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Differentiation, cell sorting and proportion regulation in the slug stage of Dictyostelium discoideum.

Recent experimental work suggests that under normal conditions cell sorting plays an important part in maintaining and re-establishing the axial pattern of cell types in the slug stage of the cellular slime mold Dictyostelium discoideum. Following removal of the anterior zone of the slug, anterior-like cells that are normally distributed throughout the posterior of the slug rapidly migrate to the anterior end of the transected slug, and new anterior-like cells appear in the posterior portion. These results provide evidence that the direct linkage between spatial location and differentiation hypothesized in positional information models of spatial pattern formation is not universal. In this paper we develop and analyze a class of mathematical models of the slug in which cell determination can be less rigidly tied to spatial location, and which involve chemotactic cell sorting to re-establish and maintain the spatial pattern of cell types. We show that these models can reproduce the qualitative aspects of the experimental observations and that sorting takes place on the observed time scale when reasonable values of the parameters are used.

Cell Differentiation

Visual discrimination of target displacement remains after damage to the striate cortex in humans.

Damage to the striate cortex usually causes blindness in those regions of the visual field which map to the area of neural damage. Nonetheless, there are reports that some patients with such damage can localize and perform certain visual discriminations between light stimuli presented within the 'blind' area of the visual field. Experiments on animals with different brain areas ablated suggest that visual function is served by two principal projection pathways from the retina. That to the striate cortex is primarily responsible for fine discrimination between stimulus parameters such as colour and spatial pattern, whereas that to the superior colliculus in the midbrain is responsible for visual localization of stimuli. The residual visual functions in patients with cortical damage are usually attributed to the non-striate retinal projection to the superior colliculus. We now present measurements of spatial discrimination in two observers with large visual field defects (scotomata) caused by damage to the striate cortical region. Both exhibit a near normal ability to discriminate displacements of targets when two lights are flashed sequentially in their defective visual field, but they are unable to discriminate spatial pattern or size. We argue that these results are consistent with the 'two visual systems' interpretation of ablation studies on non-human species.

Adult

Changes in the cortical map of the hand following postnatal median nerve injury in monkeys: modification of somatotopic aggregates.

Median nerves to the hands of 8-15-d-old marmoset monkeys were transected and precluded from regeneration by ligation. Following periods of 0.4-1.5 years, features of organization in the cortical area 3b hand map were assessed neurophysiologically, and compared to features in normally reared monkeys. Cortical features in monkeys with both histories were similar in certain respects. (1) Receptive field organization was similar in terms of tactile thresholds and receptive field size, continuity, and glabrous-hairy specificity. (2) Somatotopic organization was similar in terms of the continuity of the glabrous representation, and progressions of receptive field shifts across some parts of the hand map. (3) Finally, the overall size of the hand map did not change. In contrast, other cortical features clearly differed following these developmental histories. (1) Neurons at virtually all recording sites in normal hand maps responded to light mechanical stimulation, whereas, following injury, neurons at about 8% of the recording sites responded only to high-intensity stimuli. (2) Somatotopic organization differed in terms of the presence or absence of the representation of skin autonomously innervated by the median nerve, the number and continuity of representations of hairy skin, and the spatial interfacing of representations. (3) Finally, there were differences in the areas and widths of representations of parts of the hand. The overall impression is that there is a correspondence between the cortical features that changed most after injury, and the features that varied most in individual normal monkeys: in both circumstances the most variable features involved properties of spatial patterning across large aggregates of neurons as reflected by the size, shape, continuity, and interfacing of representations. A hypothesis is proposed that suggests that the cortical hand map normally consists of a number of representations that are capable of developing and surviving somewhat autonomously of each other. The features of spatial patterning in the mosaiclike map of these representations are influenced by postnatal availability of inputs from intact hand nerves.

Animals

Immunocytochemical study of S-100 positive glial cells in the brainstem and spinal cord of the rat embryo.

A light and electronmicroscopic immunocytochemical study of the glial cells in the brainstem and spinal cord of the 18th day rat embryo was performed using an anti-S-100 protein antiserum. Only the radial glia and the free immature glial cells are S-100 immunoreactive. Neurons are devoid of S-100 immunoreactivity. The radial glia form two paramedial plates and a great number of lateral plates, uniformly spaced along the ventral portion of the brainstem from the mesencephalon to the medulla. The S-100 protein was also detected in the perivascular membranes and glial limitans. Embryonic glia adopt a highly organized spatial pattern in the brainstem that could set the structural basis for an organized assembly of the developing nervous tissue. The use of the S-100 protein as a glial marker in the embryonic rat brain proved to be of great value. Antibodies to S-100 protein allow the demonstration of immature glial cells and a highly organized spatial pattern in the brainstem and spinal cord of the rat embryo.

Animals

Responses of spatial mechanisms can explain hyperacuity.

A recently developed nonlinear mathematical model for spatial pattern discrimination, which is formally analogous to line element models in color vision, was applied to a variety of hyperacuity tasks. The computed results are in reasonable agreement with data on vernier acuity as a function of line length and separation, chevron acuity, periodic vernier acuity using sinusoidal lines, three line bisection acuity, vernier acuity using cosine gratings, and spatial interference with vernier acuity. In agreement with model predictions, data are presented showing that vernier acuity improves as a power function of contrast. It is concluded that the nonlinear, contrast dependent responses of visual mechanisms tuned for size and orientation can explain a wide range of hyperacuity and other spatial pattern discrimination tasks.

Discrimination, Psychological

Two simple methods of spatial analysis and their applications in location-oriented health services research.

This paper illustrates the usefulness of cartographic and centrographic methods in examining the locational characteristics of health care resources, such as specialist physicians' offices. Cartographic analysis involving map comparisons not only describes the nature of particular spatial patterns, but it also suggests relevant hypotheses on the basis of observed locational relationships among the mapped phenomena. Centrographic analysis generally substantiates the findings of simple map analysis by providing certain objective quantitative measures regarding the basic characteristics of a point distribution; additionally, it generates a graphic summary, the Standard Deviational Ellipse (SDE), which offers a convenient means for direct comparison of multiple spatial patterns. The essentially complementary nature of the two methods is highlighted, and it is concluded that they are most useful when used in conjunction with one another.

Catchment Area, Health

'Clustering'--real or apparent? Probability maps of childhood cancer in the West Midlands Health Authority region.

The West Midlands Regional Children's Tumour Registry collects detailed information on all cases of childhood cancer in the West Midlands Health Authority Region (WMHAR). The distribution by electoral ward of all cases diagnosed in the WMHAR between 1980 and 1984 has been determined. Analysis has also been performed for leukaemias/non-Hodgkin's lymphomas alone. We suggest that this latter grouping should be universally employed, owing to the difficulty of accurately separating out cases of leukaemia. Both spatial analyses showed several wards with significantly excessive rates on the basis of their cumulative Poison probability. Observed/expected ratios of 3-35 were seen for cases in significant wards, which are similar to the ratios seen in analysis of incidence around nuclear installations. However, further detailed consideration of these individual significance levels in the light of the number of statistically significant wards which would occur by chance alone, due to the multiple use of the test, accounted completely for the number of wards obtained in each of the groups considered. Thus, apparent 'clustering' of cases could be mere statistical artefact. In the WMHAR, therefore, using the technique of probability mapping, no true spatial pattern of incidence was found, other than that which would occur by chance alone. This, in a large area without nuclear installations and an even mix of rural and industrialised regions, could be seen as control data for those studies which have considered cases of childhood leukaemia around nuclear facilities, where the observation of single point clusters associated with suspected sites restricts assessments of spatial pattern in the rest of the area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Directional sensitivity of sound-pressure levels in the human ear canal.

Changes in sound pressures measured in the ear canal are reported for broadband sound sources positioned at various locations about the subject. These location-dependent pressures are one source of acoustical cues for sound localization by human listeners. Sound source locations were tested with horizontal and vertical resolution of 10 degrees. Sound levels were measured with miniature microphones placed inside the two ear canals. Although the measured amplitude spectra varied with the position of the microphone in the ear canal, it is shown that the directional sensitivity at any particular frequency of the broadband stimulus is independent of microphone position anywhere within the ear canal. At any given frequency, the distribution of sound pressures as a function of sound source location formed a characteristic spatial pattern comprising one or two discrete areas from which sound sources produced maximum levels in the ear canal. The locations of these discrete areas varied in horizontal and vertical location according to sound frequency. For example, around 8 kHz, two areas of maximum sensitivity typically were found that were located laterally and were separated from each other vertically, whereas, around 12 kHz, two such areas were found located on the horizontal plane and separated horizontally. The spatial patterns of sound levels were remarkably similar among different subjects, although some frequency scaling was required to accommodate for differences in the subjects' physical sizes. Interaural differences in sound-pressure level (ILDs) at frequencies below about 8 kHz tended to increase monotonically with increasing distance of the sound source from the frontal midline and tended to be relatively constant as a function of vertical source location. At higher frequencies, however, ILDs varied both with the horizontal and with the vertical location of the sound source. At some frequencies, asymmetries between the left and right ears in a given subject resulted in substantial ILDs even for midline sound sources. These results indicate the types of horizontal and vertical spatial information that are available from sound level cues over various ranges of frequency and, within a small subject population, indicate the nature of intersubject variability.

Acoustic Stimulation

High-level expression of a sweet potato sporamin gene promoter: beta-glucuronidase (GUS) fusion gene in the stems of transgenic tobacco plants is conferred by multiple cell type-specific regulatory elements.

Genes coding for sporamin, the most abundant protein of the tuberous root of the sweet potato, are expressed at a high levels in the stems of plantlets cultured axenically on sucrose-containing medium. Their expression is also induced in leaf-petiole explants by high concentrations of sucrose. A fusion gene comprising of the 1 kb 5' upstream region of the gSPO-A1 gene coding for the A-type sporamin and the coding sequence of bacterial beta-glucuronidase (GUS) was introduced into the tobacco genome by Agrobacterium-mediated transformation. Transgenic tobacco plants cultured axenically on sucrose-containing medium expressed GUS activity predominantly in their stems. Histochemical examination of GUS activity using a chromogenic substrate showed a distinct spatial pattern of GUS staining in the stem. Strong GUS activity was detected in the internal phloem of the vascular system and at the node, especially at the base of the axillary bud. Relatively weaker GUS activity was also detected in pith parenchyma. A 5' deletion of the promoter to nucleotide -305, relative to the transcription start site, did not alter significantly the level of GUS activity or the spatial pattern of GUS staining in the stem. However, further deletions to -237 and -192 resulted in a decrease in the level of GUS activity in the stem that occurred simultaneously with the loss of GUS staining in both the internal phloem and at the base of the axillary bud. However, plants with these deletion constructs still exhibited the predominant expression pattern of GUS activity in the stem and GUS staining in the pith parenchyma cells. Deletion to -94 completely abolished the expression of GUS activity. These results indicate that a sequence between -305 and -237 contains a cis-regulatory element(s) that is required for expression of the GUS reporter gene in both the internal phloem and at the base of the axillary bud, while a sequence between -192 and -94 contains a cis-acting element(s) that is required for expression in pith parenchyma cells.

Base Sequence

An examination of the intra-SMSA distribution of carbon monoxide exposure.

Although fixed-site monitoring data have been used to estimate the spatial pattern of human exposure, the intra-urban distribution of actual exposure has not been documented. This paper used the data collected during the Environmental Protection Agency's (EPA) field investigation of personal exposure to carbon monoxide (CO) to investigate the nature of the distribution of CO with respect to residential location in the Washington, D.C. SMSA. Dot-distribution maps and analysis of variance were used to document the spatial pattern of individual-level in-home CO concentrations. The results show sampled individuals living in the SMSA center are exposed to statistically significantly higher levels of CO than are those living in the suburbs. The most important implications of this work are for exposure modeling. Further investigation is needed to determine whether incorporation of a geographic component will improve exposure prediction.

Carbon Monoxide

Plasticity in the nervous system of adult hydra. I. The position-dependent expression of FMRFamide-like immunoreactivity.

The plasticity of nerve cells expressing the neuropeptide FMRFamide was examined in adult hydra. Using a whole-mount technique with indirect immunofluorescence, the spatial pattern of neurons showing FMRFamide-like immunoreactivity (FLI) was visualized. These neurons were located in the tentacles, hypostome, and peduncle, but not in the body column or basal disc. Since every neuron in the nerve net is continuously displaced toward an extremity and eventually sloughed, the constant pattern of FLI+ neurons could arise in one of two ways. When displaced into the appropriate region, FLI- neurons are converted to FLI+ neurons, or FLI+ neurons arise by differentiation from interstitial cells. To distinguish between these two possibilities, interstitial cells, the multipotent precursors of the nerve cells, were eliminated by treatment with hydroxyurea or nitrogen mustard. Following head, or foot and peduncle, removal from these animals, the missing structures regenerated. The spatial pattern of FLI+ neurons reappeared in the newly regenerated head or peduncle. This shows FLI- neurons in the body column were converted to FLI+ when their position was changed to the head or the peduncle. When the peduncle was grafted into the body column, it was converted to basal disc or body column tissue, and FLI disappeared. The appearance and loss of FLI was always position dependent. These results indicate that the neurons in the mature nerve net can change their neuropeptide phenotype in response to changes in their position.

Animals

Effects of premature excitation and tachycardia on the spatial distribution of refractoriness and propagation of excitation in a computer model.

In this study, the spatial pattern of refractoriness and its effects on propagation of excitation during premature responses and tachycardia have been investigated using a computer model. The model simulated propagation, cycle length-dependent refractoriness, and slow propagation during the relative refractory period. Findings showed slow propagation near the origin of premature responses resulting in longer cycle lengths distal to the slowing. The nonuniform cycle lengths terminated by a premature response also represented the onset of the subsequent cycle, so the pattern of refractoriness was altered after both the premature and following cycle. This occurred even though cycle length affected only the immediately following refractory period in the model. The effect of nonuniform cycle lengths during a premature response on refractory periods after the subsequent response occurred with all cycle lengths of the later response. When the cycle length of that and further responses was sufficiently shortened to result in slowed propagation, changing spatial patterns of refractoriness and propagation occurred. The findings are evidence that responses with slow propagation during incomplete recovery of excitability can affect conduction velocity and refractoriness during multiple subsequent cycles. These effects are likely to occur in the heart but are modified by features such as sustained effects of cycle length on refractoriness, anisotropy, and electrotonic interactions.

Computer Simulation

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

To investigate the effects of colour upon motion detection, the short-range motion displacement limit (Dmax) was determined using two-frame kinematograms in which the two classes of square comprising the pattern differed both in luminance and in colour. In the second motion frame, the squares retained either the same luminance and colour as in the first frame, or they changed their colour while retaining their luminance. The experiment was repeated at three different viewing distances to investigate the effects of element angular size. Two of the four observers had normal trichromatic colour vision; the other two were dichromats (protanopes). For the trichromatic observers, the change of colour between frames made motion displacements harder to detect when the squares were large, but not when they were small. The result accords with an input of colour into motion detection at low but not at high spatial frequencies. For the dichromats, the colour change had little effect at any of the viewing distances, thus ruling out the possibility that the deleterious effects of colour substitution upon motion detection in trichromats was due to chromatic aberration or other artefacts.

Color Perception

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