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PubMed2003

Robust development as a consequence of generated positional information.

The origin and robustness of morphogenesis are studied by dynamical system modeling of a cell society, in which cells possessing internal chemical reaction dynamics interact with each other through their mutual interaction with diffusive chemicals in a two-dimensional medium. It is found that stem-type cells differentiate into various cell types (where a cell 'type' is defined by a type of intra-cellular dynamics) due to a dynamic instability caused by cell-cell interactions in a manner described by the isologous diversification theory. The differentiations are spatially regulated by the concentration of chemicals in the medium, while the chemical concentrations are locally influenced by the intra-cell dynamics. Through this reciprocal relationship, chemical concentrations come to exhibit spatial variation as differentiated cell types begin to emerge, and as a result the regulation exercised by the chemical concentrations become spatially inhomogeneous. This reinforces the process of differentiation, through which spatial patterns of differentiated cells appear. Within this reciprocal relationship, the concentration gradients are read and interpreted by the cell as positional information. A spatial order of cells realized in this process represents a stable state of the system governed by this reciprocal relationship, and that the developmental process through which this state is realized is robust with respect to perturbations. The dependence of the morphogenesis on history and the community effect in cell differentiation are also discussed.

Animals↗
PubMed1991

Formation of the cochlea in the chicken embryo: sequence of innervation and localization of basal lamina-associated molecules.

The purpose of this study was to determine the temporal and spatial gradients in the innervation of the chicken cochlea, the basilar papilla, as it develops in the early embryo. A series of white Leghorn chick embryos (Hamburger-Hamilton Stage 20-43) were prepared for serial sectioning and stained by Toluidine blue or by antibodies to fibronectin or laminin. Light microscopic observations were made on the first fiber bundles to reach each region of the basilar papilla. There is a distinct temporo-spatial pattern of the ingrowth of fiber bundles to the developing basilar papilla. The primary pattern is not described as any simple linear gradient. Fiber ingrowth begins proximally, shifts to a distal and then to a mid-proximal region. The fiber ingrowth correlates temporally and spatially with disruption of fibronectin and laminin staining of the basal lamina where fiber bundles are penetrating. This pattern may reflect not only the sequence of fiber ingrowth but also the displacement of cells and fibers in the elongating basilar papilla, which grows as a result of a contemporaneous mitotic activity throughout the structure rather than progressing from one end to the other.

Animals↗
PubMed1998

Software implementation of statistical methods for the analysis of structure and patterns in neuroanatomical objects.

Neuroanatomical research has greatly benefited from the availability of a large number of cell-specific and region-specific molecular markers. In fact, the analysis of spatial patterns of gene expression in individual cells or patterns within cell populations often provides an inroad into understanding the functional significance of distinct structures. However, it can be difficult to discern whether the arrangement of different morphologically or biochemically defined structures represents a defined pattern. To address this issue, we adapted a series of established statistical procedures for the analysis of uni- and bivariate point patterns in histological specimens. We implemented these statistical procedures in an easy-to-use computer program. The methods are scale independent and easy to expand for various applications. The utility of this approach is demonstrated with examples from tissue sections and cultured cells at the light and electron microscopical levels.

Actins↗
PubMed2006

Environmental and childhood lead contamination in the proximity of boat-repair yards in southern Thailand--I: pattern and factors related to soil and household dust lead levels.

High blood lead levels have recently been documented in schoolchildren living in communities adjacent to boat-repair yards in southern Thailand. In this study, the spatial pattern of lead contamination of soil and household dust in an area surrounding several boat-repair yards is described, and household factors associated with elevated dust lead are identified. A cross-sectional spatial study was conducted in a coastal residential area within a distance of 2 km from three major boat-repair yards situated on the east coast of peninsular Thailand. Household dust specimens were collected from an undisturbed position in the residences of children, aged 4-14 years, sampled randomly from all children living in the study area. Soil specimens were obtained from the interstices of a square grid, 70 x 70 m2, superimposed on the area. Geographic coordinates of residence and soil sampling positions were recorded and semivariograms and kriging used to contour the spatial distribution of lead in dust and soil. Environmental lead levels were also modeled in terms of direction and minimum distance from a boat-repair yard and, for household dust lead content, in terms of household variables, including occupation of household members in boat-repair work, type of house construction, and general cleanliness. Household dust and soil lead content ranged from 10 to 3025 mg/kg and from 1 to 7700 mg/kg, respectively. The distribution of soil lead peaked at the location of the boat-repair yards, but outside the yards the distribution was generally below 400 mg/kg and irregular. About 24% of household dust lead specimens were equal to or above 400 mg/kg, but showed significant decrease with increasing distance from the boat-repair yards, at rates of between 7% and 14% per 100 m. In houses where a family member was a worker in one of the major boatyards and in houses where occasional repair of small boats was undertaken, household dust lead levels were significantly elevated, by 65% (95% CI: 18-130%) and 31% (95% CI: 5-63%), respectively. Siting of boat-repair yards at a distance from residential areas and measures to reduce the spread of lead-containing dust are recommended to alleviate the problem of elevated household dust lead levels.

Adolescent↗
PubMed2001

Predetermined recruitment of calcium release sites underlies excitation-contraction coupling in rat atrial myocytes.

Excitation-contraction coupling (E-C coupling) was studied in isolated fluo-3-loaded rat atrial myocytes at 22 and 37 degrees C using rapid confocal microscopy. Within a few milliseconds of electrical excitation, spatially discrete subsarcolemmal Ca2+ signals were initiated. Twenty to forty milliseconds after stimulation the spatial overlap of these Ca2+ signals gave a 'ring' of elevated Ca2+ around the periphery of the cells. However, this ring was not continuous and substantial Ca2+ gradients were observed. The discrete subsarcolemmal Ca2+-release sites, which responded in a reproducible sequence to repetitive depolarisations and displayed the highest frequencies of spontaneous Ca2+ sparks in resting cells, were denoted 'eager sites'. Immunostaining atrial myocytes for type II ryanodine receptors (RyRs) revealed both subsarcolemmal 'junctional' RyRs, and also 'non-junctional' RyRs in the central bulk of the cells. A subset of the junctional RyRs comprises the eager sites. For cells paced in the presence of 1 mM extracellular Ca2+, the response was largely restricted to a subsarcolemmal 'ring', while the central bulk of the cell displayed a approximately 5-fold lower Ca2+ signal. Under these conditions the non-junctional RyRs were only weakly activated during E-C coupling. However, these channels are functional and the Ca2+ stores were at least partially loaded, since substantial homogeneous Ca2+ signals could be stimulated in the central regions of atrial myocytes by application of 2.5 mM caffeine. Neither the location nor activation order of the eager sites was affected by increasing the trigger Ca2+ current (by increasing extracellular Ca2+ to 10 mM) or the sarcoplasmic reticulum (SR) Ca2+ load (following 1 min incubation in 10 mM extracellular Ca2+), although with increased SR Ca2+ load, but not greater Ca2+ influx, the delay between the sequential activation of eager sites was reduced. In addition, increasing the trigger Ca2+ current or the SR Ca2+ load changed the spatial pattern of the Ca2+ response, in that the Ca2+ signal propagated more reliably from the subsarcolemmal initiation sites into the centre of the cell. Due to the greater spatial spread of the Ca2+ signals, the averaged global Ca2+ transients increased by approximately 500 %. We conclude that rat atrial myocytes display a predetermined spatiotemporal pattern of Ca2+ signalling during early E-C coupling. A consistent set of eager Ca2+ release sites with a fixed location and activation order on the junctional SR serve to initiate the cellular response. The short latency for activation of these eager sites suggests that they reflect clusters of RyRs closely coupled to voltage-operated Ca2+ channels in the sarcolemma. Furthermore, their propensity to show spontaneous Ca2+ sparks is consistent with an intrinsically higher sensitivity to Ca2+-induced Ca2+ release. While the subsarcolemmal Ca2+ response can be considered as stereotypic, the central bulk of the cell grades its response in direct proportion to cellular Ca2+ load and Ca2+ influx.

Animals↗
PubMed1975

The development of neuronal connection patterns in the visual systems of insects.

The retina of the compound eye contains a patterned spatial array of receptor cell groups whose symmetry and component numerical constancy allow the unique identification of individual cells. The axon connection patterns arising from the retina similarly are uniquely identifiable and relate by simple consistnet transpositons to the retinal position of their somata. The coincidence of these features and the epidermal origin or retinula cells provides a model system for the developmental analysis of neural patterns. It is known that the retina develops by a wave of determinative mitoses and subsequent cellular differentiation, transmitted inductively from a posteriorly situated differentiation centre, which passes over the prospective eye field independently of the growing axon connections with the optic lobe. The ganglion cells of the optic lobe are similarly produced in a temporal sequence but their subsequent differentiation depends on centripetal innervation and proceeds as a wave initiated in the retina. Axon growth between the retina and optic neuropiles occurs in this temporal sequence, appears largely non-exploratory and dependent on mechanical guidance. By contrast, individual axon connections within the neuropile form probabilistically by extensive filopod explorations between cones. Both growth between and growth within the neuropile depend upon features in the pattern of retinal development which are discussed.

Animals↗
PubMed1994

Functional architecture of vestibular primary afferents from the posterior semicircular canal of a turtle, Pseudemys (Trachemys) scripta elegans.

Physiological studies in many vertebrates indicate that vestibular primary afferents are not a homogeneous population. Such data raise the question of what structural mechanisms underlie these physiological differences and what functional role is played by afferents of each type. We have begun to answer these questions by characterizing the architecture of 110 afferents innervating the posterior canal of Pseudemys scripta. We emphasize their spatial organization because experimental evidence suggests that afferent physiological properties exhibit significant spatial heterogeneity. The sensory surface of the posterior canal comprises paired, triangular hemicristae, which are innervated by two afferent types. Bouton afferents (66% of total afferents) are found over the entire sensory surface. They differ significantly in the shape and size of their collecting areas, number of boutons, soma size, and axon diameter; this morphological variation is systematically related to the afferent's spatial position. In addition, multivariate analyses suggest that bouton afferents may comprise two subtypes: alpha afferents have delicate processes and are found throughout the crista; beta afferents are more robust and are concentrated preferentially toward the canal center. Calyx-bearing afferents comprise two morphological subtypes: dimorphs (13% of total afferents) bear calyceal and bouton endings; calyceal afferents (21%) bear calyceal endings only. Both types occur exclusively in an elliptical region near the center of each hemicrista; their morphology varies with radial distance from the center of this elliptical region. Our data provide evidence that in Pseudemys: (1) the classical vestibular afferent types (bouton, calyx, dimorph) are structurally heterogeneous, and (2) their spatial sampling characteristics are highly structured and distinctive for each type. These spatial patterns may shed light on regional differences in physiological profiles of vestibular afferents, and they raise questions about the role of this spatial heterogeneity in signaling head movement.

Animals↗
PubMed2006

An exploratory spatial analysis of pneumonia and influenza hospitalizations in Ontario by age and gender.

Pneumonia and influenza represent a significant public health burden in Canada and abroad. Knowledge of how this burden varies geographically provides clues to understanding the determinants of these illnesses, and insight into the effective management of health-care resources. We conducted a retrospective, population-based, ecological-level study to assess age- and gender-specific spatial patterns of pneumonia and influenza hospitalizations in the province of Ontario, Canada from 1992 to 2001. Results revealed marked variability in hospitalization rates by age, as well as clear and statistically significant patterns of high rates in northern rural counties and low rates in southern urban counties. A moderate yet significant level of positive spatial autocorrelation (Moran's I=0.21, P<0.05) was found in the global data, with significant, age-specific clusters of high values or 'hot spots' identified in several northern counties. Findings illustrate the need for geographically focused prevention strategies, and resource and service allocation policies informed by regional and population-specific demands.

Adolescent↗
PubMedDate not supplied

Expression of PPAR and RXR isoforms in the developing rat and human term placentas.

Placental fatty acid transfer is critical to meet the foetal requirements necessary for the biosynthesis of biological membranes, myelin, and various signaling molecules. The primary objective of this research was to elucidate the placental expression patterns of genes that may potentially regulate placental fatty acid transfer and homeostasis. In this study, we have elucidated the temporal and spatial patterns of expression of peroxisome proliferator-activated receptor (PPAR) and 9-cis retinoic acid receptor (RXR) isoforms in the junctional and labyrinth zones of the developing rat chorioallantoic placenta and in human term placenta. PPAR (alpha, beta, and gamma) and RXR (alpha, beta, and gamma) isoforms are nuclear hormone receptors that are known to regulate gene transcription and protein expression levels of fatty acid transport and metabolism mediating proteins through the formation of a DNA binding heterodimer complex. In the present study, the expression patterns of PPAR and RXR isoforms were determined in developing rat placenta and human term placenta using RT-PCR and immunohistochemical analyses. PPARalpha, beta, gamma, RXRalpha, beta and gamma were expressed in both junctional (invasive/endocrine function) and labyrinth (transport barrier) zones of the rat placenta, from day 13 to day 21 of gestation. In the human term placenta, PPARalpha, beta, gamma, RXRalpha and gamma were observed, while RXRbeta was not detected. Immunocytochemistry staining results determined the presence of PPARalpha, beta, gamma, RXRalpha and gamma to be specific to the syncytial trophoblast layer of the human chorionic villi. The presence of PPAR and RXR isoforms in both the rat and human placentas suggest that PPAR and RXR isoforms are potential regulators of placental lipid transfer and homeostasis. Our work provides a framework for the further investigation of PPAR and RXR isoform specific regulation of placental fatty acid uptake, transport and metabolism.

Adult↗
PubMed2003

Parametrically forced surface wave with a nonmonotonic dispersion relation.

Surface wave patterns that arise in a mechanically driven ferrofluid system under constant magnetic field are investigated (1) to find out what kind of spatial patterns emerge when the system acquires a nonmonotonic dispersion relation and (2) to compare its surface wave patterns with those produced in the magnetically driven system studied earlier. As the strength of the applied magnetic field increases, the initial subharmonic square lattice formed by the Faraday instability first transforms to rolls, then becomes a rhomboid lattice. The rolls and the rhomboid lattice are found to coexist for a finite range of parameter space forming patterns with mixed domains. Possible underlying mechanisms for the observed rhomboid lattice is discussed. None of the diverse superlattices observed in the magnetically driven ferrofluid system appears in the mechanically driven system studied here.

Journal Article↗
PubMed2000

Near-infrared study of fluctuations in cerebral hemodynamics during rest and motor stimulation: temporal analysis and spatial mapping.

We have noninvasively studied the motor cortex hemodynamics in human subjects under rest and motor stimulation conditions using a multichannel near-infrared tissue spectrometer. Our instrument measures optical maps of the cerebral cortex at two wavelengths (758 and 830 nm), with an acquisition time of 160 ms per map. We obtained optical maps of oxy- and deoxy-hemoglobin concentration changes in terms of amplitudes of folding average, power spectrum and coherence at the stimulation repetition frequency, and the phase synchronization index. Under periodic motor stimulation conditions, we observed coherence and frequency or phase synchronization of the local hemodynamic changes with stimulation. Our main findings are the following: (1) The amplitude of the hemodynamic response to the motor stimulation is comparable to the amplitude of the fluctuations at rest. (2) The spatial patterns of the oxy- and deoxy-hemoglobin responses to the stimulation are different. (3) The hemodynamic response to stimulation shows a spatial localization and a level of phase synchronization with the motor stimulation that depends on the stimulation period.

Adult↗
PubMed2000

The period E-box is sufficient to drive circadian oscillation of transcription in vivo.

The minimum element from the Drosophila period promoter capable of driving in vivo cycling mRNA is the 69 bp circadian regulatory sequence (CRS). In cell culture, an 18 bp E-box element from the period promoter is regulated by five genes that are involved in the regulation of circadian expression in flies. This E-box is a target for transcriptional activation by bHLH-PAS proteins dCLOCK (dCLK) and CYCLE (CYC), this activation is inhibited by PERIOD (PER) and TIMELESS (TIM) together, and inhibition of dCLK/CYC by PER and TIM is blocked by CRYPTOCHROME (CRY) in the presence of light. Here, the same 18 bp E-box region generated rhythmic expression of luciferase in flies under both light-dark cycling and constant conditions. Flies heterozygous for the Clke(jrk) mutation maintained rhythmic expression from the E-box although at a lower level than wild type. Homozygous mutant Clk(jrk) animals had drastically lowered and arrhythmic expression. In a per01 background, expression from the E-box was high and not rhythmic. Transcription mediated by the per E-box was restricted to the same spatial pattern as the CRS. The per E-box DNA element and cognate binding proteins can confer per-like temporal and spatial expression. This demonstrates in vivo that the known circadian genes that form the core of the circadian oscillator in Drosophila integrate their activities at a single DNA element.

Animals↗
PubMed1999

Slice blotting: a method for detecting the release of immunoreactive substances from living brain tissue.

The intricate circuitry of the CNS forms highly organized structures containing a multitude of transmitters, modulators and other chemical signals expressed in specific patterns and pathways. Anatomical studies with immunohistochemical and molecular biological techniques have mapped in fine detail the distribution of these substances in fixed tissue. However, the release of neuroactive substances is often under precise spatial control and is regulated by numerous physiological factors. Understanding such complex intercellular signaling systems will require the development of new spatially resolved methods for detecting secretion in living systems. A simple but powerful method is described here for visualizing and quantifying the time-integrated spatial pattern of release of chemical signals from living neural tissue. The method combines the in vitro brain slice preparation with immunostaining protocols used for antigen detection on Western blots. It has widespread potential application in biological research because it can map in vitro patterns of release of cytokines, growth factors, chemoattractants, chemorepellents, morphogens, enzymes, and other paracrine signals in spatially organized systems, subject to a variety of stimuli and conditions.

Animals↗
PubMed1986

Patterns of mortality from selected causes in an urban population.

Mortality data for selected non-cancer causes for the period 1974-1980 were analyzed for the City of Philadelphia to examine spatial patterns. Four categories of conditions--ischemic heart disease (including acute myocardial infarction), chronic liver disease and cirrhosis, cerebrovascular disease, and external causes--demonstrated significant variation in death rates. Moreover, neighborhoods with high levels of mortality for these conditions appeared in significant clusters. With the exception of ischemic heart disease, neighborhoods with high levels of mortality were characterized by below average levels of SES. A group of predominantly black neighborhoods in the central part of the city had extremely high rates for five or more of the nine causes investigated in this paper. In an earlier analysis, all but one of these neighborhoods were found to have the highest level of overall cancer mortality. These findings support the hypothesis that there are social and behavioral factors that are associated with a wide range of disease conditions, and many of these factors are associated with socioeconomic status.

Chronic Disease↗
PubMed2006

Cancer map patterns: are they random or not?

BACKGROUND: Maps depicting the geographic variation in cancer incidence, mortality or treatment can be useful tools for developing cancer control and prevention programs, as well as for generating etiologic hypotheses. An important question with every cancer map is whether the geographic pattern seen is due to random fluctuations, as by pure chance there are always some areas with more cases than expected, or whether the map reflects true underlying geographic variation in screening, treatment practices, or etiologic risk factors. METHODS: Nine different tests for spatial randomness are evaluated in very practical settings by applying them to cancer maps for different types of data at different scales of spatial resolution: breast, prostate, and thyroid cancer incidence; breast cancer treatment and prostate cancer stage in Connecticut; and nasopharynx and prostate cancer mortality in the U.S. RESULTS: Tango's MEET, Oden's Ipop, and the spatial scan statistic performed well across all the data sets. Besag-Newell's R, Cuzick-Edwards k-NN, and Turnbull's CEPP often perform well, but the results are highly dependent on the parameter chosen. Moran's I performs poorly for most data sets, whereas Swartz Entropy Test and Whittemore's Test perform well for some data sets but not for other. CONCLUSIONS: When publishing cancer maps we recommend evaluating the spatial patterns observed using Tango's MEET, a global clustering test, and the spatial scan statistic, a cluster detection test.

Adolescent↗
PubMed1993

Developmental control elements in the promoter of a Drosophila vitelline membrane gene.

DNA fragments from the 5' flanking region of Drosophila melanogaster vitelline membrane gene VM26A1 were fused to hsp/lacZ reporter genes, reintroduced via P-element-mediated germ line transformation, and functionally assayed by histological staining for beta-galactosidase activity. A developmental control element capable of promoting the basic vitelline membrane (VM) expression pattern was found within a 176-bp region. Additional multiple genetic control elements were found to be involved in modifying the level and spatial pattern of reporter gene expression but these required the 176-bp element in order to function. Unexpectedly, in isolation this 176-bp core element also promotes abnormal expression of the reporter gene in border cells of stage 8 and 9 egg chambers. This abnormal border cell expression is apparently suppressed in the native gene by an adjacent negative control element.

Animals↗
PubMed1992

The BMP proteins in bone formation and repair.

From recent advances in the fields of bone biology and pattern formation, the first clues to our understanding of embryonic skeletal development are beginning to emerge. This complex process involves an integration of spatial patterning and the differentiation of specialized cells that make up bone and cartilage. The result is a scale model of the mature skeleton which is able to grow in size to fit the adult body plan. In the mature animal, bone repair after injury appears to be similar to bone formation in the embryo, suggesting that analogous mechanisms for the control of bone formation may exist in the adult and embryonic skeletons.

Animals↗
PubMed2003

Temporal aspects of the fine-scale genetic structure in a population of Cinnamomum insularimontanum (Lauraceae).

Cinnamomum insularimontanum Hayata (Lauraceae) is an insect-pollinated, broad-leaved evergreen tree with bird-dispersed seeds. We used allozyme loci, Wright's fixation index, spatial autocorrelation statistics (Moran's I), and coancestry measures to examine changes in genetic structure among four age-classes within a recently founded study population (60 x 100 m area) in southern Korea. There were no significant differences in expected heterozygosity among age classes. However, significant genetic differentiation among age classes was detected (P<0.0001). Fixation indices within age classes showed significant deficits of observed heterozygosity, which may be caused by partial selfing. The homogeneity of genetic structure among four age-classes may reflect similar spatial patterns of seed immigration from surrounding populations occurring year after year. Finally, the average Moran's I and coancestry estimates indicated essentially random spatial distributions of alleles for each of the four age-classes and between seedlings and 2-4 year juveniles vs adult trees. These findings are very similar to those observed in the same study area for another member of the Lauraceae, Neolitsea sericea, which has a very similar life history and ecological characteristics (ie, bird-dispersed fruits, insect pollination, and a similar age structure). Together, these results suggest that the fleshy drupes of lauraceous species represent an adaptation to aid in the independent dispersal of seed by birds, which in turn may increase the genetic diversity of founders colonizing new habitats.

Biological Evolution↗