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Birthdates of neurons in the retinal ganglion cell layer of the ferret.

The present study determined the temporal and spatial patterns of genesis for neurons of different sizes in the retinal ganglion cell layer of the ferret. Fetal ferrets were exposed to tritiated thymidine on embryonic days E-22 through E-36. One to 3 months after birth, they were perfused and their retinae dissected, and autoradiographs were prepared from resin-embedded sections throughout the entire flattened retinal ganglion cell layer. Soma size differences in conjunction with separate retrograde labeling and calbindin immunocytochemical studies were used as criteria for identifying different retinal ganglion cell subtypes in juvenile and adult ferrets. Neurons of different sizes in the ganglion cell layer were generated at different stages during development. Medium sized cells were generated primarily between E-22 and E-26; the largest cells were generated between E-24 and E-29; small cells were generated between E-26 and E-32; and very small cells were generated between E-29 and E-36. The former three groups were interpreted to be three subtypes of retinal ganglion cells, while the latter group was interpreted to be displaced amacrine cells. This temporal order of the genesis of ganglion cell classes is consistent with the spatial ordering of their fibers in the mature optic chiasm and tract, and it is consistent with the developmental change in decussation pattern recently shown in the optic pathway of embryonic ferrets. The spatial pattern of genesis suggests that ganglion cells of a particular class are added to the ganglion cell layer in a centroperipheral fashion initiated in the dorsocentral retina nasal to the area centralis. No evidence was found for a wave of ganglion cell addition that proceeded in a spiralling pattern around the area centralis, as has been reported in the cat.

Animals↗

Spatial analysis and eutrophication assessment for chlorophyll a in Taihu Lake.

Spatial structure analysis and kriging analysis have been identified to be useful tools in illustrating the spatial patterns of variables. Taihu Lake is one of the largest fresh water lakes in China, and has suffered serious eutrophication in recent years due to the rapid economic development and growing environmental pollution in the Taihu Catchment. In this paper, spatial structural analysis, kriging interpolation and eutrophication assessment were carried out for chlorophyll a in the lake. Studies show that spherical model could be applied to fit all experimental variograms. Positive nuggets were observed for three directions except NE-SW direction. The variograms show some anisotropy with anisotropic ratio falling within 1.76. The spatial structural patterns of chlorophyll a in the lake were affected by factors such as distribution of pollution sources, water flow and wind. Two-dimensional ordinary block kriging was applied for interpolation process. An eutrophication assessment map was also made based on a water-quality evaluation standard. Results show that the content of chlorophyll a in Taihu Lake was quite high. The whole lake has suffered serious eutrophication. However, the eutrophic situation varied in space. Higher contents of chlorophyll a appeared mainly in the northern part of the lake.

China↗

Mesoscopic neurodynamics: from neuron to brain.

Intelligent behavior is characterized by flexible and creative pursuit of endogenously defined goals. Intentionality is a key concept by which to link neuron and brain to goal-directed behavior through brain dynamics. An archetypal form of intentional behavior is an act of observation in space-time, by which information is sought for the guidance of future action to explore unpredictable and ever-changing environments. These acts are based in the brain dynamics that creates spatiotemporal patterns of neural activity, serving as images of goals, of command sequences by which to act to reach goals, and of expected changes in sensory input resulting from intended actions. Prediction of the sensory consequences of intended action and evaluation of performance is by reafference. An intentional act is completed upon modification of the system by itself through learning. These principles are well known among psychologists and philosophers. What is new is the development of nonlinear mesoscopic brain dynamics, by which the theory of chaos can be used to understand and simulate the constructions of meaningful patterns of neural activity that implement the process of observation. The design of neurobiological experiments, analysis of the resulting data, and synthesis of explanatory models require an understanding of the hierarchical nature of brain organization, here conceived as single neurons and neural networks at the microscopic level; clinically defined cortical and subcortical systems studied by brain imaging (for example, fMRI) at the macroscopic level, and self-organizing neural populations at an intermediate mesoscopic level, at which synaptic interactions create novel activity patterns through nonlinear state transitions. The constructive neurodynamics of sensory cortices, when they are engaged in pattern recognition, is revealed by learning-dependent spatial patterns of amplitude modulation and by newly discovered radially symmetric spatial gradients of the phase of aperiodic carrier waves in multichannel subdural EEG recordings.

Animals↗

Spatial ecological and genetic structure of a mixed population of sexual diploid and apomictic triploid dandelions.

Ecological differentiation is widely seen as an important factor enabling the stable coexistence of closely related plants of different ploidy levels. We studied ecological and genetic differentiation between co-occurring sexual diploid and apomictic triploid Taraxacum section Ruderalia by analysing spatial patterns both in the distribution of cytotypes and in the distribution of genetic variation within and between the cytotypes. A significant relationship between ploidy level and elevation was found. This mode of ecological differentiation however, was not sufficient to explain the significant spatial structure in the distribution of diploids and triploids within the population. Strong congruence was found between the spatial genetic patterns within the diploids and within the triploids. We argue that this congruence is an indication of gene flow between neighbouring plants of different ploidy levels.

Demography↗

A focusing image probe for assessing neural activity in vivo.

We describe a compact, focusing image probe to record rapid optical changes from neural tissue. A gradient index (GRIN) lens served as a relay lens from tissue to a microscope objective which projected an image onto a CCD camera. The microscope objective and camera assembly was adjusted independently from the GRIN lens, allowing focus changes without disturbing the probe/tissue interface; firm contact minimized movement and specular reflectance. Fiber optics around the probe perimeter provided diffuse illumination from a 780 nm laser, or 660 and 560 nm light emitting diodes. To characterize depth-of-field, we imaged a black suture through increasing tissue thicknesses. Light modulation by the suture remained detectable down to 900 microm using 780 nm illumination. We acquired images from cardiorespiratory areas of the rat dorsal medulla, at different depths and illumination wavelengths. Images illuminated at 560 nm were dominated by vasculature flow patterns, while 660 nm illumination revealed different spatial patterns which preceded vascular flow by 40 ms and may represent cardiac-related neural activity. Using 780 nm light, image sequences triggered by the cardiac R-wave showed vascular perfusion changes with delayed and broader responses at deeper levels. Electrical stimulation within the vagal bundle caused fast optical changes which track the electrical response, with a different spatial distribution from hemodynamic signals.

Animals↗

Ecological covariates of Ascaris lumbricoides infection in schoolchildren from rural KwaZulu-Natal, South Africa.

OBJECTIVES: To identify environmental factors that could serve to predict Ascaris lumbricoides infection patterns and thus guide control efforts in the absence of epidemiological information; to assess whether A. lumbricoides infection is positively associated with the soil clay content. METHODS: Information on A. lumbricoides infection and re-infection in a cohort of primary schoolchildren and interview data on their socioeconomic background and behaviour were combined with environmental data using a geographical information system (GIS). Multivariate models served to explore the covariation of environmental and infection patterns adjusted for possible confounders. RESULTS: Prevalence maps and spatial statistics revealed considerable spatial clustering of infection in the small study area. Logistic multivariate regression models showed strong positive associations of infection with vegetation density measured as the normalized difference vegetation index (NDVI) at baseline [odds ratio (OR) for a 10% increase: 1.82; 95% confidence interval (95% CI): 1.24-2.68; P=0.002] and after re-infection (OR: 2.22; 95% CI: 1.71-2.87; P<0.001). We also found a strong negative association of re-infection with the sun exposure of the soil surface as estimated from digital elevation models (OR: 0.78; 95% CI: 0.88; P<0.001). The soil clay content was only moderately positively associated with infection and re-infection. Socioeconomic and behavioural variables, although correlated with A. lumbricoides infection, did not appear to confound the above associations in the demographically homogeneous study area. Spatial analysis of the model residuals suggested that as the models accounted for most of the spatial pattern, the model standard errors should not be affected by spatial clustering. CONCLUSION: NDVI seems to have a high potential for the prediction of A. lumbricoides infection as it was strongly associated with infection patterns in the study area. Further advantages are that NDVI information is easy to use, affordable and available with global coverage.

Aluminum Silicates↗

Atmospheric nitrogen in the Mississippi River Basin--emissions, deposition and transport.

Atmospheric deposition of nitrogen has been cited as a major factor in the nitrogen saturation of forests in the north-eastern United States and as a contributor to the eutrophication of coastal waters, including the Gulf of Mexico near the mouth of the Mississippi River. Sources of nitrogen emissions and the resulting spatial patterns of nitrogen deposition within the Mississippi River Basin, however, have not been fully documented. An assessment of atmospheric nitrogen in the Mississippi River Basin was therefore conducted in 1998-1999 to: (1) evaluate the forms in which nitrogen is deposited from the atmosphere; (2) quantify the spatial distribution of atmospheric nitrogen deposition throughout the basin; and (3) relate locations of emission sources to spatial deposition patterns to evaluate atmospheric transport. Deposition data collected through the NADP/NTN (National Atmospheric Deposition Program/National Trends Network) and CASTNet (Clean Air Status and Trends Network) were used for this analysis. NOx Tier 1 emission data by county was obtained for 1992 from the US Environmental Protection Agency (Emissions Trends Viewer CD, 1985-1995, version 1.0, September 1996) and NH3 emissions data was derived from the 1992 Census of Agriculture (US Department of Commerce. Census of Agriculture, US Summary and County Level Data, US Department of Commerce, Bureau of the Census. Geographic Area series, 1995:1b) or the National Agricultural Statistics Service (US Department of Agriculture. National Agricultural Statistics Service Historical Data. Accessed 7/98 at URL, 1998. http://www.usda.gov/nass/pubs/hisdata++ +.htm). The highest rates of wet deposition of NO3- were in the north-eastern part of the basin, downwind of electric utility plants and urban areas, whereas the highest rates of wet deposition of NH4+ were in Iowa, near the center of intensive agricultural activities in the Midwest. The lowest rates of atmospheric nitrogen deposition were on the western (windward) side of the basin, which suggests that most of the nitrogen deposited within the basin is derived from internal sources. Atmospheric transport eastward across the basin boundary is greater for NO3- than NH4+, but a significant amount of NH4+ is likely to be transported out of the basin through the formation of (NH4)2SO4 and NH4NO3 particles--a process that greatly increases the atmospheric residence time of NH4+. This process is also a likely factor in the atmospheric transport of nitrogen from the Midwest to upland forest regions in the North-East, such as the western Adirondack region of New York, where NH4+ constitutes 38% of the total wet deposition of N.

Air Pollutants↗

Electrosensory maps form a substrate for the distributed and parallel control of behavioral responses in weakly electric fish.

Electroreceptors, distributed over the body surface of weakly electric fish, code the local amplitude and phase, or timing of zerocrossing, of the animal's electric signals. These signals are generated by rhythmic discharges of the electric organ and form a dipole-like field around the animal. This field is perturbed by interference with electric fields of other fish as well as by the appearance of objects electrically different from water. The spatial and temporal structure of such perturbations can be interpreted as the electric image of interfering fields and moving objects. This strategy of assessing the environment is called 'electrolocation', a form of 'seeing' with the body surface. Electric images are analyzed in somatotopically ordered strata of neurons within the central nervous system. Primary electrosensory afferents project to somatotopically ordered layers of higher-order neurons in the electrosensory lateral line lobe (ELL) of the hindbrain. Phase and amplitude information are processed in separate layers of the ELL. The phase of the signal in a given region of the body surface is coded by the timing of spikes of spherical cells marking the zerocrossings of the electric signal. This phase information is relayed to lamina 6 of the torus semicircularis of the midbrain. Rises and falls in local amplitude are coded by the activity of different pyramidal cell types, E- and I-units, which project to various laminae of the torus above and below lamina 6. The somatotopic organization of the torus allows for computations of spatial patterns in electrosensory information. Within lamina 6, differences in the phase of signals from different parts of the body surface are computed. Differential-phase information is then relayed to deeper laminae of the torus and remains in topographic register with amplitude information. This organization allows for joint evaluation of spatially related patterns of amplitude and phase modulations on the animal's body surface within local neuronal circuits of the torus. A topographic projection of the torus relays amplitude and differential-phase information to the optic tectum where a further joint evaluation of amplitude and phase serves to control behavioral responses. The control of a particular behavioral performance, the 'jamming avoidance response', is of a distributed nature in that the representations of individual sites on the body surface contribute cumulatively to shift the electric organ pacemaker frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Habitat selection and population regulation in temporally fluctuating environments.

Understanding and predicting the distribution of organisms in heterogeneous environments lies at the heart of ecology, and the theory of density-dependent habitat selection (DDHS) provides ecologists with an inferential framework linking evolution and population dynamics. Current theory does not allow for temporal variation in habitat quality, a serious limitation when confronted with real ecological systems. We develop both a stochastic equivalent of the ideal free distribution to study how spatial patterns of habitat use depend on the magnitude and spatial correlation of environmental stochasticity and also a stochastic habitat selection rule. The emerging patterns are confronted with deterministic predictions based on isodar analysis, an established empirical approach to the analysis of habitat selection patterns. Our simulations highlight some consistent patterns of habitat use, indicating that it is possible to make inferences about the habitat selection process based on observed patterns of habitat use. However, isodar analysis gives results that are contingent on the magnitude and spatial correlation of environmental stochasticity. Hence, DDHS is better revealed by a measure of habitat selectivity than by empirical isodars. The detection of DDHS is but a small component of isodar theory, which remains an important conceptual framework for linking evolutionary strategies in behavior and population dynamics.

Animals↗

Distribution of GABAergic neurons and axon terminals in the macaque striate cortex.

Antisera to glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) have been used to characterize the morphology and distribution of presumed GABAergic neurons and axon terminals within the macaque striate cortex. Despite some differences in the relative sensitivity of these antisera for detecting cell bodies and terminals, the overall patterns of labeling appear quite similar. GABAergic axon terminals are particularly prominent in zones known to receive the bulk of the projections from the lateral geniculate nucleus; laminae 4C, 4A, and the cytochrome-rich patches of lamina 3. In lamina 4A, GABAergic terminals are distributed in a honeycomb pattern which appears to match closely the spatial pattern of geniculate terminations in this region. Quantitative analysis of axon terminals that contain flat vesicles and form symmetric synaptic contacts (FS terminals) in lamina 4C beta and in lamina 5 suggest that the prominence of GAD and GABA axon terminal labeling in the geniculate recipient zones is due, at least in part, to the presence of larger GABAergic axon terminals in these regions. GABAergic cell bodies and their initial dendritic segments display morphological features characteristic of nonpyramidal neurons and are found in all layers of striate cortex. The density of GAD and GABA immunoreactive neurons is greatest in laminae 2-3A, 4A, and 4C beta. The distribution of GABAergic neurons within lamina 3 does not appear to be correlated with the patchy distribution of cytochrome oxidase in this region; i.e., there is no significant difference in the density of GAD and GABA immunoreactive neurons in cytochrome-rich and cytochrome-poor regions of lamina 3. Counts of labeled and unlabeled neurons indicate that GABA immunoreactive neurons make up at least 15% of the neurons in striate cortex. Layer 1 is distinct from the other cortical layers by virtue of its high percentage (77-81%) of GABAergic neurons. Among the other layers, the proportion of GABAergic neurons varies from roughly 20% in laminae 2-3A to 12% in laminae 5 and 6. Finally, there are conspicuous laminar differences in the size and dendritic arrangement of GAD and GABA immunoreactive neurons. Lamina 4C alpha and lamina 6 are distinguished from the other layers by the presence of populations of large GABAergic neurons, some of which have horizontally spreading dendritic processes. GABAergic neurons within the superficial layers are significantly smaller and the majority appear to have vertically oriented dendritic processes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Late detection of breast and colorectal cancer in Minnesota counties: an application of spatial smoothing and clustering.

Cancers detected at a later disease stage are associated with significantly higher mortality risk. Lack of uniformity in county-level cancer detection rates is thus of substantial interest to state health departments and other public health professionals. In this paper, we perform several spatial analyses of breast and colorectal cancer detection data for Minnesota counties for 1995-1997. We look for outliers and clusters in the late detection rates using a number of techniques: (i). applying various mapping schemes, (ii). smoothing the data using Bayesian methods implemented via Markov chain Monte Carlo, and (iii). applying maximum likelihood techniques to test for the presence of clusters and to identify the most likely clustersOur results suggest a fairly uniform spatial pattern in both sets of detection rates. Spatially smoothed rates did not reveal clusters of counties with significantly higher late detection risk, nor were county-level covariates (such as income, education, and race) particularly helpful in explaining the rates. However, our spatial clustering approach (using the scan statistic) did produce statistically significant clusters of counties which may indicate differences of practical importance for public health.

Bayes Theorem↗

Spatial and temporal patterns of deoxyribonucleic acid synthesis and mitosis in the endometrial stroma during decidualization in the pseudopregnant rat.

A quantitative study was made of the spatial patterns of stromal cell mitosis and DNA synthesis in the endometrium of the pseudopregnant rat before and during decidualization. A colchicine block was used for mitotic counts, and DNA synthesis was studied by [3H] thymidine autoradiography. Observations were also made on the subsequent fates of [3H] thymidine-labeled stromal cells. Before the onset of decidualization, on Days 3 and 4 (vaginal cornification = Day 0), mitosis was largely confined to the subepithelial stroma along the sides and around the antimesometrial pole of the lumen. [3H] thymidine labeling and stromal mitosis following a decidualizing stimulus at noon on Day 4 of pseudopregnancy were first seen close to the uterine lumen, with subsequent spread to deeper layers of the endometrium. At noon on Day 5, mitotic figures were numerous on all sides of the lumen and at all depths in the endometrium. At later stages, mitosis and the development of polyploidy continued in the decidual tissue, but little DNA synthesis or mitosis occurred in the basal zone of the stroma adjacent to the myometrium. In this zone, many cells in animals given [3H] thymidine 18 to 24 h after induction of decidualization remained heavily labeled throughout the growth and regression of deciduomata. Labeled cells derived from the basal zone and outer edge of the decidual capsule were present in the stroma of the regenerated endometrium following the regression of deciduomata. It was concluded that although cells at all depths in the endometrial stroma undergo DNA synthesis and mitosis in the early stages of response to a decidualizing stimulus, their subsequent behavior and fate depend upon their position in the endometrium.

Animals↗

Comparison of time-delayed feedback schemes for spatiotemporal control of chaos in a reaction-diffusion system with global coupling.

Time-delayed feedback control for stabilizing time periodic spatial patterns is investigated in a generic reaction-diffusion system with global coupling. We focus on the case of low-dimensional chaos where unstable patterns admit only a single unstable mode. Spatial degrees of freedom are taken into account to define different control schemes. The efficiency of these schemes is discussed, where control forces are motivated by physical requirements as well as by the possibility of obtaining analytically exact results. We find that control schemes that contain the full feedback of the inhibitor variable may finally destroy the control performance. Thus schemes that omit the inhibitor might be more efficient. Our numerical findings are explained in terms of Floquet spectra and compared with analytical solutions of particular coupling schemes.

Journal Article↗

The dynamics of the cat retinal X cell centre.

1. The dynamics of the centre mechanism of individual cat X retinal ganglion cells is investigated. The visual stimuli consist of temporal contrast modulation of stationary patterns. In order to study the response of the centre mechanism, patterns were either sine gratings of high spatial frequency or small circular spots positioned over the receptive-field centre. 2. Responses to contrast reversal are approximately linear. However, as the modulation depth of the stimulus increases, responses become more transient. Ganglion cell responses show this phenomenon at moderate contrasts (e.g. 0.1), which do not elicit discharges that approach the maximum firing rate of the ganglion cell. 3. A sequence of dynamical models are constructed from responses elicited by sum-of-sinusoids modulation of the spatial pattern. The first model is strictly linear. It consists of a series of low-pass filters and a single high-pass filter. The linear model predicts the approximate shape of the step response, but does not account for the change in shape of the response as a function of modulation depth. 4. The second model, a quasi-linear model, allows the 'linear' dynamics to vary slowly with a neural measure of contrast. The main effect of high contrast is a shorter time constant in the high-pass filter. This model accounts qualitatively for the increased transience of the response, but fails to predict the magnitude of the effect at higher modulation depths. 5. In the third model, the transfer characteristics of the centre response adjust rapidly as contrast changes. This intrinsically non-linear model provides excellent agreement with observed response to steps and more complex modulation patterns. 6. The non-linearity necessitated by a voltage-to-spikes transduction is analysed quantitatively. In most ganglion cells, a simple truncation at 0 impulses/s (and no saturation) explains the changes in apparent gain and mean firing rate that occur as modulation depth is increased. A non-linear voltage-to-spike transduction per se cannot account for the observed effect of contrast on dynamics. 7. The parameters of the dynamical model are measured for a population of twenty-seven X ganglion cells (nineteen on-centre and eight off-centre). The low-pass stage and the strength of the high-pass stage are relatively uniform across the population. The over-all gain and the dynamics of the high-pass stage vary substantially across the population, but show no consistent dependence on the on-off distinction or on retinal location. Some implications of this variability for retinal function are discussed.

Action Potentials↗

Relationship between growth and the pattern of tooth initiation in alligator embryos.

The temporal and spatial patterns in which teeth are initiated in the growing jaws of embryos are constant for a species but different for different species. The sources of the patterns have been explained in two ways. First, they are the outcome of reactions between molecules created at stationary targets and those which diffuse through embryonic tissues (e.g., Edmund, 1960). Second, Osborn (1978) supposed that the patterns mirror the way a (mixed) population of parent cells, the tooth clone, grows. Westergaard and Ferguson (1986, 1987, 1990) concluded, from their observations of the sequence of tooth initiation in alligators, that the complicated sequences in which 20 teeth are initiated in each tooth quadrant could not be explained by jaw growth. The present study attempts to refute this criticism by means of measurements made from the raw data published by Westergaard and Ferguson. These data reveal that new teeth, here called primary teeth, are added at a constant rate at the back of the jaw. Interstitial growth of the cells between primary teeth creates space for secondary teeth in secondary regions. The secondary regions increase in length exponentially with time. The sequence in which teeth are initiated in the growing secondary regions was found to be the same in every part of the upper and lower jaws. It was accurately reproduced by a computer program based on a linear contraction rate of inhibitory zones and exponential growth of secondary regions. The results suggest that the posterior progress zone in alligator embryos grows about 125 microm a day. Newly initiated tooth germs are surrounded by an inhibitory zone about 250 microm in diameter. These zones contract from 20 to 30 microm a day until they are about 170 microm in diameter. The sequences in which tooth positions are initiated in embryos may be more the result of the pattern in which cells escape from molecules that inhibit induction rather than the pattern in which cells create molecules that initiate induction.

Alligators and Crocodiles↗

Purification of a soluble glycoprotein from the uncalcified ecdysial cuticle of the blue crab Callinectes sapidus and its possible role in initial mineralization.

A heavily glycosylated soluble protein was purified using a combination of lectin affinity and size exclusion chromatography from a soluble extract of uncalcified dorsal cuticle of blue crab Callinectes sapidus removed at ecdysis. Similarities in apparent molecular mass and carbohydrate composition suggest that this protein is the same species previously shown to disappear from soluble extracts coincidentally with the onset of mineral deposition in the newly exposed post-molt cuticle. The amino acid sequence of the N-terminal portion of the core polypeptide was determined and polyclonal antibodies were raised against both the purified glycoprotein and the peptide. Immunoblots of unfractionated soluble extracts taken at various times post-molt illustrated that the anti-peptide antibody recognized several polypeptides with electrophoretic mobilities that differ from the purified glycoprotein. These bands may be deglycosylation products which would not have been purified due to different lectin affinity or size. Immunohistochemical analysis indicated uniform protein distribution in the exocuticle at ecdysis, but decreased antibody binding at the interprismatic septa by 2 h post-molt. The location of the protein is therefore the negative image of the calcification pattern in the exocuticle and provides a spatial pattern to correlate with the previously reported temporal events. This strengthens the hypothesis that the glycoprotein under investigation is an inhibitor of calcite nucleation or of initial amorphous calcium carbonate accumulation.

Amino Acid Sequence↗

[Access to hospitalization in Brazilian municipalities in 2000: territorial distribution in the Unified National Health System].

This article investigates the effect of external factors on hospitalization patterns in Brazilian municipalities (or counties): supply, spatial configuration, socioeconomic aspects, and political context. Inpatient data from 2000 for individuals 15 years and over and most frequent hospital procedures, obtained from the National Hospital Information System (SIH-SUS), were aggregated by place of residence at the municipal level. Nested generalized additive mixed models were fitted using Bayesian inference. Probability of hospitalization is shown to increase with hospital bed supply and with primary care and local capacity, and to decrease with increasing distances and in larger and wealthier municipalities. Inclusion of random, State, and spatial patterns effects reveals regional differences in the probability of hospitalization and the main factors explaining such different patterns.

Adolescent↗

Chronic vasodilation induces matrix metalloproteinase 9 (MMP-9) expression during microvascular remodeling in rat skeletal muscle.

OBJECTIVE: The process of microvessel growth and remodeling depends on the presence of matrix metalloproteinases (MMPs) in a specific spatial pattern of expression. This study characterizes the spatial distribution of metalloproteinase-9 (MMP-9) expression during microvascular remodeling in the rat spinotrapezius muscle. METHODS: Female Sprague-Dawley rats (4 weeks old) were administered the alpha1-adrenergic blocker prazosin for 7 days to induce chronic vasodilation and associated increases in capillary and arteriolar density. MMP-9 expression was analyzed by Western blotting analysis of microdissected regions of muscle and immunolabeling of muscle sections. RESULTS: Capillary density expressed as both capillary-to-fiber ratio (C/F) and capillaries per mm2 increased significantly (p < 0.01) due to prazosin administration. Western blotting on microdissected regions of spinotrapezius muscle showed that there was an increase in MMP-9 expression in prazosin-treated animals. Additionally, the Western blots showed a presence of the activated form of MMP-9 in regions of spinotrapezius muscle containing vessels on the order of capillaries and small arterioles. Immunohistochemistry demonstrated that MMP-9 significantly increased in the muscles of treated animals in areas within the vessel walls of microvessels greater than 20 microm in diameter. However, interstitial MMP-9 expression did not significantly increase with prazosin administration. CONCLUSIONS: These results demonstrate that the expression of MMP-9 increases during in vivo microvascular remodeling in adult skeletal muscle. The MMP-9 expression is limited to larger (>20-microm diameter) microvessels, suggesting a role for MMP-9 in the remodeling of such vessels during prazosin-induced vasodilation and the subsequent capillary proliferation.

Adrenergic alpha-Antagonists↗