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PubMed1996

Re-emergence of epidemic Venezuelan equine encephalomyelitis in South America. VEE Study Group.

BACKGROUND: Venezuelan equine encephalomyelitis (VEE) virus has caused periodic epidemics among human beings and equines in Latin America from the 1920s to the early 1970s. The first major outbreak since 1973 occurred in Venezuela and Colombia during 1995, and involved an estimated 75,000 to 100,000 people. We report an epidemiological and virological investigation of this epidemic. METHODS: Virus isolates were made in cell culture from human serum, human throat swabs, and brain tissue from aborted and stillborn human fetuses, as well as from horse brain tissue and pooled mosquito collections. Human sera were also tested for VEE-specific antibodies. The serotypes of VEE isolates were identified by antigen assays, and viruses were characterised genetically by sequencing PCR products generated from the E3 and E2 genes. Phylogenetic analyses were done to determine evolutionary relations with respect to previous epidemic/epizootic and enzootic VEE virus isolates. Mosquito collections were made to identify possible vectors, and clinical findings were determined by direct observation of patients visiting hospitals and clinics in affected regions, and by inspecting patient records. Equine vaccination and vector control were used in an attempt to halt the spread of the outbreak. FINDINGS: Most affected people had an acute, self-limited febrile illness of 3 to 4 days duration. However, convulsions were often seen in children, and abortions and fetal deaths occurred in pregnant women infected with VEE virus. Antigenic characterisation of 12 virus isolates spanning the temporal and spatial range of the outbreak indicated that all are VEE serotype IC. Phylogenetic analysis revealed that all of the 1995 viruses were closely related to serotype IC viruses isolated during a large VEE outbreak that occurred in the same regions of Colombia and Venezuela from 1962-1964. A 1983 mosquito isolate from north central Venezuela was also closely related to the 1995 isolates. INTERPRETATION: This outbreak was remarkably similar to one that occurred in same regions of Venezuela and Colombia during 1962-1964. Symptoms of infected patients, estimated mortality rates, meteorological conditions preceding the epidemic, and seasonal patterns of transmission were all very similar to those reported in the previous outbreak. In addition, viruses isolated during 1995 were antigenically and genetically nearly identifical to those obtained during 1962-1964. These findings suggest that the epidemic resulted from the re-emergence of an epizootic serotype IC VEE virus. Identification of a similar virus isolate in mosquitoes in Venezuela in 1983, 10 years after epidemic/epizootic VEE activity ceased, raises the possibility of a serotype IC enzootic transmission cycle in northern Venezuela.

Adolescent↗
PubMed1993

A fractal model of HIV transmission on complex sociogeographic networks: towards analysis of large data sets.

"A paradigm of HIV (human immunodeficiency virus) transmission along very large 'sociogeographic' networks--spatially focused nets of social interaction--is extended to include fractal (dilationally self-similar) structures upon which a metric of 'sociogeographic' distance can be defined.... Techniques are sketched for determining the sociogeographic structure of a large, geographically centered social network, providing a possible empirical basis for predicting forms and rates of spread of the initial, rapid stages of an HIV outbreak for networks not yet infected, and perhaps greatly expanding the utility of routinely collected small-area administrative data sets in the design of mutually reinforcing, multifactorial disease-control strategies."

Communicable Diseases↗
PubMed2006

Alpha-herpesvirus infection induces the formation of nuclear actin filaments.

Herpesviruses are large double-stranded DNA viruses that replicate in the nuclei of infected cells. Spatial control of viral replication and assembly in the host nucleus is achieved by the establishment of nuclear compartments that serve to concentrate viral and host factors. How these compartments are established and maintained remains poorly understood. Pseudorabies virus (PRV) is an alpha-herpesvirus often used to study herpesvirus invasion and spread in the nervous system. Here, we report that PRV and herpes simplex virus type 1 infection of neurons results in formation of actin filaments in the nucleus. Filamentous actin is not found in the nucleus of uninfected cells. Nuclear actin filaments appear physically associated with the viral capsids, as shown by serial block-face scanning electron micropscopy and confocal microscopy. Using a green fluorescent protein-tagged viral capsid protein (VP26), we show that nuclear actin filaments form prior to capsid assembly and are required for the efficient formation of viral capsid assembly sites. We find that actin polymerization dynamics (e.g., treadmilling) are not necessary for the formation of these sites. Green fluorescent protein-VP26 foci co-localize with the actin motor myosin V, suggesting that viral capsids travel along nuclear actin filaments using myosin-based directed transport. Viral transcription, but not viral DNA replication, is required for actin filament formation. The finding that infection, by either PRV or herpes simplex virus type 1, results in formation of nuclear actin filaments in neurons, and that PRV infection of an epithelial cell line results in a similar phenotype is evidence that F-actin plays a conserved role in herpesvirus assembly. Our results suggest a mechanism by which assembly domains are organized within infected cells and provide insight into how the viral infectious cycle and host actin cytoskeleton are integrated to promote the infection process.

Actin Cytoskeleton↗
PubMed1984

The role of the visual cortex in response properties of lateral geniculate cells in rats.

Unitary discharges of the lateral geniculate nucleus (LGN) were analyzed in anesthetized and paralyzed rats after inactivation of visual cortical areas (VC) by cryoblockade or by depositing a cotton wick soaked in KCl (3 M). The receptive fields were mapped prior to and following the interruption of the cortico-geniculate feedback. The responsiveness of the VC was controlled by monitoring evoked potentials and the EEG. In most off-center and about half on-center cells the surround excitatory responses were markedly reduced and even totally abolished. In contrast, the center excitation remained unchanged or increased suggesting a parallel decline of the inhibitory surround. This differential influence of cortical blockade on on- or off-responses failed to appear in on-off cells whose receptive field was nonconcentrically organized. It is proposed that the VC exerts a complex influence upon geniculate physiology while the spatial center-surround relationships are under the control of the VC. The results of this investigation are comparable to those obtained in rabbits and cats.

Animals↗
PubMed2001

Phase transitions and oscillations in a lattice prey-predator model.

A coarse grained description of a two-dimensional prey-predator system is given in terms of a simple three-state lattice model containing two control parameters: the spreading rates of prey and predator. The properties of the model are investigated by dynamical mean-field approximations and extensive numerical simulations. It is shown that the stationary state phase diagram is divided into two phases: a pure prey phase and a coexistence phase of prey and predator in which temporal and spatial oscillations can be present. Besides the usual directed percolationlike transition, the system exhibits an unexpected, different type of transition to the prey absorbing phase. The passage from the oscillatory domain to the nonoscillatory domain of the coexistence phase is described as a crossover phenomena, which persists even in the infinite size limit. The importance of finite size effects are discussed, and scaling relations between different quantities are established. Finally, physical arguments, based on the spatial structure of the model, are given to explain the underlying mechanism leading to local and global oscillations.

Journal Article↗
PubMed2005

Systematic spatial analysis of gene expression during wheat caryopsis development.

The cereal caryopsis is a complex tissue in which maternal and endosperm tissues follow distinct but coordinated developmental programs. Because of the hexaploid genome in wheat (Triticum aestivum), the identification of genes involved in key developmental processes by genetic approaches has been difficult. To bypass this limitation, we surveyed 888 genes that are expressed during caryopsis development using a novel high-throughput mRNA in situ hybridization method. This survey revealed novel distinct spatial expression patterns that either reflected the ontogeny of the developing caryopsis or indicated specialized cellular functions. We have identified both known and novel genes whose expression is cell cycle-dependent. We have identified the crease region as important in setting up the developmental patterning, because the transition from proliferation to differentiation spreads from this region to the rest of the endosperm. A comparison of this set of genes with the rice (Oryza sativa) genome shows that approximately two-thirds have rice counterparts but also suggests considerable divergence with regard to proteins involved in grain filling. We found that the wheat genes had significant homology with 350 Arabidopsis thaliana genes. At least 25 of these are already known to be essential for seed development in Arabidopsis, but many others remain to be characterized.

Cell Cycle↗
PubMed2005

Nitric oxide release is induced by dopamine during illumination of the carp retina: serial neurochemical control of light adaptation.

Several lines of indirect evidence have suggested that nitric oxide may play an important role during light adaptation of the vertebrate retina. We aimed to verify directly the effect of light on nitric oxide release in the isolated carp retina and to investigate the relationship between nitric oxide and dopamine, an established neuromodulator of retinal light adaptation. Using a biochemical nitric oxide assay, we found that steady or flicker light stimulation enhanced retinal nitric oxide production from a basal level. The metabotropic glutamate receptor agonist L-amino-4-phosphonobutyric acid, inhibited the light adaptation-induced nitric oxide production suggesting that the underlying cellular pathway involved centre-depolarizing bipolar cell activity. Application of exogenous dopamine to retinas in the dark significantly enhanced the basal production of nitric oxide and importantly, inhibition of endogenous dopaminergic activity completely suppressed the light-evoked nitric oxide release. The effect of dopamine was mediated through the D1 receptor subtype. Imaging of the nitric oxide-sensitive fluorescent indicator 4,5-diaminofluorescein di-acetate in retinal slices revealed that activation of D1 receptors resulted in nitric oxide production from two main spatial sources corresponding to the photoreceptor inner segment region and the inner nuclear layer. The results taken together would suggest that during the progression of retinal light adaptation there is a switch from dopaminergic to nitrergic control, probably to induce further neuromodulatory effects at higher levels of illumination and to enable more efficient spreading of the light adaptive signal.

Adaptation, Ocular↗
PubMed2006

Discovering spatio-temporal models of the spread of West Nile virus.

Emerging infectious diseases are characterized by complex interactions among disease agents, vectors, wildlife, humans, and the environment. Since the appearance of West Nile virus (WNV) in New York City in 1999, it has infected over 8,000 people in the United States, resulting in several hundred deaths in 46 contiguous states. The virus is transmitted by mosquitoes and maintained in various bird reservoir hosts. Its unexpected introduction, high morbidity, and rapid spread have left public health agencies facing severe time constraints in a theory-poor environment, dependent largely on observational data collected by independent survey efforts and much uncertainty. Current knowledge may be expressed as a priori constraints on models learned from data. Accordingly, we applied a Bayesian probabilistic relational approach to generate spatially and temporally linked models from heterogeneous data sources. Using data collected from multiple independent sources in Maryland, we discovered the integrated context in which infected birds are plausible indicators for positive mosquito pools and human cases for 2001 and 2002.

Animals↗
PubMed2000

An improved method for rapid objective measurement of gamma camera resolution.

An improved method for an easy, rapid measurement of the intrinsic spatial resolution of a gamma camera is presented. A simplified model was previously developed based solely on mean and standard deviation measurements taken from a region of interest in bar pattern images. This led to an estimate of the modulation transfer function and the full width at half maximum (FWHM) of a line spread function (LSF). The improved method involved expanding the simplified model to incorporate input modulation, square wave input versus the assumed sinusoidal input, aperture (pixel) size, and scatter from the plastic in the bar pattern. The input square wave modulation was calculated to be unity for the typical bar patterns used for gamma camera quality control assessment. For the typical range of bar sizes available, in combination with the typical resolving capabilities of gamma cameras, the sinusoidal approximation of the bar pattern was found to be valid (<1% contribution to the measured resolution from higher harmonic frequencies present in a square wave input with an effective input modulation greater than unity by a factor of 4/pi). The aperture correction factor was calculated for numerous bar and pixel size combinations. Applying the aperture correction factor results in an improvement in the accuracy of the calculated FWHM values, especially for large apertures (pixel sizes). For a camera with a specified FWHM value of 3.5 mm, the simplified model predicts values ranging from 3.2 to 4.1 mm, when the acquisition matrix varies from 128(2) to 512(2). When the expanded model is used with the aperture correction applied, this range was reduced to 3.6-3.9 mm. The scatter correction further improved the calculated FWHM (from 3.6 to 3.8 mm). It is suggested that the expanded model should be used when more accurate measurements are desired, such as in acceptance testing.

Algorithms↗
PubMedDate not supplied

Phase effects in diagnostic radiological images.

The effect of phase on the quality of diagnostic radiological images is investigated on a theoretical basis and with the use of the computer simulations. Phase effects are divided into two categories: linear phase shift and asymmetric phase shift. Using a model of the x-ray focal spot distribution composed of two Gaussian functions, it is shown that the phase transfer function (PTF) is generally a continuous nonlinear function of spatial frequency. The linear phase shift serves only to shift the location of the image. The asymmetric phase shift in the model studied tends to accompany an improvement in the modulation transfer function (MTF) in the midfrequency region while introducing "wows" into the image. Contrast reversals are shown to be inherent in line spread functions (LSFs) which do not necessarily include linear or asymmetric phase effects, i.e., they are the result of another phenomenon.

Mathematics↗
PubMedDate not supplied

Microdensitometry using a slide projector.

We have evaluated a simple microdensitometer concept by Stanton et al. for measurements of dose distributions with high spatial resolution. A magnified image of the film is created by a slide projector and its light intensity measured with a photomultiplier with a small aperture. The projector is placed on a movable stage to allow scanning of the film. A resolution of 17 micron (full width at half maximum of the line spread function) was achieved in the film plane.

Absorptiometry, Photon↗
PubMed2006

Action potentials induce uniform calcium influx in mammalian myelinated optic nerves.

The myelin sheath enables saltatory conduction by demarcating the axon into a narrow nodal region for excitation and an extended, insulated internodal region for efficient spread of passive current. This anatomical demarcation produces a dramatic heterogeneity in ionic fluxes during excitation, a classical example being the restriction of Na influx at the node. Recent studies have revealed that action potentials also induce calcium influx into myelinated axons of mammalian optic nerves. Does calcium influx in myelinated axons show spatial heterogeneity during nerve excitation? To address this, we analyzed spatial profiles of axonal calcium transients during action potentials by selectively staining axons with calcium indicators and subjected the data to theoretical analysis with parameters for axial calcium diffusion empirically determined using photolysis of caged compounds. The results show surprisingly that during action potentials, calcium influx occurs uniformly along an axon of a fully myelinated mouse optic nerve.

Action Potentials↗
PubMed2003

Optical analysis of depolarization waves in the embryonic brain: a dual network of gap junctions and chemical synapses.

Correlated neuronal activity plays a fundamental role in the development of the CNS. Using a multiple-site optical recording technique with a voltage-sensitive dye, we previously described a novel type of depolarization wave that was evoked by cranial or spinal nerve stimulation and spread widely over the whole brain region in the chick embryo. We have now investigated developmental expression and neuronal network mechanisms of this depolarization wave by applying direct stimulation to the brain stem or upper cervical cord of E5-E11 embryos, which elicited wave activity similar to that evoked by nerve stimulation. Spatial distribution patterns of the depolarization wave changed dynamically with development, and this change appeared to be related to the regional differences in neuronal differentiation. The depolarization wave was completely eliminated by application of either gap junction blockers or an N-methyl-D-aspartate (NMDA)-receptor antagonist, indicating that functions of both gap junctions and NMDA receptors are indispensable for wave propagation. A possible interpretation of the results is that dual networks of gap junctions and chemical synaptic coupling mediate large-scale depolarization waves in the developing chick CNS.

Animals↗
PubMed2002

High-speed VSD imaging of visually evoked cortical waves: decomposition into intra- and intercortical wave motions.

In the pond turtle, Pseudemys scripta elegans, visually evoked cortical waves propagate at different velocities within the primary visual area compared with waves that pass into the secondary visual area. In an effort to separate intra- and intercortical wave motions, movies of visually evoked cortical waves recorded by high-speed voltage-sensitive dye (VSD) imaging were subjected to Karhunen-Loéve (KL) decomposition. This procedure decomposes the VSD movies into a series of basis images that capture different spatial patterns of coherent activity. Most of the energy of the compound wave motion (>95%) was captured by the three largest basis images, M(1,1), M(1,2), and M(2,1). Based on visual comparison with maps of wave front latency, KL basis image M(1,2) appears to capture the spread of depolarization within the primary visual area, whereas KL basis image M(2,1) appears to capture the spread of depolarization from the primary into the secondary visual area. The contribution of different basis images to the intra- and intercortical wave motions was tested by reconstructing the response using different combinations of KL basis images. Only KL basis images M(1,1) and M(1,2) were needed to reconstruct intracortical wave motion, while basis images M(1,1) and M(2,1) were needed to reconstruct intercortical wave motion. It was also found that the direction and speed of wave propagation could be deduced by visual inspection of the basis image projections on to the original data set. The relative advantage of KL decomposition for the analysis of complex wave motions captured by VSD imaging is discussed.

Animals↗
PubMed1994

Increased expression of tissue inhibitor of metalloproteinases (TIMP-I) and metallothionein in murine lungs after hyperoxic exposure.

Acute exposure to hyperoxia results in well-described pathophysiologic responses in the lungs, beginning with subtle, subcellular changes and ending with severe pulmonary inflammation and edema. The biologic events that underlie or accompany this injury are not well understood. Our previous studies in rabbits have shown that hyperoxia induces large increases in the mRNAs encoding metallothionein (MT) and the tissue inhibitor of metalloproteinases (TIMP-I). Here we report studies of hyperoxic lung injury in two strains of mouse that differ in their relative resistance to O2 toxicity. O2-sensitive (C57BL/6J) mice and O2-resistant (C3H/HeJ) mice were exposed to 100% O2 for up to 96 h. Lung mRNAs were assayed by primer extension and slot blot hybridization. By 72 h of hyperoxia, the sensitive strain showed large increases in MT-I, MT-II, and TIMP-I mRNAs. The resistant strain showed similar changes but with a 24-h delay. In situ hybridization demonstrated that hyperoxic lung injury was accompanied by obvious increases in TIMP-I and MT transcripts in cells surrounding arteries and large airways, where many inflammatory cells were localized. With prolonged exposure, hybridization to MT transcripts had spread throughout lung parenchyma. The two strains showed the same patterns of in situ hybridization for TIMP-I and MT transcripts but, as with the whole lung homogenates, followed a different time course. Corresponding increases in MT protein were shown to occur, using a cadmium binding assay and by immunohistochemistry. The strong spatial correlation between the presence of localized inflammation and increased TIMP-I and MT expression further supports the importance of TIMP-I and MT in acute lung injury.

Animals↗
PubMed2004

Ion channels and amino acid transporters support the growth and invasion of primary brain tumors.

The malignant growth of glial support cells causes gliomas, highly invasive, primary brain tumors that are largely resistant to therapy. Individual tumor cells spread by active cell migration, invading diffusely into the normal brain. This process is facilitated by Cl- channels that endow glioma cells with an enhanced ability to quickly adjust their shape and cell volume to fit the narrow and tortuous extracellular brain spaces. Once satellite tumors enlarge, their growth is limited by the spatial constraints imposed by the bony cavity of the skull and spinal column. Glioma cells circumvent this limitation by active destruction of peritumoral neural tissue through the release of glutamate, inducing peritumoral seizures and ultimately excitotoxic neuronal cell death. Hence, primary brain tumors support their unusual biology by taking advantage of ion channels and transporters that are designed to support ion homeostatic functions in normal brain.

Amino Acid Transport Systems↗
PubMed2001

The topography of tactile learning in humans.

The spatial distribution of learned information within a sensory system can shed light on the brain mechanisms of sensory-perceptual learning. It has been argued that tactile memories are stored within a somatotopic framework in monkeys and rats but within a widely distributed network in humans. We have performed experiments to reexamine the spread of tactile learning across the fingertips. In all experiments, subjects were trained to use one fingertip to discriminate between two stimuli. Experiment 1 required identification of vibration frequency, experiment 2 punctate pressure, and experiment 3 surface roughness. After learning to identify the stimuli reliably, subjects were tested with the trained fingertip, its first and second neighbors on the same hand, and the three corresponding fingertips on the opposite hand. As expected, for all stimulus types, subjects showed retention of learning with the trained fingertip. However, the transfer beyond the trained fingertip varied according to the stimulus type. For vibration, learning did not transfer to other fingertips. For both pressure and roughness stimuli, there was limited transfer, dictated by topographic distance; subjects performed well with the first neighbor of the trained finger and with the finger symmetrically opposite the trained one. These results indicate that tactile learning is organized within a somatotopic framework, reconciling the findings in humans with those in other species. The differential distribution of tactile memory according to stimulus type suggests that the information is stored in stimulus-specific somatosensory cortical fields, each characterized by a unique receptive field organization, feature selectivity, and callosal connectivity.

Adult↗
PubMed1988

Application of the equiweight analysis method for the evaluation of the origin of the N1 and N2 waves of visual evoked potentials.

The applicability of the equiweight analysis method was studied with a view to evaluating the position in depth of the two dominating waves of the visual evoked potentials, recorded from the scalp of human subjects upon the appearance of a sinusoidal grating. The stimulus spatial frequency was 2, 4, 8 or 16 c/deg and its contrast was 0.2 or 0.3. The data of the topographic studies confirm earlier observations that the N1 wave with latency of about 100 ms was localized medially with maximum in Oz, while the N2 wave with latency of about 150 ms was spread over a wider area of the scalp. The results of the equiweight analysis corresponded to the evidence of cortical origin of N1. The wide propagation of the N2 wave proved to be an obstacle for the applicability of the method, although it seems promising when the source of the visual evoked potential is limited in area.

Electrodes↗