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EMAP and EMAGE: a framework for understanding spatially organized data.

The Edinburgh MouseAtlas Project (EMAP) is a time-series of mouse-embryo volumetric models. The models provide a context-free spatial framework onto which structural interpretations and experimental data can be mapped. This enables collation, comparison, and query of complex spatial patterns with respect to each other and with respect to known or hypothesized structure. The atlas also includes a time-dependent anatomical ontology and mapping between the ontology and the spatial models in the form of delineated anatomical regions or tissues. The models provide a natural, graphical context for browsing and visualizing complex data. The Edinburgh Mouse Atlas Gene-Expression Database (EMAGE) is one of the first applications of the EMAP framework and provides a spatially mapped gene-expression database with associated tools for data mapping, submission, and query. In this article, we describe the underlying principles of the Atlas and the gene-expression database, and provide a practical introduction to the use of the EMAP and EMAGE tools, including use of new techniques for whole body gene-expression data capture and mapping.

Animals↗

Characterization of hypoxia induced gene 1: expression during rat central nervous system maturation and evidence of antisense RNA expression.

Although recent studies have provided a detailed understanding of cellular interactions occurring during the development of the CNS, little is known about the molecular signals which during the peri and postnatal periods ensure its maturation and functionality. Using the mammalian spinal cord as a model, we have designed experiments to examine the main changes in gene expression occurring during this critical transition. In this paper we describe the cloning and characterization of the rat hypoxia induced gene-1 (Hig-1), its expression pattern during spinal cord maturation and in situ localization of its mRNA. We show an increase in Hig-1 expression between P1 and P15 in the spinal cord and a differential spatial pattern. In the P1 spinal cord we observed preferential expression in regions of dorsal laminae II and III and laminae IX ventrally; while in P8, the distribution was more widespread and overall expression was increased. Hig-1 is also widely expressed in the brain. Results of in situ hybridization experiments, as well as particular features concerning ESTs, led us to propose the expression of an antisense mRNA. Primer-specific RTPCR demonstrates the presence of this aHig-1 transcript whose structure has not yet been characterized. The high homology between putative rHig-1 protein and human- and murine-predicted sequences, as well as its characteristic expression in the Central Nervous System, are indicative of a specific role which could be related to apoptosis signaling during postnatal maturation.

Amino Acid Sequence↗

Age effects on random-array letter cancellation tests.

OBJECTIVE: This study was designed to determine whether young and older adults differ in the spatial pattern of omission errors on random-array letter cancellation tasks. BACKGROUND: Aging is associated with declines in the speed or efficiency of visual information processing. It is unclear whether the spatial characteristics of visual exploration also change with aging. METHOD: Thirty young adults and 30 older adults each completed 21 random-array cancellation forms. Forms were systematically varied in paper size, target-to-distractor ratio, stimulus density, and target number. RESULTS: The spatial distribution of errors was not random for older adults. Younger adults expressed a trend toward nonrandom error location, but the spatial distribution did not differ between groups. There was also a strong trend toward more errors per subject in the older group. Older subjects required more time for task completion. CONCLUSIONS: The findings are consistent with a generalized age-related decline in the speed or efficiency of visual search, but the spatial properties of directed attention do not appear to be different between young and older adults.

Adolescent↗

The Roepke Lecture in Economic Geography: urban restructuring from a demographic perspective.

"The central argument of this paper is that recent research has overemphasized the notions of urban restructuring and undervalued the role of spatial demographics in understanding urban and [regional] spatial patterns. The paper examines the notions embedded in urban restructuring and suggests that a focus on several elements of demographic processes is an equally important component of understanding urban and [regional] spatial structure. A specific discussion of the Los Angeles region indicates that there is a high level of complexity in social-spatial change. Social-spatial change is not simply explained by reference to an unspecified urban restructuring."

Americas↗

Analysis of the propagation of disinhibition-induced after-discharges along the guinea-pig hippocampal slice in vitro.

1. A model has been proposed of picrotoxin-induced hippocampal in vitro after-discharges; it depends critically upon alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the recurrent excitatory connections between pyramidal neurones, and upon the ability of pyramidal neurones to generate bursts at about 10 Hz when their dendrites are sufficiently depolarized. 2. We study here the question of whether this model can account for spatial--as well as temporal--aspects of after-discharges in guinea-pig hippocampal slices. For example, can the model explain the propagation along a transverse slice of the initial burst and the secondary bursts at about the same velocity, approximately 0.10-0.20 m s-1? Under what conditions might the secondary bursts exhibit a different spatial pattern to the initial burst, as we now show can occur in longitudinal slices? To examine these questions, we increased the number of cells in our model from 100 to 8000 (in a 20 x 400 array), arranging the excitatory synaptic connections in a spatially restricted fashion, with an average extent of 1.0 mm (as suggested experimentally). 3. Our model suggests that both AMPA and NMDA receptors contribute to the propagation pattern and velocity of the initial and the secondary bursts in an after-discharge. 4. When unitary AMPA and NMDA conductances are in the range where the primary burst lasts for 100-200 ms, and there are three or four secondary bursts, then both primary and secondary bursts propagate near to the experimentally observed velocity for transverse slices. In the model, however, secondary bursts propagate at somewhat slower velocities than the initial burst. 5. The mechanisms of propagation are different for the initial and for the secondary bursts: propagation of the primary burst depends upon the initiation of electrogenesis in 'resting' dendrites by AMPA and NMDA inputs that are rapidly increasing in time. Propagation of secondary bursts depends upon the timing of calcium spikes in depolarized dendrites with slowly varying NMDA inputs; the timing of calcium spikes can be influenced by a 'wave' of AMPA input, but calcium spikes--we predict--should occur even without the AMPA input, once the after-discharge has been initiated. The blockade of firing in an intermediate region of the disinhibited slice is predicted to have different effects on the primary burst and on secondary bursts distal to the region of blockade.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Preproenkephalin mRNA expression in the developing and adult rat brain.

[Met5]-Enkephalin is derived from the protein precursor, proenkephalin A, which in turn is encoded by the preproenkephalin (PPE) gene. [Met5]-Enkephalin is not only a putative neuromodulatory substance, but also serves as a growth factor (= opioid growth factor, OGF). OGF exerts an inhibitory influence on the developing nervous system and is especially targeted to cell proliferative and differentiative events. This study examined the relationship of PPE mRNA expression to late prenatal and postnatal rat brain development. Northern blot analysis of the whole brain and cerebellum showed that message is present in the fetal nervous system on prenatal day 15 (the earliest timepoint examined), is expressed at relatively similar levels within each tissue during the first 2 postnatal weeks, and reaches adult levels by the beginning of the 3rd postnatal week. In situ hybridization methodology revealed that PPE mRNA was prominent in areas associated with cell generation. Message was found in sites of primary (i.e., ventricular region) and secondary (e.g., external germinal layer of the cerebellum) cellular replication, as well as in discrete foci of cell proliferation (e.g., medullary layer of the cerebellum). PPE mRNA was also present for varying periods of time in postmitotic cells. During development, a number of patterns (decrease, increase, and no perceptible change) of PPE mRNA could be detected in relationship to the fetal/neonatal period. Given the strong evidence (e.g., regulation of cell proliferation and differentiation, temporal and spatial patterns of peptide and zeta opioid receptor) that enkephalin immunoreactivity is associated with proliferating and differentiating neurons and glia, these results suggest that the source of [Met5]-enkephalin is both autocrine and paracrine in nature.

Aging↗

Spatial asynchrony and periodic travelling waves in cyclic populations of field voles.

We demonstrate evidence for the presence of travelling waves in a cyclic population of field voles in northern Britain by fitting simple, empirical models to spatially referenced time series data. Population cycles were broadly synchronous at all sites, but use of Mantel correlations suggested a strong spatial pattern along one axis at a projection line 72 degrees from North. We then fitted a generalized additive model to log population density assuming a fixed-form travelling wave in one spatial dimension for which the density at each site was offset in time by a constant amount from a standard density-time curve. We assumed that the magnitude of this offset would be proportional to the spatial separation between any given site and the centroid of the sampling sites, where separation is the distance between sites in a fixed direction. After fitting this model, we estimated that the wave moved at an average speed of 19 km yr-1, heading from West to East at an angle of 78 degrees from North. Nomadic avian predators which could synchronize populations over large areas are scarce and the travelling wave may be caused by density-dependent dispersal by field voles and/or predation by weasels, both of which act at a suitably small spatial scale.

Animals↗

Spatiotemporal periodicity during atrial fibrillation in the isolated sheep heart.

BACKGROUND: The activation patterns that underlie the irregular electrical activity during atrial fibrillation (AF) have traditionally been described as disorganized or random. Recent studies, based predominantly on statistical methods, have provided evidence that AF is spatially organized. The objective of this study was to demonstrate the presence of spatial and temporal periodicity during AF. METHODS AND RESULTS: We used a combination of high-resolution video imaging, ECG recordings, and spectral analysis to identify sequential wave fronts with temporal periodicity and similar spatial patterns of propagation during 20 episodes of AF in 6 Langendorff-perfused sheep hearts. Spectral analysis of AF demonstrated multiple narrow-band peaks with a single dominant peak in all cases (mean, 9.4+/-2.6 Hz; cycle length, 112+/-26 ms). Evidence of spatiotemporal periodicity was found in 12 of 20 optical recordings of the right atrium (RA) and in all (n=19) recordings of the left atrium (LA). The cycle length of spatiotemporal periodic waves correlated with the dominant frequency of their respective optical pseudo-ECGs (LA: R2=0.99, slope=0.94 [95% CI, 0.88 to 0.99]; RA: R2=0.97, slope=0.92 [95% CI, 0.80 to 1.03]). The dominant frequency of the LA pseudo-ECG alone correlated with the global bipolar atrial EG (R2=0.76, slope=0.75 [95% CI, 0.52 to 0.99]). In specific examples, sources of periodic activity were seen as rotors in the epicardial sheet or as periodic breakthroughs that most likely represented transmural pectinate muscle reentry. However, in the majority of cases, periodic waves were seen to enter the mapping area from the edge of the field of view. CONCLUSIONS: Reentry in anatomically or functionally determined circuits forms the basis of spatiotemporal periodic activity during AF. The cycle length of sources in the LA determines the dominant peak in the frequency spectra in this experimental model of AF.

Animals↗

An analysis of spatial and temporal properties of daily sulfate, nitrate and chloride concentrations at UK urban and rural sites.

Daily measurements of sulfate, nitrate and chloride in PM(10) have been made at three geographically separated UK sites over a three year period. Chloride shows a clear seasonal pattern with highest concentrations in winter, whilst sulfate and nitrate both show highest concentrations in the spring, apparently related to weather patterns. Spatial variability of both sulfate and nitrate is low in comparison to temporal variations, with high correlations of both species between all three sites, London (North Kensington), Harwell and Belfast, despite a geographic separation of 510 km. Both SO/SO(2) and NO/NO(x) ratios are considerably higher in summer than winter, reflecting a greater oxidising capacity of the atmosphere. SO(4)(2-)/NO(3)(-) ratios are higher in summer than winter, suggesting that aqueous phase oxidation of SO(2), expected to be most important in the winter months is not appreciably influencing production of sulfate aerosol, although greater dissociation of ammonium nitrate in summer may also play a role. Regression of concentrations at London, North Kensington with those from the proximate rural site of Harwell is interpreted as showing a similar effect of regional transport at the two sites and a small influence of local formation in the urban atmosphere or primary emissions, averaging 0.46 microg m(-3) of nitrate and 0.22 microg m(-3) of sulfate.

Aerosols↗

Complex regulation of early paired expression: initial activation by gap genes and pattern modulation by pair-rule genes.

The paired gene is one of approximately 30 zygotic segmentation genes responsible for establishing the segmented body plan of Drosophila melanogaster. To gain insight into the mechanism by which the paired gene is expressed in a complex temporal and spatial pattern, we have examined paired protein expression in wild-type and mutant embryos. In wild-type embryos, paired protein is expressed in several phases. Initial expression in broad domains evolves into a pair-rule pattern of eight stripes during cellularization. Subsequently, a segment-polarity-like pattern of fourteen stripes emerges. Later, at mid-embryogenesis, paired is expressed in specific regions of the head and in specific cells of the central nervous system. Analysis of the initial paired expression in the primary pair-rule mutants even-skipped, runt and hairy, and in all gap mutants suggests that the products of the gap genes hunchback, Krüppel, knirps and giant activate paired expression in stripes. With the exception of stripe 1, which is activated by even-skipped, and stripe 8, which depends upon runt, the primary pair-rule proteins are required for subsequent modulation rather than activation of the paired stripes. The factors activating paired expression in the pair-rule mode appear to interact with those activating it along the dorsoventral axis.

Animals↗

Modular representations of odorants in the glomerular layer of the rat olfactory bulb and the effects of stimulus concentration.

To study the mechanism whereby odorants are encoded in the nervous system, we studied the glomerular-layer activity patterns in the rat olfactory bulb evoked by closely related odorants from different chemical families. These odorants had a common straight-chain hydrocarbon structure, but differed systematically in their functional groups. Neural activity was mapped across the entire glomerular layer by using the ¿(14)C2-deoxyglucose method. Group responses were averaged and compared by using data matrices. The glomerular activity patterns that resulted from this analysis were comprised of modules. Unique combinations of modules were activated by each odorant, demonstrating what may be part of the neural code for odorants. Most of the modules were clustered together in the bulb, perhaps providing for enhanced contrast between related chemicals by means of lateral inhibition. We also determined whether changes in odorant concentration would affect spatial patterns of glomerular activity. Two odorants, pentanal and 2-hexanone, evoked different patterns at increased concentrations, with additional glomeruli being recruited at a great distance from glomeruli in which activity was evoked at lower concentrations. Humans report that both of these odorants change in perceived odor with increasing concentration. Three other odorants (pentanoic acid, methyl pentanoate, and pentanol) did not recruit new areas of glomerular activation with increasing concentration, and humans do not report a changed odor across concentrations of these odorants. The results suggest that changes in modular glomerular activity patterns could underlie altered odor perception across odorant concentrations, and they provide additional support for a combinatorial, spatially based code in the olfactory system.

Animals↗

Spatial coding of odorant features in the glomerular layer of the rat olfactory bulb.

In order to determine whether molecular features of odorants are represented spatially in the glomerular layer of the olfactory bulb, we used metabolic mapping of [14C] 2-deoxyglucose uptake in rats exposed to equal vapor concentrations of odorants differing systematically in chemical structure. The odorants were ethyl acetate, ethyl butyrate, isoamyl acetate, and isoamyl butyrate. Statistical analysis of anatomically standardized arrays of uptake revealed that each ester produced a characteristic spatial pattern of activity in the glomerular layer. The patterns were similar in different rats exposed to the same odorant, and their complexity increased with increasing odorant carbon number. This finding suggests that the presence of more potentially recognized molecular features is associated with a greater number of activated receptors. Individual regions of the glomerular layer responded specifically to isoamyl esters, and other regions preferred ethyl esters. Regions of similar specificity occurred in lateral and medial aspects of the bulb, the medial representation being more caudal and ventral than the lateral one. This pattern correlates with projections of olfactory sensory neurons expressing the same putative olfactory receptor gene. The patterns overlapped greatly in the posterolateral and posteromedial glomerular layer, a finding one should predict, given the large overlap in chemical structure across the aliphatic esters. Thus, molecular features appear to be encoded spatially in the glomerular layer, and the identity of the odorant may be determined by a subsequent decoding of the combination of molecular features represented in the glomerular layer.

Acetates↗

Value of morphometry, texture analysis, densitometry, and histometry in the differential diagnosis and prognosis of malignant mesothelioma.

Malignant mesothelioma is a tumour with increasing incidence due to widespread use of its causative agent, asbestos, in the past decades. The poor survival necessitates a correct differentiation from other lesions at the same site, such as hyperplastic mesothelium and carcinomas metastatic to pleura or peritoneum. Since genetic and immunohistochemical markers are not absolutely differentiating, the diagnosis is based on the histology complemented with (immuno)histochemistry. However, as the tumour presents itself in numerous heterogeneous histological forms, visual evaluation is extremely difficult. In order to evaluate the prognostic and diagnostic performance of syntactic structure analysis (SSA), chromatin texture analysis, densitometry, and morphometry, an automated KNN-classification system has been used to compare Feulgen-stained tissue sections of hyperplastic mesothelium, malignant mesothelioma, and pulmonary adenocarcinoma. In addition, we also studied most discriminative aspects in the differentiation, typing, and prediction of survival. The results indicate that for the diagnosis of malignant mesothelioma, chromatin texture parameters outperform SSA, densitometry, and morphometry (recognition score=96.8 per cent). Most discriminative parameters highlight spatial patterns of the chromatin distribution that are hard to appraise visually and directly show the benefits of a quantitative approach. Typing of the tumour is best described by SSA parameters, relating to the spatial arrangement of the cells in the tissue (recognition score=94.9 per cent). In survival time classifications, chromatin texture yields the highest recognition score (82.9 per cent), although accurate estimations are unreliable due to a large degree of misclassification.

Adenocarcinoma↗

Two-dimensional analysis of the spacing of ocular dominance columns in normally raised and strabismic kittens.

In the primary visual cortex of cats, ferrets and macaque monkeys, the thalamocortical afferents conveying signals from the two eyes terminate in alternating regions of layer IV known as ocular dominance columns. Previous experiments have indicated that the periodicity of these columns can be influenced by visual experience: compared to normally raised animals both strabismic cats and cats raised with alternating monocular exposure displayed an increased spacing of adjacent ocular dominance columns in the primary visual cortex (area 17). However, recently it was shown that the formation of ocular dominance columns begins much earlier than previously supposed, indicating that early visual experience might only have a limited influence on the development of the spatial pattern of ocular dominance columns. We therefore visualized the complete pattern of ocular dominance columns in area 17 of normally raised and strabismic kittens during early postnatal development (age 3-6 weeks), particularly focussing on littermates. In addition, we used a previously developed spatial analysis (period statistics) to quantify columnar spacing two-dimensionally. We observed a pronounced interindividual variability in both normally raised and strabismic animals, with column spacings ranging from 783 to 1362 microm. In contrast to previous reports, there were no significant differences in columnar periodicity between normally raised and strabismic cats. These data indicate that rearing has less influence on column spacing while the interindividual variability is much greater than previously supposed, suggesting that genetic differences have an influence on column spacing.

Animals↗

Local velocity representation: evidence from motion adaptation.

Adaptation to a moving visual pattern induces shifts in the perceived motion of subsequently viewed moving patterns. Explanations of such effects are typically based on adaptation-induced sensitivity changes in spatio-temporal frequency tuned mechanisms (STFMs). An alternative hypothesis is that adaptation occurs in mechanisms that independently encode direction and speed (DSMs). Yet a third possibility is that adaptation occurs in mechanisms that encode 2D pattern velocity (VMs). We performed a series of psychophysical experiments to examine predictions made by each of the three hypotheses. The results indicate that: (1) adaptation-induced shifts are relatively independent of spatial pattern of both adapting and test stimuli; (2) the shift in perceived direction of motion of a plaid stimulus after adaptation to a grating indicates a shift in the motion of the plaid pattern, and not a shift in the motion of the plaid components; and (3) the 2D pattern of shift in perceived velocity radiates away from the adaptation velocity, and is inseparable in speed and direction of motion. Taken together, these results are most consistent with the VM adaptation hypothesis.

Adaptation, Ocular↗

The functional value of Caribbean coral reef, seagrass and mangrove habitats to ecosystem processes.

Caribbean coral reef habitats, seagrass beds and mangroves provide important goods and services both individually and through functional linkages. A range of anthropogenic factors are threatening the ecological and economic importance of these habitats and it is vital to understand how ecosystem processes vary across seascapes. A greater understanding of processes will facilitate further insight into the effects of disturbances and assist with assessing management options. Despite the need to study processes across whole seascapes, few spatially explicit ecosystem-scale assessments exist. We review the empirical literature to examine the role of different habitat types for a range of processes. The importance of each of 10 generic habitats to each process is defined as its "functional value" (none, low, medium or high), quantitatively derived from published data wherever possible and summarised in a single figure. This summary represents the first time the importance of habitats across an entire Caribbean seascape has been assessed for a range of processes. Furthermore, we review the susceptibility of each habitat to disturbances to investigate spatial patterns that might affect functional values. Habitat types are considered at the scale discriminated by remotely-sensed imagery and we envisage that functional values can be combined with habitat maps to provide spatially explicit information on processes across ecosystems. We provide examples of mapping the functional values of habitats for populations of three commercially important species. The resulting data layers were then used to generate seascape-scale assessments of "hot spots" of functional value that might be considered priorities for conservation. We also provide an example of how the literature reviewed here can be used to parameterise a habitat-specific model investigating reef resilience under different scenarios of herbivory. Finally, we use multidimensional scaling to provide a basic analysis of the overall functional roles of different habitats. The resulting ordination suggests that each habitat has a unique suite of functional values and, potentially, a distinct role within the ecosystem. This review shows that further data are required for many habitat types and processes, particularly forereef and escarpment habitats on reefs and for seagrass beds and mangroves. Furthermore, many data were collected prior to the regional mass mortality of Diadema and Acropora, and subsequent changes to benthic communities have, in many cases, altered a habitat's functional value, hindering the use of these data for parameterising maps and models. Similarly, few data exist on how functional values change when environmental parameters, such as water clarity, are altered by natural or anthropogenic influences or the effects of a habitat's spatial context within the seascape. Despite these limitations, sufficient data are available to construct maps and models to better understand tropical marine ecosystem processes and assist more effective mitigation of threats that alter habitats and their functional values.

Algorithms↗

A large terrestrial carbon sink in north america implied by atmospheric and oceanic carbon dioxide data and models

Atmospheric carbon dioxide increased at a rate of 2.8 petagrams of carbon per year (Pg C year-1) during 1988 to 1992 (1 Pg = 10(15) grams). Given estimates of fossil carbon dioxide emissions, and net oceanic uptake, this implies a global terrestrial uptake of 1.0 to 2. 2 Pg C year-1. The spatial distribution of the terrestrial carbon dioxide uptake is estimated by means of the observed spatial patterns of the greatly increased atmospheric carbon dioxide data set available from 1988 onward, together with two atmospheric transport models, two estimates of the sea-air flux, and an estimate of the spatial distribution of fossil carbon dioxide emissions. North America is the best constrained continent, with a mean uptake of 1.7 +/- 0.5 Pg C year-1, mostly south of 51 degrees north. Eurasia-North Africa is relatively weakly constrained, with a mean uptake of 0.1 +/- 0.6 Pg C year-1. The rest of the world's land surface is poorly constrained, with a mean source of 0.2 +/- 0.9 Pg C year-1.

Journal Article↗

Amplified expression of a transcriptional pattern formed during development of Anabaena.

The cyanobacterium Anabaena responds to nitrogen deprivation by producing heterocysts, cells specialized for nitrogen fixation, at well-spaced intervals along its filaments. The gene hepA, required for heterocyst maturation, is expressed in response to nitrogen deprivation, prior to visible differentiation. A spatial pattern of hepA expression indistinguishable from the eventual pattern of heterocysts was made visible by fusing the hepA promoter to luxAB, which encodes bacterial luciferase. Because the resulting signal did not greatly exceed instrumental background, T7 RNA polymerase was used to increase luminescence. The hepA promoter was fused to the gene for that polymerase, and a promoter recognized by that polymerase was fused to luxAB. Filaments containing these two fusions showed spaced luminescing cells many hours before differentiation became discernible morphologically.

ATP-Binding Cassette Transporters↗