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Altered aggrecan synthesis correlates with cell and nucleus structure in statically compressed cartilage.

Previous studies have shown that static equilibrium compression of cartilage tissue in vivo and in vitro decreases chondrocyte synthesis of aggrecan molecules. In order to identify mechanisms of cellular response to loading, we have investigated alterations in cell and nucleus structure and the accompanying changes in the synthesis of aggrecan in statically compressed cartilage explants. Using glutaraldehyde fixation and quantitative autoradiography of compressed and radiolabeled cartilage disks we spatially localized newly synthesized aggrecan. Using stereological tools to analyze these same specimens we estimated the cell and nucleus volume, surface area and directional radii. We found that aggrecan synthesis was reduced overall in compressed tissue disks. However, the compression induced a spatial (radial) inhomogeneity in aggrecan synthesis which was not present in uncompressed disks. This spatial inhomogeneity appeared to be directly related to mechanical boundary conditions and the manner in which the load was applied and, therefore, may represent a spatially specific functional adaptation to mechanical loading. Coincident with reduced aggrecan synthesis, we observed reductions in cell and nucleus volume and radii in the direction of compression which were in approximate proportion to the reduction in tissue thickness. Cell and nucleus dimensions perpendicular to the direction of compression did not change significantly. Therefore the observed deformation of the cell and nucleus in statically compressed cartilage approximately followed the dimensional changes imposed on external specimen surfaces. The strong correlation observed between local changes in aggrecan synthesis and alterations in cell and nucleus structure also lend support to certain hypotheses regarding the intracellular signal transduction pathways that may be important in the biosynthetic response of chondrocytes to mechanical loading.

Aggrecans↗

The dentino-enamel junction: a structural and microanalytical study of early mineralization.

The spatial localization of enamel and dentin apatite crystals of the rat tooth has been studied by electron microscopic methods--bright field, selected-area dark field, and electron spectroscopic imaging. The sequential events of dentin calcification followed by the formation and growth of enamel crystals were determined and compared to previous studies. In dentin, initial sites of mineral deposition occur in areas subjacent to the dentino-enamel junction (DEJ). The subsequent expansion of these deposits progresses towards the DEJ to the terminal ends of dentin collagen fibrils. Concomitantly, an electron-dense enamel matrix is released by ameloblasts; with the presence of this matrix, the growth of enamel crystals occurs from the underlying calcified dentin. Enamel crystal growth continues to within close proximity of the plasma membrane of ameloblasts. A close spatial relationship between enamel and the crystals of calcified dentin collagen fibrils was observed by selected-area dark field imaging. Such areas of crystal intimacy show a co-localization of calcium and phosphorus extending from calcified collagen fibrils to enamel sheaths which encase enamel crystals. A working model of the spatial relationship between crystals of dentin and enamel is presented and discussed in light of mechanisms by which calcified dentin may promote the formation of enamel crystals.

Amelogenesis↗

Audio-spatial deficits in humans: differential effects associated with left versus right hemisphere parietal damage.

In order to study auditory spatial localization in subjects with posterior damage involving the parietal lobe, we investigated their manual pointing performances to linguistic and white noise signals distributed over six sound sources situated in the anterior auditory field at ear level. The results showed: (1) A striking difference between patterns of deficits associated with right and left damage. In subjects with right damage, auditory localization deficits occurred in the horizontal plane, were manifested as restrictions in the peripheral left auditory hemifield and tended to be related to left visual neglect. In subjects with left damage, auditory localization deficits occurred in the entire auditory field in the horizontal as well as vertical planes, and they were particularly strong in the antero-frontal region. (2) One subject with right damage and visual neglect but no left auditory spatial restriction, showed deficits in the right hemifield where sound source location tended to be overestimated. This subject also showed a better discrimination of the origin of a white noise than of a linguistic signal. Results are discussed in terms of hemispheric asymmetries of function.

Acoustic Stimulation↗

Mathematical model and simulation of retina and tectum opticum of lower vertebrates.

The processing of information within the retino-tectal visual system of amphibians is decomposed into five major operational stages, three of them taking place in the retina and two in the optic tectum. The stages in the retina involve (i) a spatially local high-pass filtering in connection to the perception of moving objects, (ii) separation of the receptor activity into ON- and OFF-channels regarding the distinction of objects on both light and dark backgrounds, (iii) spatial integration via near excitation and far-reaching inhibition. Variation of the spatial range of excitation and inhibition allows to account for typical activities observed in a variety of classes of retina ganglion cells. Mathematical description of the operations in the tectum opticum include (i) spatial summation of retinal output (mainly of class-2 and class-3 retina ganglion cells), and (ii) direct or indirect lateral inhibition between tectal cells. In the computer simulation, first the output of the mathematical retina model is computed which, then, is used as the input to the tectum model. The full spatio-temporal dynamics is taken into account. The simulations show that different combinations of strength of lateral inhibition on the one side and the response properties of the retina ganglion cells on the other side determine the response properties of tectal cell types involved in object recognition.

Amphibians↗

Orientational correlations and the effect of spatial gradients in the equilibrium steady state of hard rods in two dimensions: a study using deposition-evaporation kinetics.

Deposition and evaporation of infinitely thin hard rods (needles) is studied in two dimensions using Monte Carlo simulations. The ratio of deposition to evaporation rates controls the equilibrium density of rods, and increasing it leads to an entropy-driven transition to a nematic phase in which both static and dynamical orientational correlation functions decay as power laws, with exponents varying continuously with deposition-evaporation rate ratio. Our results for the onset of the power-law phase agree with those for a conserved number of rods. At a coarse-grained level, the dynamics of the nonconserved angle field is described by the Edwards-Wilkinson equation. Predicted relations between the exponents of the quadrupolar and octupolar correlation functions are borne out by our numerical results. We explore the effects of spatial inhomogeneity in the deposition-evaporation ratio by simulations, entropy-based arguments, and a study of the additional terms introduced in the free energy. The primary effect is that needles tend to align along the local spatial gradient of the ratio. A uniform gradient thus induces a uniformly aligned state, as does a gradient which varies randomly in magnitude and sign, but acts only in one direction. Random variations of deposition-evaporation rates in both directions induce frustration, resulting in a state with glassy characteristics.

Journal Article↗

Partially incoherent optical vortices in self-focusing nonlinear media.

We observe stable propagation of spatially localized single- and double-charge optical vortices in a self-focusing nonlinear medium. The vortices are created by self-trapping of partially incoherent light carrying a phase dislocation, and they are stabilized when the spatial incoherence of light exceeds a certain threshold. We confirm the vortex stabilization effect by numerical simulations and also show that the similar mechanism of stabilization applies to higher-order vortices.

Journal Article↗

Heterogeneous modulation of place cell firing by changes in context.

Hippocampal place cells show spatially localized activity that can be modulated by both geometric information (e.g., the distances and directions of features in the environment) and nongeometric information (e.g., colors, odors, and possibly behaviors). Nongeometric information may allow the discrimination of different spatial contexts. Understanding how nongeometric (or contextual) information affects hippocampal activity is important in light of proposals that the hippocampus may play a role in constructing a representation of spatial context. We investigated the contextual modulation of place cell activity by recording hippocampal place cells while rats foraged in compound contexts comprising black or white color paired with lemon or vanilla odor. Some cells responded to the color or odor changes alone, but most responded to varying combinations of both. Thus, we demonstrate, for the first time, that there is a heterogeneous input by contextual inputs into the hippocampus. We propose a model of contextual remapping of place cells in which the geometric inputs are selectively activated by subsets of contextual stimuli. Because it appears that different place cells are affected by different subsets of contextual stimuli, the representation of the entire context would require activity at the population level, supporting a role for the hippocampus in constructing a representation of spatial context.

Animals↗

Direct magnetic resonance detection of neuronal electrical activity.

Present noninvasive neuroimaging methods measure neuronal activity indirectly, via either cerebrovascular changes or extracranial measurements of electrical/magnetic signals. Recent studies have shown evidence that MRI may be used to directly and noninvasively map electrical activity associated with human brain activation, but results are inconclusive. Here, we show that MRI can detect cortical electrical activity directly. We use organotypic rat-brain cultures in vitro that are spontaneously active in the absence of a cerebrovascular system. Single-voxel magnetic resonance (MR) measurements obtained at 7 T were highly correlated with multisite extracellular local field potential recordings of the same cultures before and after blockade of neuronal activity with tetrodotoxin. Similarly, for MR images obtained at 3 T, the MR signal changed solely in voxels containing the culture, thus allowing the spatial localization of the active neuronal tissue.

Animals↗

Postoperative multichannel magnetoencephalography in patients with recurrent seizures after epilepsy surgery.

OBJECTIVE: Assessment of usefulness of magnetoencephalography (MEG) as a novel non-invasive technique in the diagnostic evaluation of patients with recurrent seizures after unsuccessful epilepsy surgery. MATERIAL AND METHODS: Seventeen patients in whom epilepsy surgery had failed underwent reevaluation by means of MEG in addition to standard presurgical investigations (EEG, MRI, SPECT, and neuropsychologic testing). RESULTS: Source analysis of interictal epileptic MEG discharges revealed dipole localizations immediately adjacent to the borders of previous resection in 10 of 17 patients. Standard non-invasive presurgical evaluation suggested epileptogenicity over the general area of previous resection in all patients, but did not provide any detailed spatial localizing data. Invasive EEG recordings confirmed the MEG focus localization in all of 5 patients who were selected for reoperation. Second operation at the site of previous resection achieved complete seizure control in 3 and cessation of tonic-clonic seizures in 1 of these patients. CONCLUSION: MEG may provide useful information in the diagnostic reevaluation of postoperative epileptic patients in whom skull and dura defects produce a "breach effect" which alters non-invasive and invasive EEG.

Adult↗

Upstream and downstream of ran GTPase.

Among the Ras family, Ran is a unique small G protein. It does not have a lipid modification motif at the C-terminus to bind to the membrane, which is often observed within the Ras family. Ran may therefore interact with a wide range of proteins in various intracellular locations. This means that Ran could play many different roles like nucleocytoplasmic transport, microtubule assembly and so on. All of the Ran functions should be regulated by RanGEF and RanGAP. It is an interesting issue why RCC1, a RanGEF, is localized in the nucleus and RanGAP1/Ran1p in the cytoplasm. It is possible that RCC1 checks the state of chromosomal DNA replication and transfers it to the downstream events through Ran; thereby, RCC1 would be involved in coupling the spatial localization of cellular macromolecules with the cell cycle progression. In this context, Ran will be a very important cell cycle mediator. There is yet another G protein cascade, Gtr1-Gtr2, which interacts with the Ran cycle.

Cell Cycle↗

Calcium concentration dynamics produced by synaptic activation of CA1 hippocampal pyramidal cells.

The spatial and temporal dynamics of many electrophysiological and biochemical processes in nerve cells are in turn dependent on the concentration dynamics of the second messenger calcium. We have used microfluorimetry of the calcium indicator fura-2 (Grynkiewicz et al., 1985) to measure and characterize synaptically activated calcium changes in individual CA1 pyramidal cells contained within guinea pig hippocampal slices. One component of the calcium changes was largely produced by influx through voltage-dependent Ca2+ channels (VDCCs). It consisted of large transient accumulations in the proximal-apical and basal dendrites; the amplitude was smaller in the distal-apical dendrites and the soma. This spatial profile was insensitive to the method of cell activation: stimulation of inputs located at different positions on the dendritic tree as well as antidromic stimulation produced only slight modifications. This component was not blocked by the NMDA antagonist 5-amino-4-phosphonovalerate (AP5) (Collingridge et al., 1983), was greatly reduced by Cd2+, partially reduced by nifedipine, and was increased by Bay-K 8644, providing the evidence that it was largely produced by influx through VDCCs. Blocking postsynaptic Na+ channels with QX-314 greatly reduced the accumulation amplitude, and spatial differences between proximal-dendritic and distal-dendritic regions were less pronounced, suggesting that active sodium conductances contribute significantly to the spatial activation of calcium conductances. Residual spatial differences that persist in QX-314 experiments are consistent with the idea that VDCCs have decreased density on distal-apical dendrites. A second component of accumulation was induced by ionic currents through NMDA receptor channels. It was blocked by AP5, unaffected by QX-314, attenuated and slowed down by elevated calcium buffering, and spatially localized to regions receiving activated synaptic inputs. The magnitude of this component was strongly dependent on the frequency and amplitude of synaptic activation. At high frequency, it was generally very large, often saturating the fura-2 (> 2 microM). Measurements made with the indicator furaptra also showed large localized AP5-sensitive fluorescence changes. Our results suggest that in dendritic regions near activated input fibers calcium levels may reach 2-10 microM. In general, our measurements of calcium dynamics provide an experimental basis for evaluating the spatial distribution of calcium conductances, the spatial distribution of calcium-activated electrophysiological and biochemical processes, and the spatial uniformity of calcium buffering and removal systems in CA1 hippocampal pyramidal cells. The time course and amplitude of Ca2+ transients we measured suggest that activation of Ca(2+)-dependent conductances [e.g., IK(Ca)] will be markedly different for different cellular regions.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Estimation of size of infarcted focus by spatial quantitative vectorcardiography in patients with acute anterior myocardial infarction.

The study included 113 patients with acute myocardial infarction of the left ventricular anterior wall. The patients were repeatedly followed up from the first hours of the affection onward in the course of the individual stages of treatment (stage of intensive monitoring and therapy; intermediate stage; initial rehabilitation with application of active therapy; early mobilization, activation and rehabilitation). A new approach to the estimation of the size of the infarcted focus is described, namely, the method using spatial quantitative vectorcardiography. It was found that the spatial localization of the 40-ms vector, especially its azimuth, is a specific indicator, with the aid of which the localization, extent and depth of the lesion in the left ventricular anterior wall can be assessed with a high probability in most instances. The compensatory adaptive and reparative capacity of the affected myocardium, estimated on the basis of spatial quantitative VCG, is closely correlated with the size of the infarcted focus.

Humans↗

Spatial and temporal localization of secretory IgA in healing tooth extraction sockets in a rabbit model.

PURPOSE: The purpose of this study was to look at the spatial and temporal localization of secretory IgA in healing tooth extraction sockets in a rabbit model. MATERIALS AND METHODS: Twenty-four male New Zealand White rabbits were used in the study. Incisor teeth were extracted from both jaws, and the healing extraction socket with the surrounding jaw bone was harvested at 48 hours, 4 days, and 1, 2, 4, 8, 12, and 16 weeks. Tissues were fixed, decalcified, and processed for hematoxylin and eosin and immunohistochemical staining. The sections were stained to detect secretory IgA. The stained sections were then imaged, and an automated computer program was used to detect the brown 3,3'-diaminobenzidine stain that represented the secretory IgA. The data were obtained in the form of percentage area and intensity of stain and analyzed using analysis of variance (Tukey-Kramer and Scheffé's tests). RESULTS: Spatial and temporal differences in localization of secretory IgA were observed across time frames in both jaws. CONCLUSION: The results of this study showed definite trends in the spatial and temporal localization of secretory IgA in healing tooth extraction sockets in a rabbit model.

Alveolar Process↗

What population turnaround? Some Canadian prairie settlement perspectives, 1971-1986.

The relevance of the concept of the population turnaround to the analysis of population trends in the Canadian Prairie Provinces between 1971 and 1986 is considered. "Throughout the whole period the trend to greater spatial concentration of the population has continued despite the possibility of greater dispersal. The terms population turnaround or counter-urbanization were found to be too general to summarize the varied changes in the 1970s.... In the 1980s more localized spatial trends are identified, with most places experiencing marginal growth and decline, thereby providing very different characteristics to the previous decade."

Americas↗

Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver.

Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for detection by MRS. In this study, three independent signal-to-noise ratio (SNR) optimizations were combined to enable chemical shift imaging (CSI) as a localization method in the detection of 5FU and its metabolites in tumor tissue. First, the hardware was optimized by using circularly polarized coils together with integrated preamplifiers. Second, the optimal pulse angle (Ernst angle) was determined on the basis of T(1) relaxation time measurements of 5FU. Finally, averaging of CSI phase-encoding steps was optimized by using the applied Hamming filter as a weighting function. The combination of these three methods enables the in vivo detection of 5FU and alpha-fluoro-beta-alanine (FBAL) by (19)F MRS, localized in three dimensions in tumor and liver tissue at a time resolution of 4 min at 1.5 Tesla.

Antimetabolites, Antineoplastic↗

Preliminary evidence of low cortical GABA levels in localized 1H-MR spectra of alcohol-dependent and hepatic encephalopathy patients.

OBJECTIVE: The aim of the study was to compare levels of neuroactive amino acids in the cerebral cortex of healthy subjects, recently detoxified alcohol-dependent patients, and patients with hepatic encephalopathy. METHOD: Metabolite levels were measured in the occipital cortex by using spatially localized 1H-MRS. Five recently detoxified alcohol-dependent and five hepatic encephalopathy patients with alcohol and non-alcohol-related disease were compared with 10 healthy subjects. RESULTS: The combined level of gamma-aminobutyric acid (GABA) plus homocarnosine was lower in the alcohol-dependent and hepatic encephalopathy patients than in the healthy subjects. CONCLUSIONS: The findings suggest that GABA-ergic systems are altered in both alcohol-dependent and hepatic encephalopathy patients.

Adult↗

Spatial synchrony of local populations has increased in association with the recent Northern Hemisphere climate trend.

According to ecological theory, populations whose dynamics are entrained by environmental correlation face increased extinction risk as environmental conditions become more synchronized spatially. This prediction is highly relevant to the study of ecological consequences of climate change. Recent empirical studies have indicated, for example, that large-scale climate synchronizes trophic interactions and population dynamics over broad spatial scales in freshwater and terrestrial systems. Here, we present an analysis of century-scale, spatially replicated data on local weather and the population dynamics of caribou in Greenland. Our results indicate that spatial autocorrelation in local weather has increased with large-scale climatic warming. This increase in spatial synchrony of environmental conditions has been matched, in turn, by an increase in the spatial synchrony of local caribou populations toward the end of the 20th century. Our results indicate that spatial synchrony in environmental conditions and the populations influenced by them are highly variable through time and can increase with climatic warming. We suggest that if future warming can increase population synchrony, it may also increase extinction risk.

Animals↗

Hematopoietic reconstitution after bone marrow transplantation: assessment with MR imaging and H-1 localized spectroscopy.

Magnetic resonance (MR) studies were performed in 14 patients as early as possible (21-110 days) after bone marrow transplantation (BMT). MR characteristics of lumbar vertebral bone marrow were studied with T1-weighted spin-echo imaging, water- and fat-selective imaging with a frequency-selective excitation technique, and point-resolved spatially localized proton spectroscopy. Signals from water and fat protons and their T1 and T2 values were analyzed. Water proton signal intensity correlated well with cellularity within bone marrow, as determined with parallel iliac crest biopsies. The fraction of signal from water in red bone marrow of patients with allogeneic transplants from siblings (four cases) was significantly higher than in four patients with autologous transplants. The latter showed very low cellularity in the period of about 4 weeks after BMT because of the cytotoxic pretreatment of the bone marrow. The MR results in six patients with allogeneic transplants from unrelated donors ranged widely, depending on the complications after BMT. Analysis of data obtained with the different techniques showed that water- and fat-selective MR imaging and spectroscopic methods are useful for noninvasive monitoring of hematopoietic reconstitution after BMT.

Adolescent↗