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Genetic diversity and spread of Bovine leukaemia virus isolates in Argentine dairy cattle.

Effective tools for use in control programmes against bovine leukaemia virus (BLV) infections require insight into the relationship between the variant structure of the bovine leukaemia virus and the spatial-temporal interaction of isolates and hosts. Our study showed the presence of two types of BLV isolates - Australian and Argentine - in dairy herds from various parts of Central Argentina; these isolates were characterised by RFLP on PCR amplicons, and some of them were confirmed by sequencing. One genotype (Argentine) was present in all herds, and the Australian genotype was found in two herds. Phylogenetic analysis indicated four clusters. The first cluster was composed of the Argentine isolates and one from Brazil; the second was composed of several isolates found in European countries and one from Brazil; the third cluster was composed of BLV isolates found in Japan and Germany; the fourth cluster included American and Australian isolates and those from other countries. The comparison of a number of synonymous and non-synonymous nucleotide substitutions using various BLV genes revealed purifying selection, suggesting that molecular evolution occurred under some functional constraint.

Amino Acid Sequence↗

What do retinal müller (glial) cells do for their neuronal 'small siblings'?

Müller (radial glial) cells are the predominant glia of the vertebrate retina. They arise, together with rod photoreceptor cells, bipolar cells, and a subset of amacrine cells, from common precursor cells during a late proliferative phase. One Müller cell and a species-specific number of such neurons seem to form a columnar unit within the retinal tissue. In contrast, 'extracolumnar neurons' (ganglion cells, cone photoreceptor cells, horizontal cells, and another subset of amacrine cells) are born and start differentiation before most Müller cells are generated. It may be essential for such neurons to develop metabolic capacities sufficient to support their own survival, whereas late-born ('columnar') neurons seem to depend on a nursing function of their 'sisterly' Müller cell. Thus, out of the cell types within a retinal column it is exclusively the Müller cell that possesses the enzymes for glycogen metabolism. We present evidence that Müller cells express functional insulin receptors. Furthermore, isolated Müller cells rapidly hydrolyse glycogen when they are exposed to an elevated extracellular K+ ion concentration, a signal that is involved in the regulation of neuronal-glial metabolic cooperation in the brain. Müller cells are also thought to be essential for rapid and effective retinal K+ homeostasis. We present patch-clamp measurements on Müller cells of various vertebrate species that all demonstrate inwardly rectifying K+ channels; this type of channel is well-suited to mediate spatial buffering currents. A mathematical model is presented that allows estimation of Müller cell-mediated K+ currents. A simulation analysis shows that these currents greatly limit lateral spread of excitation beyond the borders of light-stimulated retinal columns, and thus help to maintain visual acuity.

Animals↗

Convergence results for contact branching processes.

The link between the multi-type contact birth process and the spatial deterministic S-->I epidemic is exploited to give convergence results for a multi-type Markovian contact branching process. Let U(t) be the position of furthest spread by time t in a specific direction. The asymptotic speed of translation of the distribution function of U(t) is derived and U(t)/t is shown to converge in probability to this speed.

Disease Outbreaks↗

Subjective hierarchies in spatial memory.

Two experiments investigated the structure of spatial memories. Subjects learned locations of objects in spatial layouts (Experiment 1) or locations of object names on maps (Experiment 2). Physical and perceptual boundaries were absent in these spatial arrays. Subjects then participated in three tasks: item recognition, in which the variable of interest was spatial priming; free and cued recall; and Euclidean distance estimation. Ordered-tree analysis of individual subjects' recall protocols produced hierarchical trees consistent with regularities in output order. Spatial priming and distance estimations depended on whether pairs of objects appeared in the same subtree or in different subtrees. These findings indicate that spatial memories have a hierarchical component, even when physical and perceptual boundaries are nonexistent. Priming also increased with depth of clustering in ordered trees. This result supports spreading-activation theories of retrieval but provides evidence against several "non-spreading-activation" theories.

Adult↗

How the retinal network reacts to epiretinal stimulation to form the prosthetic visual input to the cortex.

We considered the problem of determining how the retinal network may interact with electrical epiretinal stimulation in shaping the spike trains of ON and OFF ganglion cells, and thus the synaptic input to first-stage cortical neurons. To do so, we developed a biophysical model of the retinal network with nine stacked neuronal mosaics. Here, we describe the model's behavior under (i) electrical stimulation of a retina with complete cone photoreceptor loss, but an otherwise intact circuitry and (ii) electrical stimulation of a fully-functional retina. Our results show that electrical stimulation alone results in indiscriminate excitation of ON and OFF ganglion cells and a patchy input to the cortex with islands of excitation among regions of no net excitation. Activation of the retinal network biases the excitation of ON relative to OFF ganglion cells, and in addition, gradually interpolates and focuses the initial, patchy synaptic input to the cortex. As stimulation level increases, the cortical input spreads beyond the area occupied by the electrode contact. Further, at very strong stimulation levels, ganglion cell responses begin to saturate, resulting in a significant distortion in the spatial profile of the cortical input. These findings occur in both the normal and the degenerated retina simulations, but the normal retina exhibits a tighter spatiotemporal response. The complex spatiotemporal dynamics of the prosthetic input to the cortex that are revealed by our model should be addressed by prosthetic image encoders and by studies that simulate prosthetic vision.

Action Potentials↗

Phase mapping of ultrashort pulses in bimodal photonic structures: a window on local group velocity dispersion.

The amplitude and phase evolution of ultrashort pulses in a bimodal waveguide structure has been studied with a time-resolved photon scanning tunneling microscope (PSTM). When waveguide modes overlap in time intriguing phase patterns are observed. Phase singularities, arising from interference between different modes, are normally expected at equidistant intervals determined by the difference in effective index for the two modes. However, in the pulsed experiments the distance between individual singularities is found to change not only within one measurement frame, but even depends strongly on the reference time. To understand this observation it is necessary to take into account that the actual pulses generating the interference signal change shape upon propagation through a dispersive medium. This implies that the spatial distribution of phase singularities contains direct information on local dispersion characteristics. At the same time also the mode profiles, wave vectors, pulse lengths, and group velocities of all excited modes in the waveguide are directly measured. The combination of these parameters with an analytical model for the time-resolved PSTM measurements shows that the unique spatial phase information indeed gives a direct measure for the group velocity dispersion of individual modes. As a result interesting and useful effects, such as pulse compression, pulse spreading, and pulse reshaping become accessible in a local measurement.

Journal Article↗

Impaired lymphoid chemokine-mediated migration due to a block on the chemokine receptor switch in human cytomegalovirus-infected dendritic cells.

Dendritic cell (DC) migration from the site of infection to the site of T-cell priming is a crucial event in the generation of antiviral T-cell responses. Here we present to our knowledge the first functional evidence that human cytomegalovirus (HCMV) blocks the migration of infected monocyte-derived DCs toward lymphoid chemokines CCL19 and CCL21. DC migration is blocked by viral impairment of the chemokine receptor switch at the level of the expression of CCR7 molecules. The inhibition occurs with immediate-early-early kinetics, and viral interference with NF-kappaB signaling is likely to be at least partially responsible for the lack of CCR7 expression. DCs which migrate from the infected cultures are HCMV antigen negative, and consequently they do not stimulate HCMV-specific CD8(+) T cells, while CD4(+)-T-cell activation is not impaired. Although CD8(+) T cells can also be activated by alternative antigen presentation mechanisms, the spatial segregation of naive T cells and infected DCs seems a potent mechanism of delaying the generation of primary CD8(+)-T-cell responses and aiding early viral spread.

Chemokine CCL19↗

Cerebral blood flow in the monkey after focal cryogenic injury.

A focal cryogenic lesion was made in the left superior frontal gyrus of the anesthetized macaque brain. Cerebral blood flow (CBF) was determined by the hydrogen clearance technique before and during the 4 hours following trauma. Local CBF in tissue adjacent to the lesion increased in the first half hour after the lesion was made and then decreased during the ensuing 3 1/2 hours. Local CBF in the contralateral superior frontal gyrus, as well as total CBF and oxygen consumption, were unchanged by cryogenic trauma. The spread of vasogenic edema into uninjured tissue probably accounts for the observed decrease in local CBF. This experimental model may assist in discovering therapy to alter favorably the spatial and temporal profile of pathologic CBF changes in tissue surrounding an acute lesion of the brain.

Animals↗

[Inputs to cerebellar dentate nucleus from the pontine nucleus in the cat].

We have reported before that there are excitatory inputs to the cerebellar dentate nucleus (DN) from the cerebral cortex. This study was performed to examine whether the pontine nucleus (PN) and the nucleus reticularis tegmenti pontis (NRTP), which are among the precerebellar nuclei that relay inputs to the cerebellar cortex, also play a role as the relay nucleus of the excitatory input to the DN. In anesthetized cats, we stimulated the PN and the NRTP, and recorded intracellular potentials from DN neurons. Short-latency EPSPs were evoked from these nuclei and their latencies ranged from 1.1 to 3.6 msec, which are compatible with monosynaptic latencies. Systematic stimulation of the PN and the NRTP with weak stimulus intensities revealed that low-threshold foci for monosynaptic EPSPs in each cell were localized in the PN or the NRTP or both. We could not find monosynaptic inputs from the red nucleus and by recurrent collaterals of the dentate output neurons. Accordingly, the possibility was excluded that the monosynaptic EPSPs evoked from the PN and the NRTP were evoked by inadvertent current spread to the descending axons of DN neurons in the brain stem. The conditioning-testing stimuli of the cerebral peduncle and the PN or the NRTP yielded spatial facilitation. This result showed that the input from the cerebral cortex to the DN was relayed by way of the PN or the NRTP.

Animals↗

Transport of Wild-Type and Recombinant Nucleopolyhedroviruses by Scavenging and Predatory Arthropods.

Wild-type and recombinant nucleopolyhedroviruses (NPVs) were compared in their capability to be transported over limited distances by the predator Podisus maculiventris (Say) and scavengers Sarcophaga bullata (Parker) and Acheta domesticus (Linnaeus) in Trichoplusia ni (Hübner) larvae infesting collards in a greenhouse microcosm. Viruses tested were variants of Autographa californica (Speyer) NPV (AcNPV): wild-type virus (AcNPV.WT), AcNPV expressing a scorpion toxin (AcNPV.AaIT), and AcNPV expressing juvenile hormone esterase (AcJHE.SG). Podisus maculiventris transported AcNPV.WT and S. bullata transported AcNPV.WT and AcNPV.AaIT. Prevalence and transport of AcNPV.WT were greater than those of AcNPV.AaIT and AcJHE.SG, regardless of whether the nontarget organism carriers were present or absent. Podisus maculiventris and S. bullata transported recombinant and wild-type NPVs at a rate of up to 62.5 cm/day, and A. domesticus transported wild-type NPV at 125 cm/day. The infected host insects, T. ni, undoubtedly contributed to viral transport in the current research. In every experiment, both the wild-type and recombinant virus spread to some degree in the plots without predators or scavengers. The relative amounts of NPVs that accumulated in soil, as indicated by bioassay mortality percentages, generally exhibited spatial patterns similar to those of T. ni mortality due to NPV on the collards plants. Thus, the predator and scavengers in the current research demonstrated some capacity to transport wild-type as well as recombinant viruses at significant rates in a greenhouse microcosm.

Journal Article↗

Visualization of enteroviral replication in myocardial tissue by ultrastructural in situ hybridization: identification of target cells and cytopathic effects.

In humans as well as in various murine models, enteroviruses are capable of inducing a severe acute and chronic myocarditis, which is characterized by myocytotoxic alterations and interstitial mononuclear infiltrates. With regard to the pathogenesis of enteroviral myocarditis, coxsackievirus B3 (CVB3)-infected immunocompetent A.CA/SnJ (H-2f) mice were used as a model to trace viral plus- and minus-strand RNA during acute and chronic organ infection by ultrastructural in situ hybridization techniques. For electron microscopic detection of enteroviral RNA in myocardial tissue, a pre-embedding hybridization technique was developed and optimized for excellent conservation of structural integrity and RNA retention. Herein, we demonstrate how the virus gains access to the myocardium during viremia involving infection of the capillary endothelial cells. In myocytes, viral replication was found to be closely associated with the generation of vesicular regions and lysis of myofibrils, resulting in complete destruction of the internal architecture of the cell. In the course of acute infection, the direct cell-to-cell spread of the virus from one myocyte to the other was found to be related with filaments of the cytoskeleton. The observation of prominent cytopathic alterations in close spatial association with viral replication before the development of the reactive cellular immune response strongly implies that the loss of host cell integrity is a direct consequence of acute viral replication. In addition to myocytes, non-heart muscle cells were found to be infected during acute as well as chronic disease. Viral replication observed in myocardial fibroblasts and immune cells such as B lymphocytes proved to be associated with minor cytopathic effects. The technique of electron microscopic in situ hybridization established for the detection of viral RNA within myocardial tissue provides a powerful tool for the elucidation of molecular and structural interrelationships in organ pathology.

Animals↗

[Intestinal schistosomiasis from Schistosoma mansoni in Madagascar: extent and center of the endemic].

Schistosoma mansoni and S. haematobium affect respectively 2 million and 500,000 persons in Madagascar. Over the past decade, S. mansoni has spread in the central Highlands of Madagascar, essentially throughout the mid-west and Antananarivo plain. To understand this recent change in the epidemiology of S. mansoni, we examined the relationship between its spatial distribution and several host factors, including labour migration, urbanization and water development projects. In the Highlands, the disease in distribution could be superimposed on the potential expansion areas of snail distribution defined in 1958. However, the distribution is not homogeneous, as for example the road between Betafo and Mandoto (South West of Antananarivo). This focal pattern described in other African countries is unique to the central Highlands of Madagascar. Rice cultivation is the main economic activity and is associated with intense water contact. The focal distribution may be related to an environmental adaptation of host-parasite interaction depending on behavioural patterns, water and soil chemistry and incompatibility between Biomphalaria pfeifferi and S. mansoni. It is also possible that these focal patterns precede homogeneous endemicity, as along the road Itasy-Tsiroanomandidy (west Antananarivo). Major water development carried out in this migration area led to a rapid endemization of the disease. In Befato-Mandoto, where soil management is more restricted, schistosomiasis due to S. mansoni seems to have been established in some foci where epidemiologic conditions are favourable (for example, traditional irrigation canals). In contrast, the spread of S. mansoni in the Antananarivo plain closely follows the settlement of an infected rural population. Epidemiologic surveys conducted on school children in the Antananarivo suburbs, where sanitary conditions are poor, showed a prevalence of 25%. Human migration linked to development projects and urbanization seems to be the principal factor associated with the spread of schistosomiasis in the mid-west area and Antananarivo plain. In the Highlands, the preferential exposure of adult labour migrants has contributed to the widening of the endemic area.

Adult↗

Pathogenic mechanisms in ischemic damage: a computational study.

The pathogenesis of penumbral tissue infarction during acute ischemic stroke is controversial. This peri-infarct tissue may subsequently die, or survive and recuperate, and its preservation has been a prime goal of recent therapeutic trials in acute stroke. Two major hypotheses currently under consideration are that penumbral tissue is recruited into an infarct by cortical spreading depression (CSD) waves, or by a non-wave self-propagating process such as glutamate excitotoxicity (GE). Careful experimental attempts to discriminate between these two hypotheses have so far been quite ambiguous. Using a computational metabolic model of acute focal stroke we show here that the spatial patterns of tissue damage arising from artificially induced foci of infarction having specific geometric shapes are inherently different. This is due to the distinct propagation characteristics underlying self-regenerating waves and non-wave diffusional processes. The experimental testing of these predicted spatial patterns of damage may help determine the relative contributions of the two pathological mechanisms hypothesized for ischemic tissue damage.

Acute Disease↗

Improvements in the determination of radionuclide distribution in the analysis of irradiated samples using double-differentiation method.

The spatial response of an 8 x 4 block detector made up of 5.6-mm-wide, 12.9-mm-high, 30-mm-thick individual detector crystals to a collimated line source of 511 keV annihilation photons was examined. The response of each crystal showed a spread around the average positioning values and distributions from adjacent crystals overlapped as the collimated source scanned the individual detectors. This leads to possible errors in the event assignment. The implementation of double differentiation or the second derivative method was proposed for the removal of scattered photons so as to reduce the overlap and, hence, avoid mis-positioning. This method is a mathematical solution implemented when analysing the results. A curve in a spatial spectrum could be considered to be a function f(x), where x is the position. When double differentiation of f(x) is carried out, then the normalized curve d2f(x) appears with some reduction in the wings. It was shown that a reduction of the scattering contribution in the tails without overestimating the contribution of scattered events could be achieved by implementing a double-differentiation process.

Radiation, Ionizing↗

Spatial genetic pattern in the land mollusc Helix aspersa inferred from a 'centre-based clustering' procedure.

The present work provides the first broad-scale screening of allozymes in the land snail Helix aspersa. By using overall information available on the distribution of genetic variation between 102 populations previously investigated, we expect to strengthen our knowledge on the spread of the invasive aspersa subspecies in the Western Mediterranean. We propose a new approach based on a centre-based clustering procedure to cluster populations into groups following rules of geographical proximity and genetic similarity. Assuming a stepping-stone model of diffusion, we apply a partitioning algorithm which clusters only populations that are geographically contiguous. The algorithm used, which is actually part of leading methods developed for analysing large microarray datasets, is that of the k-means. Its goal is to minimize the within-group variance. The spatial constraint is provided by a list of connections between localities deduced from a Delaunay network. After testing each optimal group for the presence of spatial arrangement in the genetic data, the inferred genetic structure was compared with partitions obtained from other methods published for defining homogeneous groups (i.e. the Monmonier and SAMOVA algorithms). Competing biogeographical scenarios inferred from the k-means procedure were then compared and discussed to shed more light on colonization routes taken by the species.

Animals↗

Spatial and temporal characteristics of neonatal seizures.

Thirty-two neonates (26 term and 6 premature) having seizures were prospectively recruited and studied. Using prolonged video/EEG monitoring, we quantified seizure variables (electrographic and clinical seizure durations, interictal periods and electrographic seizure spread) for all 1,420 seizures recorded. The effects of time and antiepileptic drug (AED) therapy were analyzed statistically. Seizures were generally frequent, with limited electrographic spread. However, some neonates had consistently longer interictal periods and 13% had mean interictal periods > 60 min. Seizure variables were relatively stable over time, but they changed with AED therapy. There was a trend to decreased seizure duration, increased length of interictal periods, and decreased electrographic spread. Furthermore, there was evidence of reduced clinical features after sequential AED infusions. Seizures ceased during the monitoring period in 22 neonates. Eighty-five percent of all seizures had no clinical manifestations. Among neonates with clear clinical correlates, clinical observations underestimated electrographic seizures in individual neonates by a mean of 54% (range 0-95%). Seizures generally had limited electrographic spread. Use of only four recording electrodes, characteristic of some portable EEG systems, underestimated seizures in 19 neonates, and missed all seizures in 2.

Anticonvulsants↗

[Selection and techniques of surgical procedures based on the mode of cancer spread of rectal cancer].

The author reviewed recent results of Japanese and international studies on preoperative staging, pathology of bisopied specimens, sentinel node navigation surgery, and single tumor cells in rectal cancer. Preoperative staging with high accuracy is possible using high spatial MRI imaging. Examination of circumferential resection margins is incompatible with that of lymph nodes Intersphincteric resection can be an alternative to abdominoperineal resection for selected rectal tumors located at the anorectal junction without compromising the chance for cure. Although information on sentinel node navigation surgery and isolated single cells has accumulated, the selection of surgical procedures should not be based on these investigations. We emphasize that multiinstitutional clinical trials of adjuvant chemoradiotherapy and surgical treatment are indispensable for developing treatments for rectal cancer in Japan.

Digestive System Surgical Procedures↗

Role of microscopic tissue structure in shock-induced activation assessed by optical mapping in myocyte cultures.

INTRODUCTION: Termination of ventricular fibrillation by electric shocks is believed to be due to the direct activation of large tissue mass that may be caused by microscopic virtual electrodes formed at discontinuities in tissue structure. Here, microscopic shock-induced activation was measured optically in myocyte cultures; spatially averaged microscopic Vm measurements were compared with macroscopic measurements from left ventricular (LV) tissue. METHODS AND RESULTS: Experiments were performed in linear cell strands of different width (approximately 0.1 and 0.8 mm) and isolated porcine LV preparations. Uniform field shocks were applied across strands or LV preparations during diastole and action potential (AP) plateau. Depending on shock strength, three different types of activation were observed in cell strands. Weakest shocks produced "delayed make" activation that started on the cathodal strand side after long latency and rapidly spread to the anodal side. Stronger shocks caused "make" activation with short latency and rapid spread across strands. Strongest shocks caused nonuniform "make-break" activation where the cathodal side was activated with a short latency but activation of the anodal side was delayed until after the shock end due to a large negative shock-induced polarization. Spatial averaging of Vm responses across 0.1-mm (but not 0.8-mm) strands resulted in AP upstrokes and plateau polarizations that closely resembled the Vm responses measured in LV myocardium. The shock strength for the transition between fast and delayed activation in 0.1-mm cell strands and LV myocardium was similar as well. CONCLUSION: These data provide evidence that microscopic tissue structures with dimensions of approximately hundred microns are responsible for shock-induced activation of ventricular tissue.

Action Potentials↗