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Spatial reconstruction of signals from short-wavelength cones.

Because the retinal cone mosaic samples an image only at discrete locations, our continuous visual percept must arise from a spatial reconstruction process. How this process combines information from the three cone types is presently unclear. To investigate, we asked whether L and M cone information can modify the visual system's reconstruction of signals from S cones. In Expt 1, we used a matching paradigm to measure the effect of L and M cone information on filling-in at the foveal tritanopic area. We found that a small luminance disk superimposed at the tritanopic area decreases the amount of filling-in, showing that the reconstruction of S cone signals can be influenced by the spatial pattern seen by the L and M cones. In Expt 2, we asked whether L and M cone information can modify the splotchy low-frequency alias seen when an observer views fine S cone gratings. Here there was no evidence for an interaction. We conclude that though L and M cone information can influence the visual system's reconstruction of S cone signals, this influence may be confined to relatively coarse spatial patterns.

Color Perception↗

HLA-C expression pattern is spatially different between psoriasis and eczema skin lesions.

Interactions between genetic and environmental factors underlie the immune dysregulation and keratinocyte abnormalities that characterize psoriasis. Among known psoriasis susceptibility loci (PSORS), PSORS1 on chromosome 6 has the strongest association to disease. Altered expression of some PSORS1 candidate genes has been reported but little is known about HLA-C expression in psoriasis. This study compared expression of major histocompatibility complex class Ia and HLA-C in psoriasis, allergic contact eczema, and normal skin. Although HLA-C was abundant in protein extracts from both eczema and psoriasis, a consistent and intriguing difference in the expression pattern was observed; strong immunoreactivity in the basal cell layer, polarized towards the basement membrane in psoriasis, whereas in eczema lesions HLA-C immunostaining was present mostly in suprabasal cells. Inflammatory cells in the dermis were strongly stained in both diseases. Normal skin epithelium showed less intense but similar HLA-C staining as eczema lesions. HLA class Ia expression overall resembled that of HLA-C in all samples. The distinct HLA-C expression patterns in psoriasis and eczema suggest a functional role in the specific psoriasis immune response and not only a general feature of inflammation.

Blotting, Western↗

Regulated expression of the MADS-box transcription factor SrfA mediates activation of gene expression by protein kinase A during Dictyostelium sporulation.

Cell differentiation and morphogenesis are tightly regulated during sporulation in the lower eukaryote Dictyostelium discoideum. The control of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is essential to coordinate these processes. Several signal transduction pathways are being recognized that lead to the regulation of intracellular cAMP levels. However, very little is known about the events lying downstream of PKA that are essential to activate late gene expression and terminal differentiation of the spores. We have studied the relationship between PKA and the MADS-box transcription factor SrfA, essential for spore differentiation. Constitutive activation of PKA was not able to rescue sporulation in a strain that lacks srfA suggesting the possibility that srfA functions downstream of PKA in a signal transduction pathway leading to spore maturation. A distal promoter region regulates the induction of srfA expression in the prespore region during culmination. We found that this promoter can be induced precociously by activating PKA with 8-Br-cAMP suggesting a transcriptional regulation by PKA. Moreover, precocious sporulation and expression of the spore marker spiA in a strain that overexpresses PKA, correlates with a precocious induction of srfA expression. The temporal and spatial pattern of expression was also studied in a mutant strain lacking the main adenylyl cyclase that functions during culmination, ACR. This strain is expected to have lower PKA activity and consistently, the level of srfA expression was reduced. Moreover, the temporal induction of srfA in the prespore region was also delayed during culmination. Our results strongly suggest that PKA activation during culmination leads to the induction of the expression of srfA. The correct temporal and spatial pattern of srfA expression appears to be part of a mechanism that ensures the adequate coordination of gene expression and morphogenesis.

Animals↗

The urban environment from the health perspective: the case of Belo Horizonte, Minas Gerais, Brazil.

This study aims to determine spatial patterns of mortality and morbidity for five health problems in an urban environment: homicides, adolescent pregnancy, asthma hospitalization, and two vector-borne diseases, dengue and visceral leishmaniasis. All events were obtained through the city health database and geoprocessed using residential addresses and 80 planning units consisting of census tracts. We used thematic maps, proportionate mortality/morbidity ratios by planning unit, and the overlapped rank of the 20th worse planning unit rates for each event. A spatial pattern of high rates of homicides, proportion of young mothers, and hospitalization due to asthma overlapped in socially and economically disadvantaged areas. For the two vector-borne diseases, high rates with great dispersion were found in underprivileged areas, in contrast with very low rates among higher income areas. The results indicated the coexistence of heavier disease burden for residents of urban areas where poverty and lack of effective public health policies may be modulating social health problems. For the two vector-borne diseases, an environmental intervention in one mosquito-borne disease might be playing a role in the other's incidence.

Adolescent↗

More "mapping" in brain mapping: statistical comparison of effects.

The term "mapping" in the context of brain imaging conveys to most the concept of localization; that is, a brain map is meant to reveal a relationship between some condition or parameter and specific sites within the brain. However, in reality, conventional voxel-based maps of brain function, or for that matter of brain structure, are generally constructed using analyses that yield no basis for inferences regarding the spatial nonuniformity of the effects. In the normal analysis path for functional images, for example, there is nowhere a statistical comparison of the observed effect in any voxel relative to that in any other voxel. Under these circumstances, strictly speaking, the presence of significant activation serves as a legitimate basis only for inferences about the brain as a unit. In their discussion of results, investigators rarely are content to confirm the brain's role, and instead generally prefer to interpret the spatial patterns they have observed. Since "pattern" implies nonuniform effects over the map, this is equivalent to interpreting results without bothering to test their significance, a practice most of the experimentally-trained would eschew in other contexts. In this review, we appeal to investigators to adopt a new standard of data presentation that facilitates comparison of effects across the map. Evidence for sufficient effect size difference between the effects in structures of interest should be a prerequisite to the interpretation of spatial patterns of activation.

Brain Mapping↗

Poisson process approximation for sequence repeats, and sequencing by hybridization.

Sequencing by hybridization is a tool to determine a DNA sequence from the unordered list of all l-tuples contained in this sequence; typical numbers for l are l = 8, 10, 12. For theoretical purposes we assume that the multiset of all l-tuples is known. This multiset determines the DNA sequence uniquely if none of the so-called Ukkonen transformations are possible. These transformations require repeats of (l-1)-tuples in the sequence, with these repeats occurring in certain spatial patterns. We model DNA as an i.i.d. sequence. We first prove Poisson process approximations for the process of indicators of all leftmost long repeats allowing self-overlap and for the process of indicators of all left-most long repeats without self-overlap. Using the Chen-Stein method, we get bounds on the error of these approximations. As a corollary, we approximate the distribution of longest repeats. In the second step we analyze the spatial patterns of the repeats. Finally we combine these two steps to prove an approximation for the probability that a random sequence is uniquely recoverable from its list of l-tuples. For all our results we give some numerical examples including error bounds.

Algorithms↗

Movement of badgers (Meles meles) in a high-density population: individual, population and disease effects.

The movement of 1763 badgers trapped between 36 social groups in Woodchester Park, Gloucestershire, over 18 years was analysed to determine the frequency and duration of moves, the factors associated with a predisposition to move and the spatial pattern of movements. Of those badgers whose capture history could be categorized, nearly half had moved. Of these, 73.1% were classified as 'occasional movers', 22.1% as 'permanent movers' and 4.8% as 'frequent movers'. Most adult badgers that moved made occasional moves (78.8%, n = 67). Cubs made all types of move including permanent moves (29%, n = 10). Seventy per cent of females were non-movers compared with 37% of males. Badgers were significantly more likely to move to smaller groups, whereas male badgers were significantly more likely to move to groups with a greater proportion of females. The spatial pattern of movement differed from the distribution of groups with bovine tuberculosis in the study area. However, temporal changes in movement were significantly related to the incidence of Mycobacterium bovis infection in the following year, indicating that as the movement of badgers between groups varies so does the incidence of bovine tuberculosis in the population. This finding is of central importance in the formulation of badger control policy.

Animals↗

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

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

Color Perception↗

Biomonitoring of airborne inorganic and organic pollutants by means of pine tree barks. I. Temporal and spatial variations.

Scots pine (Pinus sylvestris L.) bark samples were collected at two field sites (Neuglobsow, Rösa) and in different years between 1987 and 1996 in the east of Germany. The barks were analyzed with respect to the following inorganic and organic substances: Al, As, B, Ca, Cd, Ce, Cr, Cu, Fe, Hg, Mo, NH4+, Ni, NO3-, PO4(3)-, Pb, Sr, SO4(2)-, Ti, V, W, Zr, Zn, benzo[a]pyrene, fluoranthene, pyrene, alpha-hexachlorocyclohexane (alpha-HCH) and dichlorodiphenyltrichloroethane (DDT). In addition to bark samples from the site Rösa, 53 test sites were investigated in the Nature Park Dübener Heide. Here, the analysis of the barks aimed at discovering spatial patterns of the above-mentioned substances. Since 1991, most of the determined substances (e.g. sulfate, nitrate, calcium, lead, benzo[a]pyrene, alpha-HCH) show decreased concentration values in bark samples from both sites. Temporal variations reflect substantial infra-structural changes in eastern Germany, especially at Rösa and in the industrial region around the cities Leipzig, Halle, and Bitterfeld. Moreover, nitrate concentrations in barks are increasing since 1995. The trend can be explained with increased nitrogen emissions from motor traffic and livestock farms. Spatial patterns of sulphate and ammonia reflect inputs from power plants and agriculture in pine stands of the Nature Park Dübener Heide. The results show that barks of pine trees can be used as biomonitoring tools to indicate and characterize depositions of airborne organic and inorganic pollutants.

Agriculture↗

Sub-array normalization subject to differentiation.

From microarray measurement, we seek differentiation of mRNA expressions among different biological samples. However, each array has a 'block effect' due to uncontrolled variation. The statistical treatment of reducing the block effect is usually referred to as normalization. Our perspective is to find a transformation that matches the distributions of hybridization levels of those probes corresponding to undifferentiated genes between arrays. We address two important issues. First, array-specific spatial patterns exist due to uneven hybridization and measurement process. Second, in some cases a substantially large portion of genes are differentially expressed between a target and a reference array. For the purpose of normalization we need to identify a subset that exclude those probes corresponding to differentially expressed genes and abnormal probes due to experimental variation. Least trimmed squares (LTS) is a natural choice to achieve this goal. Substantial differentiation is protected in LTS by setting an appropriate trimming fraction. To take into account any spatial pattern of hybridization, we divide each array into sub-arrays and normalize probe intensities within each sub-array. We illustrate the problem and solution through an Affymetrix spike-in dataset with defined perturbation and a dataset of primate brain expression.

Animals↗

Inhibition of backpropagating action potentials in mitral cell secondary dendrites.

The mammalian olfactory bulb is a geometrically organized signal-processing array that utilizes lateral inhibitory circuits to transform spatially patterned inputs. A major part of the lateral circuitry consists of extensively radiating secondary dendrites of mitral cells. These dendrites are bidirectional cables: they convey granule cell inhibitory input to the mitral soma, and they conduct backpropagating action potentials that trigger glutamate release at dendrodendritic synapses. This study examined how mitral cell firing is affected by inhibitory inputs at different distances along the secondary dendrite and what happens to backpropagating action potentials when they encounter inhibition. These are key questions for understanding the range and spatial dependence of lateral signaling between mitral cells. Backpropagating action potentials were monitored in vitro by simultaneous somatic and dendritic whole cell recording from individual mitral cells in rat olfactory bulb slices, and inhibition was applied focally to dendrites by laser flash photolysis of caged GABA (2.5-microm spot). Photolysis was calibrated to activate conductances similar in magnitude to GABA(A)-mediated inhibition from granule cell spines. Under somatic voltage-clamp with CsCl dialysis, uncaging GABA onto the soma, axon initial segment, primary and secondary dendrites evoked bicuculline-sensitive currents (up to -1.4 nA at -60 mV; reversal at approximatety 0 mV). The currents exhibited a patchy distribution along the axon and dendrites. In current-clamp recordings, repetitive firing driven by somatic current injection was blocked by uncaging GABA on the secondary dendrite approximately 140 microm from the soma, and the blocking distance decreased with increasing current. In the secondary dendrites, backpropagated action potentials were measured 93-152 microm from the soma, where they were attenuated by a factor of 0.75 +/- 0.07 (mean +/- SD) and slightly broadened (1.19 +/- 0.10), independent of activity (35-107 Hz). Uncaging GABA on the distal dendrite had little effect on somatic spikes but attenuated backpropagating action potentials by a factor of 0.68 +/- 0.15 (0.45-0.60 microJ flash with 1-mM caged GABA); attenuation was localized to a zone of width 16.3 +/- 4.2 microm around the point of GABA release. These results reveal the contrasting actions of inhibition at different locations along the dendrite: proximal inhibition blocks firing by shunting somatic current, whereas distal inhibition can impose spatial patterns of dendrodendritic transmission by locally attenuating backpropagating action potentials. The secondary dendrites are designed with a high safety factor for backpropagation, to facilitate reliable transmission of the outgoing spike-coded data stream, in parallel with the integration of inhibitory inputs.

Action Potentials↗

Beta/A4 deposits and their relationship to senile plaques in Alzheimer's disease.

The density and spatial pattern of immunostained beta/A4 deposits and mature senile plaques (SP) stained by the Glees method were compared in Alzheimer's diseased brain. Thirty-seven percent of the variance in Glees SP density in a tissue could be explained by beta/A4. Both lesions were clustered with the beta/A4 clusters often larger than the Glees SP clusters. Beta/A4 and Glees SP cluster size were not correlated in a tissue. The size of Glees SP clusters was positively correlated with SP density but no correlation could be detected for beta/A4. Hence, the density and spatial pattern of beta/A4 deposits in most tissues did not predict the development of Glees SP.

Alzheimer Disease↗

Application of different spatial sampling patterns for sparse array transducer design.

In the last few years, the efforts of many researchers have been focused on developing 3D real-time scanners. The use of 2D phased-array transducers makes it possible to steer the ultrasonic beam in all directions in the scanned volume. An unacceptably large amount of transducer channels (more than 4,000) must be used, if the conventional phased array transducers are extrapolated to the 2D case. To decrease the number of channels, sparse arrays with different aperture apodization functions in transmit and receive apertures have to be designed. The design is usually carried out in 1D, and then transferred to a 2D rectangular grid. In this paper, five different 2D array transducers have been considered and their performance was compared with respect to spatial and contrast resolution. An optimization of the element placement along the diagonals using vernier arrays is suggested. The simulation results of the ultrasound fields show a decrease in the grating-lobe level of 10 dB for the diagonally optimized 2D array transducers compared to the previously designed 2D arrays which did not consider the diagonals.

Computer Simulation↗

Expression of type XII collagen by wound epithelial, mesenchymal, and ependymal cells during blastema formation in regenerating newt (Notophthalmus viridescens) tails.

Previously we showed that type XII collagen (col XII) is highly upregulated in the regenerating newt (Notophthalmus viridescens) forelimb. Here, using immunohistochemistry and in situ hybridization, we studied the pattern of expression of col XII during early stages of adult newt tail regeneration. The results show that immunoreactivity of col XII is first seen as a thin layer beneath the wound epithelium (WE) at 3 days after amputation. Reactivity associated with the mesenchyme becomes obvious at day 4 and increases considerably between days 6 and 7 after amputation. In situ hybridization indicates that the early WE-associated reactivity and later mesenchymal reactivity are due to increased col XII gene expression by the WE and mesenchyme, respectively. At 7 days after tail amputation both wound epithelial and mesenchymal cells exhibit a strong riboprobe signal. Interestingly, a distinct riboprobe signal is also seen in the cells of the outgrowing ependymal tube at day 7 but little if any col XII immunoreactivity is present. The spatial pattern of col XII gene expression changes by day 14 after amputation in that transcription in mesenchyme is maintained at a high level, in the WE it is reduced, and in ependyma it ceases to be detectable. Local deprivation of the spinal cord significantly lowers the level of col XII message in the mesenchyme. Much of this decrease in transcription is due to minimal mesenchymal cell accumulation secondary to spinal cord ablation. The temporal and spatial patterns of expression of the col XII gene in the WE, mesenchyme, and ependyma during tail regeneration strongly suggest a role for col XII in regulating both spinal cord outgrowth and spinal cord-dependent tail regeneration.

Amputation, Surgical↗

Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis.

Branching morphogenesis in the mammalian lung and Drosophila trachea relies on the precise localization of secreted modulators of epithelial growth to select branch sites and direct branch elongation, but the intercellular signals that control blood vessel branching have not been previously identified. We found that VEGF(120/120) mouse embryos, engineered to express solely an isoform of VEGF-A that lacks heparin-binding, and therefore extracellular matrix interaction domains, exhibited a specific decrease in capillary branch formation. This defect was not caused by isoform-specific differences in stimulating endothelial cell proliferation or by impaired isoform-specific signaling through the Nrp1 receptor. Rather, changes in the extracellular localization of VEGF-A in heparin-binding mutant embryos resulted in an altered distribution of endothelial cells within the growing vasculature. Instead of being recruited into additional branches, nascent endothelial cells were preferentially integrated within existing vessels to increase lumen caliber. The disruption of the normal VEGF-A concentration gradient also impaired the directed extension of endothelial cell filopodia, suggesting that heparin-binding VEGF-A isoforms normally provide spatially restricted stimulatory cues that polarize and thereby guide sprouting endothelial cells to initiate vascular branch formation. Consistent with this idea, we found opposing defects in embryos harboring only a heparin-binding isoform of VEGF-A, including excess endothelial filopodia and abnormally thin vessel branches in ectopic sites. We conclude that differential VEGF-A isoform localization in the extracellular space provides a control point for regulating vascular branching pattern.

Animals↗

Linking chronic wasting disease to mule deer movement scales: a hierarchical Bayesian approach.

Observed spatial patterns in natural systems may result from processes acting across multiple spatial and temporal scales. Although spatially explicit data on processes that generate ecological patterns, such as the distribution of disease over a landscape, are frequently unavailable, information about the scales over which processes operate can be used to understand the link between pattern and process. Our goal was to identify scales of mule deer (Odocoileus hemionus) movement and mixing that exerted the greatest influence on the spatial pattern of chronic wasting disease (CWD) in northcentral Colorado, USA. We hypothesized that three scales of mixing (individual, winter subpopulation, or summer subpopulation) might control spatial variation in disease prevalence. We developed a fully Bayesian hierarchical model to compare the strength of evidence for each mixing scale. We found strong evidence that the finest mixing scale corresponded best to the spatial distribution of CWD infection. There was also evidence that land ownership and habitat use play a role in exacerbating the disease, along with the known effects of sex and age. Our analysis demonstrates how information on the scales of spatial processes that generate observed patterns can be used to gain insight when process data are sparse or unavailable.

Animal Migration↗

Disease and dislocation: the impact of refugee movements on the geography of malaria in NWFP, Pakistan.

Studies of the health implications of refugee movements have generally focused on the effects of dislocation on the health of refugees and the impacts on health care provision at the destination. A somewhat more neglected aspect of the refugee-health research has been the impact of refugee flows on the geography of disease, i.e., how the spatial patterns of disease prevalence are modified through the influx and settlement of refugee populations. We examine this issue by examining the changing geography of malaria in Pakistan's North West Frontier Province (NWFP) between 1972 and 1997. Until the late 1970s, the highest incidence of malaria in the region was seen in the southern and eastern parts. During the 1980s, however, two and a half million Afghan refugees entered the NWFP and were housed in tented villages along the border and in some interior areas. As the decade progressed, there was a significant shift in the spatial pattern of malaria, with the regions of highest incidence shifting to the west and north, coinciding strongly with refugee concentrations. Our study draws attention to the manner in which refugee influx and settlement can alter the ecology of the disease system, leading to long-term changes in the geography of malaria.

Afghanistan↗

Biomonitoring of heavy metals and trace organics using the intertidal mussel Perna viridis in Hong Kong coastal waters.

This paper presents the results of a 6-year (1998-2003) survey of trace toxics in the intertidal mussel Perna viridis conducted by the Hong Kong Environmental Protection Department. Concentrations of heavy metals and trace organics were measured in the soft bodies of P. viridis collected from five sites in Hong Kong waters, i.e. Wu Kai Sha (Tolo Harbour), Ma Wan (Northwest), Tsim Sha Tsui (Victoria Harbour), Tai Tam (Hong Kong South) and Lamma Island (Southern Waters) in order to establish the spatial patterns of contaminants in mussels. Among the metals analysed, Cd showed a significant concentration gradient in Hong Kong waters. The levels of Cd in P. viridis were significantly higher at Ma Wan as compared to the other sites studied. Ma Wan also had relatively higher concentrations of Pb. Mn concentrations were particularly prominent at Wu Kai Sha. Significantly higher concentrations of Hg and Cu were recorded at Tai Tam and Tsim Sha Tsui. Tai Tam and Wu Kai Sha had higher levels of V; whereas higher Ni concentrations were recorded at Lamma Island and Tai Tam. No clear spatial patterns for Al, As, Cr, Fe and Zn were observed. Higher concentrations of PAHs in P. viridis were observed around urban centres impacted by sewage discharges (e.g. Tsim Sha Tsui); whereas higher PCB levels were found not only in Tsim Sha Tsui but also in less urbanised areas such as Lamma Island and Tai Tam, suggesting that these may be due to non-sewage related inputs. The study also shows that Northwest and Southern waters are subject to a higher degree of DDT pollution compared with other sites. Of the 17 dioxin compounds analysed, positive data were mostly recorded for two compounds which are of low toxicity (i.e. OCDD and 1,2,3,4,6,7,8-HpCDD) whereas the most toxic congeners (i.e. 2,3,7,8-TCDD and 1,2,3,7,8-PeCDD) were not detected in the 6 years of monitoring. In general, the levels of OCDD in P. viridis were found to be higher in Tai Tam and Lamma Island in Southern Waters of Hong Kong. This study found that the levels of some highly toxic heavy metals (i.e. Cd, Hg and Pb) in the mussel P. viridis did not exceed the recommended limits for shellfish as food in Hong Kong (i.e. Cd: 2.0 ppm; Hg: 0.5 ppm; Pb: 6.0 ppm wet weight). The levels of As and Ni in P. viridis were also well below the action limits set by the US FDA (i.e. As: 86 ppm; Ni: 80 ppm wet weight). DDT and PCB contaminations in P. viridis were below the concentrations of concern. Compared with data obtained in the 1980s, the current levels of DDTs in P. viridis were 4-16 times lower; whereas Pb concentrations recorded in Tsim Sha Tsui have also been lowered significantly. This is mainly related to reduction in local and regional pollution sources in the past 20 years.

Analysis of Variance↗