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Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat.

To examine the oxygen-dependence of glucose consumption in solid tumors, we monitored gradients of glucose, lactate, and hypoxia in R3230Ac and FSA tumors growing in Fischer 344 rats. Bioluminescence imaging, detection of Hoechst 33342, and immunostaining of the hypoxia marker EF5 [2-8-N-(2,2,3,3,3-pentafluoropropyl)acetamide] were done in serial tumor slices. Glucose and lactate levels were also determined in liver and blood. Cells were further tested for glucose consumption and lactate production in vitro. In both tumor types, EF5 staining indicated similar maximum levels of hypoxia; the most intense staining occurred in perinecrotic regions. Glucose concentrations were highest in liver, declined from blood to tumor edge, further into vital tumor regions, and were lowest close to necrosis. Glucose was significantly lower in FSA than in R3230Ac tumors. Glucose concentrations in R3230Ac tumors were consistently higher in nonhypoxic than in hypoxic areas, with maximum values equal to systemic blood levels. Glucose in FSA tumors was close to zero, regardless of the presence or absence of hypoxia. Lactate did not differ significantly between the tumor types. FSA cells in culture showed a trend towards higher aerobic glucose consumption versus R3230Ac. Both cell lines increased their lactate production to similar levels under hypoxia. We conclude that both R3230Ac and FSA tumors retain the Pasteur effect, i.e., hypoxia triggers increased glycolysis. However, our results imply that increased aerobic glucose utilization leads to low glucose levels in FSA and a situation where supply limits uptake. This explains the repeatedly observed correlation between tumor blood flow and 18F-deoxyglucose uptake.

Animals↗

Stimulus-dependent effects on tactile spatial acuity.

BACKGROUND: Previous studies have shown that spatio-tactile acuity is influenced by the clarity of the cortical response in primary somatosensory cortex (SI). Stimulus characteristics such as frequency, amplitude, and location of tactile stimuli presented to the skin have been shown to have a significant effect on the response in SI. The present study observes the effect of changing stimulus parameters of 25 Hz sinusoidal vertical skin displacement stimulation ("flutter") on a human subject's ability to discriminate between two adjacent or near-adjacent skin sites. Based on results obtained from recent neurophysiological studies of the SI response to different conditions of vibrotactile stimulation, we predicted that the addition of 200 Hz vibration to the same site that a two-point flutter stimulus was delivered on the skin would improve a subject's spatio-tactile acuity over that measured with flutter alone. Additionally, similar neurophysiological studies predict that the presence of either a 25 Hz flutter or 200 Hz vibration stimulus on the unattended hand (on the opposite side of the body from the site of two-point limen testing - the condition of bilateral stimulation - which has been shown to evoke less SI cortical activity than the contralateral-only stimulus condition) would decrease a subject's ability to discriminate between two points on the skin. RESULTS: A Bekesy tracking method was employed to track a subject's ability to discriminate between two-point stimuli delivered to the skin. The distance between the two points of stimulation was varied on a trial-by-trial basis, and several different stimulus conditions were examined: (1) The "control" condition, in which 25 Hz flutter stimuli were delivered simultaneously to the two points on the skin of the attended hand, (2) the "complex" condition, in which a combination of 25 Hz flutter and 200 Hz vibration stimuli were delivered to the two points on the attended hand, and (3) a "bilateral" condition, in which 25 Hz flutter was delivered to the two points on the attended hand and a second stimulus (either flutter or vibration) was delivered to the unattended hand. The two-point limen was reduced (i.e., spatial acuity was improved) under the complex stimulus condition when compared to the control stimulus condition. Specifically, whereas adding vibration to the unilateral two-point flutter stimulus improved spatial acuity by 20 to 25%, the two-point limen was not significantly affected by substantial changes in stimulus amplitude (between 100 - 200 microm). In contrast, simultaneous stimulation of the unattended hand (contralateral to the attended site), impaired spatial acuity by 20% with flutter stimulation and by 30% with vibration stimulation. CONCLUSION: It was found that the addition of 200 Hz vibration to a two-point 25 Hz flutter stimulus significantly improved a subject's ability to discriminate between two points on the skin. Since previous studies showed that 200 Hz vibration preferentially evokes activity in cortical area SII and reduces or inhibits the spatial extent of activity in SI in the same hemisphere, the findings in this paper raise the possibility that although SI activity plays a major role in two-point discrimination on the skin, influences relayed to SI from SII in the same hemisphere may contribute importantly to SI's ability to differentially respond to stimuli applied to closely spaced skin points on the same side of the body midline.

Journal Article↗

Phylogenetic structure of Floridian plant communities depends on taxonomic and spatial scale.

Consideration of the scale at which communities are defined both taxonomically and spatially can reconcile apparently contradictory results on the extent to which plants show phylogenetic niche conservatism. In plant communities in north central Florida, we collected species abundances in 55 0.1-ha plots in several state parks. When communities were defined narrowly to include a single phylogenetic lineage, such as Quercus, Pinus, or Ilex, neighbors tended to be less related than expected (phylogenetic overdispersion) or there was no pattern. If the same communities were defined more broadly, such as when all seed plants were included, neighbors tended to be more related than expected (phylogenetic clustering). These results provide evidence that species interactions among close relatives influence community structure, but they also show that niche conservatism is increasingly evident as communities are defined to include greater phylogenetic diversity. We also found that, as the spatial scale is increased to encompass greater environmental heterogeneity, niche conservatism emerges as the dominant pattern. We then examined patterns of trait evolution in relation to trait similarity within communities for 11 functional traits for a single phylogenetic lineage (Quercus) and for all woody plants. Among the oaks, convergent evolution of traits important for environmental filtering contributes to the observed pattern of phylogenetic overdispersion. At the broader taxonomic scale, traits tend to be conserved, giving rise to phylogenetic clustering. The shift from overdispersion to clustering can be explained by the increasing conservatism of traits at broader phylogenetic scales.

Biological Evolution↗

Phosphorylation-dependent changes in the spatial relationship between Ca-ATPase polypeptide chains in sarcoplasmic reticulum membranes.

In order to investigate possible structural changes associated with the coupling mechanisms of the Ca-ATPase in sarcoplasmic reticulum membranes, we have utilized fluorescence resonance energy transfer between spectroscopic probes covalently bound to different domains of the ATPase. Using time-correlated single photon counting, we have directly measured the energy transfer efficiency between 5-[2-[(iodoacetyl)amino]ethyl]aminonaphthalene-1-sulfonic acid (IAEDANS), that is specifically bound to the B trypic fragment at cysteines 670 and 674 and acceptors covalently bound either near the nucleotide binding site, i.e. fluorescein 5-isothiocyanate at lysine 515, also on the B fragment, or maleimide-directed probes specifically located on the A1, tryptic fragment, i.e. 4-dimethylaminoazobenzene-4'-maleimide (DABmal) or fluorescein-5-maleimide (Fmal), probably at cysteines 344 and 364. All of these donor-acceptor pairs exhibit energy transfer both within and between Ca-ATPase molecules allowing us to investigate spatial relationships between the A1 and B domains and between different ATPase polypeptide chains. Differentiation between the intra- and intermolecular components of energy transfer was accomplished in two ways: 1) by comparing the transfer efficiencies in native membranes before and after detergent solubilization and 2) by reconstituting ATPase chains that have already been labeled with either the donor or acceptor chromophores. Using this approach, we find no significant change in the intramolecular transfer efficiency between any of these donor-acceptor pairs either upon binding of calcium to the high affinity sites or upon stabilization of the phosphoenzyme intermediate, indicating that there are no large structural changes within the B tryptic fragment or, alternatively, between the A1 and B fragments. With respect to intermolecular energy transfer, we observe no effect of calcium binding on the unliganded enzyme with either donor-acceptor pair. However, formation of the phosphoenzyme intermediate results in a measurable increase in the transfer efficiency between IAEDANS and DABmal (or Fmal); this increase is reversible upon phosphoenzyme destabilization by subsequent addition of calcium. There is no corresponding change in the intermolecular component of fluorescence resonance energy transfer between IAEDANS and fluorescein 5-isothiocyanate, indicating that the change in fluorescence resonance energy transfer probably occurs as a result of reorientation of associated ATPase polypeptide chains with respect to one another.

Animals↗

Transformation of cardiac endothelium into cushion mesenchyme is dependent on ES/130: temporal, spatial, and functional studies in the early chick embryo.

ES/130 is a novel 130-kDa protein that has been linked previously to the transformation of endocardial endothelium into cushion mesenchyme. In the present study we report the localization of protein and mRNA for ES/130 in stages 7-plus through 20 chick embryos and present functional data related to a potential mechanism for ES/130. The temporal and spatial regulation of ES/130 expression suggests that this epithelial-to-mesenchymal transformation is a result of homogenetic induction. Functional studies indicate that myocardially derived ES/130 elicits expression of this protein by target AV endothelial cells, which is linked to a signal transduction cascade. The localization of ES/130 to other sites of inductive interactions (e.g., limb bud ectoderm, gut, and notochord) implies that this protein may have a more widespread importance to embryogenesis beyond its involvement in cardiac cushion tissue formation.

Animals↗

[Dependence of human EEG spatial synchronization on the geomagnetic activity on the day of experiment].

Spontaneous EEG was registered under different activity conditions in 26 volunteers. The EEG synchronisation parameters were compared with the geomagnetic and solar activity on the day of experiment. A positive correlation of the EEG data with the geomagnetic activity was revealed, being most obvious in the frontal and central areas. A negative correlation between some local EEG synchronisation parameters and different indices of the solar activity, was also revealed. The degree of synchronisation of the spontaneous EEG seems to reflect sensitivity of the human nervous system to the Earth's magnetic field. A stressor response to strong short-term disturbances in the geomagnetic field reveals itself in the form of enhancement of the EEG global synchronisation. A sedative effect of slow magnetic oscillations is locally revealed in the parameters of the EEG synchronisation within the left hemisphere as well as the interhemisphere synchronisation.

Adolescent↗

Optimal phosphor thickness for portal imaging.

A theoretical approach known as quantum accounting diagram (QAD) analysis has been used to calculate the spatial-frequency-dependent detective quantum efficiency (DQE) of two portal imaging systems: one based on a video camera and another based on an amorphous silicon array. The spatial frequency-dependent DQEs have then been used to determine indices of displayed and perceived image quality. These indices are figures of merit that can be used to optimize the design of linear imaging systems. We have used this approach to determine which of eight phosphor screen thicknesses (ranging between 67 and 947 mg/cm2) is optimal for the two designs of portal imaging systems. The physical characteristics (i.e., detection efficiencies, gains, and MTFs) of each of the eight x-ray detectors have been measured and combined with the physical characteristics of the remaining components to calculate the theoretical DQEs. In turn, the DQEs have been used to calculate theoretical indices of displayed and perceived image quality for two types of objects: a pelvis object and a pointlike object. The maximal indices of displayed and perceived image quality were obtained with screen thickness ranging between 358 and 947 mg/cm2, depending upon the imaging system design and the object being imaged. Importantly, the results showed that there is no single optimal screen thickness. The optimal thickness depended upon imaging task (e.g., detecting large, low-contrast structures, or detecting edges and small structures). Nevertheless, the results showed that there were only modest improvements in the indices of image quality for phosphor screens thicker than 350-400 mg/cm2.

Biophysical Phenomena↗

Visual, long-latency auditory and brainstem auditory evoked potentials in migraine: relation to pattern size, stimulus intensity, sound and light discomfort thresholds and pre-attack state.

We aimed to estimate primary sensory evoked potential (EP) amplitude, amplitude-intensity functions and habituation in migraine patients compared with healthy control subjects and to investigate the possible relation to check size, sound and light discomfort thresholds, and the time to the next attack. Amplitudes of cortical visual evoked potentials (VEP, check size 8' and 33'), cortical long latency auditory evoked potential (AEP NIP1; 40, 55 and 70 dB SL tones) and brainstem auditory evoked potential (BAEP wave IV-V; 40, 55 and 65 dB SL clicks) were recorded and analysed in a blind and balanced design. The difference between the response to the first and the second half of the stimulus sequence was used as a measure of habituation. Twenty-one migraine patients (16 women and five men, mean age 39.3 years, six with aura, 15 without aura) and 22 sex- and age-matched healthy control subjects were studied (18 women and four men, mean age 39.5 years). Low sound discomfort threshold correlated significantly with low levels of BAEP wave IV-V amplitude habituation (r = -0.30, P = 0.05). VEP an AEP amplitudes, habituation, and amplitude-intensity function (ASF) slopes did not differ between groups when ANOVA main factors were considered. Control group VEP habituation was found for small check stimuli (P = 0.04), while potentiation was observed for medium sized checks (P = 0.02). The eight migraine patients who experienced headache within 24 h after the test tended to have increased BAEP wave IV-V ASF slopes (P = 0.08). This subgroup did also have a significant VEP habituation to small checks (P = 0.04). No correlation was found between different modalities. These results suggest that: (i) VEP habituation/potentiation state and brainstem activatio state may depend on the attack-interval cycle in migraine; (ii) VEP habituation/ potentiation may depend on spatial stimulus frequency; (iii) phonophobia (and possibly photophobia) may depend more on subcortical (brainstem) function than on cortical mechanisms; (iv) low cortical preactivation in migraine could not be confirmed; (v) EP habituation and ASF analysis may reflect sensory modality-specific, not generalized, central nervous system states in migraine and healthy control subjects.

Acoustic Stimulation↗

Theoretical evaluation of accuracy in position and size of brain activity obtained by near-infrared topography.

Near-infrared (NIR) topography can obtain a topographical distribution of the activated region in the brain cortex. Near-infrared light is strongly scattered in the head, and the volume of tissue sampled by a source-detector pair on the head surface is broadly distributed in the brain. This scattering effect results in poor resolution and contrast in the topographic image of the brain activity. In this study, a one-dimensional distribution of absorption change in a head model is calculated by mapping and reconstruction methods to evaluate the effect of the image reconstruction algorithm and the interval of measurement points for topographic imaging on the accuracy of the topographic image. The light propagation in the head model is predicted by Monte Carlo simulation to obtain the spatial sensitivity profile for a source-detector pair. The measurement points are one-dimensionally arranged on the surface of the model, and the distance between adjacent measurement points is varied from 4 mm to 28 mm. Small intervals of the measurement points improve the topographic image calculated by both the mapping and reconstruction methods. In the conventional mapping method, the limit of the spatial resolution depends upon the interval of the measurement points and spatial sensitivity profile for source-detector pairs. The reconstruction method has advantages over the mapping method which improve the results of one-dimensional analysis when the interval of measurement points is less than 12 mm. The effect of overlapping of spatial sensitivity profiles indicates that the reconstruction method may be effective to improve the spatial resolution of a two-dimensional reconstruction of topographic image obtained with larger interval of measurement points. Near-infrared topography with the reconstruction method potentially obtains an accurate distribution of absorption change in the brain even if the size of absorption change is less than 10 mm.

Algorithms↗

Human pattern-evoked electroretinogram.

We have recorded electroretinographic (ERG) responses to grating patterns whose spatial, temporal, and contrast parameters were varied. The resultant evoked potential is dependent on spatial frequency and it exhibits a spatial band-pass characteristic. The peak frequency is dependent on retinal eccentricity. These findings are independent of temporal frequency, contrast, or mean luminance in the photopic range. These results suggest that the pattern ERG originates from a postreceptoral site.

Cerebral Cortex↗

Spatial structures in a reaction-diffusion system--detailed analysis of the "Brusselator".

Continuous dependence of spatially nonuniform concentration profiles for the 'Brussellator" reaction mechanims on the characteristic length of the system is given both for zero flux and fixed boundary conditions. Branches of solutions arising through primary bifurcation form closed curves. Secondary bifurcations giving rise to spatially asymmetric solutions exist for fixed boundary conditions. Results of a stability analysis of individual solutions are discussed. A method of composing complex spatial profiles for higher lengths from elementary solutions for smaller lenghts is suggested and tested in the case of zero flux boundary conditions. Emergence of subsequently more complex stable patterns in dependence on increasing length of the system suggests many similarities to gradual build up of complex morphogenetic patterns.

Biological Transport↗

Spatial contrast sensitivity in facial recognition.

Recognition and learning of complex images may depend on spatial processing characteristics of the visual system. Prosopagnosia, an impairment of visual learning and recognition of faces, might result from impaired perception in spatial channels carrying crucial information. We studied spatial contrast sensitivity (SCS) in two subjects with stable facial recognition defects. One had relative SCS reduction for high-frequency gratings but could process high frequencies in room light. The other had normal SCS. Both had intact spatial processing relative to image size. The results suggest that impairments in visual spatial channels are not necessary for the development of prosopagnosia.

Adult↗

Spatial variation and density-dependent dispersal in competitive coexistence.

It is well known that dispersal from localities favourable to a species' growth and reproduction (sources) can prevent competitive exclusion in unfavourable localities (sinks). What is perhaps less well known is that too much emigration can undermine the viability of sources and cause regional competitive exclusion. Here, I investigate two biological mechanisms that reduce the cost of dispersal to source communities. The first involves increasing the spatial variation in the strength of competition such that sources can withstand high rates of emigration; the second involves reducing emigration from sources via density-dependent dispersal. I compare how different forms of spatial variation and modes of dispersal influence source viability, and hence source-sink coexistence, under dominance and pre-emptive competition. A key finding is that, while spatial variation substantially reduces dispersal costs under both types of competition, density-dependent dispersal does so only under dominance competition. For instance, when spatial variation in the strength of competition is high, coexistence is possible (regardless of the type of competition) even when sources experience high emigration rates; when spatial variation is low, coexistence is restricted even under low emigration rates. Under dominance competition, density-dependent dispersal has a strong effect on coexistence. For instance, when the emigration rate increases with density at an accelerating rate (Type III density-dependent dispersal), coexistence is possible even when spatial variation is quite low; when the emigration rate increases with density at a decelerating rate (Type II density-dependent dispersal), coexistence is restricted even when spatial variation is quite high. Under pre-emptive competition, density-dependent dispersal has only a marginal effect on coexistence. Thus, the diversity-reducing effects of high dispersal rates persist under pre-emptive competition even when dispersal is density dependent, but can be significantly mitigated under dominance competition if density-dependent dispersal is Type III rather than Type II. These results lead to testable predictions about source-sink coexistence under different regimes of competition, spatial variation and dispersal. They identify situations in which density-independent dispersal provides a reasonable approximation to species' dispersal patterns, and those under which consideration of density-dependent dispersal is crucial to predicting long-term coexistence.

Animals↗

The effect of intrahippocampal insulin microinjection on spatial learning and memory.

Insulin is best known for its action on peripheral target tissues such as the adipocyte, muscle and liver to regulate glucose homeostasis. Insulin and its receptor are found in specific area of CNS with a variety of region-specific functions different from its direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions. Previous studies about the effect of insulin on memory are controversial. In the present study, the effect of insulin microinjection into CA1 region of rat hippocampus on water maze performance has been investigated. Insulin had a discrepant effect dose dependently. The spatial learning and memory were impaired with lower dose of insulin, had not changed with intermediate doses, while they improved with higher doses. These results suggest that insulin may have a dose-dependent effect on spatial learning and memory.

Animals↗

Influence of phenomenal time on perceived space.

It is known from work by Helson and King that the apparent spatial distance between stimuli presented in succession depends on the time interval between those stimuli ("tau effect"). It is also known that the apparent time (i.e., the interval of time perceived between stimuli presented in succession) depends on the spatial distance between the stimuli defining the time interval (called "kappa effect" by Cohen, Hansel, and Sylvester). For the "kappa effect," apparent time between lights and stimuli on the skin of the forearm undergoes modification depending on the apparent spatial distance, as presented in Suto's work beginning in the early 1940s. The present work is complementary to Suto's. Its purpose is to test whether apparent spatial distance depends on the objective or subjective (apparent, phenomenal) time interval. To achieve this, our crucial (third) experiment was preceded by two exploratory experiments: the first to verify the illusion in which a subdivided interval appears longer than an empty interval of the same length (Oppel-Kundt temporal illusion); the second to verify the presence of the "tau effect" with simultaneous tactual and auditory stimuli for time intervals between 1500 and 2500 msec. In the third experiment subjects received successive tactual stimuli defining two spatial distance and two time intervals. They also received auditory stimuli that produced the Oppel-Kundt illusion by making the time intervals phenomenally different. The results fill a small experimental gap by showing it is subjective (phenomenal) and not objective (physical) time that influences perceived spatial distances.

Adolescent↗

Resonance effects in the electron distribution function formation in spatially periodic fields in inert gases.

The calculations of the electron distribution function (EDF) in striationlike, sinusoidally modulated electric fields were performed to determine the dependence on spatial period length. The calculations were done for a discharge in neon at pR=2 Torr cm, i/R=5 mA/cm, and electric field E/p=1.9 V cm(-1) Torr(-1). The presence of the resonances in the EDF and macroscopic parameters has been demonstrated. These resonances correspond to S and P striations observed in experiments. An interpretation of the results is proposed based on an analytical approximation of the numerical solution. Decomposition of EDF into two factors-amplitude and body-is carried out. The amplitude of the EDF is shown to be resonantly dependent on the value of the spatial period. One maximum in the EDF is formed at the value of the spatial period corresponding to the S striation, and two maxima at the value which corresponds to the P striation. The experimental measurements of the EDF in S and P striations with high spatial resolution showed agreement between the theoretical and the experimental results. Resonance effects in the EDF formation are considered based on the linear theory in the weakly modulated electric fields.

Journal Article↗

Stability in a metapopulation model with density-dependent dispersal.

A spatially explicit metapopulation model with positive density-dependent migration is analysed. We obtained conditions under which a previously stable system can be driven to instability caused by a density-dependent migration mechanism. The stability boundary depends on the rate of increase of the number of migrants on each site at local equilibrium, on the intrinsic rate of increase at local level, on the number of patches, and on topological aspects regarding the connectivity between patches. A concrete example is presented illustrating the dynamics on the dispersal-induced unstable regime.

Animals↗

Neural mechanisms of spatial tactile discrimination: neural patterns evoked by braille-like dot patterns in the monkey.

1. The experiments reported here were designed to investigate the responses of cutaneous mechanoreceptive afferents to spatially configured dot patterns scanned across the skin. Braille-like patterns were selected because the discrimination of Braille characters must depend on spatial patterning rather than some other facet of the afferent discharge. 2. A multifactorial experimental design was used in which each afferent fibre was studied using every combination of six dot patterns, two dot sizes, two dot spacings, two contact forces and two scanning velocities. Two other factors, scanning direction relative to the skin ridges and intermittent versus continuous scanning, were studied. 3. Beside the general question concerning the response properties of the mechanoreceptive afferents, three major questions were addressed here. (i) What is the critical spatial dimension at which neural spatial patterning breaks down and below which tactual discrimination must depend on facets of the afferent discharge other than spatial neural patterning? (ii) Which mechanoreceptive population sets this critical dimension? (iii) Why is tactual discrimination enhanced by lateral scanning? 4. The results presented here suggest that the critical dimension, below which spatial neural patterning breaks down, is of the order of 1.0 mm and that the slowly adapting (SA) afferent fibres are responsible for this limit. 5. At dimensions above approximately 1.0 mm the spatial contrast between peaks and troughs in the SA discharge is markedly enhanced during scanning. When the skin is stationary the discharge rates in the SA population drop rapidly to low levels. A second possible reason for enhanced tactual discrimination during scanning is related to the increased spatiotemporal information in a coherent pattern of neural activity moving across a discrete population of afferent fibres. 6. The effects of variations in conduction velocity are analysed and it is shown that they place serious constraints on the transmission of spatiotemporal information.

Animals↗