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Beta/A4 deposits and their relationship to senile plaques in Alzheimer's disease.

The density and spatial pattern of immunostained beta/A4 deposits and mature senile plaques (SP) stained by the Glees method were compared in Alzheimer's diseased brain. Thirty-seven percent of the variance in Glees SP density in a tissue could be explained by beta/A4. Both lesions were clustered with the beta/A4 clusters often larger than the Glees SP clusters. Beta/A4 and Glees SP cluster size were not correlated in a tissue. The size of Glees SP clusters was positively correlated with SP density but no correlation could be detected for beta/A4. Hence, the density and spatial pattern of beta/A4 deposits in most tissues did not predict the development of Glees SP.

Alzheimer Disease

Expression of the c-fms proto-oncogene and of the cytokine, CSF-1, during mouse embryogenesis.

The c-fms gene encodes the cell surface receptor of the colony-stimulating factor, CSF-1. CSF-1 has recently been shown to be expressed in the maternal uterine endometrium of pregnant mice. The ontogenetic and spatial patterns of expression of the murine proto-oncogene c-fms were analyzed in the developing mouse placenta by the technique of in situ hybridization. c-fms expression was not detected in fetally derived tissues until 9.5 days postcoitum (pc) when expression first appeared in the mural trophoblast giant cells. Expression persisted at high levels in trophoblast cells throughout gestation. In the mature placenta from 13.5 days pc on, c-fms was expressed chiefly in the spongiotrophoblast layer and, to a lesser extent, in the labyrinthine trophoblast. CSF-1 expression was first detectable in the uterine epithelium at 8.5 days pc which loosely correlated with the appearance at 7.5 days of c-fms in the decidual cells around the developing egg cylinder. The time course and spatial pattern of expression of these two genes suggest a functional role for the c-fms receptor and its ligand, CSF-1, in trophoblast development and differentiation.

Animals

The onset of decline in ischemic heart disease mortality in the United States.

Temporal and spatial patterns of the onset of the decline in ischemic heart disease mortality in the United States for each of the 48 contiguous US states and the District of Columbia are examined for the years 1955-1978 for age-sex-race-specific mortality. Mortality rates are derived from National Center for Health Statistics mortality data, and a polynomial interpolation is used to estimate intercensal population counts employing 1950, 1960, 1970, and 1980 US Census data. A quadratic regression equation is used to estimate the date of highest rate, which marks the beginning of the decline for each of the US states. The temporal distribution of the onset of the decline among men occurred primarily between 1960 and 1965. Among women, the onset of decline was more variable. Furthermore, strong and regular spatial patterns were seen among the groups examined and these impressions are supported by statistical analysis. California, Maryland, and the District of Columbia were early decliners in most groups studied, whereas states in the southeast were consistently among the last to experience the onset of decline. These patterns suggest the existence of an underlying phenomenon accounting for the spread or diffusion of the onset of decline in ischemic heart disease mortality.

Adult

Spatial firing patterns of hippocampal complex-spike cells in a fixed environment.

A TV/computer technique was used to simultaneously track a rat's position in a simple apparatus and record the firing of single hippocampal complex-spike neurons. The primary finding is that many of these neurons behave as "place cells," as first described by O'Keefe and Dostrovsky (1971) and O'Keefe (1976). Each place cell fires rapidly only when the rat is in a delimited portion of the apparatus (the cell's "firing field"). In agreement with O'Keefe (1976) and many other authors, we have seen that the firing of place cells is highly correlated with the animal's position and is remarkably independent of other aspects of the animal's behavioral state. Several properties of firing fields were characterized. Firing fields are stable over long time intervals (days) if the environment is constant. They come in several shapes when the animal is in a cylindrical apparatus; moreover, the set of field shapes is different when the animal is in a rectangular apparatus. It also seems that a single cell may have more than one field in a given apparatus. By collecting a sample of 40 place cells in a fixed environment, it has been possible to describe certain features of the place cell population, including the spatial distribution of fields within the apparatus, the average size of fields, and the "intensity" of fields (as measured by maximum firing rate). We also tested the hypothesis that the firing rate of each place cell signals the animal's distance from a point (the field center) so that a weighted average of the firing of the individual cells encodes the animal's position within the apparatus. The animal's position, calculated according to this "distance hypothesis," is systematically different from the animal's true position; this implies that the hypothesis in its simplest form is wrong.

Action Potentials

Computer-assisted interpretation of visual fields in glaucoma.

Visual field abnormality is an important diagnostic sign in glaucoma. Therefore, the presence or absence of visual field loss most often strongly influences diagnostic and therapeutic decisions in glaucoma management. Interpretation of visual field results is often difficult, however. Physiological variability of perimetric sensitivity values contributes to these difficulties. It has been our aim to develop improved computer-assisted methods for the recognition of early glaucomatous field loss. Our approach has therefore been to design techniques that are highly sensitive to small but significant departures from normality. We have investigated normal physiological variability in perimetric results and combined the obtained knowledge with pathophysiological models which are sensitive to the spatial patterns of field loss commonly seen in glaucoma. Thus, we have devised probability scores in order to take the complex physiological variability into account, and developed a hemifield analysis and an arcuate cluster analysis based on the normal anatomy of the retinal nerve fibre layer. A fundamental approach in the collection of normative data and the selection of glaucoma cases used in this project has been to select subjects using non-perimetric criteria (except for the removal of large field defects). Our objective here was to reduce bias from pre-conceived ideas of visual fields. This approach was used for (1) empirical studies on physiological variability, (2) development of analysis methods, and (3) evaluation of such methods. Glaucoma patients were selected based on evaluations of optic disc appearance. Normal subjects were never eliminated on the basis of perimetric results alone. The new methods developed in these studies have significantly improved discrimination between normal and glaucomatous field results, as compared with previously available techniques. Our results indicated that the usage of probability scores was the main source of this improvement, and that the location of observed field abnormalities and spatial modelling were other important factors. Candidate methods which did not properly combine spatial and normative analyses resulted in false positive defects in the mid-periphery and/or underestimated paracentral glaucomatous field defects. Similar approaches based on classification of visual field results in terms of significances, and on recognition of specific spatial patterns of field loss could be used for other groups of diseases having visual field abnormality as an important diagnostic sign.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Distinct spatial transcriptomic patterns of substantia Nigra in Parkinson disease and Parkinsonian subtype of multiple system atrophy.

To investigate transcriptomic signatures of Parkinson's disease (PD) and the Parkinsonian subtype of Multiple System Atrophy (MSA-P) in substantia nigra pars compacta (SNpc), we conducted transcriptome analysis using in-situ hybridization on paraffin-embedded SNpc tissues from post-mortem brains. The study included 2 MSA-P patients, 2 PD patients, and 2 healthy controls (HC), with 12 regions of interest (ROIs) selected from the dorsal to ventral and medial to lateral aspects of the SNpc. A total of 72 ROIs from 6 participants were analyzed, and differentially expressed genes (DEGs) were identified by comparing MSA-P, PD and HC groups. The MSA-P group showed 88 upregulated DEGs and 326 downregulated DEGs (adjusted &#x1d45d;<0.05) compared to HC. The downregulated DEGs were significantly enriched in pathways related to ribosomal translation, immune processes, mitochondrial function, and autophagy. Notably, the dorsomedial quadrant was uniquely linked to antigen presentation, while other quadrants showed downregulation of protein synthesis. The PD group exhibited 165 upregulated DEGs and 350 downregulated DEGs (adjusted &#x1d45d;<0.05) compared to HC, with downregulated DEGs associated with ribosomal translation, mitochondrial function, and the ubiquitin-proteasome system. In both MSA-P and PD, the upregulated DEGs were not associated with any pathways or biological process in gene enrichment analysis. In network propagation analysis, amyloid precursor protein was the most significant network hub among DEGs in both MSA-P and PD. Comparing the transcriptomic signatures of SNpc between MSA-P and PD, we found immune/inflammation, mitochondrial function and neural signaling related genes were significantly downregulated in MSA-P compared to PD. Overall, the transcriptomic signature of the SNpc in MSA-P and PD revealed overlapping but distinct features, including alterations in protein synthesis, immune processes, mitochondrial function, and protein degradation systems. Future studies with larger cohorts and functional validation are needed to further elucidate these findings.

Humans

Auxin regulates the promoter of the root-inducing rolB gene of Agrobacterium rhizogenes in transgenic tobacco.

The regulation in tobacco of the rolB and rolC promoters of Agrobacterium rhizogenes pRi 1855 TL-DNA was studied by using the beta-glucuronidase (GUS) reporter system in transgenic plants. A 20- to 100-fold increase of GUS activity was selectively induced by auxin in rolB-GUS transformed mesophyll protoplasts, whereas this auxin-dependent increase was only 5-fold in rolC-GUS protoplasts. Moreover, both gene fusions exhibited similar tissue-specific expression in aerial parts but different patterns in roots. The spatial pattern of rolB-GUS expression could be strongly modified by the addition of exogenous auxin, further suggesting that auxin plays a central role in the regulation of the rolB promoter in tobacco. The tissue-specific and auxin-dependent regulation of the rolB promoter is discussed in relation to the effects of the rolB gene on rhizogenesis and on cellular responses to auxin.

Cloning, Molecular

Pattern of spatial distribution in Drosophila melanogaster.

The effect of temperature and sex on spatial distribution of Drosophila melanogaster adults was studied in a specially designed apparatus. It was observed that individuals tend to aggregate in sections of the sphere independently of sex and temperature. Nevertheless, decrease in temperature increase aggregation. The mobility of both males and females indicates a negative geotactic tendency.

Animals

Two-dimensional gel electrophoresis of human lens epithelium: a study of spatial protein patterns and aging.

The polypeptides in portions of human lens epithelium from individuals of various ages were resolved by two-dimensional (2D) gel electrophoresis. The epithelium was divided into a central area of 12.5 mm2, a surrounding area of 50.2 mm2, and an area which was outside of this region. The proteins were solubilized in urea and run on gels to determine if differences existed in the major polypeptides of the lens epithelium with regard to position in the lens as well as if differences might occur with age. The patterns obtained were remarkably similar in regions of the epithelium examined. The results also demonstrated that the composition of the major polypeptides were not substantially altered in the adult epithelium with age. Two-dimensional gels of proteins from a 3-month-old specimen prepared in a manner similar to that used during extracapsular cataract extraction were also similar to the other samples; however, this sample contained slightly increased staining of proteins greater than 30 kD.

Adult

Effects of contrast substitutions upon motion detection in spatially random patterns.

We report the effects of contrast changes between frames in a random-square kinematogram. When the contrasts of both frames are too low to permit directional discrimination, increasing the contrast of either the first or the second frame alone makes directional discrimination possible. However, at suprathreshold contrasts for motion detection, increasing the contrast of either the first or the second frame alone makes discrimination more difficult. We conclude that motion detection is a special case of contrast discrimination, in agreement with the Reichardt model of motion detection.

Contrast Sensitivity