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PubMed1998

Spatiotemporal periodicity during atrial fibrillation in the isolated sheep heart.

BACKGROUND: The activation patterns that underlie the irregular electrical activity during atrial fibrillation (AF) have traditionally been described as disorganized or random. Recent studies, based predominantly on statistical methods, have provided evidence that AF is spatially organized. The objective of this study was to demonstrate the presence of spatial and temporal periodicity during AF. METHODS AND RESULTS: We used a combination of high-resolution video imaging, ECG recordings, and spectral analysis to identify sequential wave fronts with temporal periodicity and similar spatial patterns of propagation during 20 episodes of AF in 6 Langendorff-perfused sheep hearts. Spectral analysis of AF demonstrated multiple narrow-band peaks with a single dominant peak in all cases (mean, 9.4+/-2.6 Hz; cycle length, 112+/-26 ms). Evidence of spatiotemporal periodicity was found in 12 of 20 optical recordings of the right atrium (RA) and in all (n=19) recordings of the left atrium (LA). The cycle length of spatiotemporal periodic waves correlated with the dominant frequency of their respective optical pseudo-ECGs (LA: R2=0.99, slope=0.94 [95% CI, 0.88 to 0.99]; RA: R2=0.97, slope=0.92 [95% CI, 0.80 to 1.03]). The dominant frequency of the LA pseudo-ECG alone correlated with the global bipolar atrial EG (R2=0.76, slope=0.75 [95% CI, 0.52 to 0.99]). In specific examples, sources of periodic activity were seen as rotors in the epicardial sheet or as periodic breakthroughs that most likely represented transmural pectinate muscle reentry. However, in the majority of cases, periodic waves were seen to enter the mapping area from the edge of the field of view. CONCLUSIONS: Reentry in anatomically or functionally determined circuits forms the basis of spatiotemporal periodic activity during AF. The cycle length of sources in the LA determines the dominant peak in the frequency spectra in this experimental model of AF.

Animals↗
PubMed1987

Origins and implications of frequency-doubling in the visual evoked potential.

The origins and implications of frequency-doubling (i.e., the dominance of the 4th-harmonic response instead of the reversal response) in the visual evoked potential (VEP) were investigated. Previous research demonstrated that frequency-doubling occurs in humans when sinusoidal but not square-wave luminance modulation is used to elicit the VEP, but little else is known about this intriguing phenomenon. Six adult humans viewed luminance and chromatic gratings that were presented using three different spatiotemporal combinations: 4 c/deg-3 Hz, 4 c/deg-6 Hz, and 12 c/deg-3 Hz. VEP's were recorded monopolarly from Oz using an ear reference and were subjected to a Fourier analysis. The results showed that frequency-doubling occurred only using sinusoidal luminance contrasts at 4 c/deg-3 Hz, although the relative strength of higher harmonic responses was greater for both sine- and square-wave luminance contrasts relative to their chromatic counterparts. Many hypotheses can be put forth to account for VEP frequency-doubling (none of which is entirely satisfactory); however, a plausible view is that this phenomenon is related to the magnocellular-parvocellular distinction. In general, the presence of frequency-doubling and other harmonic distortions may preclude the scalp-recorded steady-state VEP to suprathreshold luminance contrasts from describing accurately the spatiotemporal transfer characteristics of the human visual system.

Adult↗
PubMed1993

New techniques in the pharmacokinetic analysis of cancer drugs. IV. Positron emission tomography.

Positron emission tomography is a powerful tool for the absolute quantification of injected positron emitting radiotracer concentration within tissues in vivo. Very detailed spatiotemporal data can be obtained without biopsy sampling. Most chemotherapeutic agents can be labelled with a positron emitter, and human tissue and tumour pharmacokinetics can be obtained non-invasively. Its main limitations are the inability to discriminate metabolites, the short half-life of the isotopes used and the specialized equipment required. Despite this, PET has the potential to make a major contribution in the study of the pharmacokinetics of anti-cancer drugs.

Antineoplastic Agents↗
PubMed2004

Functional conserved elements mediate intestinal-type fatty acid binding protein (I-FABP) expression in the gut epithelia of zebrafish larvae.

Intestinal-type fatty acid binding protein (I-FABP) plays an important role in the intracellular binding and trafficking of long chain fatty acids in the intestine. The aim of this study, therefore, was to elucidate the regulation and spatiotemporal expression of the I-FABP gene during zebrafish larval development. We performed in vivo reporter-gene analysis in zebrafish by using a transient and transgenic approach. Green fluorescent protein-reporter analyses revealed that the proximal 192-bp region of the I-FABP promoter is sufficient to direct intestine-specific expression during zebrafish larval development. Functional dissection of a 41-bp region within this 192-bp promoter revealed that one C/EBP and two GATA-like binding sites, along with a novel 15-bp element within it are required for I-FABP gene expression in vivo. In addition, the six consensus sites (CCACATCAGCATGAA) in the 15-bp element are critical for I-FABP gene regulation in the zebrafish gut epithelia. Comparison analyses of the orthologous 15-bp element from mammalian I-FABP genes suggests that these mammalian elements are functionally equivalent to the zebrafish 15 element. These results provide the first in vivo evidence that these binding sites (C/EBP and GATA) and the novel 15-bp element contribute to intestine-specific gene expression and that they are functionally conserved across vertebrate evolution.

Animals↗
PubMed2001

Responses of rostral fastigial neurons to linear acceleration in an alert monkey.

Vestibular-only neuronal responses to angular acceleration have been systematically characterized in the rostral fastigial nucleus (FN) by several studies. However, responses of these neurons to linear acceleration have not been examined. In this study, we recorded single-unit activity of vestibular-only neurons in an alert monkey during pure sinusoidal linear acceleration along different directions in the horizontal plane. Spatiotemporal response properties were quantified by computing two-dimensional response ellipses in the horizontal plane. Based on this analysis, neurons were classified as narrowly or broadly tuned. About 29% (5/17) of neurons were broadly tuned. The other 71% (12/17) were narrowly tuned. Unlike vestibular nuclei neurons, all recorded FN neurons exhibited irregular resting discharge rates (CV*0.2). Based on studies of linear motion-sensitive neurons in the vestibular nuclei, the data suggest that irregular neurons in the rostral FN and the vestibular nuclei have similar responses to linear acceleration in behaving monkeys.

Acceleration↗
PubMed2006

TUGAI: An integrated simulation tool for ecological assessment of alternative water management strategies in a degraded river delta.

The development of ecologically sound water allocation strategies that account for the needs of riverine ecosystems is a pressing issue, especially in semiarid river basins. In the Aral Sea Basin, a search for strategies to mitigate ecological and socioeconomic deterioration has been in process since the early 1990s. The Geographic Information System-based simulation tool TUGAI has been developed to support the policy determination process by providing a simple, problem-oriented method to assess ecological effects of alternative water management strategies for the Amudarya River. It combines a multiobjective water allocation model with simple, spatially explicit statistical and rule-based models of landscape dynamics. Changes in environmental conditions are evaluated by a fuzzy habitat suitability index for Populus euphratica, which is the dominant species of the characteristic riverine Tugai forests. Water management scenarios can be developed by altering spatiotemporal water distribution in the delta area or the amount of water inflow into the delta. Outcomes of scenario analysis are qualitative comparisons of the ecological effects of different options for a time period of up to 28 years. The given approach utilizes different types of knowledge, from quantitative hydrological data to qualitative local expert knowledge. The main purpose of the tool is to integrate the knowledge in a comprehensive way to make it available for discussions on alternative policies in moderated workshops with stakeholders. In this article, the modules of the tool, their integration, and three hypothetical scenarios are presented. Based on the experience gained when developing the TUGAI tool, we propose that the general framework can be transferred to other areas where tradeoffs in water allocation between the environment and other water users are of major concern. The potential for a simulation tool to structure and inform a complex resource management situation by involving local experts and stakeholders in the development of possible future scenarios will become increasingly valuable for transparent and participatory resource management.

Conservation of Natural Resources↗
PubMed2026

Global epidemiology, genomic evolution, and clinical implications of dual- and multiple-carbapenemase-producing Klebsiella pneumoniae: A systematic qualitative review.

BACKGROUND: The global emergence of dual- and multiple-carbapenemase-producing Klebsiella pneumoniae, particularly isolates co-harbouring blaNDM and blaOXA-48/OXA-48-like determinants, represents a critical threat to global health because of limited therapeutic options and expanding genomic complexity. METHODS: This systematic qualitative review synthesized evidence from 44 English-language peer-reviewed studies published between 2017 and 2026 and indexed in Scopus, with a focus on genomic evolution and spatiotemporal distribution. RESULTS: High-risk clones ST147, ST101, and ST11 were identified as major drivers of dissemination. Genomic analysis revealed key adaptive mechanisms, including stable IncL 96-kb fusion plasmids and IS10-mediated truncation of blaNDM-1, potentially reducing fitness costs while preserving resistance. Convergence events were also documented in which dual-carbapenemase-producing isolates acquired additional colistin resistance determinants (mcr-1 or mgrB alterations) and virulence-associated markers such as iuc1. Importantly, related resistance determinants were identified beyond hospital settings, including community, environmental, and food-associated reservoirs. CONCLUSION: The shift from single to dual and multiple carbapenemase production in K. pneumoniae underscores the need for integrated genomic surveillance, improved antimicrobial stewardship, and broader reservoir monitoring to address this evolving public health threat.

Klebsiella pneumoniae↗
PubMed2003

Spatiotemporal dynamics of the auditory novelty-P3 event-related brain potential.

The spatiotemporal dynamics of the cerebral network involved in novelty processing was studied by means of scalp current density (SCD) analysis of the novelty P3 (nP3) event-related brain potential (ERP). ERPs were recorded from 30 scalp electrodes at the occurrence of novel unpredictable environmental sounds during the performance of a visual discrimination task. Increased SCD was observed at left frontotemporal (FT3), bilateral temporoparietal (TP3 and TP4) and prefrontal locations (F8-F4 and F7-F3), suggesting novelty-P3 generators located in the left auditory cortex, and bilaterally in temporoparietal and prefrontal association regions. Additional increased SCD was found at a central location (Cz) and at superior parietal locations (P3-Pz-P4). The SCD of the nP3 was therefore generated at three successive, partially overlapping, stages of neuroelectric activation. At the central location, SCD started to be significant before the onset of the nP3 waveform, contributing solely to its early phase. At temporoparietal and left frontotemporal locations, nP3 electrophysiological activity was characterized by sustained current density, starting at about 210 ms and continuing during the full latency range of the response, including its early and late phases. At its late phase, the nP3 was characterized by sharp phasic current density at prefrontal and superior parietal locations, starting at about 290 ms and vanishing at around 385 ms. Taken together, these results provide the first evidence of the cerebral spatio-temporal dynamics underlying novelty processing.

Acoustic Stimulation↗
PubMed2004

Visualization of glucocorticoid receptor and mineralocorticoid receptor interactions in living cells with GFP-based fluorescence resonance energy transfer.

Adrenal corticosteroids readily enter the brain and exert markedly diverse effects, including stress responses in the target neural cells via two receptor systems, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). It has been shown that the GR and MR are highly colocalized in the hippocampus. Given the differential action of the MR and GR in the hippocampal region, it is important to elucidate how these receptors interact with each other in response to corticosteroids. We investigated the heterodimerization of the MR and GR with green fluorescent protein-based fluorescence resonance energy transfer (FRET) microscopy in living cells with spatiotemporal manner. FRET was evaluated in three ways: (1) ratio imaging; (2) emission spectra; and (3) acceptor photobleaching. FRET analysis demonstrated that cyan fluorescent protein-GR and yellow fluorescent protein-MR form heterodimers after corticosterone (CORT) treatment both in the nucleus of cultured hippocampal neurons and COS-1 cells, whereas they do not form heterodimers in the cytoplasm. The content of the GR-MR heterodimer was higher at 10(-6) m CORT than at 10(-9) m CORT and reached a maximum level after 60 min of CORT treatment in both cultured hippocampal neurons and COS-1 cells. The distribution pattern of heterodimers in the nucleus of cultured hippocampal neurons was more restricted than that in COS-1 cells. The present study using mutant fusion proteins in nuclear localization signal showed that these corticosteroid receptors are not translocated into the nucleus in the form of heterodimers even after treatment with ligand and thus allow no heterodimerization to take place in the cytoplasm. These results obtained with FRET analyses give new insights into the sites, time course, and effects of ligand concentration on heterodimersization of the GR and MR.

Animals↗
PubMed1996

Functional magnetic resonance image analysis of a large-scale neurocognitive network.

Many "higher-order" mental functions are subserved by large-scale neurocognitive networks comprising several spatially distributed and functionally specialized brain regions. We here report statistical and graphical methods of functional magnetic resonance imaging data analysis which can be used to elucidate the functional relationships (i.e., connectivity and distance) between elements of a neurocognitive network in a single subject. Data were acquired from a normal right-handed volunteer during periodic performance of a task which demanded visual and semantic processing of words and subvocalization of a decision about the meaning of each word. Major regional foci of activation were identified (by sinusoidal regression modeling and spatiotemporal randomization tests) in left extrastriate cortex, angular gyrus, supramarginal gyrus, superior and middle temporal gyri, lateral premotor cortex, and Broca's area. Principal component (PC) analysis was initially undertaken by singular value decomposition (SVD) of the "raw" time series observed at 170 activated voxels. This revealed a large functional distance (negative connectivity) between visual processing systems and all other brain regions in the space of the first PC. SVD of a matrix of fitted time series, and a matrix of six sinusoidal regression parameters estimated at each activated voxel, were developed as less noisy (more informative) alternatives to SVD of the "raw" data. Canonical variate analysis of denoised data was then used to clarify functional relationships between the major regional foci. Visual input analysis systems (extrastriate cortex and angular gyrus) were colocalized in the space of the first canonical variate (CV) and significantly separated from all other brain regions. Semantic analysis systems (supramarginal and temporal gyri) were colocalized and significantly separated in the space of the second CV from the subvocal output system (Broca's area). These results are provisionally interpreted in terms of underlying hemodynamic events and cognitive psychological theory.

Adult↗
PubMed1998

Gene trap expression and mutational analysis for genes involved in the development of the mammalian nervous system.

We have used a large-scale gene trap approach for the isolation and mutation of genes that might play roles in the developing nervous system. After in vitro integration of two different gene trap vectors (pGT1.8geo: Skarnes et al. [1995] Proc. Natl. Acad. Sci. USA 92:6592-6596; IRES beta geo: Chowdhury et al. [1997] Nucleic Acids Res. 25:1531-1536) in mouse embryonic stem (ES) cell lines, we created 64 transgenic mouse lines. The expression analysis of the reporter gene during embryogenesis of heterozygous embryos revealed 47 lines with a variety of patterns. Around one-third (36%) of these gene trap lines showed spatiotemporal expression that was either restricted predominantly in the developing nervous system (11 lines; 17%) or widespread but with very high levels of expression in the nervous tissue (12 lines; 19%). In most cases, a correlation was found between the in vitro and the in vivo patterns of the reporter gene expression. Thus far, preliminary mutant analysis of 16 gene trap lines with potentially interesting expression patterns in the developing nervous system showed that mice homozygous for eight (50%) insertions were lethal, whereas the homozygous mice from five gene trap lines (31%) showed a lower than expected Mendelian ratio of live homozygous animals. Analysis of beta-galactosidase reporter gene expression during embryogenesis has shown that four transgenic lines are useful lacZ in situ markers for specific regions of the developing nervous system. Here, we discuss some in vivo and in vitro selection criteria that may increase the number of the trapped genes potentially involved in the control of neural development and some future strategies to improve further the efficiency of the gene trap approach.

Animals↗
PubMed2004

Use of electromagnetic midsagittal articulography in the study of swallowing.

The tongue functions as the primary articulator during the oropharyngeal stages of swallowing. However, detailed descriptions of the kinematics and spatiotemporal variability of tongue behaviors during swallowing are limited to a handful of analyses of data from the X-ray microbeam database. In this article, a new technique, electromagnetic midsagittal articulography (EMMA), is introduced for the high-resolution description of oral articulatory movements during swallowing. Data from 8 healthy, nondysphagic participants are used to illustrate the methods used for data collection and analysis. Movement data were collected for 3 fleshpoint positions on the tongue (blade, body, dorsum) during sequences of repeated discrete water swallows, and were characterized for variables of spatiotemporal variability and 4 discrete kinematic parameters (movement amplitude, peak velocity, duration, and kinematic stiffness). These data show that the movement trajectories measured using EMMA are consistent with descriptions from previous X-ray microbeam studies, indicating that EMMA is a feasible method for the detailed study of tongue movements during swallowing.

Adult↗
PubMed2002

Signal processing and physiological modeling--part 1: Surface analysis.

Signal processing offers a wide spectrum of theories, methods, and algorithms for addressing a variety of problems ranging from noise reduction, restoration, detection (of events or changes), spatiotemporal dynamics estimation, source localization, and pattern recognition. However, the classical assumptions (stationarity, linearity, etc.) usually do not apply in real situations. Recent advances, such as time-scale and time-frequency transforms, data fusion, long-range dependence, and higher order moments, do not always provide sufficiently robust solutions. In this article, the basic properties and generic features of biomedical signals are examined using a wide range of examples. Algorithmic results are presented to show not only the potential performance but also the limitations of the processing resources at our disposal. The last section describes and discusses signal matching, scenario recognition, and data fusion.

Algorithms↗
PubMed2001

Linear and nonlinear analysis of the stability of gestural organization in speech movement sequences.

Recent procedures have been developed that allow the analysis of gestural stability across repetitions of phrase-length utterances by linearly normalizing aspects of the articulatory signal. This process produces an index of variability called spatiotemporal index, or STI (Smith, Goffman, Zelaznik, Ying, & McGillem, 1995). Consistent findings that different STIs underlie changes in speaking rates in normally speaking adults have been found in subsequent studies by Smith and colleagues. However some researchers have raised concerns that linearly normalized data do not adequately account for the nonlinear aspects in the articulatory signal (Lucero, Munhall, Gracco, & Ramsey, 1997). The present study compared findings from linear and nonlinear normalization procedures in the analysis of lower-lip displacement of phrase-length utterances for a group of 8 speakers and across three rates. Findings indicated that at a group level, gestural stability, although higher for each rate contingency, was similar to that found in earlier STI studies. However, variability was greater, and 4 of the 8 subjects failed to consistently demonstrate greater stability at habitual rate, followed by fast and then slow rate. A nonlinearly normalized analysis of the same data produced significantly lower stability indices, and variability was also reduced. It is argued that a nonlinear normalization procedure based on lower-lip displacement holds advantages in the analysis of phrase-length speech data over both linear and alternative nonlinear normalization techniques.

Adolescent↗
PubMed2003

Real-time independent component analysis of fMRI time-series.

Real-time functional magnetic resonance imaging (fMRI) enables one to monitor a subject's brain activity during an ongoing session. The availability of online information about brain activity is essential for developing and refining interactive fMRI paradigms in research and clinical trials and for neurofeedback applications. Data analysis for real-time fMRI has traditionally been based on hypothesis-driven processing methods. Off-line data analysis, conversely, may be usefully complemented by data-driven approaches, such as independent component analysis (ICA), which can identify brain activity without a priori temporal assumptions on brain activity. However, ICA is commonly considered a time-consuming procedure and thus unsuitable to process the high flux of fMRI data while they are acquired. Here, by specific choices regarding the implementation, we exported the ICA framework and implemented it into real-time fMRI data analysis. We show that, reducing the ICA input to a few points within a time-series in a sliding-window approach, computational times become compatible with real-time settings. Our technique produced accurate dynamic readouts of brain activity as well as a precise spatiotemporal history of quasistationary patterns in the form of cumulative activation maps and time courses. Results from real and simulated motor activation data show comparable performances for the proposed ICA implementation and standard linear regression analysis applied either in a sliding-window or in a cumulative mode. Furthermore, we demonstrate the possibility of monitoring transient or unexpected neural activities and suggest that real-time ICA may provide the fMRI researcher with a better understanding and control of subjects' behaviors and performances.

Algorithms↗
PubMed2006

Expression of Drosophila MAGE gene encoding a necdin homologous protein in postembryonic neurogenesis.

The MAGE (melanoma antigen) family is characterized by a large conserved domain termed MAGE homology domain. Originally identified MAGE genes encoding tumor rejection antigens are expressed only in cancers and male germ cells. Necdin, which contains the MAGE homology domain, is highly expressed in postmitotic cells such as neurons and skeletal muscle cells. The human necdin gene NDN is transcribed only from the paternal allele through genomic imprinting, and its deficiency is implicated in the pathogenesis of the neurodevelopmental disorder Prader-Willi syndrome. Although over 30 MAGE genes have been identified in humans, fruit fly (Drosophila melanogaster) has only a single MAGE gene that encodes a protein similar to necdin homologous MAGE proteins. In this study, we analyzed the spatiotemporal expression patterns of MAGE mRNA and the encoded protein during fly development. Whole-mount embryo in situ hybridization analysis revealed that MAGE mRNA was highly expressed at the syncytial blastoderm stage and in the ventral and procephalic neurogenic regions of the ectoderm during gastrulation. In contrast, MAGE expression was nearly undetectable in postmitotic neurons of the central nervous system at late embryonic stages. During postembryonic neurogenesis, MAGE was highly expressed in neural stem cells (neuroblasts) and their progeny (ganglion mother cells and postmitotic neurons) at larval and pupal stages. MAGE was also expressed in postmitotic neurons including mushroom body neurons and retinal photoreceptors in adulthood. These results indicate that MAGE expression lasts throughout the postembryonic neurogenesis in Drosophila.

Animals↗
PubMed2026

Identification of the BrSK gene family in flowering Chinese cabbage and functional characterization of BrSK2 subfamily involvement in heat stress.

Glycogen synthase kinase 3 (GSK3) kinases are evolutionarily conserved regulators of plant development and stress signaling, yet their contributions to thermotolerance in cool-adapted Brassica crops remain poorly understood. Here, we identified 16 BrSK genes in the Caixin (Brassica rapa ssp. chinensis var. parachinensis) genome, all harboring intact catalytic motifs indicative of functional kinase activity. Spatiotemporal expression profiling revealed preferential accumulation of BrSK transcripts in stem apices and floral organs during reproductive transition, while promoter analysis identified abundant heat- and abiotic stress-responsive cis-elements. Under heat stress, BrSK21, BrSK22, and BrSK23 displayed striking genotype-specific expression dynamics. BrSK21/22/23 transcripts were stably suppressed in the heat-tolerant cultivar '49-19' but transiently declined before rapidly rebounding in the heat-sensitive 'Liuye 50', mirroring RNA-seq profiles. Protein-protein interaction assays (Y2H, BiFC, and LCI) demonstrated specific associations between BrSK kinases and BrHSFA1. Functional validation via VIGS revealed that silencing of BrSK21 significantly enhanced thermotolerance, with triple silencing of BrSK21/22/23 conferring additive protection, indicating functional redundancy within the BrSK2 subfamily. Collectively, these findings establish the BrSK2 subfamily as negative regulators of heat tolerance in Caixin, likely via modulation of BrHSFA1 expression. This work identifies high-priority targets for molecular breeding of climate-resilient Brassica vegetables.

Plant Proteins↗
PubMed2005

Dynamic properties of thalamic neurons for vision.

A striking property of neurons in the lateral geniculate nucleus (LGN) of the thalamus is the ability to dynamically filter and transform the temporal structure of their retinal spike input. In particular, LGN neurons respond to visual stimuli with either burst spike responses or tonic spike responses. While much is known from in vitro studies about the cellular mechanisms that underlie burst and tonic spikes, relatively little is known about the sensory stimuli that evoke these two categories of spikes. This review examines recent progress that has been made towards understanding the spatiotemporal properties of visual stimuli that evoke burst and tonic spikes. Using white-noise stimuli and reverse-correlation analysis, results show that burst and tonic spikes carry similar, but distinct, information to cortex. Compared to tonic spikes, burst spikes (1) occur with a shorter latency between stimulus and response, (2) have a greater dependence on stimuli with transitions from suppressive to preferred states, and (3) prefer stimuli that provide increased drive to the receptive field center and even greater increased drive to the receptive field surround. These results are discussed with an emphasis placed on relating the cellular constraints for burst and tonic activity with the functional properties of the early visual pathway during sensory processing.

Action Potentials↗