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PubMed2003

A heparin derived oligosaccharide normalizes the fear response of old Brown Norway rats.

Old animals exhibit impaired spatial learning and an exaggerated response to stress. It was predicted that the heparin derived oligosaccharide (HDO), C3, would reverse these age-related deficits. Young (4-5 months) and old (19-20 months) Brown Norway male rats ingested C3 (25 mg/kg per day, p.o.) or vehicle (drinking water) daily for 42-44 days. Two weeks after the initiation of drug treatment, the rats were examined using a series of behavioral tests. The old control rats evidenced: (1) increased neophobia and reduced exploratory behavior in a novel open field (OF); and (2) exaggerated freezing during the acquisition and retention of a conditioned response (CR) to a Pavlovian light-shock pairing ("foreground" conditioning). C3 treatment attenuated or reversed this age-related impairment of emotional behavior. Analysis of spatial learning using the Morris water maze (MWM), and of CR formation to the place in which the foreground conditioning was conducted ("background" conditioning) during context dependent fear conditioning (CDFC) did not reveal major age or drug effects on memory processes. It is hypothesized that C3 repairs damage to the extracellular matrix (ECM) that occurs during the aging process and thereby normalizes age-related exacerbated fear behaviors without affecting mnestic processes.

Aging↗

PubMed1999

Differentiating between clonal growth and limited gene flow using spatial autocorrelation of microsatellites

In plant populations alleles often deviate from a random distribution and reveal positive autocorrelation at short distances. In species with both clonal and sexual reproduction, such clustering may be because ramets of the same genet were sampled at nearby locations. Alternatively, clustering may be the result of limited gene flow through pollen or seeds (isolation-by-distance). Here, we modify a conventional spatial autocorrelation analysis using the join-count statistic in order to differentiate between these two causes of genetic structure. We examined the distribution of seven microsatellite loci representing 37 alleles in a 20 x 80 m plot of a perennial population of eelgrass Zostera marina L. In analysing join-counts between all like genotypes we found significant genetic autocorrelation among ramets at distances between 1 and 7 m (P < 0. 001). We then excluded joins between clonemates which were identified from the expected likelihood of their seven-locus genotypes. Without joins within genets, no autocorrelation was evident, indicating that most of the significant genetic clustering was caused by clonal spread. At distances up to 27 m, alleles were distributed at random, indicating a panmictic population at this spatial scale. These results illustrate the need for an a priori estimation of genet-ramet structure in clonally reproducing plants in order to avoid erroneous inferences about putative gene flow at various spatial scales.

Journal Article↗

PubMed2004

Parallel processing across neural systems: implications for a multiple memory system hypothesis.

A common conceptualization of the organization of memory systems in brain is that different types of memory are mediated by distinct neural systems. Strong support for this view comes from studies that show double (or triple) dissociations between spatial, response, and emotional memories following selective lesions of hippocampus, striatum, and the amygdala. Here, we examine the extent to which hippocampal and striatal neural activity patterns support the multiple memory systems view. A comparison is made between hippocampal and striatal neural correlates with behavior during asymptotic performance of spatial and response maze tasks. Location- (or place), movement, and reward-specific firing patterns were found in both structures regardless of the task demands. Many, but not all, place fields of hippocampal and striatal neurons were similarly affected by changes in the visual and reward context regardless of the cognitive demands. Also, many, but not all, hippocampal and striatal movement-sensitive neurons showed significant changes in their behavioral correlates after a change in visual context, irrespective of cognitive strategy. Similar partial reorganization was observed following manipulations of the reward condition for cells recorded from both structures, again regardless of task. Assuming that representations that persist across context changes reflect learned information, we make the following conclusions. First, the consistent pattern of partial reorganization supports a view that the analysis of spatial, response, and reinforcement information is accomplished via an error-driven, or match-mismatch, algorithm across neural systems. Second, task-relevant processing occurs continuously within hippocampus and striatum regardless of the cognitive demands of the task. Third, given the high degree of parallel processing across allegedly different memory systems, we propose that different neural systems may effectively compete for control of a behavioral expression system. The strength of the influence of any one neural system on behavioral output is likely modulated by factors such as motivation, experience, or hormone status.

Animals↗

PubMed2001

Gender effects on aggression, dominance rank, and affiliative behaviors in a flock of captive adult cockatiels (Nymphicus hollandicus).

Agonistic and affiliative behaviors and spatial positioning were studied in a small psittacine species, Nymphicus hollandicus. Subjects studied were flock-housed breeders including five hens and seven cocks. Fifteen-minute focal animal samples were collected for the entire flock in a randomly distributed order during mate selection and the onset of the breeding season. All agonistic behaviors were recorded, including the winner and loser of each interaction, along with allopreening and copulation behavior. Point samples were recorded every 60s to determine social spacing. Rates of aggression were significantly higher for male cockatiels than female cockatiels. Results based on dyadic agonistic interactions showed males to rank significantly higher in the social hierarchy than females. Associations within the flock were not random. Individual birds associated more with specific birds than would be predicted by chance. Analysis of spatial data revealed that there were both same-sex and opposite-sex preferred associations within the flock. Male cockatiels engaged in allopreening behavior with females significantly more than with other males. Observations of breeding and nesting behaviors revealed pairs, a triad, and extra-pair mating.

Journal Article↗

PubMed1980

Orientation-specific adaptation: effects of checkerboards on the detectability of gratings.

The predictive values of Fourier analysis and local-feature analysis of spatial stimuli were compared in an orientation-specific adaptation experiment. Observers adapted to checkerboard patterns, which have fundamental Fourier components oriented 45 degrees away from the edges. Detection of gratings was found to be maximally impaired when fundamental Fourier components of adaptation and test patterns were in the same orientation and minimal when edges were aligned. The orientation spread and amount of adaptation effect were similar to that found in previous experiments which employed sinusoids as adaptation and test stimuli.

Adaptation, Ocular↗

PubMed2003

Application of a data-mining method based on Bayesian networks to lesion-deficit analysis.

Although lesion-deficit analysis (LDA) has provided extensive information about structure-function associations in the human brain, LDA has suffered from the difficulties inherent to the analysis of spatial data, i.e., there are many more variables than subjects, and data may be difficult to model using standard distributions, such as the normal distribution. We herein describe a Bayesian method for LDA; this method is based on data-mining techniques that employ Bayesian networks to represent structure-function associations. These methods are computationally tractable, and can represent complex, nonlinear structure-function associations. When applied to the evaluation of data obtained from a study of the psychiatric sequelae of traumatic brain injury in children, this method generates a Bayesian network that demonstrates complex, nonlinear associations among lesions in the left caudate, right globus pallidus, right side of the corpus callosum, right caudate, and left thalamus, and subsequent development of attention-deficit hyperactivity disorder, confirming and extending our previous statistical analysis of these data. Furthermore, analysis of simulated data indicates that methods based on Bayesian networks may be more sensitive and specific for detecting associations among categorical variables than methods based on chi-square and Fisher exact statistics.

Algorithms↗

PubMed2000

Testing local dependence of spatial structures on images

Associations between two spatial processes can be due to a real dependence between the two processes or to the dependence on common underlying variables. We propose to test the existence of a real dependence by use of local tests, leading to a global test of real dependence and a map of local interactions. We present first how classical interaction tests based on random rotations between completely observed processes such as those developed by Berman (Berman. Appl. Statist. (1986) 35, 54-62), can be integrated in local analyses. For this purpose, tests are first performed locally, and the distribution of their p-values is then compared to the corresponding value under the null hypothesis. A similar approach is proposed to test non-stationarity of a point pattern by using distance statistics popularized by Diggle (Diggle. Statistical Analysis of Spatial Point Patterns. (1983) Academic Press, New York). The problem of testing the interaction between a random field and a censoring area pattern process is discussed and an approach similar to the preceding ones is then proposed. The methods are mainly applied to agricultural examples but they can be applied to any microscopical images for which one wishes to analyse the spatial structure.

Journal Article↗

PubMed2026

Disentangling the cellular composition of FLCN-mutated tumors in Birt-Hogg-Dubé Syndrome by spatial transcriptomics.

Birt-Hogg-Dubé (BHD) syndrome is a hereditary cancer predisposition syndrome caused by pathogenic variants in the folliculin (FLCN) gene and is associated with an increased risk of multifocal renal tumors. FLCN-mutated tumors (FMTs) often exhibit morphological heterogeneity with mixed morphological features resembling renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC), yet the molecular basis underlying the heterogeneous morphologic features and the morphologic-genomic correlations remain poorly defined. In our prior work, we identified mutually exclusive expressions of L1 cell adhesion molecule (L1CAM) and forkhead box I1 tboxI1 (FOXI1) labeling the two morphologically distinct cellular populations in BHD-associated FMTs, leading to the hypothesis that these two tumor compartments may have distinct molecular features and may reflect different nephron epithelial differentiation states. In this follow-up study, we tested this hypothesis using L1CAM and FOXI1 as morphology-guided markers for spatial transcriptomic profiling of the distinct tumor compartments in FMTs with the NanoString GeoMX Digital Spatial Profiler (DSP). Six FMTs from three patients with BHD and three normal kidney tissues were analyzed. L1CAM+ and FOXI1+ area of interest (AOI) were collected from tumor areas with various tumor compositions, including L1CAM+ dominant, FOXI1+ dominant, and mixed tumor areas. Spatial transcriptomic analysis identified distinct gene expression signatures in L1CAM+ and FOXI1+ FMT compartments independent of the local tumor compositions. FOXI1+ tumor cells showed robust enrichment for intercalated cells (IC)-associated gene signatures. In contrast, L1CAM+ tumor cells exhibited a heterogeneous transcriptional profile, with partial overlap across a spectrum of renal tubular epithelial cell types rather than a definitive principal cell-like identity. Despite this compartment-specific differences, both compartments share expression of a panel of tumor signature genes, including glycoprotein nmb (GPNMB) gene, and a core of cancer related biological functions and signaling pathways. Together, these findings refined the prior dichotomous model of BHD-associated renal tumors and support a model in which L1CAM+ and FOXI1+ tumor compartments represent divergent evolutionary or differentiation states with a common FLCN-mutant neoplastic transcriptional program. This spatial transcriptomic profiling provides molecular evidence for the morphological heterogeneity of FMTs and insights on the tumor biology of BHD-associated FMTs.

Birt-Hogg-Dubé↗

PubMed2006

Noninvasive quantitative measurement of colloid transport in mesoscale porous media using time lapse fluorescence imaging.

We demonstrate noninvasive quantitative imaging of colloid and solute transport at millimeter to decimeter (meso-) scale. Ultraviolet (UV) excited fluorescent solute and colloid tracers were independently measured simultaneously during co-advection through saturated quartz sand. Pulse-input experiments were conducted at constant flow rates and ionic strengths 10(-3), 10(-2) and 10(-1) M NaCl. Tracers were 1.9 microm carboxylate latex microspheres and disodium fluorescein. Spatial moments analysis was used to quantify relative changes in mass distribution of the colloid and solute tracers over time. The solute advected through the sand at a constant velocity proportional to flow rate and was described well by a conservative transport model (CXTFIT). In unfavorable deposition conditions increasing ionic strength produced significant reduction in colloid center of mass transport velocity over time. Velocity trends correlated with the increasing fraction of colloid mass retained along the flowpath. Attachment efficiencies (defined by colloid filtration theory) calculated from nondestructive retained mass data were 0.013 +/- 0.03, 0.09 +/- 0.02, and 0.22 +/- 0.05 at 10(-3), 10(-2), and 10(-1) M ionic strength, respectively, which compared well with previously published data from breakthrough curves and destructive sampling. Mesoscale imaging of colloid mass dynamics can quantify key deposition and transport parameters based on noninvasive, nondestructive, spatially high-resolution data.

Colloids↗

PubMed2001

Bayesian partitioning for estimating disease risk.

This paper presents a Bayesian nonlinear approach for the analysis of spatial count data. It extends the Bayesian partition methodology of Holmes, Denison, and Mallick (1999, Bayesian partitioning for classification and regression, Technical Report, Imperial College, London) to handle data that involve counts. A demonstration involving incidence rates of leukemia in New York state is used to highlight the methodology. The model allows us to make probability statements on the incidence rates around point sources without making any parametric assumptions about the nature of the influence between the sources and the surrounding location.

Bayes Theorem↗

PubMed2000

ERN1, a novel ethylene-regulated nuclear protein of Arabidopsis.

Employing differential display of mRNA to investigate the transcriptionally regulated part of the ethylene response pathway in etiolated seedlings of Arabidopsis thaliana, a novel ethylene-regulated nuclear-localized protein, designated ERN1, was identified. ERN1 is one of four genes whose differential expression was confirmed by RNA blot analysis. ERN1 is represented by a single-copy gene in the Arabidopsis genome. Its expression is suppressed by ethylene in wild-type Arabidopsis but not in the ethylene-insensitive etr1-1 mutant. To gain first insight into the biological role of ERN1, a promoter-beta-glucuronidase (GUS) gene fusion was constructed and the expression in various organs from early to late developmental stages was examined. The analysis revealed spatial and temporal expression patterns that correlate with developmental processes known to be affected by ethylene. Evidence is given that the level of expression of ERN1 is regulated through the ethylene signal transduction pathway via CTR1 and EIN3, indicating that ERN1 acts downstream of EIN3.

Amino Acid Sequence↗

PubMed2005

Spatially selective laser irradiation method controlled by real-time image analysis: optical aspects.

We present a spatially selective irradiation method for laser treatment of biological surfaces. The purpose is to irradiate only the pathological targets and to preserve the healthy surrounding parts. We are interested here in the optical arrangement of the device and in the evaluation of its physical limitations before it is used for medical purposes. The method uses real-time image analysis applied to the video imagery of the surface to be treated. The result of the image analysis generates the control signal to a spatial light modulator, allowing us to project an adequate repartition of laser irradiance on the surface to be treated. Experimental results demonstrate a spatial selectivity of approximately 10 microm for a 6.7 mm x 5 mm field. The optical system has no moving parts (unlike galvanometric scanners) and is able to irradiate multiple targets simultaneously with different doses.

Equipment Design↗

PubMed1995

[Development of criteria and identification of areas most hazardous for the health of the population due to chemicals present in the environment. I. Proposed criteria for choosing health indicators].

Factors of communal and occupational environments, and particularly exposure to chemicals, belong to major causes of spatial differentiation of health situation. The authors propose criteria for choosing of negative health indicators in order to identify areas most hazardous to the population health because of the presence of chemicals in the environment. Following the diagnostic indices of the environment pollution and measures based on them two areas were identified: A--areas of the greatest ecological hazard and B--the most clean area as a reference point for area A. For the chosen group of health indicators whose levels can be determined in both areas A and B, relative risk was developed. In order to choose health indicators essential in view of the environmental hazard, alternative criteria were proposed: an arbitrrarycriterion, a criterion based on confidence interval for relative risk, and a criterion based on ch2 statistics and on confidence interval for relative risk. Finally chosen indicators and synthetic measures based on them will provide the ground for a comprehensive analysis of spatially differentiated health situation because of the environment pollution with particular reference to chemical factors.

Chi-Square Distribution↗

PubMed1997

A Quantitative Method for Delineating Regions: An Example for theWestern Corn Belt Plains Ecoregion of the USA

/ A method was developed to systematically delineate boundaries forecological classification of regions. The process entailed the use ofsmall-scale digital data to quantify spatial concordance among environmentalattribute data sets. The data sets were grouped into spatially related themesusing cluster analysis and multidimensional scaling. Selected data sets werethen used either individually or collectively to divide the study area intosubregions that exhibited different environmental attributes. The method wasapplied to a previously defined ecological unit, the western Corn Belt of thecentral United States. The results showed that the portion of the study areawith intensive corn and soybean production was identifiable using each of thethree input data sets selected for partitioning (soil associations; AVHRRremote-sensing imagery; and a combined data set of landform, forest, andsoils data). The classification of other portions of the study area washighly dependent on the type and scale of the input data. The systematicmethodology used here offers advantages over other methods for identifyingecological regions in that the results from the systematic approach can bereproduced, the boundaries between ecological units can be revised based onnew or more accurate data, important ecological processes are explicitlychosen to delineate boundaries, and transition zones between regions can bequantified.KEY WORDS: Ecoregions; Spatial analysis; Corn Belt; Iowa; GIS;Regionalization

Journal Article↗

PubMed2006

Assessing impacts of typhoons and the Chi-Chi earthquake on Chenyulan watershed landscape pattern in central Taiwan using landscape metrics.

The Chi-Chi earthquake (ML=7.3) occurred in the central part of Taiwan on September 21, 1999. After the earthquake, typhoons Xangsane and Toraji produced heavy rainfall that fell across the eastern and central parts of Taiwan on November 2000 and July 2001. This study uses remote sensing data, landscape metrics, multivariate statistical analysis, and spatial autocorrelation to assess how earthquake and typhoons affect landscape patterns. It addresses variations of the Chenyulan watershed in Nantou County, near the earthquake's epicenter and crossed by Typhoon Toraji. The subsequent disturbances have gradually changed landscape of the Chenyulan watershed. Disturbances of various types, sizes, and intensities, following various tracks, have various effects on the landscape patterns and variations of the Chenyulan watershed. The landscape metrics that are obtained by multivariate statistical analyses showed that the disturbances produced variously fragmented patches, interspersed with other patches and isolated from patches of the same type across the entire Chenyulan watershed. The disturbances also affected the isolation, size, and shape-complexity of patches at the landscape and class levels. The disturbances at the class level more strongly affected spatial variations in the landscape as well as patterns of grasslands and bare land, than variations in the watershed farmland and forest. Moreover, the earthquake with high magnitude was a starter to create these landscape variations in space in the Chenyulan watershed. The cumulative impacts of the disturbances on the watershed landscape pattern had existed, especially landslides and grassland in the study area, but were not always evident in space and time in landscape and other class levels.

Conservation of Natural Resources↗

PubMed2006

Selective matrix attachment regions in T helper cell subsets support loop conformation in the Ifng gene.

Cytokine genes undergo progressive changes in chromatin organization when naïve CD4+ T helper (Th) cells differentiate into committed Th1 and Th2 lineages. Here, we analyzed nuclear matrix attachment regions (MARs) in the Ifng gene by DNA array technique in unactivated and activated CD4+ Th cells. This approach was combined with analysis of spatial organization of the Ifng gene by chromosome conformation capture approach to assess the relationship between the gene conformation and matrix attachment organization in functionally different cell subsets. We report that the Ifng gene in unactivated cells displays a linear conformation, but in T-cell receptor-activated cells, it adopts a loop conformation. The selective MARs support the spatial gene organization and characteristically define the Ifng gene in functionally different cell subsets. The pattern of interaction of the Ifng gene with the nuclear matrix dynamically changes in a lineage-specific manner in parallel with the changes in Ifng gene conformation. The data suggest that such structural dynamics provide the means for transcriptional regulation of the Ifng gene in the course of activation and differentiation of CD4+Th cells.

Animals↗

PubMed1997

A quantitative comparison of some FADS methods in renal dynamic studies using simulated and phantom data.

Simulated and phantom data were used to determine if factor analysis of dynamic structures (FADS) methods can be used quantitatively. FADS methods tested included variants of apex seeking, the intersection method, cluster analysis and spatial constraints. These were compared with a region-of-interest (ROI) approach. Simulated renal studies were prepared using from three to six homogeneous structures. These corresponded to two blood background structures; two structures (one pathological) for parenchyma; and two structures (one pathological) for the collecting system. Time-activity curves for background, parenchyma and collecting system were obtained for each method and compared with the true curve. A kidney phantom was modelled using a tunnelled vessel filled with chelating material A variable flow was controlled by a peristaltic pump representing the renal filtration of fluid. The glomerular filtration rate (GFR) was estimated using FADS and ROI-based methods and compared with the values measured experimentally. Most FADS methods perform well in the absence of pathology, but less well than the ROI-based method when pathology is present. Some FADS methods perform better than the ROI-based method when background estimation is a problem as in the GFR experiment. For quantitative analysis, the success of FADS depends on the validity of the underlying assumptions and on the appropriate nature of the constraints.

Computer Simulation↗

PubMed2000

Use of phosphosynapsin I-specific antibodies for image analysis of signal transduction in single nerve terminals.

We have developed a semi-quantitative method for indirectly revealing variations in the concentration of second messengers (Ca(2+), cyclic AMP) in single presynaptic boutons by detecting the phosphorylation of the synapsins, excellent nerve terminal substrates for cyclic AMP- and Ca(2+)/calmodulin-dependent protein kinases. For this purpose, we employed polyclonal, antipeptide antibodies recognising exclusively synapsin I phosphorylated by Ca(2+)/calmodulin-dependent protein kinase II (at site 3) or synapsins I/II phosphorylated by either cAMP-dependent protein kinase or Ca(2+)/calmodulin-dependent protein kinase I (at site 1). Cerebellar granular neurones in culture were double-labelled with a monoclonal antibody to synapsins I/II and either of the polyclonal antibodies. Digitised images were analysed to determine the relative phosphorylation stoichiometry at each individual nerve terminal. We have found that: (i) under basal conditions, phosphorylation of site 3 was undetectable, whereas site 1 exhibited some degree of constitutive phosphorylation; (ii) depolarisation in the presence of extracellular Ca(2+) was followed by a selective and widespread increase in site 3 phosphorylation, although the relative phosphorylation stoichiometry varied among individual terminals; and (iii) phosphorylation of site 1 was increased by stimulation of cyclic AMP-dependent protein kinase but not by depolarisation and often occurred in specific nerve terminal sub-populations aligned along axon branches. In addition to shedding light on the regulation of synapsin phosphorylation in living nerve terminals, this approach permits the spatially-resolved analysis of the activation of signal transduction pathways in the presynaptic compartment, which is usually too small to be studied with other currently available techniques.

Animals↗