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PubMed2003

Programmable modification of cell adhesion and zeta potential in silica microchips.

Spatial patterning of thin polyacrylamide films bonded to self-assembled monolayers on silica microchannels is described as a means for manipulating cell-adhesion and electroosmotic properties in microchips. Streaming potential measurements indicate that the zeta potential is reduced by at least two orders of magnitude at biological pH, and the adhesion of several kinds of cells is reduced by 80-100%. Results are shown for cover slides and in wet-etched silica microchannels. Because the polyacrylamide film is thin and transparent, this film is consistent with optical manipulation of cells and detection of cell contents. The spatial patterning technique is straightforward and has the potential to aid on-chip analysis of single adherent cells.

Acrylic Resins↗
PubMed1999

Autoradiographic [3H]nimodipine distribution after experimental spinal cord injury in rats.

Because of its potential for augmentation of blood flow and protection of neurons after neurological insult, nimodipine has been investigated as a treatment of spinal cord injury (SCI). The results have been inconsistent, possibly because of poor delivery of nimodipine to the injured spinal cord. The following study was designed to determine the delivery of nimodipine to the injured spinal cord. It was also hoped that information about the temporal and spatial pattern of binding of nimodipine after SCI might further elucidate the relationship between calcium channel activation and injury. Fourteen female Wistar rats were divided into three groups: control (n = 3), 30 min post-SCI (n = 6); and 4 h post-SCI (n = 5). The injury was produced by acute clip compression for 1 min at T1. [3H]Nimodipine was administered 5 min after laminectomy in the control group, and at the above-specified times after injury in the SCI groups. The drug was then allowed to equilibrate for 30 min before the animals were killed. The spatial patterns and concentrations of [3H]nimodipine in various segments of the spinal cord were autoradiographically determined. The highest concentrations of [3H]nimodipine were at the injury site after SCI. Also, the mean [3H]nimodipine concentrations in all sites in each animal were higher in the injury groups than in the control group (p < 0.05). This study indicates that delivery of this agent to the injured cord is possible, and provides evidence of widespread Ca2+ channel activation in the first 4 h after injury.

Animals↗
PubMed1998

Spatial analysis of lymphatic filariasis distribution in the Nile Delta in relation to some environmental variables using geographic information system technology.

Geographic information system (GIS) was used to analyze the spatial distribution of filariasis in the Nile Delta. The study involved 201 villages belonging to Giza, Qalubiya, Monoufiya, Gharbiya, and Dakahliya governorates. Villages with similar microfilarial (mf) prevalence rates were observed to cluster within 1-2 km distance, then, clustering started to decrease significantly with distance up to 5 km (Pearson correlation coefficient = -0.98). the likelihood of negative and high prevalence villages being contiguous was very low (approximately 1.8%, n = 612 village-pairs) indicating homogeneity in disease processes within the defined spatial scales. Of the villages located within 2 km from the main Nile branches (n = 46), 95% exhibited low prevalence. In addition, the spatial pattern of mf prevalence was shown to be negatively associated with annual rainfall and relative humidity, while it was positively associated with annual daily temperature. Average mf prevalence in warmer, relatively drier areas receiving 25 mm of rain was significantly higher (3.9%) than that in less warmer but more humid areas receiving 50 mm of rain (1.6%) (P < 0.0001). Based on the results of the present study, GIS was used to generate a "filariasis risk map" that could be used by health authorities to efficiently direct surveillance and control efforts. This investigation identified some of the factors underlying filariasis spatial pattern, quantified clustering and demonstrated the potential of GIS application in vector-borne disease epidemiology.

Animals↗
PubMed1999

Integration of signaling networks that regulate Dictyostelium differentiation.

In Dictyostelium amoebae, cell-type differentiation, spatial patterning, and morphogenesis are controlled by a combination of cell-autonomous mechanisms and intercellular signaling. A chemotactic aggregation of approximately 10(5) cells leads to the formation of a multicellular organism. Cell-type differentiation and cell sorting result in a small number of defined cell types organized along an anteroposterior axis. Finally, a mature fruiting body is created by the terminal differentiation of stalk and spore cells. Analysis of the regulatory program demonstrates a role for several molecules, including GSK-3, signal transducers and activators of transcription (STAT) factors, and cAMP-dependent protein kinase (PKA), that control spatial patterning in metazoans. Unexpectedly, two component systems containing histidine kinases and response regulators also play essential roles in controlling Dictyostelium development. This review focuses on the role of cAMP, which functions intracellularly to mediate the activity of PKA, an essential component in aggregation, cell-type specification, and terminal differentiation. Cytoplasmic cAMP levels are controlled through both the regulated activation of adenylyl cyclases and the degradation by a phosphodiesterase containing a two-component system response regulator. Extracellular cAMP regulates G-protein-dependent and -independent pathways to control aggregation as well as the activity of GSK-3 and the transcription factors GBF and STATa during multicellular development. The integration of these pathways with others regulated by the morphogen DIF-1 to control cell fate decisions are discussed.

Animals↗
PubMed2005

Cytoplasmic and nuclear markers reveal contrasting patterns of spatial genetic structure in a natural Ipomopsis hybrid zone.

Spatial variation in natural selection may play an important role in determining the genetic structure of hybridizing populations. Previous studies have found that F1 hybrids between naturally hybridizing Ipomopsis aggregata and Ipomopsis tenuituba in central Colorado differ in fitness depending on both genotype and environment: hybrids had higher survival when I. aggregata was the maternal parent, except in the centre of the hybrid zone where both hybrid types had high survival. Here, we developed both maternally (cpDNA PCR-RFLP) and biparentally inherited (nuclear AFLP) species-diagnostic markers to characterize the spatial genetic structure of the natural Ipomopsis hybrid zone, and tested the prediction that the majority of natural hybrids have I. aggregata cytoplasm, except in areas near the centre of the hybrid zone. Analyses of 352 individuals from across the hybrid zone indicate that cytoplasmic gene flow is bidirectional, but contrary to expectation, most plants in the hybrid zone have I. tenuituba cytoplasm. This cytotype distribution is consistent with a hybrid zone in historical transition, with I. aggregata nuclear genes advancing into the contact zone. Further, nuclear data show a much more gradual cline than cpDNA markers that is consistent with morphological patterns across the hybrid populations. A mixture of environment- and pollinator-mediated selection may contribute to the current genetic structure of this hybrid system.

Base Sequence↗
PubMed2006

Spatial genetic pattern in the land mollusc Helix aspersa inferred from a 'centre-based clustering' procedure.

The present work provides the first broad-scale screening of allozymes in the land snail Helix aspersa. By using overall information available on the distribution of genetic variation between 102 populations previously investigated, we expect to strengthen our knowledge on the spread of the invasive aspersa subspecies in the Western Mediterranean. We propose a new approach based on a centre-based clustering procedure to cluster populations into groups following rules of geographical proximity and genetic similarity. Assuming a stepping-stone model of diffusion, we apply a partitioning algorithm which clusters only populations that are geographically contiguous. The algorithm used, which is actually part of leading methods developed for analysing large microarray datasets, is that of the k-means. Its goal is to minimize the within-group variance. The spatial constraint is provided by a list of connections between localities deduced from a Delaunay network. After testing each optimal group for the presence of spatial arrangement in the genetic data, the inferred genetic structure was compared with partitions obtained from other methods published for defining homogeneous groups (i.e. the Monmonier and SAMOVA algorithms). Competing biogeographical scenarios inferred from the k-means procedure were then compared and discussed to shed more light on colonization routes taken by the species.

Animals↗
PubMed1997

Multiple positive cis elements regulate the asymmetric expression of the SpHE gene along the sea urchin embryo animal-vegetal axis.

The mechanism that establishes the maternally determined animal-vegetal axis of sea urchin embryos is unknown. We have analyzed the cis-regulatory elements of the SpHE gene of Strongylocentrotus purpuratus, which is asymmetrically expressed along this axis, in an effort to identify components of maternal positional information. Previously, we defined a regulatory region that is sufficient to provide correct nonvegetal expression of a beta-galactosidase reporter gene (Wei, Z., Angerer, L. M., Gagnon, M. L., and Angerer, R. C., Dev. Biol. 171, 195-211, 1995). We have now analyzed this region intensively in order to determine if the spatial pattern is controlled by nonvegetal-positive activities or by vegetal-negative activities. The regulatory sequences, except the basal promoter, were mutated by either deletion or sequence replacement. None of these mutations resulted in ectopic beta-gal expression in vegetal cells, showing that no single negative cis element is responsible for the lack of vegetal SpHE transcription. Surprisingly, even short segments of the regulatory region containing only several identified cis elements also direct nonvegetal expression. Furthermore, the SpHE basal promoter functions effectively in vegetal cells in combination with cis-acting elements derived from the PMC-specific gene, SM50. We conclude that the spatial pattern of SpHE transcription is achieved by multiple positive activities concentrated in nonvegetal cells. The vegetal expression of SM50 also is regulated only by positive activities (Makabe, K. W., Kirchhamer, C. V., Britten, R. J., and Davidson, E. H., Development 121, 1957-1970, 1995). A chimeric promoter containing both SpHE and SM50 regulatory sequences is active ubiquitously, suggesting that these regulators are not reciprocally repressive. These observations suggest a model in which the SpHE and SM50 genes are activated by separate sets of positive maternal activities concentrated, respectively, in nonvegetal and vegetal domains of the early embryo.

Animals↗
PubMed2005

Exploring scale-dependent correlations between cancer mortality rates using factorial kriging and population-weighted semivariograms.

This paper presents a geostatistical methodology which accounts for spatially varying population size in the processing of cancer mortality data. The approach proceeds in two steps: (1) spatial patterns are first described and modeled using population-weighted semivariogram estimators, (2) spatial components corresponding to nested structures identified on semivariograms are then estimated and mapped using a variant of factorial kriging. The main benefit over traditional spatial smoothers is that the pattern of spatial variability (i.e. direction-dependent variability, range of correlation, presence of nested scales of variability) is directly incorporated into the computation of weights assigned to surrounding observations. Moreover, besides filtering the noise in the data the procedure allows the decomposition of the structured component into several spatial components (i.e. local versus regional variability) on the basis of semivariogram models. A simulation study demonstrates that maps of spatial components are closer to the underlying risk maps in terms of prediction errors and provide a better visualization of regional patterns than the original maps of mortality rates or the maps smoothed using weighted linear averages. The proposed approach also attenuates the underestimation of the magnitude of the correlation between various cancer rates resulting from noise attached to the data. This methodology has great potential to explore scale-dependent correlation between risks of developing cancers and to detect clusters at various spatial scales, which should lead to a more accurate representation of geographic variation in cancer risk, and ultimately to a better understanding of causative relationships.

Journal Article↗
PubMed2002

How synchronization properties among second-order sensory neurons can mediate stimulus salience.

Spatial patterns of glomerular activity in the vertebrate olfactory bulb and arthropod antennal lobe reflect an important component of first-order olfactory representation and contribute to odorant identification. Higher concentration odor stimuli evoke broader glomerular activation patterns, resulting in greater spatial overlap among different odor representations. However, behavioral studies demonstrate results contrary to what these data might suggest: Honeybees are more, not less, able to discriminate among odorants applied at higher concentrations. Using a computational model of the honeybee antennal lobe, the authors show that changes in synchronization patterns among antennal lobe projection neurons, as observed electrophysiologically, could parsimoniously underlie these observations. The results suggest that stimulus salience, as defined behaviorally, is directly correlated with the degree of synchronization among second-order olfactory neurons.

Animals↗
PubMed1998

The Marshall R. Urist Young Investigator Award. Gene expression during autograft lumbar spine fusion and the effect of bone morphogenetic protein 2.

A prospective animal study of posterolateral lumbar spine arthrodesis was performed to determine the temporal and spatial pattern of gene expression and to determine the effect of recombinant human bone morphogenetic protein 2 on the gene expression pattern of a healing spine fusion mass. In Group 1, 20 adult New Zealand rabbits underwent L4-L5 posterolateral intertransverse process arthrodesis using autograft alone. Two rabbits were euthanized at each of the following points: 0, 2, and 4 days, and 1, 2, 3, 4, 5, 6, and 10 weeks after surgery. The same surgical technique was used for 16 rabbits in Group II, except that the autograft first was soaked in a solution of recombinant human bone morphogenetic protein 2 before implantation. Ribonucleic acid was extracted from different regions of the fusion mass at each point and analyzed for expression of bone and cartilage related genes using reverse transcription polymerase chain reaction. A reproducible temporal sequence and spatial pattern of gene expression was found in healing spine fusions. In the central portion of the fusion mass a temporal lag in gene expression was observed that parallels the lag in healing within the central zone previously observed in histologic studies. Treatment of bone graft with recombinant human bone morphogenetic protein 2 resulted in an increase in the early expression of bone morphogenetic protein 6 which was associated with expression of higher levels of Type I collagen, osteocalcin, and other bone related genes. These findings suggest that central nonunion may be associated with delayed expression of osteoblast related genes in the central region of the forming fusion mass. The growth factor, recombinant human bone morphogenetic protein 2, increased the level of bone related gene expression throughout the fusion mass, eliminated the delay in healing within the central zone, and may decrease the likelihood of a nonunion.

Animals↗
PubMed2003

[Biological characteristics and spatial distribution of Chorthippus dubius population on high mountain grassland].

Based on rearing observations and surveys in Ganjia High-Mountain Grassland, Xiahe County, Gansu Province, the occurrence period, ingestion capacity, spatial pattern, and dynamics of Chorthippus dubius were studied. The results showed that this grasshopper had only one generation in a year. Its eggs wintered in the soil, and in the next year, they began to hatch from the last ten days of May to the first ten days of June. The hatching peak took place from the middle ten days to the last ten days of June. The majority of the nymphs possessed 4 instars, and about 23% of them possessed 5 instars. The developmental duration of the nymphs underwent about 70 days, and the longevity of the adults lasted for 42 days. The ingestion capacity of the nymphs was 368. 3 mg, and that of the adults was 743.8 mg. The spatial pattern of 1-2 instars belonged to an aggregated distribution, and that of 3-5 instars belonged to even and random distribution.

Animals↗
PubMed2003

Modulation of p53 after maternal exposure to all-trans-retinoic acid in Swiss Webster mouse fetuses.

The response to exposure of all-trans-retinoic acid (RA) during development varies from physiologic to severe teratogenic outcomes and is dependent upon the dose and the stage of development in all species. Effects of RA-mediated teratogenesis may be due to its ability to cause apoptosis. We have recently reported the modulation of p53 in murine stem cells by RA. The aim of this study was to characterize the temporal and spatial pattern of p53 expression in Swiss Webster mouse fetuses following maternal treatment with a single oral dose of 100 mg/kg body weight of RA during organogenesis. RA treatment resulted in a decreased p53 mRNA level in fetuses 24, 48, and 72 h after maternal treatment as detected by semiquantitative reverse transcriptase polymerase chain reaction. Western blot analysis showed a decrease in p53 protein at 24 and 48 h. Immunohistochemistry revealed decreased localization of p53 in the neuroepithelium of fetuses exposed to RA in utero. RA treatment also resulted in decreased nuclear p21 and decreased expression of cytosolic as well as nuclear p27 at 72 h in the fetuses. These results demonstrated that RA-mediated teratogenesis is accompanied by a reduction in the temporal and spatial pattern of p53 gene and protein expression in addition to the disruption of the cell cycle by modulation of p21 and p27.

Abnormalities, Drug-Induced↗
PubMed2001

Matrix and cell injury due to sub-impact loading of adult bovine articular cartilage explants: effects of strain rate and peak stress.

Mechanical overloading of cartilage has been implicated in the initiation and progression of osteoarthrosis. Our objectives were to identify threshold levels of strain rate and peak stress at which sub-impact loads could induce cartilage matrix damage and chondrocyte injury in bovine osteochondral explants and to explore relationships between matrix damage, spatial patterns of cell injury, and applied loads. Single sub-impact loads characterized by a constant strain rate between 3 x 10(-5) and 0.7 s(-1) to a peak stress between 3.5 and 14 MPa were applied, after which explants were maintained in culture for four days. At the higher strain rates, matrix mechanical failure (tissue cracks) and cell deactivation were most severe near the cartilage superficial zone and were associated with sustained increased release of proteoglycan from explants. In contrast, low strain rate loading was associated with cell deactivation in the absence of visible matrix damage. Furthermore, cell activity and proteoglycan synthesis were suppressed throughout the cartilage depth, but in a radially dependent manner with the most severe effects at the center of cylindrical explants. Results highlight spatial patterns of matrix damage and cell injury which depend upon the nature of injurious loading applied. These patterns of injury may also differ in terms of their long-term implications for progression of degradative disease and possibilities for cartilage repair.

Animals↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1989

A chromosome rearrangement suggests that donor and recipient sites are associated during Tam3 transposition in Antirrhinum majus.

We describe the structure of a chromosome rearrangement which changes the spatial pattern of expression of the pallida gene of Antirrhinum majus. The rearrangement involves a chromosome inversion of ~6 map units with one breakpoint at the end of a copy of the transposable element Tam3 located in the promoter region of the pallida locus. The sequence at the breakpoints shows that 5-7 bp, present once in the progenitor, has been duplicated and flanks both ends of the inversion. We propose that this structure arose from an aberrant Tam3 transposition, suggesting a model for normal transposition which involves physical association between donor and recipient sites. This may explain why transposition of plant transposable elements such as Ac in maize occurs preferentially to recipient sites closely linked to the donor site. Excision of the Tam3 copy located at the end of the chromosome inversion, results in a unique spatial pattern of pallida gene expression as a consequence of replacing all sequence 70 bp upstream of transcription by a new sequence. This pattern may be the result of deleting specific upstream components which regulate pallida expression and/or of changing the relative chromosome position of the pallida gene.

Journal Article↗
PubMed2005

Visuo-motor pathways in humans revealed by event-related fMRI.

Whether different brain networks are involved in generating unimanual responses to a simple visual stimulus presented in the ipsilateral versus contralateral hemifield remains a controversial issue. Visuo-motor routing was investigated with event-related functional magnetic resonance imaging (fMRI) using the Poffenberger reaction time task. A 2 hemifield x 2 response hand design generated the "crossed" and "uncrossed" conditions, describing the spatial relation between these factors. Both conditions, with responses executed by the left or right hand, showed a similar spatial pattern of activated areas, including striate and extrastriate areas bilaterally, SMA, and M1 contralateral to the responding hand. These results demonstrated that visual information is processed bilaterally in striate and extrastriate visual areas, even in the "uncrossed" condition. Additional analyses based on sorting data according to subjects' reaction times revealed differential crossed versus uncrossed activity only for the slowest trials, with response strength in infero-temporal cortices significantly correlating with crossed-uncrossed differences (CUD) in reaction times. Collectively, the data favor a parallel, distributed model of brain activation. The presence of interhemispheric interactions and its consequent bilateral activity is not determined by the crossed anatomic projections of the primary visual and motor pathways. Distinct visuo-motor networks need not be engaged to mediate behavioral responses for the crossed visual field/response hand condition. While anatomical connectivity heavily influences the spatial pattern of activated visuo-motor pathways, behavioral and functional parameters appear to also affect the strength and dynamics of responses within these pathways.

Adult↗
PubMed2000

Odorant molecular length: one aspect of the olfactory code.

Organic acid odorants of differing carbon number produce systematically different spatial patterns of [(14)C]2-deoxyglucose uptake in the glomerular layer of the olfactory bulb. Because increasing carbon number correlates with progressive increases in several molecular features, including hydrophobicity, length, and volume, we determined which of these properties was most associated with systematic changes in the location of an anterior, dorsomedial module responding to fatty acids. We exposed groups of rats to two series of organic acids that each had the same number of carbons, but differed in their hydrocarbon structures. These straight-chained, branched, cyclic, and double-bonded molecules differed independently in hydrophobicity, length, and volume. The only molecular property that was strongly correlated with the location of the module was molecular length, suggesting that this molecular feature is the principal determinant of the chemotopic organization of glomeruli within the module. We also found that distinct hydrocarbon structures produced large differences in spatial patterns of 2-deoxyglucose uptake in posterior parts of the bulb. Even subtly distinct structural isomers evoked posterior responses that differed greatly. The odorant 2-methylbutyric acid evoked much greater uptake in the posterior bulb than did its structural isomer 3-methylbutyric acid (isovaleric acid). These data suggest that posterior portions of the bulb may encode specific steric features of odorant molecules and that some odorant features may have an inherent or acquired greater representation than do others.

Animals↗