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Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease.

The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (< 10 microm) blood vessels in four patients. The data suggest that, of the amyloid-beta subtypes, the clusters of classic amyloid-beta deposits appear to be the most closely related to blood vessels and especially to the larger-diameter, vertically penetrating arterioles in the upper cortical laminae.

Aged↗

Analysis by confocal scanning laser microscopy imaging of the spatial distribution of intermediate filaments in foetal and adult rat liver cells.

Confocal scanning laser microscopy has been used to make three-dimensional observations of the spatial distribution of cytoskeleton intermediate filaments in rat liver hepatocytes, at various stages during foetal development and in the adult. Single and double immuno-labelling with fluorescein and Texas Red fluorescence have been used to study the intracellular spatial distribution of C18 cytokeratin and vimentin. Simultaneous confocal imaging with double-fluorescence emission requires an image processing step for the correction of 'contamination' effects due to the overlap between fluorescein and Texas Red emission spectra. At the pre-natal period (day 20 of gestation) each type of intermediate filament labelling is only present in a certain cellular category, C18 cytokeratin in hepatocytes and vimentin in mesenchymal cells. However, at the earliest developmental stages (day 12 of gestation), vimentin and cytokeratin seem to be found in the same type of cells, probably mesenchymal cells. Some striking developmental changes, associated with the differentiation of the liver parenchyma, are observed for both C18 cytokeratin and vimentin. In earlier foetal stages, C18 filaments are scarce, hazily labelled and randomly distributed inside the hepatocytic cytoplasm. Late during foetal development (days 18-20 of gestation), hepatocytic cytokeratin filaments are abundant, well individualized and sharply labelled. The hepatocytes are arranged in a muralium duplex architecture (two-cell-thick sheets) and the labelling intensity measured in the hepatocytic cytoplasm at the basal pole is double that measured at the sinusoidal pole, while, in the adult, hepatocytes are arranged in a muralium simplex architecture (one-cell-thick sheets) and cytokeratin filaments have a symmetrical distribution in relation to the nuclear region.

Animals↗

Discrimination of the spatial distribution of concurrently active sound sources: some experiments with stereophonic arrays.

Several experiments are described in which subjects were required to discriminate differences in the spatial distribution of concurrently active sound sources in stereophonic arrays. For pure tone stimuli and binaural listening, systematic discrimination functions were observed when relatively small intersource frequency differences (approximately 30 Hz) were present. For tonal stimuli, this discrimination task was reliably performed only for frequencies below 1500 Hz. Additional tests were conducted with amplitude-modulated tonal stimuli, low- and high-frequency uncorrelated noise, correlated low-frequency noise, and, with the uncorrelated low-frequency noise, for stimuli presented in both the vertical plane and under monaural listening conditions. The results of all of these manipulations support the notion that the spatial distribution of sources in a stereophonic array can be appreciated if disparate low-frequency energy is available from the sources in a horizontal configuration. The implications of these results are discussed relative to acoustic processing in the natural environment.

Auditory Perception↗

Methods for analyzing the spatial distribution of chiasmata during meiosis based on recombination data.

Using genetic recombination data to make inferences about chiasmata on the tetrad during meiosis is a classic problem dating back to Weinstein's paper in 1936 (Genetics 21, 155-199). In the last few years, Weinstein's methods have been revived and applied to new problems, but a number of important statistical issues remain unresolved. Recently, we developed improved statistical methods for studying the frequency distribution of the number of chiasmata (Yu and Feingold, 2001, Biometrics 57, 427-434). In the current article, we develop methods for the complementary issue of studying the spatial distribution of chiasmata. Somewhat different statistical approaches are needed for the spatial problem than for the frequency problem because different scientific questions are of interest. We explore the properties of the maximum likelihood estimate (MLE) for chiasma spatial distributions and propose improvements to the estimation procedures. We develop a class of statistical tests for comparing chiasma patterns in tetrads that have undergone normal meiosis and tetrads that have had a nondisjunction event. Finally, we propose an EM algorithm to find the MLE when the observed data is ambiguous, as is often the case in human datasets. We apply our improved methods to reanalyze a dataset from the literature studying the association between crossover location and meiotic nondisjunction of chromosome 21.

Algorithms↗

Quantitative assessment of the spatial distribution of low attenuation areas on X-ray CT using texture analysis in patients with chronic pulmonary emphysema.

An automated and quantitative assessment of the spatial distribution of low attenuation areas (LAA) on X-ray CT was performed using texture analysis in chronic pulmonary emphysema (CPE) patients. LAA was defined as those areas having a density less than the mean minus one SD of the control (-960 HU). The probability of change from non-LAA to LAA between a given pair of pixels with horizontal intervals of i pixels (RNi) was evaluated, because this reflects the interaction between LAA and non-LAA regions with different resolutions. The relationship between the percentage area of the LAA over the total area of the entire lung field (LAA%) was subsequently estimated. The RNi increased sharply as the i value increased from 1 to 5, but then almost became a plateau for i values larger than 5. This suggests that the fundamental structures in the LAA areas ranged from 1 x 1 to 5 x 5 pixels in size. RN1-LAA% and RN5-LAA% plots produced curves which were convex, with peak values at approximately 50 LAA% of 0.09 and 0.18, respectively. In the RN5/RN1-LAA% plot, the RN5/RN1 ratio remained constant at 2.0 regardless of the LAA%. A random process simulation was performed to determine the patterns of LAA proliferation if the spatial distribution of the LAA units was random. When the unit size was kept constant, the results of the simulation did not fit the empirical relationship between the LAA% and the three parameters (RN1, RN5 and RN5/RN1). The simulation provided the best-fitting curves when the unit size of the LAA increased in proportion with the LAA%, starting from a 1 x 1 pixel size increasing at a ratio 1 x 1/(5 LAA%). This suggested that the LAA units do not proliferate randomly in spatial orientation at a fixed unit size, but rather spread throughout the whole lung field in a congregated form whilst increasing their unit size. Thus, it may be concluded that healthy lung tissues near emphysematous lesions have a high probability of suffering from emphysema in the future. This may be due to a direct effect of the neighboring emphysematous lesion or due to a pathologic change in the larger bronchii which dominate both the healthy tissues and the emphysematous lesions.

Aged↗

A distributed-parameter model of the myelinated human motor nerve fibre: temporal and spatial distributions of electrotonic potentials and ionic currents.

The double cable model is used to investigate the electrotonic responses of the myelinated human motor nerve fibre to 100 ms depolarizing and hyperpolarizing current pulses. The model calculations provide estimates of the spatial and temporal distributions of the transaxonal and transmyelin components of the electrotonic potentials, both in different segments of the fibre and at different moments during and after the pulses. The temporal distributions of the potentials exhibit fast (rise time < 1 ms) and slow (from 10 to 100 ms) components, while the discontinuous spatial distributions of the potentials reflect the heterogeneous structure of the fibre. The distributions of the transaxonal and transmyelin currents along the fibre, and their contributions from different ionic channels, are also explored. The different axolemmal channel types beneath the myelin sheath make an important contribution to the responses to the long-lasting current pulses.

Action Potentials↗

Determining the spatial distribution of viable and nonviable bacteria in hydrated microcosm dental plaques by viability profiling.

AIMS: The aim of this study was to use confocal laser scanning microscopy (CLSM) to examine the spatial distribution of both viable and nonviable bacteria within microcosm dental plaques grown in vitro. Previous in vivo studies have reported upon the distribution of viable bacteria only. METHODS AND RESULTS: Oral biofilms were grown on hydroxyapatite (HA) discs in a constant-depth film fermenter (CDFF) from a saliva inoculum. The biofilms were stained with the BacLight LIVE/DEAD system and examined by CLSM. Fluorescence intensity profiles through the depth of the biofilm showed an offset between the maximum viable intensity and the maximum nonviable intensity. Topographical differences between the surface properties of the viable and nonviable biofilm virtual surfaces were also measured. CONCLUSIONS: The profile of fluorescence intensity from viable and nonviable staining suggested that the upper layers of the biofilm contain proportionally more viable bacteria than the lower regions of the biofilm. SIGNIFICANCE AND IMPACT OF STUDY: Viability profiling records the transition from predominantly viable to nonviable bacteria through biofilms suggesting that this technique may be of use for quantifying the effects of antimicrobial compounds upon biofilms. The distribution of viable bacteria was similar to that found in dental plaque in vivo suggesting that the CDFF produces in vitro biofilms which are comparable to their in vivo counterparts in terms of the spatial distribution of viable bacteria.

Bacteria↗

Temporal and spatial distributions of ozone in Atlanta: regulatory and epidemiologic implications.

Relationships between ambient levels of selected air pollutants and pediatric asthma exacerbation in Atlanta were studied retrospectively. As a part of this study, temporal and spatial distributions of ambient ozone concentrations in the 20-county. Atlanta metropolitan area during the summers of 1993, 1994, and 1995 were assessed. A universal kriging procedure was used for spatial interpolation of aerometric monitoring station data. In this paper, the temporal and spatial distributions of ozone are described, and regulatory and epidemiologic implications are discussed. For the study period, the Atlanta ozone nonattainment area based on the 1-h, exceedance-based standard of 0.12 ppm is estimated to expand--from 56% of the Atlanta MSA by area and 71% by population to 88% by area and 96% by population--under the new 8-h, concentration-based standard of 0.08 ppm. Regarding asthma exacerbation, a 4% increase in pediatric asthma rate per 20-ppb increase in ambient ozone concentration was observed (p-value = 0.001), with ambient ozone level representing a general indicator of air quality due to its correlations with other pollutants. The use of spatial ozone estimates in the epidemiologic analysis demonstrates the need for control of demographic covariates in spatiotemporal assessments of associations of ambient air pollutant concentrations with health outcome.

Air Pollution↗

Spatial distribution and accumulation of low density lipoproteins in the abdominal aorta of swine: determination by a novel electrotransfer procedure.

An immunotransfer procedure has been developed which can determine both the spatial distribution of low density lipoproteins (LDL) along the intima-media of large blood vessels such as the aorta, and can quantify LDL accumulation along its length. Aortas which were opened longitudinally along their ventral aspect were positioned so that their intimal side abutted against a gel containing glyoxyl agarose to which anti-LDL had been covalently coupled. LDL was electrophoresed out of the agarose gel where it was immunofixed. This distribution was then visualized first by incubating the gel with 125I-anti-LDL which bound to free epitopes on the immunofixed LDL, and second by subjecting the washed and dried gel to autoradiography. Plasma LDL was applied to wells of different shapes and sizes in an agarose gel substituting for aortic tissue, and the transfer procedure was performed as described. The resultant patterns matched those of the original wells, suggesting that the spatial distribution of LDL in the autoradiogram probably mimicked that in the aortic tissue. The transfer procedure appeared to be specific for the antigen under study since minimal silver grains were observed in autoradiograms when an IgG fraction of nonimmune serum was used in place of anti-LDL. Application of increasing concentrations of LDL to wells in a gel substituting for tissue, resulted in a dose-dependent increase in autoradiographic grain density. If such standards were applied to gels adjacent to tissue samples, the amounts of LDL in the tissue could be quantified from the standard curve of grain density versus LDL concentration. The distribution of LDL along the abdominal aortas of 10- and 31-week-old swine was determined by converting autoradiographic grain densities to isopleths of LDL concentrations by computer assisted image analysis. These distributions were focal and were found to range between 10 and 225 ng of apoB/mm2 of intimal surface area. This procedure lends itself not only to studies relating lipoprotein accumulation to atherogenesis, but also to any studies dealing with tissue accumulation of macromolecules.

Animals↗

Spatial distribution of cell division rate can be deduced from that of p34(cdc2) kinase activity in maize leaves grown at contrasting temperatures and soil water conditions.

We have investigated the spatial distributions of cell division rate, p34(cdc2) kinase activity, and amount of p34(cdc2a) in maize (Zea mays) leaves grown at contrasting temperatures and soil water conditions. An original method for calculating cell division rate in all leaf tissues is proposed. In all studied conditions, cell division rate was stable and maximum in the first 2 cm beyond the leaf insertion point, declined afterward, and reached zero at 7 cm from the insertion point. The spatial distribution of p34(cdc2) kinase activity, expressed on a per cell basis, followed the same pattern. In contrast, the amount of p34(cdc2a) was maximum in the first centimeter of the leaf, declined afterward, but remained at 20% of maximum in more distal zones with a near-zero cell division rate. A mild water deficit caused a reduction in cell division rate and p34(cdc2) kinase activity by approximately 45% in all leaf zones, but did not affect the amount of p34(cdc2a). Growth temperature affected to the same extent cell division rate and p34(cdc2) kinase activity, but only if p34(cdc2) kinase activity was assayed at growth temperature, and not if a standard temperature was used in all assays. A common linear relationship between cell division rate and p34(cdc2) kinase activity applied to all causes of changes in cell division rate, i.e. cell aging, water deficit, or changes in temperature. It is shown that temperature has two distinct and additive effects on p34(cdc2) kinase activity; first, an effect on the rate of the reaction, and second, an effect on the amount of p34(cdc2a).

CDC2 Protein Kinase↗

The macular pigment. II. Spatial distribution in primate retinas.

The spatial density distribution of macular pigment in primate retinas was described by two-wavelength microdensitometry of retinal sections. The macular pigment is most dense along the path of the receptor axons in the center of the fovea. Another band of high density is present in the inner plexiform layer in many retinas. The density in both fiber layers declines to low, relatively constant levels within 1 mm eccentricity. Both the total retinal density of macular pigment and the contributions of subsets of the retinal layers were estimated by integrating along the path of light traversing the retina from the vitreal surface to the outer segments. The integrated densities were measured at several eccentricities to establish the profile of macular pigment density along a diameter through the fovea. The macular pigment profile was unimodal in some cases and trimodal in others. The main central peak always occurred in the center of the fovea. The total retinal density of the central peak ranged from 0.42-1.0 absorbance. Most of the pigment is interposed between the outer segments and the stimulating light and is effective as a visual filter. The macular pigment is dichroic, with the major axis of absorption oriented tangential to a circle centered on the fovea. This is consistent with commonly accepted explanations of Haidinger 's brushes.

Animals↗

Automated cytometry of muscle fibre sections: size and spatial distribution of the four fibre types in young and adult rats.

An automated cytometry program was applied to the extensor digitorum longus muscle of young and adult rats. Lesser diameter and spatial distribution of about 4000 fibres were measured in digital images from ATPase-stained muscle sections. All fibre types grow thicker with age, but the coefficient of variation of the diameter is age-independent. At both ages, 2B fibres have the largest mean diameter and are most frequent. 2A fibres in young rats present a diameter smaller or equal to type 1 but then show a faster increase in size; their relative number increases from 20 to 28%. Consequently type 2A displays the most important change with age. The spatial distribution of fibres is mathematically expressed; most images show a random distribution of type 1 and type 2 fibres. Taking into account the variation of fibre size of each type, the number of fibres which should be measured in order to reach a specified precision was calculated.

Analysis of Variance↗

Life history and spatial distribution of the enchytraeid worm Cognettia sphagnetorum (Oligochaeta) in metal-polluted soil: below-ground sink-source population dynamics?

We studied the life history, metal-avoidance behavior, spatial distribution, and population growth of enchytraeid worms (Cognettia sphagnetorum [Oligochaeta]) originating from two sites: one uncontaminated, and another patchily polluted by heavy metals. Effects of patchy soil contamination on populations were studied in microcosms. In uncontaminated soil, worms from the polluted site had lower viability and reduced growth rate as juveniles but higher growth rate as adults compared to worms from the unpolluted site. They were also smaller in size at fragmentation (reproduction). Worms from the polluted site reached a larger population size than worms from the unpolluted site. Hence, worms from the polluted site seemed to allocate more energy to reproduction, because such a strategy can be highly adaptive when living in a less-polluted patch (the source) in, on average, a highly polluted environment. The C. sphagnetorum actively avoided Cu-contaminated soil, with the response being stronger in individuals from the contaminated site. When an unpolluted patch (the source) was surrounded by a toxic environment (the sink), worms were found in the sink, either because intraspecific competition overrode the avoidance behavior or because of random walk migration. As a result, total population size in these microcosms were as high as those in totally uncontaminated microcosms. Our results indicate that avoidance behavior and increased allocation to reproduction, together with the observed dispersal pattern, can be an adaptive strategy for C. sphagnetorum in the presence of small, less-polluted patches in, on average, a hostile environment. Hence, sink-source population regulation can explain spatial distribution and survival of C. sphagnetorum in patchily polluted field soils. When such population dynamics occur, this pattern should be taken into account when population densities in the field are monitored for ecological risk-assessment procedures concerning toxicants.

Adaptation, Physiological↗

Spatial distribution of cytoskeleton intermediate filaments during fetal rat hepatocyte differentiation.

The construction of the liver parenchyma throughout fetal development depends on the elaboration of intercellular contacts between epithelial cells and between epithelial and mesenchymal cells. During this time, the spatial distribution of cytokeratins in hepatocytes shows a striking evolution as demonstrated by confocal microscopy and image analysis. In the early stages of fetal rat development, the liver is mainly a hematopoietic organ and hepatocytes represent fewer than 40% of all liver cells. At this time, cytokeratin filaments are scarce and are randomly distributed inside the cytoplasm. A coexpression of desmin and cytokeratin is found in some cells. Intercellular contacts between epithelial and mesenchymal cells are more numerous than between epithelial cells. Later in development, hepatocytes are arranged in a "muralium duplex" architecture (two-cell-thick sheets). Contacts between hepatocytes become more numerous and bile canaliculi become well developed. The density of cytokeratin filaments increases and appears to be very high near the bile canaliculi. In adult liver, hepatocytes are arranged in a "muralium simplex" architecture. Cytokeratin filaments show a symmetrical distribution in relation to the nuclear region. The highest density of filaments is found near the cytoplasmic membrane. Variations of the spatial distribution of intermediate filaments throughout hepatocyte differentiation were investigated in a pilot study using computerized image analysis. We found significant differences between the filament networks in fetal and adult hepatocytes.

Animals↗

Imaging of axonal damage in multiple sclerosis: spatial distribution of magnetic resonance imaging lesions.

We performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course (relapsing with at least partial remissions or secondary progressive disease). Lesions were segmented on the conventional proton density and T2-weighted magnetic resonance images, and lesion distribution images were generated for, each patient. The conventional magnetic resonance and spectroscopic images were transformed into a standard brain-based stereotaxic coordinate space, allowing comparison of images from different patients on a voxel-by-voxel basis. The spatial distribution of lesions in the transformed magnetic resonance images did not differ significantly between the relapsing and the progressive disease groups. We then generated from the individual data sets, group lesion probability distribution images for the relapsing and the progressive disease groups. The spatial distribution of metabolites was characterized with respect to lesion distribution using the magnetic resonance spectroscopic images transformed into stereotaxic space and averaged. The neuronal marker N-acetylaspartate was diffusely lower in the multiple sclerosis patients than in normal control subjects. Comparison of the averaged metabolite and T2-weighted lesion probability images confirmed loss of N-acetylaspartate in regions of both high and low lesion probability. This suggests that diffuse axonal volume loss or dysfunction extends beyond the inflammatory lesions of multiple sclerosis, perhaps due to microscopic disease or wallerian degeneration along projection pathways of axons traversing the lesions.

Adult↗

The spatial distribution of spindle microtubules in anaphase 3Y1 cells.

The spatial distribution of the microtubules (MT) in the rat 3Y1 cells in mitosis was investigated by immunoelectron microscopy and computer-graphic reconstruction of serial thin sections. In anaphase the interzone-MT increased in number gradually with advancing phase, while the kinetochore-MT in half-spindles decreased. The interzone-MT overlapped with each other at the equatorial region of the cell, and they formed a specific structure called the 'stem bodies'. The ends of the interzone-MT opposite to the stem bodies often attached to chromosomes but not to the poles. The stem bodies were not labeled with immunogold particles of anti-alpha tubulin. Some of the stem bodies or MT which originate from stem bodies were found just beneath the plasma membrane in the equatorial region where abundant actin filaments appear showing the formation of the contractile ring and subsequently the cleavage furrow begins. On the basis of these observations it is assumed that the interzone-MT is involved both in the separation of chromosomes in anaphase and in the formation of the cleavage furrow in telophase.

Anaphase↗

Modelling the spatial distribution of SO2 and NOx emissions in Ireland.

The spatial distributions of sulphur dioxide (SO2) and nitrogen oxides (NOx) emissions are essential inputs to models of atmospheric transport and deposition. Information of this type is required for international negotiations on emission reduction through the critical load approach. High-resolution emission maps for the Republic of Ireland have been created using emission totals and a geographical information system, supported by surrogate statistics and landcover information. Data have been subsequently allocated to the EMEP 50 x 50-km grid, used in long-range transport models for the investigation of transboundary air pollution. Approximately two-thirds of SO2 emissions in Ireland emanate from two grid-squares. Over 50% of total SO2 emissions originate from one grid-square in the west of Ireland, where the largest point sources of SO2 are located. Approximately 15% of the total SO2 emissions originate from the grid-square containing Dublin. SO2 emission densities for the remaining areas are very low, < 1 t km-2 year-1 for most grid-squares. NOx emissions show a very similar distribution pattern. However, NOx emissions are more evenly spread over the country, as about 40% of total NOx emissions originate from road transport.

Air Movements↗

Spatial distribution of the EOG in the rat; a variation with odour quality.

The spatial distribution of olfactory receptors in the rat has been studied by simultaneous recordings of the electroolfactograms (EOGs) from areas of the olfactory mucosa. The potentials were recorded from the dorsal surface of the cribriform plate, leaving the mucosa and the nasal cavities intact. The ratio between the peak amplitude of the EOG potentials served as a measure of the relative sensitivity of one area against the other. The results obtained by stimulating with 31 substances at 38 positions demonstrate a non-homogeneous distribution of different receptors. Each substance gives a spatial pattern of response efficiency. The response distributions are mapped on the cribriform plate for the different odours.

Animals↗