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p57Kip2 (cdkn1c): sequence, splice variants and unique temporal and spatial expression pattern in the rat pancreas.

The cyclin-dependent kinase (CDK) inhibitor p57Kip2 (CDKN1C) is a negative regulator of cell proliferation, binding to a variety of cyclin-CDK complexes and inhibiting their kinase activities in vitro. The p57Kip2 gene is imprinted and the maternal allele is expressed in terminally differentiated cells, including human beta-cells. Somatic loss of p57Kip2 expression is associated with increased beta-cell proliferation in the focal form of Hyperinsulinism of Infancy. We cloned and sequenced the rat ortholog of p57Kip2, and demonstrate that it is highly homologous to the mouse gene. However, the human and rodent genes are quite divergent. Despite having highly homologous C- and N-terminal domains, the mid-portion of the human gene is entirely different from that of its rodent counterparts. Expression of p57Kip2 was evaluated during fetal and postnatal development, and a highly cell-specific, temporal and spatial expression profile was found. In contrast to other tissues, the expression pattern in rat pancreas was entirely opposite from that previously reported in man, with high levels of expression in rodent exocrine cells, but no expression in beta-cells during any stage of development. These findings demonstrate that p57Kip2 expression is highly regulated. In the pancreas, the functional significance of this gene appears to be quite different in humans when compared with rodents, suggesting that a better understanding of the function of this protein may provide new insights into the mechanisms involved in the control of human beta-cell mass.

Alternative Splicing↗

The role of working memory in spatial enumeration: patterns of selective interference in subitizing and counting.

Articulatory suppression (repeatedly pronouncing a syllable or word while carrying out another task) is thought to interfere selectively with the phonological store in working memory. Although suppression interferes with temporal enumeration (enumerating successive light flashes), to date there has been little evidence of such interference in spatial enumeration (enumerating units laid out in space at one time)--a finding with serious ramifications for theories of enumeration. Participants carried out a spatial enumeration task, enumerating 1-8 dots while listening to a metronome (baseline condition) or while carrying out a secondary task to the rhythm of the metronome (dual-task condition). There were four secondary tasks: simple articulation (saying a letter), complex articulation (alternating between two letters), simple tapping (tapping a finger), and complex tapping (alternating between two fingers). Interference varied with number of items, but the pattern differed from that observed with temporal enumeration.

Association Learning↗

Lateral induction by juxtacrine signaling is a new mechanism for pattern formation.

Many signaling molecules in epithelia are now known to function in a membrane-bound form, binding to receptors on immediately neighbouring cells. This "juxtacrine" mode of communication has been well studied in the case of lateral inhibition, where ligand binding at the cell surface downregulates ligand and receptor expression, and is known to generate spatial patterns with a wavelength of exactly two cells. However, recent evidence shows that a number of juxtacrine signals can lead to the opposite phenomenon of lateral induction. Here, we use mathematical modeling to show that such positive feedback, in combination with juxtacrine communication, provides a novel mechanism for the generation of spatial patterns, with wavelengths that vary with parameters and can be many cell lengths.

Body Patterning↗

Identification of temporal and spatial expression patterns of amelogenin isoforms during mouse molar development.

Amelogenin synthesis is initiated in a restricted time frame during odontogenesis. Polypeptides translated from several alternatively spliced isoforms of amelogenin mRNA have been identified in ameloblasts and odontoblasts. Recent studies suggest that the isoforms deleting exons 6a, 6b, and 6c produce polypeptides that might exert regulatory functions governing the late stages of ameloblast and odontoblast differentiation. Herein, the spatial and temporal expression of mouse amelogenin mRNA isoforms M194, M180, M73, and M59 have been determined around the perinatal development period using splice form-specific probes. Expression levels and distribution patterns varied with developmental stage and cell location. Amelogenin mRNA expression was most prominent within the enamel organ at boundaries between cell layers, beginning at the newborn stage (PN0.5). Odontoblasts supported the expression of M73 and M59 mRNA from developmental stages PN0.5 to PN1.5 (1 d of age). In contrast, ameloblasts expressed predominantly the M180 mRNA isoform with full exon 6 but devoid of exon 4. In the enamel organ, the stratum intermediun cells supported expression of the full-length isoform, M194, including the full exon 6 and exon 4 sequences, and strikingly, expression of M180 message was inhibited. In conclusion, ameloblasts, odontoblasts, and stratum intermedium cells demonstrate selective alternative splicing patterns of the amelogenin pre-mRNA transcript.

Aging↗

Restricted mating dispersal and strong breeding group structure in a mid-sized marsupial mammal (Petrogale penicillata).

Ecological genetic studies have demonstrated that spatial patterns of mating dispersal, the dispersal of gametes through mating behaviour, can facilitate inbreeding avoidance and strongly influence the structure of populations, particularly in highly philopatric species. Elements of breeding group dynamics, such as strong structuring and sex-biased dispersal among groups, can also minimize inbreeding and positively influence levels of genetic diversity within populations. Rock-wallabies are highly philopatric mid-sized mammals whose strong dependence on rocky terrain has resulted in series of discreet, small colonies in the landscape. Populations show no signs of inbreeding and maintain high levels of genetic diversity despite strong patterns of limited gene flow within and among colonies. We used this species to investigate the importance of mating dispersal and breeding group structure to inbreeding avoidance within a 'small' population. We examined the spatial patterns of mating dispersal, the extent of kinship within breeding groups, and the degree of relatedness among brush-tailed rock-wallaby breeding pairs within a colony in southeast Queensland. Parentage data revealed remarkably restricted mating dispersal and strong breeding group structuring for a mid-sized mammal. Breeding groups showed significant levels of female kinship with evidence of male dispersal among groups. We found no evidence for inbreeding avoidance through mate choice; however, anecdotal data suggest the importance of life history traits to inbreeding avoidance between first-degree relatives. We suggest that the restricted pattern of mating dispersal and strong breeding group structuring facilitates inbreeding avoidance within colonies. These results provide insight into the population structure and maintenance of genetic diversity within colonies of the threatened brush-tailed rock-wallaby.

Animals↗

Looking for dangerous places: some aspects of medical geography and disease mapping.

Medical geography investigates spatial patterns in the distribution of disease occurrence. The origins of the field can be traced to antiquity, but mapping of disease did not appear until the mid-19th century. Maps can reveal distinctive spatial patterns of certain diseases and may suggest environmental correlates. The geographical distribution of many infectious diseases, such as malaria, with well-known ecology are usually easily understood. The etiology of certain chronic non-infectious diseases which exhibit noticeable geographic variation is often complex. A map of cerebrovascular disease mortality rates in Appalachia is used as an example of an application of modern medical geography.

Africa↗

Assessment of cutaneous blood flow by using topographical perfusion mapping techniques.

The ability of laser Doppler scanning to reproduce the spatial pattern of cutaneous vascular conductance (CVC) in a 6.25-cm2 area of skin was evaluated at supine rest (28 degrees C), during thermal stress (cold and heat), and during baroreceptor unloading with -40-mmHg lower body negative pressure (LBNP). The spatial pattern of resting CVC was similar on 3 different days, varying by 6 +/- 3%. During cold stress, 89 +/- 2% of the skin area showed a decrease in skin blood flow (37 +/- 2%), whereas heat stress increased CVC in 94 +/- 5% of the skin area. During LBNP, the pattern of CVC response was not uniform, and frequency analysis indicated that 47 +/- 5% of the pixels showed a reduction in CVC (>1 SE), 28 +/- 2% of the skin area were unaffected, and the remaining 26 +/- 5% of the pixels showed some increase in CVC. These data indicate the ability of topographical perfusion mapping to provide quantitative and reproducible information about the spatial distribution of CVC. In addition, the site-to-site variability in reflex control of skin blood flow during LBNP is intriguing and requires more rigorous evaluation.

Baroreflex↗

Ontogenic regulation of spatial differentiation in the crypt-villus axis of normal and isografted small intestine.

Despite rapid proliferation, the mammalian intestinal epithelium maintains precise spatial differentiation from crypt to villus tip and from duodenum to colon. During perinatal life, the rodent gut undergoes a dramatic morphogenesis, resulting in formation of the crypt-villus and duodenal-colonic axes. The ontogeny of regional differences in gene expression in the emerging vertical axis has not been well described. We used the liver fatty acid binding protein (L-FABP) and apolipoprotein (apo) AIV genes as markers of neonatal enterocytic differentiation. In situ hybridization analyses revealed that both genes exhibit unique spatial patterns of expression along the jejunal crypt-villus axis during ontogeny, characterized by increased cellular mRNA levels in villus base enterocytes. To examine the requirement for a normal luminal environment to generate these precise patterns of cellular gene expression, we employed intestinal isograft techniques. Fetal intestines were implanted as early as embryonic day 12. Appropriate expression of the apo AIV and L-FABP genes was recapitulated during villus morphogenesis in fetal life. However, spatial patterns of gene expression in the isografted postnatal cryptvillus axis were altered. The preferential accumulation of L-FABP and apo AIV mRNA in villus base enterocytes was never observed in isografts. These results suggest that a "basal" differentiation program is encoded in fetal endoderm and mesenchyme, yet extracellular substances contained in the lumen or extrinsic to the intestine play an important modulatory role in generating spatial differentiation during ontogeny.

Aging↗

Enhancement of odorant-induced mucosal activity patterns in rats trained on an odorant identification task.

Previous studies have demonstrated that there are intrinsic spatial patterns of odorant sensitivity across the rat olfactory mucosa. The question of how these patterns are determined and whether they are modifiable with experience remains open. Therefore, the present study examined whether the odorant-induced spatial activity patterns which are characteristic of different odorants would be altered by experience. Odorant exposure was achieved as a consequence of training and testing on a five odorant identification task in which rats were trained to differentially report (i.e. identify) the odorants propanol, ehtylacetoacetate, carvone, citral, and propyl acetate. At the completion of testing, each animal was sacrificed and their mucosal activity patterns recorded using optical techniques and a voltage-sensitive dye. Using the dye, di-4-ANEPPS, we monitored the fluorescence changes at 100 contiguous sites with a 10 x 10 photodiode array on the olfactory mucosa of each rat's septum and medial surface of the turbinates in response to the same five odorants. The recorded spatial activity patterns of trained animals were compared to those of age-matched controls. For the trained animals, both mucosal surfaces showed a significant increase in the average response magnitude. Furthermore, for the septal mucosa only, there was a significant increase in the distinctiveness of an odorant's characteristic 'hot spot'.

1-Propanol↗

Linking linear programming and spatial simulation models to predict landscape effects of forest management alternatives.

Forest management planners require analytical tools to assess the effects of alternative strategies on the sometimes disparate benefits from forests such as timber production and wildlife habitat. We assessed the spatial patterns of alternative management strategies by linking two models that were developed for different purposes. We used a linear programming model (Spectrum) to optimize timber harvest schedules, then a simulation model (HARVEST) to project those schedules in a spatially explicit way and produce maps from which the spatial pattern of habitat could be calculated. We demonstrated the power of this approach by evaluating alternative plans developed for a national forest plan revision in Wisconsin, USA. The amount of forest interior habitat was inversely related to the amount of timber cut, and increased under the alternatives compared to the current plan. The amount of edge habitat was positively related to the amount of timber cut, and increased under all alternatives. The amount of mature northern hardwood interior and edge habitat increased for all alternatives, but mature pine habitat area varied. Mature age classes of all forest types increased, and young classes decreased under all alternatives. The average size of patches (defined by age class) generally decreased. These results are consistent with the design goals of each of the alternatives, but reveal that the spatial differences among the alternatives are modest. These complementary models are valuable for quantifying and comparing the spatial effects of alternative management strategies.

Computer Simulation↗

Interactions between environment, species traits, and human uses describe patterns of plant invasions.

Although invasive alien species (IAS) are a major threat to biodiversity, human health, and economy, our understanding of the factors controlling their distribution and abundance is limited. Here, we determine how environmental factors, land use, life-history traits of the invaders, residence time, origin, and human usage interact to shape the spatial pattern of invasive alien plant species in South Africa. Relationships between the environmental factors and the extrinsic and intrinsic attributes of species were investigated using RLQ analysis, a multivariate method for relating a species-attribute table to an environmental table by way of a species presence/absence table. We then clustered species according to their position on the RLQ axes, and tested these groups for phylogenetic independence. The first three axes of the RLQ explained 99% of the variation and were strongly related to the species attributes. The clustering showed that, after accounting for environmental factors, the spatial pattern of IAS in South Africa was driven by human uses, life forms, and reproductive traits. The seven clusters of species strongly reflected geographical distribution, but also intrinsic species attributes and patterns of human use. Two of the clusters, centered on the genera Acacia and Opuntia, were phylogenetically non-independent. The remaining clusters comprised species of diverse taxonomic affinities, but sharing traits facilitating invasion in particular habitats. This information is useful for assessing the extent to which the potential spread of recent introductions can be predicted by considering the interaction of their biological attributes, region of origin, and human use.

Agriculture↗

Local cone and rod system function in progressive cone dystrophy.

PURPOSE: To compare the patterns of local cone and rod system impairment in patients with progressive cone dystrophy (CD) using psychophysical and electrophysiological techniques. METHODS: Local cone system function was assessed by measuring cone system thresholds (visual fields) and cone-mediated multifocal electroretinograms (mfERGs). Rod system function was assessed by measuring rod system thresholds (visual fields) and rod-mediated mfERGs. The results in a group of eight patients with CD were compared with those in an age-similar control group. RESULTS: All the patients had abnormal cone system visual field thresholds and cone-mediated mfERGs. Cone system psychophysical thresholds were elevated for targets presented within the central 10 degrees, but were within normal limits for targets at peripheral locations. Cone-mediated mfERG measures of amplitude scale and time scale were abnormal for most of the hexagons tested. Most of the rod-mediated psychophysical thresholds and mfERGs were within normal limits. Rod system losses tended to be patchy and scattered throughout the area tested. CONCLUSIONS: There was poor correspondence among local measures of cone and rod system losses in these patients with CD. The results suggest that the spatial pattern of cone system losses in this disease differs from the spatial pattern of rod system losses.

Adolescent↗

Homeobox-containing gene transiently expressed in a spatially restricted pattern in the early sea urchin embryo.

In the sea urchin embryo, the lineage founder cells whose polyclonal progenies will give rise to five different territories are segregated at the sixth division. To investigate the mechanisms by which the fates of embryonic cells are first established, we looked for temporal and spatial expression of homeobox genes in the very early cleavage embryos. We report evidence that PlHbox12, a paired homeobox-containing gene, is expressed in the embryo from the 4-cell stage. The abundance of the transcripts reaches its maximum when the embryo has been divided into the five polyclonal territories--namely at the 64-cell stage--and it abruptly declines at later stages of development. Blastomere dissociation experiments indicate that maximal expression of PlHbox12 is dependent on intercellular interactions, thus suggesting that signal transduction mechanisms are responsible for its transcriptional activation in the early cleavage embryo. Spatial expression of PlHbox12 was determined by whole-mount in situ hybridization. PlHbox12 transcripts in embryos at the fourth, fifth, and sixth divisions seem to be restricted to the conditionally specified ectodermal lineages. These results suggest a possible role of the PlHbox12 gene in the early events of cell specification of the presumptive ectodermal territories.

Amino Acid Sequence↗

The effect of distance from home on attendance at a small rural health centre in Papua New Guinea.

BACKGROUND: The willingness of patients in the rural tropics to seek medical care at primary health care facilities is influenced by the distance they have to travel, but few studies have tried to estimate these distance effects. METHODS: Distance decay effects in attendance rates were estimated from a database of 4348 attendances at a rural health centre in Papua New Guinea, linked to demographic and house position data for the catchment population. Small-scale spatial patterns and differences between diagnoses, age groups and gender are described. RESULTS: Attendance decreased markedly with distance both overall (50% decrease at 3.5 km) and for patients with malaria or acute respiratory infections. This decrease was non-linear (on log scale) with distance. Although constant over time, there were big differences in this distance effect among age and gender groups: Female patients showed less distance decay in adolescents and adults, but higher in the infant group. Spatial patterns accounted for 32% of the variation in age- and gender-specific attendance rates. Of the spatial effects more than 50% were due to distance effects. CONCLUSIONS: Distance effects were similar in magnitude to those reported elsewhere, suggesting that distance effects may be generalizable to many parts of the rural tropics. The non-linearity of distance decay implies that a bell-shaped demand function should be used in health planning.

Adolescent↗

Timing of cardiac contraction in humans mapped by high-temporal-resolution MRI tagging: early onset and late peak of shortening in lateral wall.

Mechanical asynchrony is an important parameter in predicting the response to cardiac resynchronization therapy, but detailed knowledge of cardiac contraction timing in healthy persons is scarce. In this work, timing of cardiac contraction was mapped in 17 healthy subjects with high-temporal-resolution (14 ms) MRI myocardial tagging and strain analysis. Both the onset time of circumferential shortening (T(onset)) in early systole and the time of peak circumferential shortening (T(peak)) at end systole were determined. The onset of shortening width (time needed for 20-90% of the left ventricle to start shortening) was small (35 +/- 9 ms). A distinct spatial pattern for T(onset) was found, with earliest onset in the lateral wall and latest onset in the septum (P = 0.001). Compared with T(onset), T(peak) had a larger width (121 +/- 22 ms) and an opposite spatial pattern, with peak shortening occurring earlier in the septum than in the lateral wall (P < 0.001). Postsystolic shortening (T(peak) later than aortic valve closure; P < 0.05) was observed in 13 of the 30 cardiac segments, mainly in the lateral and basal segments. Shortening in these segments continued 58 +/- 14 ms after aortic valve closure, during which circumferential shortening increased from 16.9 +/- 1.2% to 20.0 +/- 1.5%. Maps of the timing of contraction in normal subjects may serve as a reference in detecting mechanical asynchrony due to intraventricular conduction defects or ischemia.

Adult↗

Spatial genetic structure of human populations in Japan.

We studied spatial patterns for 24 allele frequencies representing 15 systems (blood antigens, enzymes, serum proteins, color blindness, and cerumen) in Japan. The total number of samples over all systems and localities is 1125. We investigated patterns of genetic variation graphically as interpolated allele frequency surfaces, as one-dimensional and directional correlograms, and by testing for the direction of maximal genetic autocorrelation. We examined the allele frequency surfaces by various techniques of spatial autocorrelation analysis and found 13 allele frequency surfaces from 9 genetic systems exhibiting significant spatial patterns. Several surfaces have clinal patterns along the major axis of the Japanese archipelago; others tend toward a maximum or minimum in south-central Honshu. Yet other allele frequencies show long-distance differentiation or patchiness. We discovered seven areas of rapid genetic change by using the wombling method. These areas largely reflect maritime and montane barriers, and some are associated with dialectal boundaries in these populations. The observed patterns support the hybridization or dual structure hypothesis for the peopling of Japan.

Alleles↗

Residual spatial correlation between geographically referenced observations: a Bayesian hierarchical modeling approach.

BACKGROUND: Analytic methods commonly used in epidemiology do not account for spatial correlation between observations. In regression analyses, this omission can bias parameter estimates and yield incorrect standard error estimates. We present a Bayesian hierarchical model (BHM) approach that accounts for spatial correlation, and illustrate its strengths and weaknesses by applying this modeling approach to data on Wuchereria bancrofti infection in Haiti. METHODS: A program to eliminate lymphatic filariasis in Haiti assessed prevalence of W. bancrofti infection in 57 schools across Leogane Commune. We analyzed the spatial pattern in the prevalence data using semi-variograms and correlograms. We then modeled the data using (1) standard logistic regression (GLM); (2) non-Bayesian logistic generalized linear mixed models (GLMMs) with school-specific nonspatial random effects; (3) BHMs with school-specific nonspatial random effects; and (4) BHMs with spatial random effects. RESULTS: An exponential semi-variogram with an effective range of 2.15 km best fit the data. GLMM and nonspatial BHM point estimates were comparable and also were generally similar with the marginal GLM point estimates. In contrast, compared with the nonspatial mixed model results, spatial BHM point estimates were markedly attenuated. DISCUSSION: The clear spatial pattern evident in the Haitian W. bancrofti prevalence data and the observation that point estimates and standard errors differed depending on the modeling approach indicate that it is important to account for residual spatial correlation in analyses of W. bancrofti infection data. Bayesian hierarchical models provide a flexible, readily implementable approach to modeling spatially correlated data. However, our results also illustrate that spatial smoothing must be applied with care.

Animals↗

How do frugivores track resources? Insights from spatial analyses of bird foraging in a tropical forest.

Frugivores often track ripe fruit abundance closely across local areas despite the ephemeral and typically patchy distributions of this resource. We use spatial auto- and cross-correlation analyses to quantify spatial patterns of fruit abundance and avian frugivory across a 4-month period within a forested 4.05-ha study grid in Puerto Rico. Analyses focused on two tanager species, Spindalis portoricensis and Nesospingus speculiferus, and their principal food plants. Three broad questions are addressed: (1). at what spatial scales is fruit abundance and frugivory patchy; (2). at what spatial scales do frugivores respond to fruit abundance; and (3). to what extent do spatial patterns of frugivory overlap between bird species? Fruit patch size, species composition, and heterogeneity was variable among months, despite fruit patch locations remaining relatively consistent between months. Positive correlations between frugivory and fruit abundance suggested tanagers successfully tracked fruit abundance. Frugivory was, however, more localized than fruit abundance. Scales of spatial overlap in frugivory and monthly variation in the foraging locations of the two tanager species suggested that interspecific facilitation may have been important in determining bird foraging locations. In particular, S. portoricensis, a specialist frugivore, may have relied on the loud calls of the gregarious generalist, N. speculiferus, to find new foraging areas. Such a mechanism could help explain the formation of mixed species feeding flocks and highlights the potential importance of facilitation between species that share resources.

Animals↗