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MPTP produces a mosaic-like pattern of terminal degeneration in the caudate nucleus of dog.

This paper describes the spatial pattern of terminal degeneration in the caudate nucleus and putamen of the dog following an injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Marked inhomogeneities in the filed of terminal degeneration were found in the head of the caudate nucleus, which are reminiscent of the fundamental patch/matrix organization of the striatum. Using MPTP as a selective lesioning method, our results provide further evidence that the dopaminergic, nigrostriatal projection has a heterogeneous organization.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Liesegang pattern formation in kappa-carrageenan gel.

We report a new class of the spatial pattern formation process in which the gel plays essential roles. The system studied here is the solution of kappa-carrageenan in which potassium chloride is diffused. The solution transforms into the gel state with the diffusion of potassium chloride. Then the stripe pattern, which is perpendicular to the direction of the diffusion of potassium chloride, appears within the gel. The pattern thus formed in the gel is studied as a function of the concentration of the solution of potassium chloride. We find that the dense region of the stripe pattern consists of the liquid crystalline gel, whereas the dilute region is the amorphous gel. The transition from the amorphous gel to the liquid crystalline gel, hence, occurs in the gel state of kappa-carrageenan. The gel behaves as a pattern-forming substance as well as the supporting medium of the pattern in this system. The period and the thickness of the layers of liquid crystalline gel are analyzed. Both the period and the thickness of the layers are found to depend strongly on the concentration of the solution of potassium chloride.

Journal Article↗

Patterns of elevated free calcium and calmodulin activation in living cells.

The temporal and spatial dynamics of intracellular signals and protein effectors are being defined as a result of imaging using fluorescent reagents within living cells. We have described a new class of fluorescent analogues termed optical biosensors, which sense chemical or molecular events through their effects on protein transducers. One example of this new class of indicators is MeroCaM, an environmentally sensitive fluorophore which when it is attached to calmodulin reflects the activation of calmodulin by calcium in vitro. We report here that the rise in free calcium and MeroCaM activation occur in the same period during serum stimulation of quiescent fibroblasts. MeroCaM activation also correlates with the spatial pattern of increased free calcium and the contraction of transverse fibres during wound healing. Finally, migrating fibroblasts in the later stages of wound-healing exhibit an increasing gradient of free calcium and MeroCaM activation from the front to the rear.

3T3 Cells↗

Role of Bud3p in producing the axial budding pattern of yeast.

Yeast cells can select bud sites in either of two distinct spatial patterns. a cells and alpha cells typically bud in an axial pattern, in which both mother and daughter cells form new buds adjacent to the preceding division site. In contrast, a/alpha cells typically bud in a bipolar pattern, in which new buds can form at either pole of the cell. The BUD3 gene is specifically required for the axial pattern of budding: mutations of BUD3 (including a deletion) affect the axial pattern but not the bipolar pattern. The sequence of BUD3 predicts a product (Bud3p) of 1635 amino acids with no strong or instructive similarities to previously known proteins. However, immunofluorescence localization of Bud3p has revealed that it assembles in an apparent double ring encircling the mother-bud neck shortly after the mitotic spindle forms. The Bud3p structure at the neck persists until cytokinesis, when it splits to yield a single ring of Bud3p marking the division site on each of the two progeny cells. These single rings remain for much of the ensuing unbudded phase and then disassemble. The Bud3p rings are indistinguishable from those of the neck filament-associated proteins (Cdc3p, Cdc10p, Cdc11p, and Cdc12p), except that the latter proteins assemble before bud emergence and remain in place for the duration of the cell cycle. Upon shift of a temperature-sensitive cdc12 mutant to restrictive temperature, localization of both Bud3p and the neck filament-associated proteins is rapidly lost. In addition, a haploid cdc11 mutant loses its axial-budding pattern upon shift to restrictive temperature. Taken together, the data suggest that Bud3p and the neck filaments are linked in a cycle in which each controls the position of the other's assembly: Bud3p assembles onto the neck filaments in one cell cycle to mark the site for axial budding (including assembly of the new ring of neck filaments) in the next cell cycle. As the expression and localization of Bud3p are similar in a, alpha, and a/alpha cells, additional regulation must exist such that Bud3p restricts the position of bud formation in a and alpha cells but not in a/alpha cells.

Amino Acid Sequence↗

Bithorax phenocopy and pattern formation. II. A model of prepattern formation.

Phenocopy maps are constructed from the spatial pattern of the phenocopy spots using a distance function defined on the frequencies with which two compartments transform separately and jointly. The temporal changes in distances between different compartments in turn enable us to make inferences concerning the diffusion-like processes involved in prepattern formation of the metathorax. A model is presented which accounts for the data in terms of the propagation of two wavefronts in sequence and in approximately orthogonal directions. Sensitivity to transformation by ether is limited in time to the interval between the passing of the two wavefronts. Changes caused by 13 successive generations of ether treatment can be interpreted in terms of alterations in the timing and rates of wave propagation. A comparison of phenocopy and fate maps suggests that the prepatterning processes affect primarily the blastoderm cytoplasm or surface membrane.

Animals↗

Recent mass balance of polar ice sheets inferred from patterns of global sea-level change.

Global sea level is an indicator of climate change, as it is sensitive to both thermal expansion of the oceans and a reduction of land-based glaciers. Global sea-level rise has been estimated by correcting observations from tide gauges for glacial isostatic adjustment--the continuing sea-level response due to melting of Late Pleistocene ice--and by computing the global mean of these residual trends. In such analyses, spatial patterns of sea-level rise are assumed to be signals that will average out over geographically distributed tide-gauge data. But a long history of modelling studies has demonstrated that non-uniform--that is, non-eustatic--sea-level redistributions can be produced by variations in the volume of the polar ice sheets. Here we present numerical predictions of gravitationally consistent patterns of sea-level change following variations in either the Antarctic or Greenland ice sheets or the melting of a suite of small mountain glaciers. These predictions are characterized by geometrically distinct patterns that reconcile spatial variations in previously published sea-level records. Under the--albeit coarse--assumption of a globally uniform thermal expansion of the oceans, our approach suggests melting of the Greenland ice complex over the last century equivalent to -0.6 mm yr(-1) of sea-level rise.

Journal Article↗

Spatial and temporal patterns of expression of Noggin and BMP4 in embryonic and postnatal rat hippocampus.

Recent studies indicate that bone morphogenetic protein-4 (BMP4) and Noggin not only play an important role in the early development of the nervous system, but may also play a role in postnatal central nervous system (CNS) development. In this study, we examined the relative levels and localization of Noggin and BMP4 mRNA in the hippocampus of rats of different developmental stages with reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). RT-PCR showed that the temporal changes in the levels of expression of Noggin and BMP4 were different. The peak level of expression of Noggin mRNA was observed at embryonic day 13 (E13), subsequently gradually declined at 1-3 months (P1-3M) postnatal, and was detected only at a low level at P18M. In contrast, the expression of BMP4 mRNA increased gradually during embryonic development, reached a maximal level at 3 weeks (W) postnatal, and declined only slightly through P18M. In situ hybridization revealed that at embryonic stages, Noggin mRNA was localized throughout all hippocampal regions, whereas at early postnatal ages, Noggin mRNA was primarily localized in the anterior subiculum. At embryonic and early postnatal stages, no significant BMP4 mRNA expression was detectable in the hippocampus. At later postnatal ages, however, Noggin and BMP4 mRNA expression was observed in similar patterns. At 1-3 months postnatal, expression of BMP4 was observed mainly in the dentate gyrus and in the CA1-CA3 pyramidal cell layers. Lower hybridization signals were observed in the hilus and subiculum. Taken together, our results demonstrate that Noggin and BMP4 are expressed in embryonic and postnatal hippocampus, and that the temporal and spatial patterns of their expression are developmentally regulated. These data suggest that Noggin and BMP4 play important roles in hippocampal development.

Aging↗

PCR detection of Tetramicra brevifilum (Microspora) infection in turbot (Scophthalmus maximus L.) musculature.

This study investigated the spatial distribution of Tetramicra brevifilum spores in the musculature of infected turbot Scophthalmus maximus, with the aim of identifying the most appropriate body locations for diagnostic assays. A PCR protocol optimized for the detection of T. brevifilum spores in turbot muscle is also described. In fish showing low- and moderate-intensity infection, the spatial distribution of spores was best fitted by a negative binomial distribution, indicating a clumped spatial pattern; the negative binomial coefficient k was lower for fish with low-intensity infection, indicating a more markedly clumped pattern in these fish. In fish with high-intensity infection, the spatial distribution of spores was best fitted by the Poisson distribution, indicating a random pattern. In both low- and moderate-intensity infection, spores were present at highest density in the musculature adjoining the dorsal fins. Samples for PCR were therefore obtained from this location. PCR amplification was of the small subunit ribosomal DNA (SSUrDNA), using a pair of species-specific primers that amplify the 1250 bp product. The PCR protocol developed showed better sensitivity than microscopical techniques (detection rate by microscopy 25%, versus 42% by PCR), suggesting that it may be useful for routine screening for Tetramicra brevifilum infection in cultured turbot.

Animals↗

Pre-MBT patterning of early gene regulation in Xenopus: the role of the cortical rotation and mesoderm induction.

Patterning events that occur before the mid-blastula transition (MBT) and that organize the spatial pattern of gene expression in the animal hemisphere have been analyzed in Xenopus embryos. We present evidence that genes that play a role in dorsoventral specification display different modes of activation. Using early blastomere explants (16-128-cell stage) cultured until gastrula stages, we demonstrate by RT-PCR analysis that the expression of goosecoid (gsc), wnt-8 and brachyury (bra) is dependent on mesoderm induction. In contrast, nodal-related 3 (nr3) and siamois (sia) are expressed in a manner that is independent of mesoderm induction, however their spatially correct activation does require cortical rotation. The pattern of sia and nr3 expression reveals that the animal half of the 16-cell embryo is already distinctly polarized along the dorsoventral axis as a result of rearrangement of the egg structure during cortical rotation. Similar to the antagonistic activity between the ventral and the dorsal mesoderm, the ventral animal blastomeres can attenuate the expression of nr3 and sia in dorsal animal blastomeres. Our data suggest that no Nieuwkoop center activity at the blastula stage is required for the activation of nr3 and sia in vivo.

Animals↗

Spatial statistics and geographical information systems in epidemiology and public health.

This chapter surveys the principles behind spatial statistics and geographic information systems (GIS), and their application to epidemiology and public health. Like the other introductory chapters, it is aimed mainly to facilitate understanding in the chapters specific to certain diseases that follow, and to provide a short introduction to the field. A brief overview of spatial statistics and GIS is provided in the introduction. The sections that follow explore the ways in which we can map the distribution of disease, ways in which we can look for spatial patterns in the distribution of disease, and ways in which we can apply spatial statistics and GIS to the problem of identifying the causal factors of observed patterns. In the last section I discuss some of the ways in which these techniques have been applied to assist decision making for disease intervention, and conclude by discussing future developments in the field, and some of the issues surrounding the integration of spatial statistics and GIS.

Animals↗

Memory, attention, and executive function in chronic fatigue syndrome.

OBJECTIVES: To examine cognitive function in chronic fatigue syndrome. METHODS: Twenty patients with chronic fatigue syndrome recruited from primary care and 20 matched normal controls were given CANTAB computerised tests of visuospatial memory, attention, and executive function, and verbal tests of letter and category fluency and word association learning. RESULTS: Patients with chronic fatigue syndrome were impaired, predominantly in the domain of memory but their pattern of performance was unlike that of patients with amnesic syndrome or dementia. They were normal on tests of spatial pattern recognition memory, simultaneous and delayed matching to sample, and pattern-location association learning. They were impaired on tests of spatial span, spatial working memory, and a selective reminding condition of the pattern-location association learning test. An executive test of planning was normal. In an attentional test, eight subjects with chronic fatigue syndrome were unable to learn a response set; the remainder exhibited no impairment in the executive set shifting phase of the test. Patients with chronic fatigue syndrome were also impaired on verbal tests of unrelated word association learning and letter fluency. CONCLUSION: Patients with chronic fatigue syndrome have reduced attentional capacity resulting in impaired performance on effortful tasks requiring planned or self ordered generation of responses from memory.

Adult↗

Volvox carteri as a model for studying the genetic and cytological control of morphogenesis.

The green alga Volvox carteri has a very simple and regular adult form that arises through a short sequence of well-defined morphogenetic steps. A mature gonidium (asexual reproductive cell) initiates a stereotyped sequence of rapid cleavage divisions that will produce all of the cells found later in an adult. A predictable subset of these divisions are asymmetric and result in production of a small set of germ cells in a precise spatial pattern. Throughout cleavage, all intracellular components are held in predictable spatial relationships by a cytoskeleton of unusually regular structure, while neighboring cells are also held in fixed spatial relationships by an extensive network of cytoplasmic bridges that form as a result of incomplete cytokinesis. As a result of these two orienting mechanisms combined, dividing cells are arranged around the anterior-posterior axis of the embryo with precise rotational symmetry. These relationships are maintained by the cytoplasmic bridge system when the embryo that was inside out at the end of cleavage turns right-side out in the gastrulation-like process of inversion. Inversion is driven by a cytoskeleton-mediated sequence of cell shape changes, cellular movements and coordinated contraction. Then, by the time the cytoplasmic bridges begin to break down shortly after inversion, a preliminary framework of extracellular matrix (ECM) has been formed. The ECM traps the cells and holds them in the rotational relationships that were established during cleavage, and that must be maintained in order for the adult to be able to swim. Transposon tagging is now being used to clone and characterize the genes regulating these morphogenetic processes.

Chlorophyta↗

Long-wavelength instabilities of three-dimensional patterns.

Long-wavelength instabilities of steady patterns, spatially periodic in three dimensions, are studied. All potentially stable patterns with the symmetries of the simple-, face-centered- and body-centered-cubic lattices are considered. The results generalize the well-known Eckhaus, zigzag, and skew-varicose instabilities to three-dimensional patterns and are applied to two-species reaction-diffusion equations modeling the Turing instability.

Journal Article↗

Propagation through electrically coupled cells. Effects of regional changes in membrane properties.

The normal process of excitation of the heart involves propagation of action potentials through cardiac regions of different anatomy and different intrinsic membrane properties. Although our understanding of these properties is still incomplete, it is well accepted that the parameters measured from a single cell penetration in an electrical syncytium (e.g., action potential duration, rate of rise, and velocity) reflect not only the properties of that cell but also the electrotonic interactions with other cells to which the recorded cell is electrically coupled. We have used simulation techniques to predict the spatial distribution of action potential parameters resulting from discretely localized alterations in the intrinsic membrane properties of some of the cells of an electrical syncytium. We have shown that the resulting spatial distribution is markedly different for alterations in plateau and pacemaker currents vs. rising phase currents, and that other factors, such as the site of stimulation and the underlying spatial pattern of cell-cell coupling resistance, also modify the spatial distribution of action potential properties resulting from a discrete regional change in intrinsic membrane properties.

Action Potentials↗

Spatial memory and integration processes in congenital blindness.

The paper tests the hypothesis that difficulties met by the blind in spatial processing are due to the simultaneous treatment of independent spatial representations. Results showed that lack of vision does not impede the ability to process and transform mental images; however, blind people are significantly poorer in the recall of more than a single spatial pattern at a time than in the recall of the corresponding material integrated into a single pattern. It is concluded that the simultaneous maintenance of different spatial information is affected by congenital blindness, while cognitive processes that may involve sequential manipulation are not.

Adolescent↗

Effects of dispersal mechanisms on spatio-temporal development of epidemics.

The nature of pathogen transport mechanisms strongly determines the spatial pattern of disease and, through this, the dynamics and persistence of epidemics in plant populations. Up to recently, the range of possible mechanisms or interactions assumed by epidemic models has been limited: either independent of the location of individuals (mean-field models) or restricted to local contacts (between nearest neighbours or decaying exponentially with distance). Real dispersal processes are likely to lie between these two extremes, and many are well described by long-tailed contact kernels such as power laws. We investigate the effect of different spatial dispersal mechanisms on the spatio-temporal spread of disease epidemics by simulating a stochastic Susceptible-infective model motivated by previous data analyses. Both long-term stationary behaviour (in the presence of a control or recovery process) and transient behaviour (which varies widely within and between epidemics) are examined. We demonstrate the relationship between epidemic size and disease pattern (characterized by spatial autocorrelation), and its dependence on dispersal and infectivity parameters. Special attention is given to boundary effects, which can decrease disease levels significantly relative to standard, periodic geometries in cases of long-distance dispersal. We propose and test a definition of transient duration which captures the dependence of transients on dispersal mechanisms. We outline an analytical approach that represents the behaviour of the spatially-explicit model, and use it to prove that the epidemic size is predicted exactly by the mean-field model (in the limit of an infinite system) when dispersal is sufficiently long ranged (i.e. when the power-law exponent a</=2).

Disease Outbreaks↗

Abnormal muscle coactivation patterns during isometric torque generation at the elbow and shoulder in hemiparetic subjects.

To study abnormal spatial patterns of muscle activation in hemiparetic stroke, we compared EMG activity in paretic and contralateral elbow and shoulder muscles of 10 hemiparetic subjects during 1.5-s voluntary isometric contractions, against five to eight different loads. Isometric forces were generated in eight directions, referenced to a plane orthogonal to the long axis of the forearm, and were recorded by a three degrees of freedom load cell, mounted at the wrist. Surface and intramuscular EMGs of six elbow and six shoulder muscles were recorded from both impaired and contralateral upper extremities of each subject. The spatial characteristics of EMG activation of individual muscles were summarized using two measures. The first, called the 'net resultant EMG vector' is a new measure which calculated the vector sum of EMG magnitudes for each of the eight directions, and the second, index of EMG focus, is a measure of the range of EMG activation recorded for each load level. Use of these measures permitted us to describe spatial EMG characteristics quantitatively, which has not been done previously. We observed consistent and statistically significant shifts in the resultant EMG vector directions in the impaired limb, especially in shoulder and other proximal muscles. Significant increases in the angular range of EMG activity were also identified and were most evident at the elbow. Correlation analysis techniques were used to assess the degree of coactivation of different muscle pairs. There were consistent EMG coactivation patterns observed across all subjects (both normal and hemiparetic). However, in spasticparetic limbs, additional novel coactivational relationships were also recorded, especially between elbow flexors/shoulder abductors and elbow extensors/shoulder adductors. These novel coactivation patterns represent a reduction in the number of possible muscle combinations, or in the number of possible 'synergies' in the paretic limb of the stroke subject. This reduction in number of 'synergies' could result from a loss of descending command options; from an increased reliance on residual, descending brainstem pathways (such as the reticulospinal and vestibulospinal projections); from changes in spinal interneuronal excitability; or from a combination of several of these factors. The relative merits of these hypotheses are addressed.

Adult↗

Peripodial cells regulate proliferation and patterning of Drosophila imaginal discs.

Cells employ a diverse array of signaling mechanisms to establish spatial patterns during development. Nowhere is this better understood than in Drosophila, where the limbs and eyes arise from discrete epithelial sacs called imaginal discs. Molecular-genetic analyses of pattern formation have generally treated discs as single epithelial sheets. Anatomically, however, discs comprise a columnar cell monolayer covered by a squamous epithelium known as the peripodial membrane. Here we demonstrate that during development, peripodial cells signal to disc columnar cells via microtubule-based apical extensions. Ablation and targeted gene misexpression experiments demonstrate that peripodial cell signaling contributes to growth control and pattern formation in the eye and wing primordia. These findings challenge the traditional view of discs as monolayers and provide foundational evidence for peripodial cell function in Drosophila appendage development.

Animals↗