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A study of the gait characteristics of patients with chronic osteoarthritis of the knee.

PURPOSE: There is scant information at present on the effects of severe osteoarthritis (OA) of the knee joint on gait. In the present study the kinematic and kinetic parameters of gait and the pattern of activation of four lower limb muscles were examined during walking at a self-selected pace on level ground. The spatiotemporal parameters of gait were also computed. METHODS: Measurements were made using a three-dimensional optico-electronic motion analysis system integrated with a force plate and telemetered electromyography. RESULTS: Fifty-eight patients with severe OA of the knee and 25 age-matched healthy control subjects were examined. Patients demonstrated a significantly reduced walking speed, shorter stride length and a more prolonged stance phase of the gait cycle compared with the control subjects. They also had less range of motion at the hip, knee and ankle, joints and generated less moments and powers at the ankle and more moments at the knee than the control group. The differences were statistically significant for all parameters except the degree of ankle plantar flexion in stance. Activation of the rectus femoris muscle was prolonged in the patients group. CONCLUSIONS: It is concluded that the observed gait abnormalities were due to instability of the knee joint in stance. This may have important clinical implications for the rehabilitation of patients with severe OA of the knee.

Aged↗

Dynamical mechanism for coexistence of dispersing species without trade-offs in spatially extended ecological systems.

Most prior studies on the role of dispersal in the coexistence of competing species have emphasized the need for trade-offs between competitive and colonizing abilities for coexistence. Theoretical studies of the evolution of dispersal recently have revealed an alternative mechanism for the coexistence of species differing solely in dispersal rates in spatially extended systems. We present an analysis and numerical evidence indicating that chaotic synchronism, occurring in an extremely intermittent form, is an important feature of the spatiotemporal variation in fitness required for the coexistence of species without trade-offs.

Animals↗

Dynamical behavior of a complex fluid near an out-of-equilibrium transition: approaching simple rheological chaos.

We report here an extensive study of sustained oscillations of the viscosity of a complex fluid near an out-of-equilibrium transition. Using well defined protocols, we perform rheological measurements of the onion texture near a layering transition in a Couette flow. This complex fluid exhibits sustained oscillations of the viscosity, on a large time scale (500 s) at controlled stress. These oscillations are directly correlated to an oscillating microstructural change of the texture of the fluid. We observe a great diversity of dynamical behavior and show that there is a coupling with spatial effects in the inverted Delta v direction. This is in agreement with a careful analysis of the temporal series of the viscosity with the dynamical system theory. This analysis indicates that the observed dynamical responses do not strictly correspond to three-dimensional chaotic states, probably because some spatiotemporal effects are present and are likely to play an important role.

Journal Article↗

Spatiotemporal activity patterns during respiratory rhythmogenesis in the rat ventrolateral medulla.

One of the most important brain rhythms is that which generates involuntary breathing movements. The lower brain stem contains neural circuitry for respiratory rhythm generation in mammals. To date, microsectioning and selective lesioning studies have revealed anatomical regions necessary for respiratory rhythmogenesis. Although respiratory neurons distributed within these regions can be identified by their firing patterns in different phases of the respiratory cycle, conventional electrophysiology techniques have limited the study of spatial organization within this network. Optical imaging techniques offer the potential for monitoring the spatiotemporal activity of large groups of neurons simultaneously. Using high-speed voltage-sensitive dye imaging and spatial correlation analysis in an arterially perfused in situ preparation of the juvenile rat, we determined the spatial distribution of respiratory neuronal activity in a region of the ventrolateral respiratory group containing the pre-Bötzinger complex (pBC) during spontaneous eupneic breathing. While distinctly pre- and postinspiratory-related responses were spatially localizable on length scales less than 100 microm, we found the studied area on whole exhibited a spatial mixture of phase-spanning and postinspiratory-related activity. Additionally, optical recordings revealed significant widespread hyperpolarization, suggesting inhibition in the same region during expiration. This finding is consistent with the hypothesis that inhibitory neurons play a crucial role in the inspiration-expiration phase transition in the pBC. To our knowledge this is the first optical imaging of a near fully intact in situ preparation that exhibits both eupneic respiratory activity and functional reflexes.

Action Potentials↗

Expression of p67 (Munc-18), Cdk5, P-NFH and syntaxin during development of the rat cerebellum.

Cyclin-dependent kinases (cdks), which regulate the cell division cycle, have also been found in postmitotic neurons. Cdk5, isolated from neural tissue, has been shown to phosphorylate neurofilaments (NFs). Instead of cyclins, however, other neuron-specific activators of cdk5 have been identified including a 67-kD protein (p67) which is identical to a syntaxin-binding protein (n-sec-1, Munc 18) that is thought to play a role in synaptic vesicle trafficking and transmitter release. These functions for p67 are not mutually exclusive since regulation of edk5 phosphorylation of cytoskeletal proteins may modulate axonal dynamics during growth, synaptogenesis and vesicle transport. To gain further insight into the role of p67 in neural tissue, we carried out a Western blot and immunohistochemical analysis of the developing rat cerebellum using antibodies to cdk5, p67, syntaxin and phosphorylated and nonphosphorylated neurofilaments. We assumed that spatiotemporal colocalizations of antigens might correlate with proposed functions for p67. The immunoblots showed that all antigens were developmentally regulated, and increased in expression from PN2 to the adult, with p67 and cdk5 showing a close temporal correlation. Immunohistochemically, p67 colocalized with cdk5 and P-NFH in selected fiber tracts, particularly those in the deep cerebellum. For the most part, p67 also showed strong colocalization patterns with syntaxin in regions of synaptogenesis throughout development such as the molecular layer and glomeruli of the inner nuclear layer. Finally, certain fiber tracts, the afferent fibers, climbing and mossy fibers and particularly the basket cell fibers that envelop and innervate Purkinje cell somata and dendrites, displayed colocalization of cdk5 and P-NFH without expressing any p67. Given the limitations of colocalization data in defining functional relationships, the results are consistent with the hypothesis that p67 is a multifunctional protein, its activity during cerebellum development dependent upon the neuronal phenotype, its location and its state of developmental maturation.

Animals↗

Particle image correlation spectroscopy (PICS): retrieving nanometer-scale correlations from high-density single-molecule position data.

A new data analysis tool that resolves correlations on the nanometer length and millisecond timescale is derived. This tool, adapted from methods of spatiotemporal image correlation spectroscopy, exploits the high positional accuracy of single-particle tracking. While conventional tracking methods break down if multiple particle trajectories intersect, our method works in principle for arbitrarily large molecule densities and diffusion coefficients as long as individual molecules can be identified. The method is computationally cheap and robust and requires no a priori knowledge about the dynamical coefficients, as opposed to other methods. We demonstrate the validity of the method by Monte Carlo simulations and by application to single-molecule tracking data of membrane-anchored proteins in live cells. The results faithfully reproduce those obtained by conventional tracking. Upon activation, a fraction of the small GTPase H-Ras is confined to domains of <200 nm diameter, which further substantiates the prediction that membrane organization is a determinant in cellular signaling.

Algorithms↗

Ontogeny of rhythmic motor patterns generated in the embryonic rat spinal cord.

Patterned spontaneous activity is generated in developing neuronal circuits throughout the CNS including the spinal cord. This activity is thought to be important for activity-dependent neuronal growth, synapse formation, and the establishment of neuronal networks. In this study, we examine the spatiotemporal distribution of motor patterns generated by rat spinal cord and medullary circuits from the time of initial axon outgrowth through to the inception of organized respiratory and locomotor rhythmogenesis during late gestation. This includes an analysis of the neuropharmacological control of spontaneous rhythms generated within the spinal cord at different developmental stages. In vitro spinal cord and medullary-spinal cord preparations isolated from rats at embryonic ages (E)13.5-E21.5 were studied. We found age-dependent changes in the spatiotemporal pattern, neurotransmitter control, and propensity for the generation of spontaneous rhythmic motor discharge during the prenatal period. The developmental profile of the neuropharmacological control of rhythmic bursting can be divided into three periods. At E13.5-E15.5, the spinal networks comprising cholinergic and glycinergic synaptic interconnections are capable of generating rhythmic activity, while GABAergic synapses play a role in supporting the spontaneous activity. At late stages (E18.5-E21.5), glutamate drive acting via non- N-methyl-d-aspartate (non-NMDA) receptors is primarily responsible for the rhythmic activity. During the middle stage (E16.5-E17.5), the spontaneous activity results from the combination of synaptic drive acting via non-NMDA glutamatergic, nicotinic acetylcholine, glycine, and GABA(A) receptors. The modulatory actions of chloride-mediated conductances shifts from predominantly excitatory to inhibitory late in gestation.

Acetylcholine↗

Cortex-based independent component analysis of fMRI time series.

The cerebral cortex is the main target of analysis in many functional magnetic resonance imaging (fMRI) studies. Since only about 20% of the voxels of a typical fMRI data set lie within the cortex, statistical analysis can be restricted to the subset of the voxels obtained after cortex segmentation. While such restriction does not influence conventional univariate statistical tests, it may have a substantial effect on the performance of multivariate methods. Here, we describe a novel approach for data-driven analysis of single-subject fMRI time series that combines techniques for the segmentation and reconstruction of the cortical surface of the brain and the spatial independent component analysis (sICA) of the functional time courses (TCs). We use the mesh of the white matter/gray matter boundary, automatically reconstructed from high-spatial-resolution anatomical MR images, to limit the sICA decomposition of a coregistered functional time series to those voxels which are within a specified region with respect to the cortical sheet (cortex-based ICA, or cbICA). We illustrate our analysis method in the context of fMRI blocked and event-related experimental designs and in an fMRI experiment with perceptually ambiguous stimulation, in which an a priori specification of the stimulation protocol is not possible. A comparison between cbICA and conventional hypothesis-driven statistical methods shows that cortical surface maps and component TCs blindly obtained with cbICA reliably reflect task-related spatiotemporal activation patterns. Furthermore, the advantages of using cbICA when the specification of a temporal model of the expected hemodynamic response is not straightforward are illustrated and discussed. A comparison between cbICA and anatomically unconstrained ICA reveals that--beside reducing computational demand--the cortex-based approach improves the fitting of the ICA model in the gray matter voxels, the separation of cortical components and the estimation of their TCs, particularly in the case of fMRI data sets with a complex spatiotemporal statistical structure.

Algorithms↗

Expression of glycosaminoglycans during development of the rat retina.

PURPOSE: To investigate the spatiotemporal expression of glycosaminoglycans during development of the rat retina. METHODS: Hyaluronan and sulfated glycosaminoglycans, including chondroitin sulfate, heparan sulfate and keratan sulfate were detected using biotinylated hyaluronan binding protein, immunohistochemical analysis, respectively, in the rat retina at various stages of development. RESULTS: Hyaluronan was expressed in the nerve fiber layer, inner plexiform layer and outer plexiform layer during early postnatal stages (postnatal day 1-14; P1-P14) and was undetectable after P21. In contrast, hyaluronan was faintly observed in the photoreceptor layer on P7, and gradually increased up to P49. The spatiotemporal expression pattern of chondroitin sulfate was similar to that of hyaluronan. Heparan sulfate was also detected in the nerve fiber layer, inner plexiform layer and outer plexiform layer during early postnatal stages (P1-P14). In addition, heparan sulfate was expressed in the inner limiting membrane during all stages of development. Keratan sulfate was not detected in the retina at any stage of development. CONCLUSIONS: Hyaluronan, chondroitin sulfate and heparan sulfate are expressed in nerve fiber-rich layers during early postnatal stages and may regulate neurite outgrowth. In adulthood, both hyaluronan and chondroitin sulfate are expressed in the photoreceptor layer and may consist of the interphotoreceptor matrix. In addition, heparan sulfate is expressed in the inner limiting membrane throughout the various stages of development and may be associated with the structure of the inner limiting membrane.

Animals↗

Motion-based analysis of spatial patterns by the human visual system.

BACKGROUND: It is known that the visibility of patterns presented through stationary multiple slits is significantly improved by pattern movements. This study investigated whether this spatiotemporal pattern interpolation is supported by motion mechanisms, as opposed to the general belief that the human visual cortex initially analyses spatial patterns independent of their movements. RESULTS: Psychophysical experiments showed that multislit viewing could not be ascribed to such motion-irrelevant factors as retinal painting by tracking eye movements or an increase in the number of views by pattern movements. Pattern perception was more strongly impaired by the masking noise moving in the same direction than by the noise moving in the opposite direction, which indicates the direction selectivity of the pattern interpolation mechanism. A direction-selective impairment of pattern perception by motion adaptation also indicates the direction selectivity of the interpolation mechanism. Finally, the map of effective spatial frequencies, estimated by a reverse-correlation technique, indicates observers' perception of higher spatial frequencies, the recovery of which is theoretically impossible without the aid of motion information. CONCLUSIONS: These results provide clear evidence against the notion of separate analysis of pattern and motion. The visual system uses motion mechanisms to integrate spatial pattern information along the trajectory of pattern movement in order to obtain clear perception of moving patterns. The pattern integration mechanism is likely to be direction-selective filtering by V1 simple cells, but the integration of the local pattern information into a global figure should be guided by a higher-order motion mechanism such as MT pattern cells.

Adult↗

Analysis, classification, and coding of multielectrode spike trains with hidden Markov models.

It is shown that hidden Markov models (HMMs) are a powerful tool in the analysis of multielectrode data. This is demonstrated for a 30-electrode measurement of neuronal spike activity in the monkey's visual cortex during the application of different visual stimuli. HMMs with optimized parameters code the information contained in the spatiotemporal discharge patterns as a probabilistic function of a Markov process and thus provide abstract dynamical models of the pattern-generating process. We compare HMMs obtained from vector-quantized data with models in which parametrized output processes such as multivariate Poisson or binomial distributions are assumed. In the latter cases the visual stimuli are recognized at rates of more than 90% from the neuronal spike patterns. An analysis of the models obtained reveals important aspects of the coding of information in the brain. For example, we identify relevant time scales and characterize the degree and nature of the spatiotemporal variations on these scales.

Animals↗

[New methods of analysis of gait in the evaluation of the action of anti-inflammatory drugs. Apropos of naproxen].

Two nontraumatizing and reproducible tools for quantitative gait analysis as part of the objective evaluation of nonsteroidal antiinflammatory drugs are reported. The Bessou gait analyzer is a simple mechanical device which measures spatiotemporal and kinematic parameters (stride length; duration of stride, weight-bearing, and forward swing; speed and peak speed of swing; and overall speed of walking). The ELITE system is a considerably more complex instrument for analyzing three-dimensional motions through high-speed shape recognition. Computerized data management allows not only to determine the spatiotemporal parameters listed above but also to study displacements of selected landmarks in several planes and to derive joint angles and angular speeds. Coupling of the ELITE system to a force platform and to telemetric transmission surface electromyography substantially expands the range of data provided. The mechanical gait analyzer was used to evaluate the effects of naproxen in 11 patients with osteoarthritis of the knee; another similar study in 13 patients with osteoarthritis of the hip is ongoing. Gait was recorded before and after daily administration of naproxen for seven days. After treatment, walking speed was significantly increased as a result of increased stride length and decreased stride duration. Durations of monopodal and bipodal weight-bearing decreased concomitantly with the increase in speed, whereas duration of forward swing remained unchanged. These data demonstrating improved kinematic gait parameters show that naproxen is effective in reducing the adverse mechanical effects of pain. This study also demonstrates the usefulness of gait analysis for evaluating drugs.

Aged↗

Spike cluster analysis in neocortical localization related epilepsy yields clinically significant equivalent source localization results in magnetoencephalogram (MEG).

OBJECTIVE: In magnetoencephalogram (MEG) recordings of patients with epilepsy several types of sharp transients with different spatiotemporal distributions are commonly present. Our objective was to develop a computer based method to identify and classify groups of epileptiform spikes, as well as other transients, in order to improve the characterization of irritative areas in the brain of epileptic patients. METHODS: MEG data centered on selected spikes were stored in signal matrices of C channels by T time samples. The matrices were normalized and euclidean distances between spike representations in vector space R(CxT) were input to a Ward's hierarchical clustering algorithm. RESULTS: The method was applied to MEG data from 4 patients with localization-related epilepsy. For each patient, distinct spike subpopulations were found with clearly different topographical field maps. Inverse computations to selected spike subaverages yielded source solutions in agreement with seizure classification and location of structural lesions, if present, on magnetic resonance images. CONCLUSIONS: With the proposed method a reliable categorization of epileptiform spikes is obtained, that can be applied in an automatic way. Computation of subaverages of similar spikes enhances the signal-to-noise ratio of spike field maps and allows for more accurate reconstruction of sources generating the epileptiform discharges.

Adult↗

Identification and morphogenesis of the eminentia thalami in the zebrafish.

This study documents early zebrafish brain expression patterns (2-5 days postfertilization) of proliferating neural (PCNA) as well as early-determined (Pax6, Zash-1a, Zash-1b, neurogenin1, neuroD) and differentiating (Hu-proteins) neuronal cells. These patterns are used to outline the spatiotemporal local dynamics of secondary neurogenesis as well as neuronal migration and differentiation in the region of the eminentia thalami. The analysis presented not only allows identification for the first time of the eminentia thalami in the zebrafish model system (because it forms a neurogenin1/neuroD-guided locus of neurogenesis in contrast to adjacent preoptic region and ventral thalamus) but furthermore shows that the entopeduncular complex is a derivative of the embryonic zebrafish eminentia thalami, which has never been reported for a teleost before. An analysis of the relevant literature shows that the mammalian entopeduncular nucleus/avian paleostriatum primitivum/reptilian globus pallidus clearly are part of the basal ganglia (i.e., the pallidum). In amniote embryos, an anterior entopeduncular area is recognized at the base of the medial ganglionic eminence (i.e., the future pallidum; part of alar plate of prosomere 5), separate from the more posterior eminentia thalami (alar prosomere 4). There is a comparable periventricular eminentia thalami in (young and adult) amphibians and teleosts. However, the migrated anterior entopeduncular nucleus of anuran amphibians likely is homologous to part of the pallidum of other vertebrates and has no developmental relationship to the eminentia thalami. In contrast, the migrated teleostean entopeduncular complex does not correspond to a pallidal division but is indeed the adult derivative of the early-recognized eminentia thalami as shown in this study.

Animals↗

Reconstructing the evolutionary history of China: a caveat about inferences drawn from ancient DNA.

The decipherment of the meager information provided by short fragments of ancient mitochondrial DNA (mtDNA) is notoriously difficult but is regarded as a most promising way toward reconstructing the past from the genetic perspective. By haplogroup-specific hypervariable segment (HVS) motif search and matching or near-matching with available modern data sets, most of the ancient mtDNAs can be tentatively assigned to haplogroups, which are often subcontinent specific. Further typing for mtDNA haplogroup-diagnostic coding region polymorphisms, however, is indispensable for establishing the geographic/genetic affinities of ancient samples with less ambiguity. In the present study, we sequenced a fragment (approximately 982 bp) of the mtDNA control region in 76 Han individuals from Taian, Shandong, China, and we combined these data with previously reported samples from Zibo and Qingdao, Shandong. The reanalysis of two previously published ancient mtDNA population data sets from Linzi (same province) then indicates that the ancient populations had features in common with the modern populations from south China rather than any specific affinity to the European mtDNA pool. Our results highlight that ancient mtDNA data obtained under different sampling schemes and subject to potential contamination can easily create the impression of drastic spatiotemporal changes in the genetic structure of a regional population during the past few thousand years if inappropriate methods of data analysis are employed.

Asian People↗

Use of wavelet and fast Fourier transforms in pharmacodynamics.

Progress has been made in the development and application of mechanism-based pharmacodynamic models for describing the drug-specific and physiological factors influencing the time course of responses to the diverse actions of drugs. However, the biological variability in biosignals and the complexity of pharmacological systems often complicate or preclude the direct application of traditional structural and nonstructural models. Mathematical transforms may be used to provide measures of drug effects, identify structural and temporal patterns, and visualize multidimensional data from analyses of biomedical signals and images. Fast Fourier transform (FFT) and wavelet analyses are two methodologies that have proven to be useful in this context. FFT converts a signal from the time domain to the frequency domain, whereas wavelet transforms colocalize in both domains and may be utilized effectively for nonstationary signals. Nonstationary drug effects are common but have not been well analyzed and characterized by other methods. In this review, we discuss specific applications of these transforms in pharmacodynamics and their potential role in ascertaining the dynamics of spatiotemporal properties of complex pharmacological systems.

Animals↗

Cytochrome P450RAI(CYP26) promoter: a distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism.

The catabolism of retinoic acid (RA) is an essential mechanism for restricting the exposure of specific tissues and cells to RA. We recently reported the identification of a RA-inducible cytochrome P450 [P450RAI(CYP26)], in zebrafish, mouse, and human, which was shown to be responsible for RA catabolism. P450RAI exhibits a complex spatiotemporal pattern of expression during development and is highly inducible by exogenous RA treatment in certain tissues and cell lines. Sequence analysis of the proximal upstream region of the P450RAI promoter revealed a high degree of conservation between zebrafish, mouse, and human. This region of the promoter contains a canonical retinoic acid response element (5'-AGT-TCA-(n)5-AGTTCA-3'), embedded within a 32-bp region (designated R1), which is conserved among all three species. Electrophoretic mobility shift assays using this element demonstrated the specific binding of murine retinoic acid receptor-gamma (RARgamma) and retinoid X receptor-alpha (RXRalpha) proteins. Transient transfection experiments with the mouse P450RAI promoter fused to a luciferase reporter gene showed transcriptional activation in the presence of RA in HeLa, Cos-1, and F9 wild-type cells. This activation, as well as basal promoter activity, was abolished upon mutation of the RARE. Deletion and mutational analyses of the P450RAI promoter, as well as DNase I footprinting studies, revealed potential binding sites for several other proteins in conserved regions of the promoter. Also, two conserved 5'-TAAT-3' sequences flanking the RARE were investigated for their potential importance in P450RAI promoter activity. Moreover, these studies revealed an essential requirement for a G-rich element (designated GGRE), located just upstream of the RARE, for RA inducibility. This element was demonstrated to form complexes with Sp1 and Sp3 using nuclear extracts from either murine F9 or P19 cells. Together, these results indicate that the P450RAI-RARE is atypical in that conserved flanking sequences may play a very important role in regulating RA inducibility and expression of P450RAI(CYP26).

Animals↗

Osteopontin in kainic acid-induced microglial reactions in the rat brain.

The present study was performed to investigate the spatial and temporal expression of osteopontin (OPN) mRNA in the rat brain after kainic acid-induced seizures, and to determine whether this phenomenon is associated spatiotemporally with the microglial reaction. The expression of OPN mRNA was detected using an in situ hybridization technique and Northern blot analysis. Following intraperitoneal injection of kainic acid (10 mg/kg), OPN mRNA was expressed in selective vulnerable areas, including the hippocampus, thalamus, hypothalamus, amygdala, and entorhinal cortex. Comparison of the morphology and localization with the established microglial marker OX-42 in the adjacent sections positively identified the OPN-expressed cells as microglia. Furthermore, double labeling experiments revealed that OPN mRNA expression was confined to ameboid-like cells among microglia stained with GSI-B4, an another microglial marker. These findings from a rat model of seizure support the notion that OPN can be synthesized in a subpopulation of reactive microglial cells. It can therefore be assumed that in the response of the brain to excitotoxic injury, synthesis of OPN occurs generally in a subset of activated microglia.

Animals↗