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Gradients of cellular maturation and synaptogenesis in the superior colliculus of the fetal rhesus monkey.

Light (LM) and electron microscopic (EM) qualitative and quantitative analyses were employed to determine the tempo and spatial gradients of synaptogenesis and cellular differentiation in the superficial superior colliculus (SC) of the rhesus monkey between embryonic (E) days E47 and E84. By E47, a majority of the neurons of the prospective superficial gray layer (SGS) have arrived at their final positions and contribute to a uniform band of small, darkly Nissl-stained neurons at the outer surface of the SC. By E54, cells in the middle of the rostral pole of the superficial SC become considerably larger, paler staining, and less densely packed than the more medially or laterally located cells. These regional differences, which extend posteriorly through about the middle of the SC at this age, are evident on both the LM and EM levels and were confirmed by a quantitative EM analysis of the cytodifferentiation and synaptogenesis in the SGS. Several overlapping EM probes made across the medial, middle, and lateral regions of the SGS at each of three coronal levels reveal consistently more developed neuropil and smaller amounts of extracellular space in the middle region than in the medial and lateral portions of the more anterior SC. Further, the densities of synapses, both in terms of synapses/micron2 of total cross-sectional area and synapses/micron2 of neuropil alone, are also higher in the middle than the peripheral regions. Most of the middle-peripheral differences found in the mid-E50s are still evident by the early E60s, but have disappeared by midgestation (E80s). The present results are interpreted to indicate that the middle region of the SGS at a given transverse level begins to mature significantly earlier than the medial or lateral areas. Since our previous 3H-thymidine analysis (Cooper and Rakic, '81a) failed to reveal significant regional variation in the time of neuron origin in the superficial SC, the observed spatiotemporal gradients of neuronal maturation in the primate SGS probably do not arise from underlying gradients of cellular proliferation.

Animals↗

The electroencephalogram through a software microscope: non-invasive localization and visualization of epileptic seizure activity from inside the brain.

OBJECTIVE: We developed a novel non-invasive analysis to localize the source and visualize the time course of electrical activity generated inside the brain but unclear from the scalp. This analysis applies to signals with unique waveform characteristics, such as seizures. METHODS: The method extracts activity from an EEG data matrix as a spatiotemporal component having waveforms uncorrelated to the other concurrent activities. The method also provides the location and orientation of the dipole generating this activity. We applied this method to ten scalp seizures in three patients with temporal lobe epilepsy and single-focus seizures confirmed by intracerebral recordings. A realistic head model based on MRI was used for computation of field distributions. RESULTS: When seizure activity was still not visually identifiable on the scalp, the method demonstrated in all scalp seizures a source in the temporal neocortex corresponding clearly to the region of seizure activity in intracerebral recordings. Frequency characteristics of the estimated activities also resembled those of the intracerebral seizures. CONCLUSIONS: This method enables estimation of focal brain activity when its effect on scalp EEG is unclear to visual examination. It works in situations where currently available source analyses methods, which require noiseless definite activity, are not applicable.

Brain↗

A single mechanism for both luminance and chromatic grating vernier tasks: evidence from temporal summation.

Vernier thresholds are determined by luminance rather than chromatic contrast when both are present in vernier targets. The role of luminance and chromatic mechanisms in vernier performance under equiluminant conditions remains uncertain. Temporal summation functions for vernier thresholds with luminance and red-green equiluminant gratings were compared to those for detection thresholds with similar stimuli. Vernier thresholds showed similar temporal summation for luminance and chromatic gratings, which is consistent with a single mechanism underlying vernier performance in the two conditions. However, detection thresholds showed a shorter temporal summation duration for luminance gratings than for chromatic gratings, which suggests that two different mechanisms underlie detection thresholds. Analysis of physiological data supports the hypothesis that the frequency-doubled response of ganglion cells in the magnocellular pathway can provide accurate spatiotemporal information for vernier performance at equiluminance.

Animals↗

Speed modulation in swimming frogs.

Swimming movements of 7 European green frogs (Rana esculenta) were studied, starting from the detailed analysis of the speed and timing of the propulsive, glide, and recovery phases of their intermittent swimming behavior. First, the authors identified the spatiotemporal factors used by the frogs to modulate their swimming behavior. None of the gait variables correlated strongly with average swimming speed, and no significant correlations were found between variables belonging to different phases. There did not seem to be an obvious control strategy. Instantaneous speeds at the transition of the different phases all increased significantly with average speed, however. The strong correlation between maximal speed at the end of propulsion and the speed averaged over a cycle might reflect the dominance of the propulsive phase in the determination of the overall swimming speed. The modulation of swimming speed thus seemed largely comparable with the regulation of jumping distance. That finding was confirmed in a mathematical model, in which the positive correlations between both glide and recovery speeds, on the one hand, and average speed, on the other, were shown to be only mathematical consequences of the strong impact of the propulsive phase on overall swimming performance. That finding suggests that the correlations did not result from an active control strategy.

Animals↗

Arginine-metabolizing enzymes in the developing rat small intestine.

Before weaning, arginine biosynthesis from citrulline most likely takes place in the small intestine rather than in the kidney. We studied the expression of ornithine cycle enzymes in the rat small intestine during perinatal development. The spatiotemporal patterns of expression of ornithine aminotransferase, carbamoylphosphate synthetase, ornithine transcarbamoylase, argininosuccinate synthetase, argininosuccinate lyase, and arginase mRNAs were studied by Northern blot analysis and in situ hybridization. In addition, the expression of carbamoylphosphate synthetase and argininosuccinate synthetase protein was studied by immunohistochemistry. Before birth, the developmentally more mature proximal loops of the intestine expressed the mRNAs at higher concentrations than the more distal loops. After birth, this difference was no longer obvious. The mRNAs of argininosuccinate synthetase and argininosuccinate lyase, the enzymes that metabolize citrulline to arginine, were detectable only in the upper part of the villi, whereas the other mRNAs were concentrated in the crypts. The distribution of argininosuccinate synthetase protein corresponded with that of the mRNA, whereas carbamoylphosphate synthetase protein was present in all enterocytes of the crypts and villi. Hepatic arginase mRNA could not be detected in the enterocytes. The spatial distribution of the respective mRNAs and proteins along the villus axis of the suckling small intestine indicates that the basal enterocytes synthesize citrulline, whereas the enterocytes in the upper half of the villus synthesize arginine.

Animals↗

Identification of N-myc regulatory regions involved in embryonic expression.

Our knowledge on the regulation of the N-myc proto-oncogene expression comes mostly from in vitro studies. Very few in vivo analyses have been performed to identify the regulatory elements involved in N-myc developmental expression. In the present study, we defined DNA regions required for the regulated expression of N-myc during early embryogenesis. We showed that the expression of N-myc driven by the human N-myc sequences previously described to control N-myc expression in appropriate cell types in vitro cannot rescue the mouse N-myc mutant phenotype, suggesting that regulatory elements necessary for N-myc embryonic expression were missing. To identify the regulatory DNA regions involved in N-myc expression, transgenic mouse lines carrying N-myc/lacZ reporter constructs were generated. Beta-galactosidase staining analysis at different stages of gestation revealed that >16 kb of mouse N-myc genomic sequences are required to recapitulate the entire spatiotemporal expression pattern of the endogenous N-myc gene between embryonic d 8.5 and 11.5. This observation supported the notion that the sequences previously identified by in vitro assays were not sufficient to reproduce the N-myc embryonic expression pattern. However, regulatory elements that can direct specific expression in the visceral arches, the limb buds, the CNS, and the dorsal root ganglia are included into the mouse N-myc genomic sequences tested. Altogether, these findings indicated that the regulation of the spatiotemporal expression pattern of N-myc during development necessitates multiple regulatory DNA elements.

Animals↗

Analysis of calcium imaging signals from the honeybee brain by nonlinear models.

Recent Ca(2+)-imaging studies on the antennal lobe of the honeybee (Apis mellifera) have shown that olfactory stimuli evoke complex spatiotemporal changes of the intracellular Ca(2+) concentration, in which stimulus-dependent subsets of glomeruli are highlighted. In this work we use nonlinear models for the quantitative identification of the spatial and temporal properties of the Ca(2+)-dependent fluorescence signal. This technique describes time series of the Ca(2+) signal as a superposition of biophysically motivated model functions for photobleaching and Ca(2+) dynamics and provides optimal estimates of their amplitudes (signal strengths) and time constants together with error measures. Using this method, we can reliably identify two different stimulus-dependent signal components. Their delays and rise times, delta(c1) = (0.4 +/- 0.3) s, tau(c1) = (3.8 +/- 1.2) s for the fast component and delta(c2) = (2.4 +/- 0.6) s, tau(c2) = (10.3 +/- 3.2) s for the slow component, are constant over space and across different odors and animals. In chronological experiments, the amplitude of the fast (slow) component often decreases (increases) with time. The pattern of the Ca(2+) dynamics in space and time can be reliably described as a superposition of only two spatiotemporally separable patterns based on the fast and slow components. However, the distributions of both components over space turn out to differ from each other, and more work has to be done in order to specify their relationship with neuronal activity.

Algorithms↗

Spatiotemporal features of severe air pollution in northern Taiwan.

BACKGROUND, AIMS AND SCOPE: This research attempted to identify the dominant factors simultaneously affecting the airborne concentrations of five air pollutants with principal component analysis and to determine the meteorologically related parameters that cause severe air-pollution events. According to the definition of subPSI and PSI values through the U.S. EPA, the historical raw data of five criteria air pollutants, SO2, CO, O3, PM10 and NO2, were calculated as daily subPSI values. In addition to the airborne concentrations, this study simultaneous collected the surface meteorological parameters of the Taipei meteorological station, established by the Central Weather Bureau. METHODS: Principal component analysis was conducted to screen severe air pollution scenarios for five air pollutants: SO2, CO, O3, PM10 and NO2. The concentrations of various air pollutants measured at 17 air-quality stations in northern Taiwan from 1995 to 2001 were transformed into daily subPSI values. The correlation analysis of the five air pollutants and four meteorological parameters (wind speed, temperature, mixing height and ventilation rate) were included in this research. After screening severe air pollution scenarios, this study recognized the synoptic patterns easily causing the severe air-pollution events. RESULTS AND DISCUSSION: Analytical results showed that the eigenvalues of the first two principal components for SO2, CO, O3, PM10 and NO2 were greater than 1. The first component of five air pollutants explained 64, 64, 67, 76 and 63% of subPSI variance for SO2, CO, O3, PM10 and NO2, respectively. Only the correlation coefficient of NO2 and CO had statistically significant positive values (0.82); other pollutant pairs presented medium (0.4 to 0.7) or low (0 to 0.4) positive values. The correlation coefficients for air pollutants and three meteorological parameters (wind speed, mixing height and ventilation index) were medium or low negative values. In northern Taiwan, spring was most likely induced high concentrations and the component scores of the first component for SO2, CO, PM10 and NO2; summer was the worst season that caused high O3 episodes. Consequently, the analytical results of factor loadings for the first principal component and emission inventory of various sources revealed that mobile sources were dominant factors affecting ambient air quality in northern Taiwan. CONCLUSION: According to the results of principal component analysis for the five air pollutants, the first two of 17 components were cited as major factors and explained 71% of subPSI variance. Based on the inventory of NOx emissions and the isopleth diagram of factor loading for the first component, mobile sources in the southwest Taipei City accounted for the highest factor loading values and emission inventory values. Synoptic analysis and principal component analysis demonstrated that three types of weather patterns (high-pressure recirculation, prefrontal warm sector and the southwesterly wind system) easily caused the severe air-pollution scenarios. In summary, if severe air-pollution days occurred, the average meteorological parameters experienced adverse conditions for diffusing air pollutants; that is, the average values of wind speed, mixing height and ventilation index were lower than 2.1 ms(-1), 360 m and 800 m2s(-1), respectively. If one of the three synoptic patterns were to occur in combination with adverse meteorological conditions, severe air-pollution events would be developed. RECOMMENDATION AND OUTLOOK: By utilizing synoptic patterns, this work found three weather systems easily caused severe air-pollution events over northern Taiwan. Analytical results showed, respectively, the wind speed and mixing height were less than 2.1 m/s and 360 m during severe air-pollution events.

Air Movements↗

Cellular patterns in the inner retina of adult zebrafish: quantitative analyses and a computational model of their formation.

The mechanisms that control cellular pattern formation in the growing vertebrate central nervous system are poorly understood. In an effort to reveal mechanistic rules of cellular pattern formation in the central nervous system, quantitative spatial analysis and computational modeling techniques were applied to cellular patterns in the inner retina of the adult zebrafish. All the analyzed cell types were arrayed in nonrandom patterns tending toward regularity; specifically, they were locally anticlustered. Over relatively large spatial scales, only one cell type exhibited consistent evidence for pattern regularity, suggesting that cellular pattern formation in the inner retina is dominated by local anticlustering mechanisms. Cross-correlation analyses revealed independence between the patterns of different cell types, suggesting that cellular pattern formation may involve multiple, independent, homotypic anticlustering mechanisms. A computational model of cellular pattern formation in the growing zebrafish retina was developed, which featured an inhibitory, homotypic signaling mechanism, arising from differentiated cells, that controlled the spatial profile of cell fate decisions. By adjusting the spatial profile of this decaying-exponential signal, the model provided good estimates of all the cellular patterns that were observed in vivo, as objectively judged by quantitative spatial pattern analyses. The results support the hypothesis that cellular pattern formation in the inner retina of zebrafish is dominated by a set of anticlustering mechanisms that may control events at, or near, the spatiotemporal point of cell fate decision.

Animals↗

Spatiotemporal linkage in infant interlimb coordination.

Timing and direction of movement of the arms and hands of 7- and 11-month-old infants were examined during bimanual reaching for a transparent cube. Videotape analysis of frames from release of the hands to initial contact of one hand with the cube revealed that hand movement was more often temporally linked for 7-month infants than for 11-month infants. Also, at 7 months, the hands moved toward the cube in the same direction, whereas at 11 months, they moved in opposite (complementary) directions. Thus, although both 7- and 11-month infants perform bimanual reaching, at 7 months the 2 hands are linked both in timing and direction of movement in a fashion different than at 11 months.

Child Development↗

Nucleotide sequence and spatiotemporal expression of the Vibrio cholerae vieSAB genes during infection.

The iviVII gene of Vibrio cholerae was previously identified by a screen for genes induced during intestinal infection. In the present study, nucleotide sequence analysis revealed that iviVII is a 1,659-bp open reading frame, herein designated vieB, that is predicted to be last in a tricistronic operon (vieSAB). The deduced amino acid sequence of VieS exhibited similarity to the sensor kinase component, and those of VieA and VieB were similar to the response regulator components, respectively, of the two-component signal transduction family. Analysis of transcriptional fusions to a site-specific DNA recombinase reporter, tnpR, revealed that vieS and vieA are transcribed during in vitro growth in a vieAB-independent and vieA-dependent manner, respectively. In contrast, transcription of vieB occurred exclusively during infection and was not dependent upon VieB. We conclude that the vieSAB genes are differentially regulated, at least during laboratory growth. Use of a V. cholerae strain harboring a vieB::tnpR transcriptional fusion allowed the kinetics and location of vieB expression within the intestine to be determined. We found that vieB transcription is induced shortly after infection of the proximal and mid-small intestine.

Amino Acid Sequence↗

Color-opponent receptive fields derived from independent component analysis of natural images.

Independent Component Analysis (ICA) of images of natural scenes has been shown to generate basis functions, or filters, which resemble spatial [Bell & Sejnowski (1997). Vision Research, 37, 3327-3338; van Hateren & van der Schaaf (1998). Proceedings of the Royal Society of London B, 265, 359-366] and spatiotemporal [van Hateren & Ruderman (1998) Proceedings of the Royal Society of London B, 265, 2315-2320] receptive fields of simple cells of the striate cortex. ICA yields statistically independent components which provide for a redundancy-reduced representation of the data. Using one of several published algorithms [Lee (1998). Independent component analysis: theory and applications. Boston; Kluwer Academic], we applied linear ICA to color images of natural scenes. The resulting independent component filters (ICFs) separate into either luminance or color filters. The luminance filters are localized and oriented edge detectors as reported previously. The color filters resemble either blue-yellow or red-green double-opponent receptive fields with various orientations. An equal number of each type of filter (luminance, red-green, and blue-yellow) is obtained. Thus, ICA predicts that spatiochromatic information is coded in statistically independent luminance, blue-yellow, and red-green opponent pathways with a relatively equal representation and specific spatial profiles at the cortical level.

Algorithms↗

Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-alpha responsive promoters.

In breast cancer and normal estrogen target tissues, estrogen receptor-alpha (ERalpha) signaling results in the establishment of spatiotemporal patterns of gene expression. Whereas primary target gene regulation by ERalpha involves recruitment of coregulatory proteins, coactivators, or corepressors, activation of these downstream promoters by receptor signaling may also involve partnership of ERalpha with other transcription factors. By using an integrated, genome-wide approach that involves ChIP-chip and computational modeling, we uncovered 13 ERalpha-responsive promoters containing both ERalpha and c-MYC binding elements located within close proximity (13-214 bp) to each other. Estrogen stimulation enhanced the c-MYC-ERalpha interaction and facilitated the association of ERalpha, c-MYC, and the coactivator TRRAP with these estrogen-responsive promoters, resulting in chromatin remodeling and increased transcription. These results suggest that ERalpha and c-MYC physically interact to stabilize the ERalpha-coactivator complex, thereby permitting other signal transduction pathways to fine-tune estrogen-mediated signaling networks.

Animals↗

Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner.

Autoimmune regulator (AIRE) is responsible for the development of organ-specific autoimmune disease in a monogenic fashion. Rare and low levels of tissue expression together with the lack of AIRE-expressing cell lines have hampered a detailed analysis of the molecular dynamics of AIRE. Here we have established cell lines stably transfected with AIRE and studied the regulatory mechanisms for its subcellular expression. We found that nuclear body (NB) formation by AIRE was dependent on the cell cycle. Biochemical fractionation revealed that a significant proportion of AIRE is associated with the nuclear matrix, which directs the functional domains of chromatin to provide sites for gene regulation. Upon proteasome inhibition, AIRE NBs were increased with concomitant reduced expression in the cytoplasm, suggesting that subcellular targeting of AIRE is regulated by a ubiquitin-proteasome pathway. We also found that AIRE NBs compete for cAMP-response element-binding protein-binding protein/p300, a common coactivator of transcription, with the promyelocytic leukemia gene product. These results suggest that the transcriptional regulating activities of AIRE within a cell are controlled and organized in a spatiotemporal manner.

Animals↗

Expression of claudins in murine tooth development.

Claudins belong to a family of transmembrane proteins that were identified as components of tight junction strands. We carried out comparative in situ hybridization analysis of 11 claudin genes (claudin1 - claudin11) during murine odontogenesis from the formation of the epithelial thickening to the cytodifferentiation stage. We identify dynamic spatiotemporal expression of 9 of the 11 claudins. At the early bell stage, two claudins (claudin1 and 4) are specifically expressed in stratum intemedium, whereas only one claudin is expressed in each of the preameloblasts (claudin2) and preodontoblasts (claudin10). At the bud stage, when the first epithelial differentiation pathways are being established, localized expression of six claudins (claudin1, 3, 4, 6, 7, and 10) identify spatial specific interactions, suggesting a hitherto unobserved complexity of epithelial organization, within the early tooth primordium.

Animals↗

Principal components in three-ball cascade juggling.

To uncover the underlying control structure of three-ball cascade juggling, we studied its spatiotemporal properties in detail. Juggling patterns, performed at fast and preferred speeds, were recorded in the frontal plane and subsequently analyzed using principal component analysis and serial correlation techniques. As was expected on theoretical grounds, the principal component analysis revealed that maximally four instead of the original six dimensions (3 balls x 2 planar coordinates) are sufficient for describing the juggling dynamics. Juggling speed was shown to affect the number of dimensions (four for the fast condition, two for the preferred condition) as well as the smoothness of the time evolution of the eigenvectors of the principal component analysis, particularly around the catches. Contrary to the throws and the zeniths, and regardless of juggling speed, consecutive catches of the same hand showed a markedly negative lag-one serial correlation, suggesting that the catches are timed so as to preserve the temporal integrity of the juggling act.

Biomechanical Phenomena↗

Seasonal cycle of VOCs in apartments.

To assess the adverse health effects of volatile organic compounds (VOCs), epidemiological studies combine the health outcome of individuals with their concomitant VOC exposure. While the latter is representative of the studied period, health effects might also be the result of long-term exposure or emerge in consequence of a peak pollution throughout the year. To address these problems, additional information about the spatiotemporal distribution of VOCs is necessary. The present paper aims at elucidating the spatial and temporal variation of VOC concentrations in Leipzig, Germany. The analysis is based on 1499 indoor and 222 outdoor measurements taken in the period between 1994 and 2001. All data were collected in the frame of epidemiological studies (Diez et al., 1999; Fritz et al., 1998; Schulz et al., 1999). The analysis comprised concentrations of 30 VOCs belonging to the groups of alkanes, cycloalkanes, aromatics, volatile halogenated hydrocarbons, and terpenes. We found that the VOC load in indoor air is, on average, 10 times higher than outdoors. For the studied period there was a clear downward tendency for all VOCs in apartments in Leipzig, except for terpenes which show an upward trend in the period 1996-99. In indoor air we observe an annual cycle for the total VOC concentration as well as the sum concentrations of the above called groups. Highest concentrations occur during the winter months, approximately three times higher than the summer burden. We summarize this finding in a seasonal model, which is fitted to our measurements. Based on the model we develop a procedure for seasonal adjustment, which enables to roughly estimate the annual peak concentration utilizing one monthly observation.

Air Pollution, Indoor↗

The cutaneous rabbit revisited.

In the cutaneous rabbit effect (CRE), a tactile event (so-called attractee tap) is mislocalized toward an adjacent attractor tap. The effect depends on the time interval between the taps. The authors delivered sequences of taps to the forearm and asked participants to report the location of one of the taps. The authors replicated the original CRE findings and observed a smaller but significant mislocalization when the attractor tap preceded the attractee tap. These results are consistent with the CRE arising from spatiotemporal interactions between the sensory codes for each individual tap. In subsequent experiments, the authors showed that the CRE was not affected by either gaze direction or concurrent auditory temporal information. The authors propose a model that explains the CRE by the spatiotemporal dynamics of an early, unimodal, sensory map.

Acoustic Stimulation↗