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PubMed2005

Wave similarity mapping shows the spatiotemporal distribution of fibrillatory wave complexity in the human right atrium during paroxysmal and chronic atrial fibrillation.

INTRODUCTION: The complexity of waveforms during atrial fibrillation may reflect critical activation patterns for the arrhythmia perpetuation. In this study, we introduce a novel concept of map, based on the analysis of the wave morphology, which gives a direct evidence in the human right atrium on the spatiotemporal distribution of fibrillatory wave complexity in paroxysmal (PAF) and chronic (CAF) atrial fibrillation. METHODS AND RESULTS: Electrograms were recorded from a 64-electrode catheter in the right atrium of 15 patients during PAF (n = 8) and CAF (n = 7). Wave similarity maps were constructed by calculating the degree of morphological similarity of activation waves (S) at each atrial site and by following its temporal evolution. During PAF the spatiotemporal distribution of the waveforms was highly consistent across the subjects and was determined by the anatomic location. Wave similarity maps showed the existence of an extended area with low similarity index, which covered the low posteroseptal atrium (S = 0.28 +/- 0.09) and the septal region (S = 0.22 +/- 0.04), and the presence of a large tongue with high similarity index, which penetrated the lateral wall (S = 0.55 +/- 0.08) starting from the high anterolateral atrium (S = 0.54 +/- 0.06). A completely different spatiotemporal pattern was seen during CAF. No distinct regions with different similarity indexes were recognized, but a uniformly distributed low similarity index (S = 0.27 +/- 0.07) was found. The spatial pattern was highly stable in time with fluctuations of S < 0.04. CONCLUSION: Quantification of the spatiotemporal distribution of fibrillatory wave complexity is feasible in humans by wave similarity mapping. Anatomic anchoring of waveforms during PAF and pattern destruction during CAF was determined.

Adult↗
PubMedDate not supplied

Independent component analysis of temporal sequences subject to constraints by lateral geniculate nucleus inputs yields all the three major cell types of the primary visual cortex.

Information maximization has long been suggested as the underlying coding strategy of the primary visual cortex (V1). Grouping image sequences into blocks has been shown by others to improve agreement between experiments and theory. We have studied the effect of temporal convolution on the formation of spatiotemporal filters--that is, the analogues of receptive fields--since this temporal feature is characteristic to the response function of lagged and non-lagged cells of the lateral geniculate nucleus. Concatenated input sequences were used to learn the linear transformation that maximizes the information transfer. Learning was accomplished by means of principal component analysis and independent component analysis. Properties of the emerging spatiotemporal filters closely resemble the three major types of V1 cells: simple cells with separable receptive field, simple cells with non-separable receptive field, and complex cells.

Action Potentials↗
PubMed1993

Immunocytochemical analysis of a novel carbohydrate differentiation antigen (CDA-3C2) associated with olfactory and otic systems during embryogenesis in the rat.

Carbohydrate differentiation antigens are known to display specific patterns of expression during mammalian development and are thought to participate in significant morphogenetic events. In the present study, two monoclonal antibodies that react with a novel carbohydrate differentiation antigen (CDA-3C2) were used to analyze, by light microscopy, the spatiotemporal distribution of this unique high molecular weight antigen during embryogenesis in the rat. Correlative analysis of the development of peripheral neural structures, in which CDA-3C2 was expressed, was carried out with an anti-neurofilament antibody. Enzymatic digestion, combined with Western blots, reveal that the CDA-3C2 epitope is a carbohydrate which is carried on a high molecular weight glycoprotein with a mass of greater than 1 million Daltons. Characteristic of carbohydrate antigens, immunoreactivity was found in several distinct cellular patterns: only along the apical border of cells, along lateral and basal membranes of cells, and extracellular-like staining in the mesenchyme. During neurulation, CDA-3C2 showed differential staining in the ectoderm, distinguishing lateral from neural regions. Following closure of the neural tube, there was a striking specificity of expression of CDA-3C2 in the periphery, found almost exclusively in olfactory and otic epithelial structures. While CDA-3C2 is found in placode-derived tissues that subserve sensory transduction, it appears to be primarily associated with the supportive cells (and their secretions) in both otic and olfactory regions and less so with the sensory cells. The data suggest that a unique carbohydrate antigen on a large macromolecule may play a role in neurulation and/or morphogenesis of the placode-derived otic and olfactory structures.

Animals↗
PubMed2001

Arachidonic acid modulates the spatiotemporal characteristics of agonist-evoked Ca2+ waves in mouse pancreatic acinar cells.

In pancreatic acinar cells analysis of the propagation speed of secretagogue-evoked Ca2+ waves can be used to examine coupling of hormone receptors to intracellular signal cascades that cause activation of protein kinase C or production of arachidonic acid (AA). In the present study we have investigated the role of cytosolic phospholipase A2 (cPLA2) and AA in acetylcholine (ACh)- and bombesin-induced Ca2+ signaling. Inhibition of cPLA2 caused acceleration of ACh-induced Ca2+ waves, whereas bombesin-evoked Ca2+ waves were unaffected. When enzymatic metabolization of AA was prevented with the cyclooxygenase inhibitor indomethacin or the lipoxygenase inhibitor nordihydroguaiaretic acid, ACh-induced Ca2+ waves were slowed down. Agonist-induced activation of cPLA2 involves mitogen-activated protein kinase (MAPK) activation. An increase in phosphorylation of p38(MAPK) and p42/44(MAPK) within 10 s after stimulation could be demonstrated for ACh but was absent for bombesin. Rapid phosphorylation of p38(MAPK) and p42/44(MAPK) could also be observed in the presence of cholecystokinin (CCK), which also causes activation of cPLA2. ACh-and CCK-induced Ca2+ waves were slowed down when p38(MAPK) was inhibited with SB 203580, whereas inhibition of p42/44(MAPK) with PD 98059 caused acceleration of ACh- and CCK-induced Ca2+ waves. The spreading of bombesin-evoked Ca2+ waves was affected neither by PD 98059 nor by SB 203580. Our data indicate that in mouse pancreatic acinar cells both ACh and CCK receptors couple to the cPLA2 pathway. cPLA2 activation occurs within 1-2 s after hormone application and is promoted by p42/44(MAPK) and inhibited by p38(MAPK). Furthermore, the data demonstrate that secondary (Ca2+-induced) Ca2+ release, which supports Ca2+ wave spreading, is inhibited by AA itself and not by a metabolite of AA.

Acetylcholine↗
PubMed2003

Differentially expressed nucleolar TGF-beta1 target (DENTT) in mouse development.

Differentially expressed nucleolar TGF-beta1 target (DENTT) is a recently identified gene whose mRNA is differentially affected by TGF-beta1 in TGF-beta1-responsive human lung cancer cells and who is a new member of the TSPY/TSPY-like/SET/NAP-1 (TTSN) protein superfamily. Here, we report that mouse DENTT mRNA contains a 2031-bp open reading frame that encodes a predicted polypeptide of 677-amino acids with a relative molecular mass of 77,671 Da. The mouse and human DENTT sequences show 77% and 78% homology at the nucleotide and amino acid level, respectively. Mouse DENTT is predicted to be a nuclear protein with two nuclear localization signals (NLS), two coiled-coil regions, and a domain that shows significant identity to a region that defines the TTSN superfamily. Green fluorescent protein (GFP)-tagged full-length mouse DENTT transfected into COS-7 cells showed localization predominantly in the nucleolus. Reverse transcription-polymerase chain reaction amplification, Northern hybridization, and Western blot analyses showed expression of mouse DENTT mRNA and protein throughout mouse embryogenesis. Immunohistochemical staining analysis showed that DENTT is expressed in multiple tissues in a defined spatiotemporal pattern during mouse embryogenesis. The heart and primitive brain were the first organs of the embryo that showed immunoreactivity for the DENTT antibody by day 8 of development (E8). In the developing mouse brain, the choroid plexus was intensely stained for DENTT in all stages of development. The spinal cord and dorsal root ganglia were also positive for DENTT staining beginning in the 11-day-old embryo (E11), where homogeneous immunostaining was observed throughout the developing neurons. By day 16 of development (E16), only a small subset of the neuronal population in the spinal cord and dorsal root ganglia was positively stained for DENTT. DENTT immunoreactivity increased steadily with maturation as the differentiation of cartilage and osteoblasts proceeded and reached a maximum in the growth plate during endochondral ossification. DENTT expression was also detected in multiple rodent cell types in vitro, including mouse F9 embryonal carcinoma (EC) cells. Addition of retinoic acid or sodium butyrate to F9 EC cells showed a rapid decrease in expression of DENTT protein occurring by 1 hr that continued to decrease to almost undetectable levels after 24 hr. Cotransfection of full-length mouse DENTT expression plasmid with 3TPLux or COL7A1Luc Luciferase reporter plasmids into F9 EC cells significantly increased the level of 3TPLux reporter transcription while decreasing the level of COL7A1Luc reporter transcription, suggesting that DENTT may play multiple roles in modulating transcriptional responses. These findings suggest new roles for the TTSN superfamily during embryogenesis and differentiation.

3T3 Cells↗
PubMed2001

A field theory of consciousness.

This article summarizes a variety of current as well as previous research in support of a new theory of consciousness. Evidence has been steadily accumulating that information about a stimulus complex is distributed to many neuronal populations dispersed throughout the brain and is represented by the departure from randomness of the temporal pattern of neural discharges within these large ensembles. Zero phase lag synchronization occurs between discharges of neurons in different brain regions and is enhanced by presentation of stimuli. This evidence further suggests that spatiotemporal patterns of coherence, which have been identified by spatial principal component analysis, may encode a multidimensional representation of a present or past event. How such distributed information is integrated into a holistic precept constitutes the binding problem. How a precept defined by a spatial distribution of nonrandomness can be subjectively experienced constitutes the problem of consciousness. Explanations based on a discrete connectionistic network cannot be reconciled with the relevant facts. Evidence is presented herein of invariant features of brain electrical activity found to change reversibly with loss and return of consciousness in a study of 176 patients anesthetized during surgical procedures. A review of relevant research areas, as well as the anesthesia data, leads to a postulation that consciousness is a property of quantum-like processes, within a brain field resonating within a core of structures, which may be the neural substrate of consciousness. This core includes regions of the prefrontal cortex, the frontal cortex, the pre- and paracentral cortex, thalamus, limbic system, and basal ganglia.

Brain↗
PubMed1998

Restricted spatiotemporal expression of lactoferrin during murine embryogenesis.

Lactoferrin is a member of the transferrin family of iron-binding proteins to which several physiological functions have been ascribed. While there is a wealth of evidence about the distribution and function of this protein in the adult, the expression and function, if any, of lactoferrin during embryogenesis has not been investigated. In the current study, the spatiotemporal distribution of lactoferrin was analyzed during normal murine embryonic development. This analysis demonstrated that lactoferrin is expressed in three distinct patterns during embryogenesis. First, lactoferrin is expressed at the 2-cell stage in the preimplantation embryo where it continues to be expressed until the blastocyst stage when expression ceases. The second phase of lactoferrin expression is not detected until the latter half of gestation when the protein is detected in the myeloid cells, beginning in the fetal liver at embryonic day 11 and later in the spleen and bone marrow coinciding with the onset and diversification of myelopoiesis in these organs during embryogenesis. Finally, lactoferrin is detected in a variety of glandular epithelial cells and/or their secretions, including respiratory and oral epithelia which is consistent with the expression pattern observed for this protein in the adult where it plays an important role in host defense at the mucosal surface. Taken together, these analyses indicate that the role of lactoferrin in the developing embryo is restricted to the preimplantation stage and development of first and second line host defense systems.

Animals↗
PubMed1986

Methodological problems in evolutionary biology. VII. The species plague.

Various philosophers and evolutionary biologists have recently defended the thesis that species are individuals rather than sets. A decade of debates, however, did not suffice to settle the matter. Conceptual analysis shows that many of the key terms involved ("individuation", "evolutionary species", "spatiotemporal restrictedness", "individual") are ambiguous. Current disagreements should dissolve once this is recognized. Explication of the concepts involved leads to new programs for philosophical research. It could also help biology by showing how extant controversies concerning evolution may have conceptual rather than factual roots.

Animals↗
PubMed2006

[Differences in anticipatory postural adjustments between self-generated and triggered gait initiation in 20 healthy subjects].

OBJECTIVE: Preparation of upper-limb movements differs between self-paced and triggered conditions. This study analyzed the anticipatory postural adjustments (APAs) of gait initiation in normal subjects in 2 conditions: self-generated and triggered by a "beep" sound. METHODS: We recorded kinematic, spatiotemporal parameters of the first two steps by means of video motion analysis (6 infrared cameras), and kinetic parameters (using a force platform and the optoelectronic system) in 20 normal subjects. Two conditions: 1) self-generated initiation; and 2) initiation triggered by a "beep" sound were studied to evaluate the APA phase, by recording kinetic data (duration of the APAs, trajectory of the center of pressure, speed and trajectory of the center of mass). Kinematic data (first and second step speed, length and duration) were also recorded. RESULTS: First step speed and length were increased in self-paced gait initiation compared to triggered gait initiation in controls. We found no difference between the 2 conditions in terms of second step kinematic data. It was caused by a significant difference between the 2 conditions for the temporal characteristics of anticipatory postural adjustments (APAs) in the initiation of the first step, which was longer when normal subjects performed self-generated gait initiation. The trajectory of center of pressure and center of mass remained the same in the 2 conditions. CONCLUSION: APAs of gait initiation process are delayed under self-paced condition, although they do not differ qualitatively between reaction time and self-paced condition. Neuphysiological support of self-generated movement could explain these differences.

Acoustic Stimulation↗
PubMed2007

Cortical abnormalities in epilepsy revealed by local EEG synchrony.

Abnormally strong functional linkage between cortical areas has been postulated to play a role in the pathogenesis of partial epilepsy. We explore the possibility that such linkages may be manifest in the interictal EEG apart from epileptiform disturbances or visually evident focal abnormalities. We analyzed samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in nine patients with medically intractable partial epilepsy, measuring interelectrode synchrony using the mean phase coherence algorithm. This analysis revealed areas of elevated local synchrony, or "hypersynchrony" which had persistent spatiotemporal characteristics that were unique to each patient. Measuring local synchrony in a subdural grid results in a map of the cortical surface that provides information not visually apparent on either EEG or structural imaging. We explore the relationship of hypersynchronous areas to the clinical evidence of seizure localization in each case, and speculate that local hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a valuable aid to clinical ICEEG interpretation.

Adolescent↗
PubMed2005

Spatiotemporal elements of macaque v1 receptive fields.

Neurons in primary visual cortex (V1) are commonly classified as simple or complex based upon their sensitivity to the sign of stimulus contrast. The responses of both cell types can be described by a general model in which the outputs of a set of linear filters are nonlinearly combined. We estimated the model for a population of V1 neurons by analyzing the mean and covariance of the spatiotemporal distribution of random bar stimuli that were associated with spikes. This analysis reveals an unsuspected richness of neuronal computation within V1. Specifically, simple and complex cell responses are best described using more linear filters than the one or two found in standard models. Many filters revealed by the model contribute suppressive signals that appear to have a predominantly divisive influence on neuronal firing. Suppressive signals are especially potent in direction-selective cells, where they reduce responses to stimuli moving in the nonpreferred direction.

Action Potentials↗
PubMed2006

Influence of carrying heavy loads on soldiers' posture, movements and gait.

Military personnel are required to carry heavy loads whilst marching; this load carriage represents a substantial component of training and combat. Studies in the literature mainly concentrate on physiological effects, with few biomechanical studies of military load carriage systems (LCS). This study examines changes in gait and posture caused by increasing load carriage in military LCS. The four conditions used during this study were control (including rifle, boots and helmet carriage, totalling 8 kg), webbing (weighing 8 kg), backpack (24 kg) and a light antitank weapon (LAW; 10 kg), resulting in an incremental increase in load carried from 8, 16, 40 to 50 kg. A total of 20 male soldiers were evaluated in the sagittal plane using a 3-D motion analysis system. Measurements of ankle, knee, femur, trunk and craniovertebral angles and spatiotemporal parameters were made during self-paced walking. Results showed spatiotemporal changes were unrelated to angular changes, perhaps a consequence of military training. Knee and femur ranges of motion (control, 21.1 degrees +/- 3.0 and 33.9 degrees +/- 7.1 respectively) increased (p < 0.05) with load (LAW, 25.5 degrees +/- 2.3 and 37.8 degrees +/- 1.5 respectively). The trunk flexed significantly further forward, confirming results from previous studies. In addition, the craniovertebral angle decreased (p < 0.001) indicating a more forward position of the head with load. It is concluded that the head functions in concert with the trunk to counterbalance load. The higher muscular tensions necessary to sustain these changes have been associated with injury, muscle strain and joint problems.

Adolescent↗
PubMed2006

Perturbation analysis for competing reactions with initially separated components.

We study a competitive reaction-diffusion system with initially separated components. In this system, two similar species on one side of the system compete to react with the species on the other side. The competition is due to significant differences in the microscopic reaction constants and the initial densities of the two competing species. In the short-time limit, each of the competitive reactions is considered as perturbation with respect to the diffusion, the latter is essential for the effective mixing of the reactants. We identify the small parameters required for the perturbation analysis of the competitive scheme. The resulting perturbative expressions provide the rich spatiotemporal reaction front patterns, which were experimentally observed for Cr3+ + Xylenol Orange (XO) --> products, where the aggregated and nonaggregated forms of Cr3+ in aqueous solution compete to react with the XO.

Journal Article↗
PubMed2002

The neuronal basic helix-loop-helix transcription factor NSCL-1 is dispensable for normal neuronal development.

The neuronal stem cell leukemia (NSCL) basic helix-loop-helix factors are neural cell-specific transcription factors. We have disrupted the NSCL-1 gene by homologous recombination and replaced the coding region with a beta-galactosidase reporter cassette to study the role of NSCL-1 in neuronal development and to follow the fate of NSCL-1 mutant cells. NSCL-1 mutant mice are viable and fertile on various genetic backgrounds and do not show any obvious signs of neurological malfunction. No differences in the distribution of NSCL-1 mutant or heterozygous neuronal cells were observed in the diencephalon, hippocampus, neocortex, and cerebellum at different stages of development. Likewise, no defects were found in the laminar organization of the cortex, and the distinct neuronal subpopulation appeared normal during development of the neocortex. Analysis of sensory neurons which strongly express NSCL-1 revealed that the spatiotemporal expression of neuronal differentiation factors, such as NeuroD and SCG-10, was not altered in developing distal and proximal cranial ganglia of mutant mice. In the cerebellum expression of NSCL-1 was confined to the proliferative and premigratory zone of the external granular layer and the internal granular layer. Interestingly, unlike cerebella of Math1(-/-) or NeuroD2(-/-) mice, NSCL-1-deficient mice have no obvious developmental defect, and neurons of the cerebellum appeared fully differentiated. Despite similar expression patterns of NSCL-1 and NSCL-2 in various areas of the diencephalon, including the arcuate nucleus and paraventricular nucleus, NSCL-1(-/-) mice are fertile and show no adult onset of obesity like NSCL-2 mutant mice. Double-mutant NSCL-1(-/-)-NSCL-2(-/-) mice do not show any additional obvious malformations of the central nervous system, although both genes are expressed in a largely overlapping pattern. Our results argue against a simple functional redundancy within the NSCL gene family.

Animals↗
PubMed2001

Bmp4 mediates apoptotic cell death in the developing chick eye.

The bone morphogenetic protein (BMP) expression in vertebrates suggests a reiterative function of these molecules during eye development. However, genetic analysis in mice has provided only partial information. Using the chick embryo as a model system, we have analyzed possible additional functions of BMP4 during optic cup formation. Here we describe the expression pattern of Bmp4 and Bmp7 and we show that, in contrast to the mouse, the prospective lens placode ectoderm expresses high levels of Bmp4 but no Bmp7. After optic vesicle invagination, Bmp4 is expressed in the prospective dorsal neural retina, where BmprIA, BmprII, and Smad1, components of the BMP4 signal transduction pathway, are also expressed. In toto terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeling analysis shows that the dorsal optic cup is the site of a spatiotemporally restricted apoptosis, which parallels the expression not only of Bmp4 but also of Msx1 and Msx2, genes implicated in BMP4-mediated apoptosis. The use of optic vesicle cultures as well as in ovo local addition of BMP4 and its antagonist Noggin proves that the local activity of BMP4 is responsible for programmed cell death in the dorsal optic cup. In addition, we show that Noggin is able to reduce the rate of cell proliferation in the dorsal part of the optic cup whereas BMP4 increases the number of BrdU-positive cells in retina cultures. These results provide evidence that BMP4 contributes to eye development by promoting cell proliferation and programmed cell death.

Animals↗
PubMed2003

Orientation opponency in human vision revealed by energy-frequency analysis.

Studies of second-order visual processing have primarily been concerned with understanding the mechanisms for detecting spatiotemporal variations in such attributes as contrast, orientation, spatial frequency, etc. Here, we have examined the orientation characteristics of second-order processes using bandpass noise whose Fourier energy is sinusoidally modulated across orientation, rather than across space or time. Sensitivity for detecting orientation-energy modulations was measured as a function of modulation frequency. The sensitivity function was bandpass, with a pronounced peak at an orientation frequency of 4 cycles/pi. An inverse Fourier transform of the sensitivity function revealed a filter profile displaying a centre-surround antagonism across orientation, with an excitatory centre within 6-9 deg and inhibitory lobes at 15-20 deg from the filter's centre. The degree of centre-surround antagonism increased with stimulus size far beyond the spatial range of the first-order filters (more than 64 times the dominant spatial wavelength of the noise carrier). These results suggest that second-order processing involves 'orientation-opponent' channels that extract differences in first-order outputs across orientation over a wide area of the visual field.

Contrast Sensitivity↗
PubMed1999

A spatiotemporal model of cyclic kinematics and its application to analyzing nonrigid motion with MR velocity images.

We present a method (DMESH) for nonrigid cyclic motion analysis using a series of velocity images covering the cycle acquired, for example, from phase-contrast magnetic resonance imaging. The method is based on fitting a dynamic finite-element mesh model to velocity samples of an extended region, at all time frames. The model offers a flexible tradeoff between accuracy and reproducibility with controllable built-in spatiotemporal smoothing, which is determined by the fineness of the initially defined mesh and the richness of included Fourier harmonics. The method can further provide a prediction of the analysis reproducibility, along with the estimated motion and deformation quantities. Experiments have been conducted to validate the method and to verify the reproducibility prediction. Use of the method for motion analysis using displacement information (e.g., from magnetic resonance tagging) has also been explored.

Aortic Valve Stenosis↗
PubMed2002

Optical imaging of glycinergic inhibition in the vestibular and cochlear nuclei.

Using multiple-site optical recording techniques, the spatiotemporal activity was observed in both the cochlear and vestibular nucleus in newborn mice. The optical responses were obviously enhanced by bath-applied strychnine. A quantitative analysis showed higher enhancements to occur in the cochlear nucleus than in the vestibular nucleus. Optical imaging enables us to visualize the spatiotemporal extent of the inhibitory receptive field after the application of strychnine.

Animals↗