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PubMed2000

Ontogeny of spatial discrimination in mice: a longitudinal analysis in the modified open-field with objects.

The present longitudinal study investigated the emergence of spatial discrimination and reaction to novelty in CD-1 mice, using a modified open-field test with four objects, a test in which responses to both spatial rearrangement of familiar objects and object novelty are assessed. Male and female mice were tested on postnatal days (pnd) 18, 28, 46 and 90. Locomotor activity was highest on pnd 90, whereas time spent on objects before rearrangement was highest on pnd 46. Eighteen-day old mice were unable to detect both object rearrangement and object novelty, suggesting immaturity in processing spatial information. On days 28 and 46 mice showed a clear response to object novelty, actively exploring the unfamiliar object placed in the arena, while at these ages object displacement elicited a generalized increase of exploration, not directed towards the displaced objects. A clear and selective response to object displacement emerged only at adulthood (day 90).

Animals↗
PubMed1996

Spatio-temporal pattern of N-methyl-D-aspartate receptor NR1 mRNA expression during postnatal development of visual structures of the rat brain.

N-methyl-D-aspartate (NMDA) excitatory amino acid receptors (NMDAR) play a pivotal role in various physiological and pathological responses of the central nervous system (CNS), including such phenomena of neuronal plasticity as cortical development. Hence, it could be suggested that expression of genes coding for NMDAR components can be differentially regulated throughout the development. To test this notion we analyzed with in situ hybridization mRNA levels of NMDAR subunit designated as NR1, during time of development (1-6 weeks postnatally) spanning the critical period of functional formation of major visual structures of the rat brain, namely visual cortex (VC), superior colliculus (SC), and lateral geniculate nucleus (LGN). The highest levels of NR1 mRNA were found in the VC and SC at the onset of the critical period, i.e., 21 days postnatally, whereas in the LGN a tendency toward a similar pattern of expression was observed. Analysis of spatial distribution of NR1 mRNA in the SC and VC revealed that an adult-like laminar pattern of expression was also achieved between 14 and 21 days postnatally. This pattern of expression corroborates with developmentally regulated changes in an overall density of cell bodies in these areas.

Animals↗
PubMed2000

FMR1 gene and fragile X syndrome.

Taxonomic features of fragile X syndrome (FXS) associated with the fragile X mutation have evolved over several decades. Males are more severely impacted cognitively than females, but both show declines in IQ scores as they age. Although many males with FXS exhibit autistic-like features, autism does not occur more frequently in males with FXS than among males with mental retardation (MR). FXS is caused by inactivation of the FMR1 gene located on Xq27.3. FMRP, the protein produced by FMR1, has been detected in most organs and in brain. In cells, it is located primarily in cytoplasm and contains motifs found in RNA-binding proteins. The FMRP N-terminal contains a functional nuclear localization signal which permits the protein to shuttle between cytoplasm and nucleus. FMR1 knockout mice show subtle behavioral and visual-spatial difficulties. Analysis of their brain tissue suggests absence of FMRP impairs synaptic maturation. Individuals with the fragile premutation produce FMRP, and the phenotype associated with the premutation has been controversial. However, there seems to be a higher incidence of premature ovarian failure in women with the premutation than is found in the general female population. This may be related to unusual increases in mRNA levels in premutation carriers.

Animals↗
PubMed2000

Genetic structure of Quechua-speakers of the Central Andes and geographic patterns of gene frequencies in South Amerindian populations.

A sample of 141 Quechua-speaking individuals of the population of Tayacaja, in the Peruvian Central Andes, was typed for the following 16 genetic systems: ABO, Rh, MNSs, P, Duffy, AcP1, EsD, GLOI, PGM1, AK, 6-PGD, Hp, Gc, Pi, C3, and Bf. The genetic structure of the population was analyzed in relation to the allele frequencies available for other South Amerindian populations, using a combination of multivariate and multivariable techniques. Spatial autocorrelation analysis was performed independently for 13 alleles to identify patterns of gene flow in South America as a whole and in more specific geographic regions. We found a longitudinal cline for the AcP1*a and EsD*1 alleles which we interpreted as the result of an ancient longitudinal expansion of a putative ancestral population of modern Amerindians. Monmonnier's algorithm, used to identify areas of sharp genetic discontinuity, suggested a clear east-west differentiation of native South American populations, which was confirmed by analysis of the distribution of genetic distances. We suggest that this pattern of genetic structures is the consequence of the independent peopling of western and eastern South America or to low levels of gene flow between these regions, related to different environmental and demographic histories.

Gene Frequency↗
PubMedDate not supplied

A new protocol for evaluating putative causes for multiple variables in a spatial setting, illustrated by its application to European cancer rates.

We introduce a statistical protocol for analyzing spatially varying data, including putative explanatory variables. The procedures comprise preliminary spatial autocorrelation analysis (from an earlier study), path analysis, clustering of the resulting set of path diagrams, ordination of these diagrams, and confirmatory tests against extrinsic information. To illustrate the application of these methods, we present incidence and mortality rates of 31 organ- and sex-specific cancers in Europe; these rates vary markedly with geography and type of cancer. Additionally, we investigated three factors (ethnohistory, genetics, and geography) putatively affecting these rates. The five variables were correlated separately for the 31 cancers over European reporting stations. We analyzed the correlations by path analysis, k-means clustering, and nonmetric multidimensional scaling; coefficients of the 31 path diagrams modeling the correlations vary substantially. To simplify interpretation, we grouped the diagrams into five clusters, for which we describe the differential effects of the three putative causes on incidence and mortality. When scaled, the path coefficients intergrade without marked gaps between clusters. Ethnic differences make for differences in cancer rates, even when the populations tested are ancient and complex mixtures. Path analysis usefully decomposes a structural model involving effects and putative causes, and estimates the magnitude of the model's components. Smooth intergradation of the path coefficients suggests the putative causes are the results of multiple forces. Despite this continuity of the path diagrams of the 31 cancers, clustering offers a useful segmentation of the continuum. Etiological and other extrinsic information on the cancers map significantly into the five clusters, demonstrating their epidemiological relevance.

Biometry↗
PubMed1987

Cranial variation in European populations: a spatial autocorrelation study at three time periods.

This study reports on spatial variation of 10 cranial variables in European populations at 3 time periods. Means for these variables, based on 137, 108, and 183 samples from the Early Medieval, Late Medieval, and Recent periods, were subjected to one-dimensional and directional spatial autocorrelation analyses. Significant spatial structure was found for most variables. It becomes more pronounced as time progresses. The spatial patterns are not strongly clinal. Correlograms based on distances computed from all variables are monotonic only to 900, 1,650, and 1,350 km for the three periods. Regional patterns are seen for most variables and become more structured and significant with time. There is little similarity among the correlograms of the variables at any one period and virtually none among periods. Inferences about spatial structure of these populations, based on spatial autocorrelation analysis, suggest a pattern dominated by migration, followed by expansion and admixture rather than selection or chance fluctuations. The patterns of morphometric change seem to reflect the patterns of linguistic change in these areas.

Cephalometry↗
PubMed1994

Genetic variation in North Africa and Eurasia: neolithic demic diffusion vs. Paleolithic colonisation.

The hypothesis that both genetic and linguistic similarities among Eurasian and North African populations are due to demic diffusion of neolithic farmers is tested against a wide database of allele frequencies. Demic diffusion of farming and languages from the Near East should have determined clines in areas defined by linguistic criteria; the alternative hypothesis of cultural transmission does not predict clines. Spatial autocorrelation analysis shows significant gradients in three of the four linguistic families supposedly affected by neolithic demic diffusion; the Afroasiatic family is the exception. Many such gradients are not observed when populations are jointly analyzed, regardless of linguistic classification. This is incompatible with the hypothesis that major cultural transformations in Eurasia (diffusion of related languages and spread of agriculture) took place without major demographic changes. The model of demic diffusion seems therefore to provide a mechanism explaining coevolution of linguistic and biological traits in much of the Old World. Archaeological, linguistic, and genetic evidence agree in suggesting a multidirectional process of gene flow from the Near East in the neolithic. However, the possibility should be envisaged that some allele frequency patterns can predate the neolithic and depend on the initial spread of Homo sapiens sapiens from Africa into Eurasia.

Agriculture↗
PubMed2003

An attention modulated response to disgust in human ventral anterior insula.

The human brain is expert in analyzing rapidly and precisely facial features, especially emotional expressions representing a powerful communication vector. The involvement of insula in disgust recognition has been reported in behavioral and functional imaging studies. However, we do not know whether specific insular fields are involved in disgust processing nor what the processing time course is. Using depth electrodes implanted during presurgical evaluation of patients with drug-refractory temporal lobe epilepsy, we recorded intracerebral event-related potentials to human facial emotional expressions, that is, fear, disgust, happiness, surprise, and neutral expression. We studied evoked responses in 13 patients with insular contacts to specify the insular fields involved in disgust processing and assess the timing of their activation. We showed that specific potentials to disgust beginning 300 milliseconds after stimulus onset and lasting 200 milliseconds were evoked in the ventral anterior insula in four patients. The occurrence and latency of event-related potentials to disgust in the ventral anterior insula were affected by selective attention. The analysis of spatial and temporal characteristics of insular responses to disgust facial expression lead us to underline the crucial role of ventral anterior insula in the categorization of facial emotional expressions, particularly the disgust.

Attention↗
PubMed2001

Postnatal development of corticospinal axon terminal morphology in the cat.

The corticospinal system undergoes important postnatal development, leading to the mature topography and specificity of connections. The purpose of this study was to determine the time-course of development of corticospinal axonal branching and varicosity density within the cervical gray matter. Corticospinal neurons were labeled after small injections of the anterograde tracer biotinylated dextran amine into the primary motor cortex of cats. Tracer injection and transport times were adjusted to examine labeling at 25, 35, 55, and 75 days and in adults. We measured the numbers and lengths of nonreconstructed terminal and preterminal branches and the numbers and locations of axon varicosities. We found significant age-dependent increases in all morphologic measures. At 25 days, corticospinal axon branching was sparse, with only a few scattered varicosities. By day 35, the mean number of branches, varicosities per branch, and varicosity density increased. Several morphologic measures did not increase between day 35 and 55, but further changes occurred between 55 days and maturity. Beginning around day 55, there was extensive development of small terminal axon branches with high densities of varicosities. We also found, by using spatial point analysis, that there was an age-dependent increase in varicosity clustering. Our results show for the first time that terminal and preterminal corticospinal axon branches increase in complexity during a protracted early postnatal period. This developmental period extended beyond the early postnatal period of activity-dependent refinement of the topography of terminations. Comparison with the time-course of maturation of the cortical motor representation revealed development of substantial, albeit incomplete, branching and varicosity density of CS axons before cortical motor circuits effectively drive their spinal targets.

Aging↗
PubMed2003

Genetic diversity within the R408W phenylketonuria mutation lineages in Europe.

The R408W phenylketonuria mutation in Europe has arisen by recurrent mutation in the human phenylalanine hydroxylase (PAH) locus and is associated with two major PAH haplotypes. R408W-2.3 exhibits a west-to-east cline of relative frequency reaching its maximum in the Balto-Slavic region, while R408W-1.8 exhibits an east-to-west cline peaking in Connacht, the most westerly province of Ireland. Spatial autocorrelation analysis has demonstrated that the R408W-2.3 cline, like that of R408W-1.8, is consistent with a pattern likely to have been established by human dispersal. Genetic diversity within wild-type and R408W chromosomes in Europe was assessed through variable number tandem repeat (VNTR) nucleotide sequence variation and tetranucleotide short tandem repeat (STR) allelic associations. Wild-type VNTR-8 chromosomes exhibited two major cassette sequence organizations: (a1)5-b3-b2-c1 and (a1)5-b5-b2-c1. R408W-1.8 was predominantly associated with (a1)5-B5-B2-C1. Both wild-type vntr-3 and r408w-2.3 chromosomes exhibited a single invariant cassette sequence organization, a2-b2-c1. STR allele distributions associated with the cassette variants were consistent with greater diversity in the wild-type VNTR-8 lineage and were suggestive of different levels of diversity between R408W-1.8 and R408W-2.3. The finding of greater genetic diversity within the wild-type VNTR-8 lineage compared to VNTR-3 suggests that VNTR-8 may be older within the European population. However, in the absence of a more extensive STR data-set, no such conclusions are possible for the respective R408W mutant lineages.

Amino Acid Substitution↗
PubMed2004

Analysis of nerve fibers and their distribution in histologic sections of the human brain.

The field of quantitative analysis and subsequent mapping of the cerebral cortex has developed rapidly. New powerful tools have been applied to investigate large regions of complex folded gyrencephalic cortices in order to detect structural transition regions that might partition different cortical fields of disjunct neuronal functions. We have developed a new mapping approach based on axoarchitectonics, a method of cortical visualization that previously has been used only indirectly with regard to myeloarchitectonics. Myeloarchitectonic visualization has the disadvantage of producing strong agglomerative effects of closely neighbored nerve fibers. Therefore, single and neurofunctional-relevant parameters such as axonal branchings, axon areas, and axon numbers have not been determinable with satisfying precision. As a result, different staining techniques had to be explored in order to achieve a suitable histologic staining for axon visualization. The best results were obtained after modifying the Naoumenko-Feigin staining for axons. From these contrast-rich stained histologic sections, videomicroscopic digital image tiles were generated and analyzed using a new fiber analysis framework. Finally, the analysis of histologic images provided topologic ordered parameters of axons that were transferred into parameter maps. The axon parameter maps were analyzed further via a recently developed traverse generating algorithm that calculated test lines oriented perpendicular to the cortical surface and white matter border. The gray value coded parameters of the parameter maps were then transferred into profile arrays. These profile arrays were statistically analyzed by a reliable excess mass approach we recently developed. We found that specific axonal parameters are preferentially distributed throughout granular and agranular types of cortex. Furthermore, our new procedure detected transition regions originally defined by changes of cytoarchitectonic layering. Statistically significant inhomogeneities of the distribution of certain axon quantities were shown to indicate a subparcellation of areas 4 and 6. The quantification techniques established here for the analysis of spatial axon distributions within larger regions of the cerebral cortex are suitable to detect inhomogeneities of laminar axon patterns. Hence, these techniques can be recommended for systematic and observer-supported cortical area mapping and parcellation studies.

Aged↗
PubMed1996

Substrate selection early after reperfusion of ischemic regions in the working rabbit heart.

Several substrates are available in vivo for oxidation by the myocardium. Although substrate selection has been studied extensively in normoxic myocardium, relatively little is known about substrate preference very early during reperfusion after ischemia. Carbon-13 isotopomer analysis was used to study substrate usage by nonischemic and reperfused-ischemic myocardium in a working heart that was subjected to 15 min or regional ischemia and reperfused for 5 min. Compared with nonischemic myocardium, the contribution of acetoacetate to acetyl coenzyme A was increased in the reperfused-ischemic region, and the contribution of exogenous lactate was decreased. Free fatty acid oxidation, however, was not different in the two regions. These results indicate that (1) early during reperfusion, ketone body oxidation may be more significant than has been emphasized, (2) the relative contribution of fatty acids to acetyl coenzyme A is not sensitive to ischemia followed by reperfusion, and (3) Carbon-13 magnetic resonance spectroscopy methods may be used for analysis of spatial heterogeneity of metabolism in the heart.

Acetoacetates↗
PubMedDate not supplied

Spatial distribution of neurons in tissue culture wells: implications for sampling methods to estimate population size.

Many laboratory procedures require the counting of cells in culture. While many cultured cells may be counted by automated methods, neuronal cultures often require manual cell counting methods that are prohibitively time-consuming. This paper examines methods of sampling from tissue culture wells for estimating total cell counts. Performance of sampling and estimation schemes will depend in part on how the cells distribute themselves within a well. Spatial statistical analysis techniques are applied to the known total number and distribution of neurons in two wells counted in a grid scheme to demonstrate some important features of the neuron distributional patterns. Based on these two wells and simulated realizations from other point processes, a new sampling and estimation technique using open wedge-shaped sampling regions radiating from the centre of the well is proposed. This method is shown to result in more accurate estimates of the total number of neurons in the well than standard methods.

Animals↗
PubMed1996

NMR-based, molecular dynamics- and random walk molecular mechanics-supported study of conformational aspects of a carbohydrate ligand (Gal beta 1-2Gal beta 1-R) for an animal galectin in the free and in the bound state.

The binding of a carbohydrate to a lectin may affect the conformation of the ligand. To address this question for the galectin from chicken liver, the conformation of Gal beta 1-2Gal beta 1-R was analyzed in the free and in the galectin-bound state with 2D-ROESY- and 1D- as well as 2D-transferred NOE-experiments. A computer-assisted analysis of spatial parameters of the ligand by molecular dynamics (MD) and random walk molecular mechanics (RAMM) calculations, taking different dielectric constraints from epsilon = 1 to epsilon = 80 and various force fields into account, were instrumental to define the energetic minima of the free state. NMR-derived interresidual distance constraints enabled a conformational mapping. The two overlapping interresidual distance constraints obtained from transferred-NOE experiments of the galectin-ligand complex clearly support the notion that the conformation of the disaccharide in the bound state is at least very close to its global energy minimum state in solution.

Animals↗
PubMed1996

Children's analysis of hierarchical patterns: evidence from a similarity judgment task.

Three experiments in this study examined the development of young children's analysis of spatial patterns, specifically hierarchical letter and geometric forms. In a forced choice task, 4- and 6-year-olds and adult subjects chose one of two choice forms as most similar to a target form. Specific stimulus manipulations were introduced to assess children's ability to segment and integrate hierarchically organized information under different conditions. In Experiment 1 adults served as subjects in a computerized version that provided both choice and response latency data. In Experiments 2 and 3 children and adults participated in a pencil and paper version of the forced choice task. Results showed that although children as young as 4 years of age demonstrated substantial analytic competence, their ability to integrate the parts of the spatial array to form a coherent whole was weaker and more easily disrupted than that of the older children and adults.

Age Factors↗
PubMed2001

Cortical correlates of gesture processing: clues to the cerebral mechanisms underlying apraxia during the imitation of meaningless gestures.

The clinical test of imitation of meaningless gestures is highly sensitive in revealing limb apraxia after dominant left brain damage. To relate lesion locations in apraxic patients to functional brain activation and to reveal the neuronal network subserving gesture representation, repeated H2(15O)-PET measurements were made in seven healthy subjects during a gesture discrimination task. Observing paired images of either meaningless hand or meaningless finger gestures, subjects had to indicate whether they were identical or different. As a control condition subjects simply had to indicate whether two portrayed persons were identical or not. Brain activity during the discrimination of hand gestures was strongly lateralized to the left hemisphere, a prominent peak activation being localized within the inferior parietal cortex (BA40). The discrimination of finger gestures induced a more symmetrical activation and rCBF peaks in the right intraparietal sulcus and in medial visual association areas (BA18/19). Two additional foci of prominent rCBF increase were found. One focus was located at the left lateral occipitotemporal junction (BA 19/37) and was related to both tasks; the other in the pre-SMA was particularly related to hand gestures. The pattern of task-dependent activation corresponds closely to the predictions made from the clinical findings, and underlines the left brain dominance for meaningless hand gestures and the critical involvement of the parietal cortex. The lateral visual association areas appear to support first stages of gesture representation, and the parietal cortex is part of the dorsal action stream. Finger gestures may require in addition precise visual analysis and spatial attention enabled by occipital and right intraparietal activity. Pre-SMA activity during the perception of hand gestures may reflect engagement of a network that is intimately related to gesture execution.

Adult↗