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PubMed2004

CompuCell, a multi-model framework for simulation of morphogenesis.

MOTIVATION: CompuCell is a multi-model software framework for simulation of the development of multicellular organisms known as morphogenesis. It models the interaction of the gene regulatory network with generic cellular mechanisms, such as cell adhesion, division, haptotaxis and chemotaxis. A combination of a state automaton with stochastic local rules and a set of differential equations, including subcellular ordinary differential equations and extracellular reaction-diffusion partial differential equations, model gene regulation. This automaton in turn controls the differentiation of the cells, and cell-cell and cell-extracellular matrix interactions that give rise to cell rearrangements and pattern formation, e.g. mesenchymal condensation. The cellular Potts model, a stochastic model that accurately reproduces cell movement and rearrangement, models cell dynamics. All these models couple in a controllable way, resulting in a powerful and flexible computational environment for morphogenesis, which allows for simultaneous incorporation of growth and spatial patterning. RESULTS: We use CompuCell to simulate the formation of the skeletal architecture in the avian limb bud. AVAILABILITY: Binaries and source code for Microsoft Windows, Linux and Solaris are available for download from http://sourceforge.net/projects/compucell/

Animals↗
PubMed2005

Altered TCR signaling from geometrically repatterned immunological synapses.

The immunological synapse is a specialized cell-cell junction that is defined by large-scale spatial patterns of receptors and signaling molecules yet remains largely enigmatic in terms of formation and function. We used supported bilayer membranes and nanometer-scale structures fabricated onto the underlying substrate to impose geometric constraints on immunological synapse formation. Analysis of the resulting alternatively patterned synapses revealed a causal relation between the radial position of T cell receptors (TCRs) and signaling activity, with prolonged signaling from TCR microclusters that had been mechanically trapped in the peripheral regions of the synapse. These results are consistent with a model of the synapse in which spatial translocation of TCRs represents a direct mechanism of signal regulation.

Amino Acid Motifs↗
PubMed2000

Ecological determinants and temporal stability of the within-river population structure in Atlantic salmon (Salmo salar L.).

A gene diversity analysis was performed using microsatellite loci in order to (i) describe the extent and pattern of population structure in Atlantic salmon (Salmo salar L.) within a river system; (ii) establish the importance of quantifying the signal:noise ratio in accurately estimating population structure; and (iii) assess the potential usefulness of two evolutionary models in explaining within-river population structure from the ecological and habitat characteristics of Atlantic salmon. We found weak, yet highly significant microscale spatial patterning after accounting for variance among temporal replicates within sites. Lower genetic distances were observed among temporal samples at four sampling sites whereas no evidence for temporal stability was observed at the other three locations. The component of genetic variance attributable to either temporal instability and/or random sampling errors was almost three times more important than the pure spatial component. This indicates that not considering signal:noise ratio may lead to an important overestimation of genetic substructuring in situations of weak genetic differentiation. This study also illustrates the usefulness of the member-vagrant hypothesis to generate a priori predictions regarding the number of subpopulations that should compose a species, given its life-history characteristics and habitat structure. On the other hand, a metapopulation model appears better suited to explain the extent of genetic divergence among subpopulations, as well as its temporal persistence, given the reality of habitat patchiness and environment instability. We thus conclude that the combined use of both models may offer a promising avenue for studies aiming to understand the dynamics of genetic structure of species found in unstable environments.

Animals↗
PubMed1996

Dermatoglyphic variation in Europe.

We describe the geographic variation patterns of 236 dermatoglyphic variables (118 for each sex) for 74 samples in Europe. Using principal components analysis and rotating to simple structure, we simplified these patterns to the first 20 axes, representing 74.2% of covariation. We then used heterogeneity tests, interpolated surfaces, one-dimensional and directional correlograms, and distances between correlograms to analyze the factor scores of these 20 axes. We also ordinated the 74 localities. The data are remarkable for showing little spatial autocorrelation, despite significant heterogeneity among localities. Only three factor axes exhibit consistently significant correlograms, indicating that there are few spatial patterns in the original variables in Europe. Almost all correlations between pairs of variables occur within serially homologous character sets and are thus developmentally determined. There is some support for demic diffusion from the southeast in finger patterns and ridge counts. We compare these results to those of previous studies and note that Lapps and Icelanders are outliers with respect to both genetics and finger tip variables, whereas Tatars are outliers with respect to craniometrics and dermatoglyphics.

Analysis of Variance↗
PubMed1979

Functional organization of rat olfactory bulb analysed by the 2-deoxyglucose method.

The spatial patterns of activity elicited in the rat olfactory bulb under different odor conditions have been analysed using the 2-deoxyglucose (2DG) technique. Rats were injected with 14C-2DG, exposed to controlled environments of amyl acetate, camphor, cage air, dimethyl disulfide, and pure air and autoradiographs prepared by the method of Sokoloff. Amyl acetate was associated with regions of glomerular layer densities in the anterolateral and mid- to posteromedial parts of the bulbar circumference, as previously reported. The extents of the densities increased with increasing concentration. Camphor odor was associated with regions of increased density in the anterodorsal and mid- to posteromedial parts of the bulb. Exposure to cage air produced scattered densities in the posteromedial and posterolateral bulb. Exposure to dimethyl disulfide gave variable results. Pure air was associated with a minimal number of small dense foci. The results with amyl acetate, camphor and cage air suggest that patterns for different odors are distinguishably different but overlapping. The regions of activity are greatest in extent and density with the highest odor concentrations. These define the regions within which more restricted and isolated foci appear at lower concentrations. The results thus provide evidence for the specific role of spatial factors in the neural processing of odor quality and odor concentration.

Acetates↗
PubMed1994

Reverse occlusion leads to a precise restoration of orientation preference maps in visual cortex.

In the visual system of young kittens, the layout of the cortical maps for ocular dominance and orientation preference converges to an equilibrium state within the first few weeks of life and normally remains largely unchanged. If during the critical period, however, patterned visual experience is restricted to only one eye for a few days, cortical neurons lose their ability to respond to stimulation of the deprived eye. We used the 'reverse occlusion' protocol together with chronical optical imaging to investigate how the profound anatomical changes accompanying monocular deprivation affect the spatial pattern of the cortical orientation preference map. We report here that after 1 week of monocular deprivation, cortical orientation maps for the deprived eye had vanished. But we also discovered that after subsequent reverse occlusion the restored orientation maps were very similar to the original maps. This demonstrates that in spite of functional disconnection of one eye after monocular deprivation, the layout of cortical orientation maps, when re-established for this eye, is not formed from scratch but is strongly influenced by previous experience.

Animals↗
PubMed1989

Prepupal differentiation in Drosophila: distinct cell types elaborate a shared structure, the pupal cuticle, but accumulate transcripts in unique patterns.

The components of the pupal cuticle are the main differentiation products synthesized by both the larval and adult epidermis during the prepupal period of Drosophila development. The pupal cuticle is formed in vitro by imaginal discs in response to a 6 h pulse of 20-hydroxyecdysone (20-HE). We previously described the isolation and initial characterization of four ecdysone-dependent genes (EDGs) whose expression in imaginal discs occurs only in response to a pulse of 20-HE. In this report, we demonstrate that the pattern of temporal and tissue-specific expression of these EDGs in vivo is like that expected for genes that encode pupal cuticle proteins. Transcripts of these genes are detected in prepupae only in the epidermis and only when cuticle components are synthesized and secreted. Nonetheless, their temporal and spatial patterns of accumulation differ. EDG-84A-1 transcripts accumulate only in prepupae and only in imaginal cells. EDG-78E and EDG-64CD transcripts accumulate at the same time in both larval and imaginal cells. EDG42-A transcripts appear first in prepupae in imaginal cells and then, after a 2-4 h lag, in larval cells. It is evident that some genes are not restricted in their expression to only larval or imaginal epidermis.

Animals↗
PubMed1991

Distribution patterns of muscle fibre types in major muscles of the bull (Bos taurus).

The study describes the variations in distribution and cross-sectional area (fibre size) of three muscle fibre types (I, IIA, IIB) in 34 of the largest muscles of the bull (Bos taurus). The animals had been kept strictly unexercised for one year before slaughter. Representative sampling was done at 15 positions within each muscle, and from 2700 to 4500 fibres were analysed in each muscle. Different intermuscular patterns are described. The overall volume fraction (%) of type I fibres was about 10% higher in the forepart muscles than in the hindpart muscles (41% and 31%, respectively), while the mean content of type IIB fibres was similar. Type I fibres were particularly abundant in antigravity muscles. Of these, the hindlimb muscles contained 50% more type I fibres (by weight) than those of the forelimb. Typical antigravity antagonists contained very few type I fibres. In the thigh cross-section the proportion of type I fibres was highest in the anterior and medial parts, while the IIB fibres tended to be concentrated in the superficial and posterior parts. Intramuscular patterns were revealed, with type I fibres becoming gradually more abundant from superficial to deep regions, while IIB fibres had an opposite distribution. This was particularly evident in the thigh proper and in the scapular region. Within each fasciculus of all the muscles, the muscle fibre types formed a general spatial pattern. Type I fibres in the muscles of the forepart were on average about 15% larger than those of the muscles in the hindpart. The IIB fibres were on average about 10% larger in the hindpart than in the forepart muscles. A covariation between the proportion of type I and IIB fibres and their cross-sectional area was indicated.

Adenosine Triphosphatases↗
PubMed2006

Spatial heterogeneity in parasite infections at different spatial scales in an intertidal bivalve.

Spatial heterogeneities in the abundance of free-living organisms as well as in infection levels of their parasites are a common phenomenon, but knowledge on parasitism in invertebrate intermediate hosts in this respect is scarce. We investigated the spatial pattern of four dominant trematode species which utilize a common intertidal bivalve, the cockle Cerastoderma edule, as second intermediate host in their life cycles. Sampling of cockles from the same cohort at 15 sites in the northern Wadden Sea (North Sea) over a distance of 50 km revealed a conspicuous spatial heterogeneity in infection levels in all four species over the total sample as well as among and within sampling sites. Whereas multiple regression analyses indicated the density of first intermediate upstream hosts to be the strongest determinant of infection levels in cockles, the situation within sites was more complex with no single strong predictor variable. However, host size was positively and host density negatively correlated with infection levels and there was an indication of differential susceptibility of cockle hosts. Small-scale differences in physical properties of the habitat in the form of residual water at low tide resulted in increased infection levels of cockles which we experimentally transferred into pools. A complex interplay of these factors may be responsible for within-site heterogeneities. At larger spatial scales, these factors may be overridden by the strong effect of upstream hosts. In contrast to first intermediate trematode hosts, there was no indication for inter-specific interactions. In other terms, the recruitment of trematodes in second intermediate hosts seems to be largely controlled by pre-settlement processes both among and within host populations.

Animals↗
PubMed2004

Geographical variation and partition of metals in tissues of Octopus vulgaris along the Portuguese coast.

Zinc, Cu, Cd, Pb and Hg were determined in mantle, arm and digestive gland of 59 individuals of Octopus vulgaris captured at six sites along the Portuguese coast. Metal concentrations in tissues did not vary significantly (P<0.05) with size/weight, sex or sexual stage. The abundance of metals in each analysed tissue was: Zn>Cu>>Cd>Pb>Hg. Concentrations in the digestive gland reached one (Pb, Hg) and two (Zn, Cu, Cd) orders of magnitude higher than those found in arm and mantle, which indicates that the digestive gland contains the major storage sites for these elements, acting as a detoxification organ. However, concentrations in the digestive gland showed contrasting geographic patterns: Zn, Pb, Cu and Hg were higher in the Southern stations, while Cd levels increased drastically in Northern stations. This increase is in line with the contrasting Cd distribution in coastal waters. The lack of relations between metal concentration in tissues and biological parameters facilitates the recognition of those spatial patterns. The geographical contrast of Cd is extended to the accumulation in mantle and arm. A possible explanation for these enhanced values is that threshold level for Cd accumulation in digestive gland was attained and detoxification processes eventually modified.

Animals↗
PubMed1977

Variola minor in Braganca Paulista county, 1956: a trend-surface analysis.

Trend-surface analysis (TSA), a form of polynomial regression used in geology, ecology and geography, was applied to analysis of the spread of an epidemic of variola minor in a small Brazilian city. Cubic surfaces gave a generalized map of the space-time distribution of the epidemic, allowing those parts of the city to be identified where variola minor was spreading rapidly or slowly. The epidemic spread relatively quickly over the core area of the city, especially to the peripherally located household dwellings in a northeast to south-west direction. The dwellings of adults and pre-school children introducing the disease into their households broadly followed the overall pattern. School child introductory cases from a southern-located school yielded a saddle-shaped contour pattern, centered about the school; but this pattern was not repeated for the school serving the northern half of the city, which showed a ridge-shaped pattern dipping toward the west. Cubic surfaces for the influence of certain household and individual characteristics were investigated, but showed only week trends. The nearest match to the bowl-shaped overall pattern of introductory dates was provided by the vaccination level of the households. From this application, it appears that TSA permits the identification of regional trends in an objective manner and gives a quantitative measure of the importance of these regional trends in terms of the overall variation in the spatial pattern.

Adult↗
PubMed1989

Imaginal disc-autonomous expression of a defect in sensory bristle patterning caused by the lethal(3)ecdysoneless1 (1(3)ecd1) mutation of Drosophila melanogaster.

The temperature-sensitive mutation 1(3)ecd1 of Drosophila melanogaster is known to autonomously impair the ability of the larval prothoracic gland to produce the steroid molting hormone ecdysone in response to stimulation by the tropic neuropeptide prothoracicotropic hormone. It is shown that autonomous expression of the 1(3)ecd1 mutation in metamorphosing imaginal tissues disrupts the spatial pattern of sensory bristles. Transfer of homozygous mutant animals to the restrictive temperature at the time of pupariation resulted in the elimination of sensory microchaetae and macrochaetae. This effect was specific to the sensory bristles; nonsensory bristles were not eliminated, nor were other types of innervated cuticular sense organs. In the case of the dorsal thoracic macrochaetae, normal ecd gene function is required during an early period of bristle development (0-18 h after puparium formation at 20 degrees C). It is during this period that important determinative events take place in developing imaginal tissues that are responsible for the establishment of bristle progenitor cells. It is proposed that the ecd gene product may be required for the response of certain classes of cells to specific, regulatory signals.

Animals↗
PubMed1994

Positioning of cell growth and division after osmotic stress requires a MAP kinase pathway.

The yeast Saccharomyces cerevisiae has a genetic program for selecting and assembling a bud site on the cell cortex. Yeast cells confine their growth to the emerging bud, a process directed by cortical patches of actin filaments within the bud. We have investigated how cells regulate budding in response to osmotic stress, focusing on the role of the high osmolarity glycerol response (HOG) pathway in mediating this regulation. An increase in external osmolarity induces a growth arrest in which actin filaments are lost from the bud. This is followed by a recovery phase in which actin filaments return to their original locations and growth of the original bud resumes. After recovery from osmotic stress, haploid cells retain an axial pattern of bud site selection while diploids change their bipolar budding pattern to an increased bias for forming a bud on the opposite side of the cell from the previous bud site. Mutants lacking the mitogen-activated protein (MAP) kinase encoded by HOG1 or the MAP kinase kinase encoded by PBS2 (previously HOG4) show a similar growth arrest after osmotic stress. However, in the recovery phase, the mutant cells (a) do not restart growth of the original bud but rather start a new bud, (b) fail to restore actin filaments to the original bud but move them to the new one, and (c) show a more random budding pattern. These defects are elicited by an increase in osmolarity and not by other environmental stresses (e.g., heat shock or change in carbon source) that also cause a temporary growth arrest and shift in actin distribution. Thus, the HOG pathway is required for repositioning of the actin cytoskeleton and the normal spatial patterns of cell growth after recovery from osmotic stress.

Actins↗
PubMed2003

Examining landscape dynamics at a watershed scale using Landsat TM imagery for detection of wintering hooded crane decline in Yashiro, Japan.

It is usually inappropriate to define rectangular land areas or administrative units as the extent for quantifying landscapes that possess hierarchical structure. As a functional unit established by geophysical relationships, the watershed is one of many natural scales in the hierarchical landscape. We examined the dynamics of the Yashiro watershed of Japan at the landscape level using pattern metrics based on Landsat thematic mapper (TM) imagery from 1985 to 1998. This watershed provides important habitats for the hooded crane (Grus monachus), a vulnerable species. While its world population has remained stable, the number wintering at Yashiro has declined in recent years. Changes in landscape metrics reveal that the spatial pattern within the watershed underwent homogenization due to depopulation of local people and shifts in local energy requirements and forest management policy at Yashiro. Specific changes include: a decrease in bare land area from 6.2% to 1.0% of the landscape, increased forest cover from 69.2% to 76.1%, reduction in patch number from 1194 to 616 and enlarged mean patch size, and a decrease in total edge from 223,740 m to 158,040 m. The rate of change in landscape metrics indicates a rapid change towards homogeneity in the landscape since 1990. The temporal changes in hooded crane populations corresponded to the changes in landscape. An alternative explanation has been proposed that decline of the species is influenced by landscape dynamics affecting both habitat selection and food resources. Conservation at the watershed scale is suggested to be complementary to the current conservation measures of the species.

Animals↗
PubMed1994

Measurements of ultrasonic pulse arrival time and energy level variations produced by propagation through abdominal wall.

Ultrasonic pulse arrival time and energy level variations introduced by propagation through human abdominal wall specimens have been measured. A hemispheric transducer transmitted an ultrasonic pulse that was detected by a linear array transducer after propagation through an abdominal wall section. The array was translated in the elevation direction to collect data over a two-dimensional aperture. Differences in arrival time and energy level between the measured waveforms and calculated references that account for geometric delay and spreading were found. Plots of waveforms compensated for geometric path, maps of time delay differences and energy level fluctuations, and statistics derived from these for water paths and tissue paths characterize the measurement system and describe the time delay differences and energy level fluctuations caused by 14 different human abdominal wall specimens. Repeated measurements using the same specimens show that individual tissue path measurements are reproducible, the results depend on specimen position, and frozen storage of a specimen for three months does not appear to alter the time delay differences and energy level fluctuations produced by the specimen. Comparison of measurements at room and body temperature indicates that appreciably higher time delay differences occur at body temperature while energy level fluctuations and time delay difference patterns are less affected. For the 14 different abdominal wall specimens, the rms time delay differences and energy level fluctuations have average values of 43.0 ns and 3.30 dB, respectively, and the associated correlation lengths of the time delay differences and energy level fluctuations are 7.90 and 2.28 mm, respectively. The spatial patterns of time delay difference and energy level fluctuation in the reception plane appear largely uncorrelated, although some background variations in energy level fluctuation are similar to features in time delay difference maps. The results provide important new information about the variety and range of ultrasonic wave front arrival and energy variations caused by transmission through abdominal wall.

Abdominal Muscles↗
PubMed2001

Possible roles for stanniocalcin during early skeletal patterning and joint formation in the mouse.

Stanniocalcin (STC) is a polypeptide hormone discovered first in fish and more recently in mammals. In mammals, the gene is widely expressed and the hormone is, so far, known to be involved in regulating the transport of calcium or phosphate across renal and gut epithelia, and into neuronal cells. Gene expression is also high during development, and in an earlier study we mapped the temporal and spatial pattern of gene expression in the mouse urogenital system. Our data suggested that STC probably acted as a signaling molecule that was produced in mesenchyme cells and targeted to epithelial cell layers in both kidney and testes. Here we have examined STC mRNA and protein distributions between developmental stages E10.5 and E18.5 in the axial and appendicular skeleton. In the axial skeleton, STC was transiently expressed in a rostral-caudal fashion during vertebral development; protein appeared to be made in intervertebral disc mesenchyme cells and targeted to vertebral hypertrophic and prehypertrophic chondrocytes. By stage E18.5, the STC gene was active only in vertebral perichondrocytes. The pattern of expression in the appendicular skeleton was equally striking. Early in development, STC gene expression defined the initial lengths of bone primordia. The gene was expressed in mesenchyme cells at either ends of precartilaginous condensations defining future long bones and the secreted protein was targeted to the chondroblasts. Later on during joint formation, STC was highly expressed in interzone cells that defined all future joints. After cavitation, STC gene expression was greatest in perichondrocytes lining the joints. Underlying resting, proliferative and prehypertrophic chondrocytes appeared to be the targets of STC both during and after cavitation. Therefore, its pattern of expression was indicative of a role in early skeletal patterning and joint formation. Moreover, as occurs during urogenital development, it appeared that STC is made in undifferentiated mesenchyme cells and sequestered by those destined to differentiate.

Animals↗
PubMed2000

Spatiotemporal Patterns of Laccase Activity in Interacting Mycelia of Wood-Decaying Basidiomycete Fungi.

A BSTRACTInterspecific fungal interactions are important ecological processes, whereas their physiological mechanisms are little understood. The aim of this work was to study how activity of fungal extracellular laccase was changed across mycelia during interactions between white- and brown-rot basidiomycetes from different wood decay stages. Qualitative assay of eight species interacting with each other in all combinations showed four spatial patterns of laccase activity: (I) laccase activity present both in contact zone and mycelium, (II) laccase activity only in contact zone, (III) laccase activity in mycelium but not in contact zone, (IV) no laccase activity. Presence of laccase activity only in the contact zone was more frequent than expected from random samples associated with mycelia that replaced other ones. On the other hand, the presence of laccase activity in the mycelium but not in the contact zone was only attributed to fungal species that were replaced by their antagonists. After one month, laccase activity was distributed over mycelia more homogeneously than after 6 days of interactions. In interacting mycelia, laccase activity was higher than in control and increasing with time. Saprotrophic fungi from late successional stages of wood decay generally had higher laccase activity than early succession saprotrophic and pathogenic fungi. The qualitative assays were confirmed by quantitative assay of total laccase activity. Significance of the results in antagonistic fungal interactions as well as in the processes of hyphal tip growth and mycelium senescence is discussed.

Journal Article↗
PubMed1998

Elastogenesis in the developing chick lung is transcriptionally regulated.

The overall goals of this study were to establish the level at which elastin gene expression is regulated during chick lung embryogenesis and to identify the temporal and spatial relationships among elastogenesis, smooth muscle cell differentiation, and cell proliferation. A comparison of lung elastin mRNA and transcriptional levels during embryogenesis shows that elastin expression is developmentally regulated at the transcriptional level. The increase in elastogenic activity occurs during the late stages of lung embryogenesis and coincides with terminal maturation of the tertiary bronchi. In situ hybridization analysis demonstrates that the increase in elastin mRNA expression is confined to the tertiary bronchial respiratory subunits, connective tissue septa, and supporting vasculature of the lung parenchyma. Immunohistochemical localization of smooth muscle cell alpha-actin and tropoelastin suggests that alpha-actin-immunoreactive cells of the lung parenchyma are a major contributor to the increase in elastin expression during embryogenesis. This observation is also reflected by Northern blot analysis, which demonstrates a temporal coincidence in the increase of both alpha-actin and elastin mRNA levels. Histone mRNA expression, which was used as an index of cellular proliferation, reveals a level and spatial pattern inversely related to that of the elastin transcript. Tissue transfections of chick lungs isolated from 18-day embryos with various elastin gene deletion/reporter constructs illustrate that the elastin promoter is not promiscuous within a tissue environment and that sequences spanning the -500 to +2 region are capable of directing promoter activity spatially comparable to the endogenous elastin gene.

Actins↗