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[Optimal strategies of spatial distribution: the Olli effect].

The selection of strategies of spatial distribution of individuals has been studied. In case of non-monotonous dependence of reproduction coefficient on the mean population density, a cluster formation is possible. At low mean densities, parity strategies of spatial distribution are realized, and at high densities, non-parity ones. A generalized notion of parity strategy of spatial distribution has been proposed. It includes such expenditures as expenditure for the movement of an individual, defense of the territory etc. A problem of evolutionary stability of different strategies of spatial distribution has been discussed.

Animals

A general, computer-based method for study of the spatial distribution of muscle fiber types in skeletal muscle.

The present method provides detailed quantitative information on the spatial distribution of the muscle fiber types in skeletal muscle. This is accomplished by comparing the measured spatial distribution of the fiber types with a computer-simulated random pattern. The method is based on a registration of the absolute frequency for six principal categories of fiber contacts (I-I, I-IIA, I-IIB, IIA-IIA, IIA-IIB, IIB-IIB). A computer program was designed to simulate a random pattern of fibers. The simulations were performed with high accuracy with regard to fiber type proportion and the number of neighbouring fibers. The computer then calculated the frequency for each of the different categories of fiber contacts in the simulated random pattern. The measured distribution of fiber contacts could thus be compared to the simulated random pattern. In three bovine muscles studied, the spatial distribution of the muscle fiber types showed a similar pattern. The muscle fibers had a distinct tendency to be surrounded by fibers of a different type. In all three muscles the difference between the measured and the simulated random pattern was statistically significant (p less than 10(-3).

Animals

Spatial distribution of dopamine, methotrexate and antipyrine during continuous intracerebral microperfusion.

The spatial distributions of 3 model drugs, [14C]dopamine hydrochloride (DA), [3H]sodium methotrexate (MTX) and [14C]antipyrine (AP), were determined after 6 days continuous microperfusion of the diencephalon of rabbits. The basic pattern of distribution was the same for each drug: the tissue concentration, expressed as a function of the perfusate concentration, was maximal at the cannula tip, and declined sharply with radial distance from the tip. However, at any given distance, concentrations of radioisotopes derived from DA and MTX, both ionized, lipid-insoluble drugs, were one to two orders of magnitude higher than those derived from AP, a lipid-soluble drug. Although concentrations of isotopes derived from DA and MTX were in the same range, their distribution patterns were consistently different. The results demonstrate that intracerebrally microperfused drugs may have quantitatively different spatial distributions, related to their physicochemical characteristics and/or their binding and metabolism in brain tissue.

Animals

Spatial distribution of immature Culicoides variipennis (Coq.).

Circadian fluctuation in the spatial distribution of immature Culicoides variipennis (Coq.) was studied in Saltville, Virginia, USA during the summer of 1983. Pupae and early instar larvae (1st and 2nd) were localized above the shoreline in the top cm of mud and displayed little migration from this region during the 24 hr sampling period, however, later instar larvae (3rd and 4th) showed marked migration patterns. Most larval movement was horizontal rather than vertical and was confined to the top cm of mud. Late instar larvae moved towards the water during the day but migrated up above shoreline during the night. Seasonal fluctuation in larval spatial distribution was also studied. Larvae appeared to move progressively downward into the mud during the autumn. However, when the site became frozen the majority of larvae occupied a narrow liquid interface between the ice cover and the frozen mud beneath.

Animals

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)

Perforant path activation of the hippocampus: spatial distribution, effects of urethane and atropine.

Spatial distribution of field responses evoked by perforant path stimulation were studied in the hippocampus of both anaesthetized and drug-free rats. Simultaneous recordings with an array of 4 electrodes allowed us to construct a 2-dimensional map of the evoked field potentials. In addition, we examined the effects of atropine-SO4 and urethane on the amplitude of the dentate response. Trisynaptic activation of the CA1 region occurred regularly in the drug-free rat while CA1 population spikes were rarely seen in the anaesthetized animal. The latency of the CA1 population spike was shortest at the fimbrial side and increased gradually towards the subicular side. In the dentate gyrus atropine increased the amplitude of the population spike. We suggest that atropine may interfere with the septo-hippocampal feed-forward inhibition, and urethane may decrease the effectiveness of the perforant path-granule cell synapse, as well as the intrahippocampal excitatory circuit.

Animals

Spatial distribution of twitch and tonic fibres in a snake muscle one myofibre thick.

The spatial distribution of twitch and tonic fibres in a snake muscle one myofibre thick (ventral costocutaneous) has been investigated. It was found that small groups of like fibres were favoured at the expense of larger groups when compared with sequences generated by a computer in which fibres were distributed randomly. The number of times that like fibres occurred next to one another was used as another measure of their spatial distribution. The number of adjacencies of like fibres was less than the expected number of adjacencies determined both by random sequences and by probability theory. The expected number of adjacencies determined by means of random sequences and a priori probability theory were almost identical. This dispersion of like fibres may reflect processes that occur during muscle development and may have functional implications.

Animals

Spatial distribution of rat fungiform papillae.

The objective of this study was to determine the spatial distribution of fungiform papillae on the rat's tongue. Since each fungiform papilla in the rat has a single taste bud, the spatial distribution of fungiform papillae is equivalent to the location of taste buds on the anterior tongue. A mean total number of 187 fungiform papillae per tongue were found which were about equally divided between the two lateral halves of the tongue. Over 50% of the total number of fungiform papillae were located on the tongue tip for an average density of 3.4 papillae/mm2,while the dorsal surface of the tongue had an average density of 1.3 papillae/mm2 of tongue surface. Papillae were absent on the dorsal midline, but a paracentral line of papillae running from anterior to posterior was a consistent finding. Though not identical, the distribution of papillae was essentially the same on different tongues. The functional significance of the papilla distribution is not understood, but electrophysiological experiments show evidence of neural interaction of papillae which are clustered together. The distribution of papillae and the distribution of nerve fibers which innervate them must be evaluated together in order to appreciate the significance of the distribution of fungiform papillae and their associated taste buds.

Animals

Spatial distribution of late potentials assessed by signal-averaged body surface mapping.

In order to evaluate the spatial location of late potentials (LPs), we designed a new system for the body surface mapping of signal-averaged, filtered ECG using 45 thoracic unipolar leads (5 X 9 array). Signals from patients with old myocardial infarction (MI, N = 8), arrhythmogenic right ventricular dysplasia (N = 1) and dilated cardiomyopathy (N = 2) were amplified and passed through a digital bandpass filter (60-300Hz). Departure maps, LP isopotential maps, and LP30 area maps were generated and superimposed. The LP30 duration was determined as the section between the filtered QRS endpoints and points 30 msec before. Isopotential maps of the LPs showed distinct positive and negative regions. In 8 cases with MI, the extreme was related to the zones indicated by departure maps, and LP30 area maps also corresponded to the departure areas. Most importantly, the spatial distribution for the LP30 area map was different for each type of disease. In conclusion, body surface LP isopotential maps and LP30 area maps may provide useful information concerning the spatial distribution of LPs.

Arrhythmias, Cardiac

Postnatal development of cat hind limb motoneurons. I: Changes in length, branching structure, and spatial distribution of dendrites of cat triceps surae motoneurons.

The postnatal development of length, branching structure, and spatial distribution of dendrites of triceps surae motoneurons, intracellularly stained with horseradish peroxidase, was studied from birth up to 44-46 days of postnatal (d.p.n.) age in kittens and compared with corresponding data from adult cats. The number of dendrites of a triceps surae motoneuron was about 12, and the arborization of each dendrite generated an average of 12-15 terminal branches. There was no net change in the number of dendrites of a neuron or in the degree of branching of the dendrites despite the occurrence of both a transient remodeling of the dendritic branching structure and changes of the spatial distribution of the dendritic branches during postnatal development. The perisomatic territory in the transverse plane occupied by the dendritic branches of a motoneuron increased in parallel with the overall growth of the spinal cord. Thus, the relative size of the dendritic territory in this plane was kept almost constant, whereas dendritic branches projecting in the rostrocaudal direction grew much faster than the spinal cord and also became more numerous. At birth the rostro-caudal dendritic span of individual motoneurons bridged 1:6 to 1:5 of the L7 spinal cord segment length; this figure was 1:3 at 22-24 d.p.n. Hence, in this direction, the growing dendritic branches invaded novel dendritic territories. The change in dendritic branch length from birth to 6 weeks of age corresponded to an average growth rate of 2 to 4 microns per dendritic branch and day, which implies that the total increase in length of the dendrites of a neuron could amount to 1 mm/day. The increase in branch length did not occur in a uniform or random manner; instead, it followed a spatiotemporal pattern with three phases: From birth to 22-24 d.p.n., growth was particularly prominent in greater than or equal to 3rd order preterminal and 2nd through 6th order terminal branches. From 22-24 to 44-46 d.p.n., a large increase in branch length confined to terminal branches of greater than or equal to 3rd branch orders was observed. As indicated by topological analysis, this length increase was probably due in part to a resorption of peripheral dendritic branches during this stage of development. From 44-46 d.p.n. to maturity, the increase of dendritic branch length was restricted to preterminal branches of low (less than or equal to 4th) branch order.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Cyclic GMP-activated channels of salamander retinal rods: spatial distribution and variation of responsiveness.

1. Patch-clamp methods were used to investigate the areal density and spatial location of cyclic GMP-activated channels in the surface membrane of salamander rod outer segments. 2. The density of active channels (i.e. channels able to respond to cyclic GMP) in patches excised from outer segments was determined from the number of active channels, N, and the membrane area, A. N was estimated from the current induced by a saturating concentration of cyclic GMP, while A was estimated from the electrical capacitance of the patch. 3. In patches excised from forty-one isolated outer segments prepared in the light the active channel density varied over a remarkable range: 0.34-629 microns-2, with a mean of 166 microns-2. Density was not correlated with patch area in this or any of the conditions studied. 4. The spatial distribution of open channels on the outer segment of a transducing rod was measured by recording the local dark current at various positions with a loose-patch electrode. The apparent density of open channels varied by only about +/- 50% around the circumference of the outer segment and up and down its length. This indicates that the wide range of densities in excised patches did not result from sampling a non-uniform spatial distribution of channels. 5. Patches excised from sixteen dark-adapted whole cells with healthy appearances and saturating light responses of normal size had active channel densities of 1.1-200 microns-2, with a mean of 60 microns-2. Patches from twenty light-adapted whole cells had similar densities. Many densities from the whole cells were much lower than expected. This, and the wide variation in densities, suggests that obtaining a patch often lowered the density of active channels. The number of channels in a patch was quite stable from 1 s to 30 min after excision, ruling out progressive denaturation or adsorption of channels to the glass as a cause for this effect. 6. The mean active channel density in patches excised from whole cells was lower with calcium present in the external solution than with calcium absent (80 vs. 152 microns-2, n = 36 and 30 respectively). 7. We conclude that copies of the channel protein were present at a density of at least 650 microns-2 in the surface membrane of the outer segment and that the distribution of channels was fairly uniform on a 1 micron scale.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Ocular

Spatial distribution of connexin43, the major cardiac gap junction protein, in the developing and adult rat heart.

The developmental appearance and spatial distribution pattern of gap junctions were studied in prenatal and adult rat hearts. Gap junctions were visualized immunohistochemically with an antibody raised against a unique cytoplasmic epitope of connexin43, and the spatial distribution pattern was determined by three-dimensional reconstruction. The results demonstrate that from embryonic day 13 onward, connexin43 becomes detectable immunohistochemically in the myocardium of atria and ventricles. No expression is initially detectable in the myocardium of the sinus venosus, the sinoatrial node, the posterior wall of the atrium and pulmonary veins, the interatrial septum, the atrioventricular canal, including atrioventricular node and bundle, the interventricular septum, and the outflow tract. The developmental increase in the density of gap junctions in atria and ventricles of prenatal hearts correlates well with the reported developmental increase in conduction velocity. Whereas connexin43 becomes expressed in the derivatives of the sinus venosus (except for the sinoatrial node) and in the subepicardial layer of the ventricular free wall shortly before birth, it remains undetectable in the atrioventricular node and bundle and the proximal part of the ventricular conduction tissue, even in the adult heart. The apparent absence of an abundant expression of connexin43 at a location with a supposedly high conduction velocity (i.e., the atrioventricular bundle and bundle branches) is unexpected. These observations were confirmed in studies of the adult mouse heart, which showed, in addition, that connexin32 is not expressed in any part of the heart.

Aging

Spatial distribution of nociceptive processing in the rat spinal cord.

1. Quantitative 2-deoxyglucose (2-DG) experiments were undertaken to determine the spatial distribution of nociceptive responses in the rat spinal cord. Twenty unanesthetized, paralyzed rats with T2 transected spinal cords were divided into groups (n = 4) and stimulated with non-noxious (35 degrees C) or graded noxious temperatures (45 degrees, 47 degrees, 48 degrees, and 49 degrees C). Stimulation was delivered by cyclical immersion of one hind paw in a temperature-controlled water bath. 2. When stimulation began, 50 microCi of 2-DG was injected into the rat, and timed sequential blood samples were drawn to monitor plasma glucose and 2-DG levels. On termination of stimulation, spinal cords were removed, sectioned, and prepared for autoradiography. Local rates of spinal cord metabolism were obtained by microcomputer analysis of autoradiographs. 3. Nociceptive stimulation produced increases in glucose utilization in some of the grey matter laminae previously implicated in nociceptive processing. Within the nociceptive range, 49 degrees and 48 degrees C intensities elicited significantly greater responses than did 45 degrees C stimulation. 4. The rostrocaudal spatial distribution of nociceptive responses was most extensive within laminae V-VI with stimulus-evoked metabolic activity extending 9 mm from L2-L5. Similarly, metabolic increases occurred over 7 mm within lamina VII. In contrast, metabolic activity within the upper dorsal horn (laminae I-IV) extended only 3 mm and was limited to L4. Metabolic patterns within laminae VIII-IX sharply differed from those within other laminae in that no increases occurred within L4, although regions of L3 and L5 were responsive to stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

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

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

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

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

The relative spatial distribution of CFU-S in the mouse spleen.

Mouse spleens were separated into white and red pulp fractions and into axial and marginal fractions for analysis of the relative concentration of hemopoietic stem cells (CFU-S) with respect to their spatial distribution in the spleen. Of the total splenic CFU-S population, 80% was in the red pulp fraction. The CFU-S concentration in this fraction was 11 times higher than in the white pulp fraction, which contained lymphoid follicles, periarteriolar sheaths, surrounding marginal zones, and occasional fragments of red pulp areas. Within the red pulp, CFU-S were spatially distributed with high concentrations in the subcapsular regions and decreasing frequency toward the median intersept of the spleen, where the CFU-S frequency was about one-fifth that found in the subcapsular area. The data suggest that marginal zones contain relatively more CFU-S than the follicles themselves.

Animals