modification of a method relying on complete strips across two diameters of each nerve was the least efficient sampling approach. It had the additional disadvantage of introducing systematic errors which could affect the accuracy of measurements made on nerve trunks with heterogeneous spatial distributions of fibre size and number. This paper completes an investigation into random sampling errors influencing morphometric estimates of fibre size based on uni- or multifascicular nerve trunks.

Animals↗

Receptive fields of cat's non-relay lateral geniculate and perigeniculate neurons.

Two groups of neurons are postulated to serve as inhibitory interneurons for principal lateral geniculate cells: intrageniculate interneurons and the perigeniculate neurons. We analysed the spatiotemporal characteristics of receptive fields (RFs) of cells from both groups identified by their anatomical position and responses to electrical stimulation of the optic chiasm and visual cortex. Intrageniculate interneuronal RFs resembled in all respects those of relay cells. One third of perigeniculate neurons had erratic responses to visual stimuli. Those which responded well to flashing stimuli possess large (up to 20 degrees) spatially heterogeneous ON/OFF type RFs. Spatiotemporal extents of excitatory domains of both intrageniculate interneurons and perigeniculate neurons RFs correspond to the extents of inhibitory domains in the principal cell RFs which were described previously.

Animals↗

[Biodegradation of polycyclic aromatic hydrocarbons and its application to the bioremediation of contaminated soils and sludges].

Polycyclic aromatic hydrocarbons (PAHs) are a group of priority pollutants due to their toxic, mutagenic, and carcinogenic properties. They are found in high concentration in many soils and sludges, mainly those associated with petroleum, gas-production and wood-preservation industries. Application of microorganisms for the remediation of contaminated soils and sludges has gained interest as a promising technique in comparison to the conventional practices of landfilling, incineration or solvent extraction. This paper reviews the controlling variables of the biodegradation of PAHs as well as the use of solid-phase and slurry-phase bioremediation techniques. The acceptance of bioremediation technology requires the demonstration of its efficacy, reliability, predictability of the field performance from lab-scale treatability studies, and economical advantage. Some limitations in the biodegradation of high-molecular-weight PAHs and failures in the control of scale-depending factors (mass transport, spatial heterogeneities, abiotic losses) can reduce its effectiveness. Methodology used for the systematic evaluation of bioremediation is also reviewed.

Biodegradation, Environmental↗

Three-dimensional DNA image cytometry by confocal scanning laser microscopy in thick tissue blocks of prostatic lesions.

DNA ploidy provides important information for the evaluation of the prognosis of prostate cancer. For the purpose of DNA cytometry and nuclear measurements, we developed an image processing system for the acquisition and processing of three-dimensional (3D) images based on confocal scanning laser microscopy (CSLM). The advantage of the CSLM is the preservation of the tissue architecture and the possibility of multilabeling. It is possible to determine both individual nuclear features and cellular features and the degree of the spatial heterogeneity of several markers. Special attention was paid to the development of the automatic method for the 3D segmentation of cell nuclei. Thick tissue slides (100 microm), stained for DNA with chromomycin A3, from 4 patients (with benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and well-and poorly-differentiated adenocarcinoma of the prostate), were studied in order to test the practicability of the developed methodology. DNA histograms showed a single peak in the diploid range for the hyperplasia and PIN cases. For the case of well-differentiated carcinoma, 2 peaks were observed, 1 in the diploid range and I in the tetraploid range. The case of poorly-differentiated carcinoma was characterized by an aneuploid distribution. For the cases of PIN and carcinomas, we observed a considerable variation of the volume of nuclei.

Adenocarcinoma↗

The spatial and temporal heterogeneity of regional ventilation: comparison of measurements by two high-resolution methods.

High-resolution estimates of ventilation distribution in normal animals utilizing deposition of fluorescent microsphere aerosol (FMS technique) demonstrate substantial ventilation heterogeneity, but this finding has not been confirmed by an independent method. Five supine anesthetized sheep were used to compare the spatial and temporal heterogeneity of regional ventilation measured by both the FMS technique and by a ventilation model utilizing the data from computed tomography images of xenon gas washin (CT/Xe technique). An aerosol containing 1 microm fluorescent microspheres (FMS) was administered via a mechanical ventilator delivering a 2-s end-inspiration hold during each breath. Following the aerosol administration, sequential CT images of a transverse lung slice were acquired during each end-inspiration hold during washin of a 65% Xenon/35% oxygen gas mixture (CT/Xe technique). Four paired FMS and CT/Xe measurements were done at 30 min intervals, after which the animals were sacrificed. The lungs were extracted, air-dried and sliced in 1cm transverse sections. The lung section corresponding to the CT image was cut into 1 cm3 cubes, with notation of spatial coordinates. The individual cubes were soaked in solvent and the four fluorescent signals were measured with a fluorescence spectrophotometer. The color signals were normalized by the mean signal for all pieces and taken as the FMS estimate of ventilation heterogeneity. The CT images were clustered into 1 cm3 voxels and the rate of increase in voxel density was used to calculate voxel ventilation utilizing the model of . The regional ventilation voxel measurements were normalized by the mean value to give a CT/Xe estimate of ventilation heterogeneity comparable to the normalized FMS measurements. The overall of heterogeneity of ventilation at the 1 cm3 level of resolution was comparable by both techniques, with substantial differences among animals (coefficient of variation ranging from 37% to 74%). The repeated within-animal measurements by both techniques gave consistent values. Both techniques showed comparable large-scale distribution of regional ventilation in the caudal lobes of the supine animals. There were appreciable differences in the temporal variability of ventilation among animals. This study provides an independent confirmation of the scale-dependent heterogeneity of ventilation described by previous FMS aerosol studies of ventilation heterogeneity.

Animals↗

Spatial and temporal heterogeneity of superficial muscle strain during in situ fixed-end contractions.

Numerical models of contracting muscle offer a powerful tool to study local mechanical load. For validation of these models, the spatial and temporal distribution of strain was quantified in fixed-end contracting rat tibialis anterior muscle in situ at optimal muscle length (L(o)) and at 120 degrees plantar flexion as well as at 125 and 33Hz stimulation frequency. We studied the hypothesis that after termination of stimulation in situ muscle segments near the motor endplates elongate while segments away from the endplates shorten. We show that both spatial and temporal inhomogeneities in muscle deformation occurred during contraction. Muscle plateau shortening strain equalled 4.1%. Maximal plateau shortening of a muscle segment was much larger (9.6%) and occurred distally (at 0.26 of the scaled length of the muscle). Manipulating torque levels by decreasing the stimulation frequency at the same muscle length induced a decrease in torque ( approximately 20%) with a smaller effect on the level and no effect on the pattern of muscle deformation. During relaxation, distal segments actively shortened at the expense of proximal muscle segments, which elongated. The segments undergoing lengthening were nearer to motor endplates than segments undergoing shortening. In conclusion, the present study provides experimental data on magnitude of contraction-induced deformation needed for validation of numerical models. Local muscle deformation is heterogeneous both temporally and spatially and may be related to proximity to the motor endplates.

Animals↗

Spatial, temporal, and genetic heterogeneity in host populations and the design of immunization programmes.

The relevance of heterogeneity in infectious disease transmission to the design of immunization programmes is examined by the use of simple deterministic models of recurrent epidemic behaviour. In the context of spatial heterogeneity it is shown that an optimal vaccination programme, which concentrates on groups with relatively high density, can lead to eradication with overall coverage levels less than those estimated by a model which assumes homogeneity in host spatial distribution. Age-related heterogeneity in transmission can result in higher or lower coverage levels than those predicted by models which assume age-independent transmission, depending on the quantitative detail of how transmission changes with age. Genetic heterogeneity in host susceptibility to infection is shown to produce effects that are similar to those induced by age-related changes in transmission. It is concluded that much greater attention should be focused on transmission heterogeneity in future work on models of recurrent epidemic behaviour and the design of immunization programmes.

Biometry↗

Carbon dioxide fluxes in a spatially and temporally heterogeneous temperate grassland.

Landscape position, grazing, and seasonal variation in precipitation and temperature create spatial and temporal variability in soil processes, and plant biomass and composition in grasslands. However, it is unclear how this variation in plant and soil properties affects carbon dioxide (CO2) fluxes. The aim of this study is to explore the effect of grazing, topographic position, and seasonal variation in soil moisture and temperature on plant assimilation, shoot and soil respiration, and net ecosystem CO2 exchange (NEE). Carbon dioxide fluxes, vegetation, and environmental variables were measured once a month inside and outside long-term ungulate exclosures in hilltop (dry) to slope bottom (mesic) grassland throughout the 2004 growing season in Yellowstone National Park. There was no difference in vegetation properties and CO2 fluxes between the grazed and the ungrazed sites. The spatial and temporal variability in CO2 fluxes were related to differences in aboveground biomass and total shoot nitrogen content, which were both related to variability in soil moisture. All sites were CO2 sinks (NEE>0) for all our measurements taken throughout the growing season; but CO2 fluxes were four- to fivefold higher at sites supporting the most aboveground biomass located at slope bottoms, compared to the sites with low biomass located at hilltops or slopes. The dry sites assimilated more CO2 per gram aboveground biomass and stored proportionally more of the gross-assimilated CO2 in the soil, compared to wet sites. These results indicate large spatio-temporal variability of CO2 fluxes and suggest factors that control the variability in Yellowstone National Park.

Carbon Dioxide↗