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Host spatial heterogeneity and extinction of an SIS epidemic.

Spatially explicit epidemic models explore population-level consequences of interactions between neighboring infectious and susceptible individuals. Most such models equate local and global host density, so that each individual interacts with the same number of neighbors. But many natural populations exhibit heterogeneity in local abundance. Therefore, we let host dispersion vary from uniform to clumped in a spatial epidemic with recovery. We analytically approximated the epidemic with a branching process to show how the probability of pathogen extinction could depend on the degree of host clumping. We then simulated the detailed model across a range of parameter combinations. Both approaches to the problem indicate that host spatial aggregation strongly increases the chance of pathogen extinction.

Animals↗

Retrovirus-mediated gene transfer and galactocerebrosidase uptake into twitcher glial cells results in appropriate localization and phenotype correction.

Galactocerebrosidase (GALC) is deficient in all tissues from human patients and animal models with globoid cell leukodystrophy (GLD) or Krabbe disease. The deficiency results in decreased lysosomal catabolism of certain galactolipids including galactosylceramide and psychosine that are synthesized maximally during myelination. According to current theories, the accumulation of psychosine in humans and animals with GLD induces oligodendrocyte degeneration and myelination ceases. Transduction of oligodendrocytes from twitcher mice with a retroviral vector containing the GALC cDNA can correct the enzyme deficiency in these cells. Our data show that twitcher astrocytes and oligodendrocytes can internalize exogenous GALC, as well as donate the enzyme to the mutant glial cells. Antibodies against human GALC localized the GALC antigen in retrovirally transduced cells and cells receiving enzyme via cell to cell secretion and uptake to the lysosomal fraction. In fact immunocytochemical studies in transduced oligodendrocytes revealed that the GALC colocalizes in vesicles lysosomal-associated membrane protein-2 (LAMP2) (+). Moreover, labeling cells with anti-GALC and a marker for oligodendrocytes demonstrated that, upon differentiation, transduced, twitcher oligodendrocytes attained the normal branched process configuration, while untransduced cells show only abnormal morphology. Phenotype correction in mutant oligodendrocytes has also been observed after enzyme transfer. These studies indicate that GALC activity supplied to cultured oligodendrocytes from twitcher mice by different methods can correct the pathological phenotype of these cells.

Animals↗

Coupling and the Non-degeneracy of the Limit in Some Plasmid Reproduction Models

We settle a problem raised by Seneta and Tavare concerning the normalized limits of several plasmid reproduction models. We also show that for countably infinitely many type branching processes the extinction probability and the mass at the origin of the supercritical limit need not be the same, in contrast to the finite type case. Copyright 1997 Academic Press

Journal Article↗

The epidemic in a closed population with all susceptibles equally vulnerable; some results for large susceptible populations and small initial infections.

Kendall's (1956) approach to the 'general' epidemic is generalized by dropping the assumptions of constant infectivity and random recovery or death of ill individuals. A great deal of attention is paid to the biological background and the heuristics of the model formulation. Some new results are: (1) the derivation of Kermack's and McKendrick's integral equation from what seems to be the most general set of assumptions in section 2.2, (2) the use of Kermack's and McKendrick's final value equation to arrive at a finite time version of the threshold theorem for the general case, comparable to the for the case of only one Markovian state of illness in section 2.5, (3) the analysis of the behaviour of the solutions of the integral equation when the starting infection approaches zero in section 2.7, (4) the derivation of the probability structure of a general branching process, after conditioning on extinction in section 3.6, (5) the statement of the generalized versions of Kendall's ideas in the form of precise limit conjectures in section 4, (6) the derivation of a closed expression for the limit epidemic resulting from (3) in appendix 4.

Disease Outbreaks↗

On the probability of loss of new mutations in the presence of linkage disequilibrium.

A new selectively neutral mutation occurs in a multilocus genetic background that has achieved a stable equilibrium at which there is a linkage disequilibrium. Perturbation techniques are applied to an extension of the branching process formulation of Fisher in order to address the question of extinction probabilities. We show that under appropriate conditions the probability of extinction of the new mutant is increased by the existence of linkage disequilibrium in the genetic background.

Linkage Disequilibrium↗

Three-dimensional organization of smooth muscle cells in blood vessels of laboratory rodents.

Three-dimensional aspects of smooth muscle cells of the microvasculature were studied ultrastructurally in laboratory rodents by means of serial thin sections and reconstruction of muscle cell models. It was demonstrated that a muscle cell of an arteriole (luminal diameter (LD) 17 microns) in hamster striated muscle was spindle-shaped, 70 microns long, and wound twice round the vessel axis. The volume of the cell was calculated as 750 microns3 and its surface area as 1330 microns2. A muscle cell in an arteriole (LD 6 microns) in the rat retina was irregular in shape, about 22 microns long, and had branched processes. The cell volume was calculated as 139 microns3 and its surface area as 298 microns2.

Animals↗

Surface labelling of oligodendrocytes with anti-myelin serum in cell cultures from the rat brain. Light- and electron-microscopic immunocytochemical studies.

Antiserum produced in rabbits against purified myelin contains antibodies that bind to the surface of cells having multiple branched processes in live cultures of cerebral hemispheres of newborn rats. The identity of these cells was determined by double immunolabelling experiments with other specific antigenic markers (W1 Wolfgram protein, myelin basic proteins, glial fibrillary acidic protein). It was demonstrated that the cells are a subclass of oligodendrocytes which have reached a certain degree of maturation; nearly all of them contain basic proteins. Indeed, a number of oligodendrocytes, that contain the W1 protein, and may or may not have processes, are not surface-labelled in similar conditions. The usefulness of such an anti-myelin serum in the isolation of pure oligodendrocytes is discussed.

Animals↗

A scanning electron-microscopic study of "supramarginal cells" in the pituitary cleft of the rat.

Unusual cells lying above the marginal cellular layer of the rat pituitary cleft were studied by SEM and TEM. These cells - from their location termed supramarginal cells - have a characteristically irregular cell body from which arise a number of long and thin branched processes ending among the microvilli and cilia of the marginal cells delimiting the anterior and posterior walls of the cleft. Some supramarginal cells are star-shaped elements with thin extensions, others have a triangular or spindle-shaped body from which emerge long ameboid processes with fibril-like projections. Miniblebs, miniruffles, occasional veils and short microvilli extend over the surface of these elements. Supramarginal cells are very similar to the "Kolmer epiplexus cells" originally found on the choroid plexus or other areas of the third ventricular wall where they are known as "supraependymal cells". Present evidence suggests that supramarginal cells of pituitary cleft might have phagocytic properties and an hematogenous origin as monocytes and, as such, closely resemble Kolmer epiplexus cells of brain ventricles. Others might arise from "folliculo-stellate cells" or closely related marginal cells once they become free into the pituitary cleft. Supramarginal cells are recognized as motile phagocytes acting as scavengers and possibly regulating the extracellular environment of the cleft and associated adenohypophysial tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fine structure of taste buds in the barbel of the catfish, Ictalurus punctatus.

Taste buds occur in the epithelium of the catfish barbel along its entire length. Two major cell types, light and dark cells, occupy the upper two-thirds of the taste bud. A third cell type, the basal cell, lies on the basal lamina and is essentially separated from the light and dark cells by a plexus of unmyelinated nerve fibers. The dark cells have branching processes, both apically and basally whereas the light cells have a single apical process and many basal processes. The apical processes of dark cells contain secretory granules, while the apical processes of light cells contain an abundant agranular endoplasmic reticulum. Light cell nuclei contain bundles of 10 nm filaments, often arranged in the shape of a cup or ring, but nucleoli are rarely seen. It is suggested that this morphology indicates a low degree of RNA synthesis by light cells. The basal cells contain large numbers of vesicles, about 60 nm in diameter, which are sometimes seen in clumps in relation to an adjacent nerve fiber in a configuration resembling a synapse. Curiously, although basal cells present a large surface to the basal lamina, there are no hemidesmosomes. This suggests that the basal cell does not originate from the epidermis.

Animals↗

The hypothalamus of Lacerta sicula R. I. A Golgi study on the caudal hypothalamus.

The posterior (caudal) hypothalamus of the lizard, Lacerta sicula R. was investigated by means of Golgi methods. The periventricular grey is formed mainly by isodendritic bipolar and multipolar neurons, while in the lateral hypothalamus a more stellate form of neuronal elements is encountered. CSF-contacting neurons are restricted to the tuberal area and to the paraventricular organ. In the latter area they are highly differentiated and endowed with laterally branched processes. The overall pattern of the lizard hypothalamus (organization of neuropil, lateral nuclei, appearance of cell clusters, morphology of the neuronal elements) represents an intermediate stage in the phylogenetic development of the hypothalamus, being more advanced than the amphibian stage.

Animals↗

Distribution and ultrastructure of S-100-immunoreactive cells in the human thymus.

The present study deals with the localization and ultrastructure of S-100-immunoreactive cells in the human thymus. These immunoreactive cells are distributed mainly in the medulla with some scattered elements in the cortex. Electron-microscopic observation revealed that the cells are characterized by an irregularly shaped nucleus, tubulovesicular structures in the cytoplasm and characteristic interdigitations of the plasma membrane. The cells often embrace lymphocytes with their branched processes. On the basis of these morphological features, the immunostained elements were identified as interdigitating cells (IDCs). The immunocytochemistry for S-100 visualizes the precise distribution and extension of the IDCs under the light microscope and indicates that the IDCs form no structural networks such as those established by the thymic epithelial cells. Since the IDCs in human lymph nodes have also been reported to contain S-100-like immunoreactivity, S-100 protein can be regarded as a useful marker for identifying the IDCs in the human thymus and other lymphoid organs.

Adult↗

Aggregation of cell surface receptors by multivalent ligands.

Using a combination of branching processes and kinetic equations a solution is provided to the problem of describing the size of aggregates formed on cell surfaces when multivalent ligands bind and cross-link multivalent receptors. A criterion is given for the onset of gelation in infinite 2-dimensional systems, which may be relevant to the phenomenon of ligand-induced receptor patching.

Animals↗

Susceptible-infected-removed epidemic models with dynamic partnerships.

The author extends the classical, stochastic, Susceptible-Infected-Removed (SIR) epidemic model to allow for disease transmission through a dynamic network of partnerships. A new method of analysis allows for a fairly complete understanding of the dynamics of the system for small and large time. The key insight is to analyze the model by tracking the configurations of all possible dyads, rather than individuals. For large populations, the initial dynamics are approximated by a branching process whose threshold for growth determines the epidemic threshold, R0, and whose growth rate, lambda, determines the rate at which the number of cases increases. The fraction of the population that is ever infected, omega, is shown to bear the same relationship to R0 as in models without partnerships. Explicit formulas for these three fundamental quantities are obtained for the simplest version of the model, in which the population is treated as homogeneous, and all transitions are Markov. The formulas allow a modeler to determine the error introduced by the usual assumption of instantaneous contacts for any particular set of biological and sociological parameters. The model and the formulas are then generalized to allow for non-Markov partnership dynamics, non-uniform contact rates within partnerships, and variable infectivity. The model and the method of analysis could also be further generalized to allow for demographic effects, recurrent susceptibility and heterogeneous populations, using the same strategies that have been developed for models without partnerships.

Communicable Diseases↗

C-PON immunoreactive neurons in the neostriatum of the hedgehog (Erinaceus europaeus): a correlated light- and electron-microscopic study.

The present study provides light- and electron-microscopic immunocytochemical data on the presence of neurons that are immunoreactive to the C-terminal flanking peptide of neuropeptide Y, C-PON, in the neostriatum of the hedgehog (Erinaceus europaeus). Positive neurons have mostly fusiform or round perikarya from which two to four poorly branched processes arise. Immunostained fibers and puncta are also evenly distributed throughout the neostriatum. Ultrastructurally, each neuron exhibits a deeply invaginated nucleus surrounded by abundant cytoplasm with a well-developed rough endoplasmic reticulum and Golgi apparatus. Positive neurons receive symmetric and asymmetric synapses from unlabeled terminals. The results of this study can be correlated with previous findings, as the C-PON-positive neurons of the hedgehog resemble medium-sized neostriatal neurons that are known to be local circuit neurons exhibiting C-PON in the rat. Thus, a high degree of C-PON neuronal system phylogenetic conservation and function can be postulated for the neostriatum of mammals.

Animals↗

Intralobular heterogeneity of perisinusoidal stellate cells in porcine liver.

The aim of the present investigation was to elucidate the intralobular heterogeneity of the perisinusoidal stellate cells (fat-storing cells, lipocytes) in the porcine liver. Their three-dimensional structure, desmin immunoreactivity and vitamin-A storage were studied by use of the Golgi silver, immunocytochemical and gold chloride methods. In order to locate the stellate cells, the hepatic lobules were divided into 10 zones. The stellate cells were readily identified in Golgi preparations by their striking dendritic appearance with branching processes encompassing the sinusoids. The stellate cells in the centrolobular zones were conspicuously dendritic with longer processes in comparison to those emitted by periportal elements. Such arborizations were studded with numerous thorn-like microprojections. Desmin immunoreaction in the periportal zones was stronger than that in the centrolobular zones. Vitamin-A storage in the stellate cells was well developed in zones 2-4, but reduced gradually toward the central region. The perisinusoidal stellate cells display marked heterogeneity in morphology and function based on their zonal location in the hepatic lobule.

Animals↗

The three-dimensional cytoarchitecture of the interstitial tissue in the rat kidney.

The cytoarchitecture of the interstitial tissue of the rat kidney was studied by combined scanning and transmission electron microscopy. The renal interstitium is composed of an elaborate network of stellate sustentacular cells. In the cortex, sustentacular cells radiate thin branching processes to form a fine reticulum, which supports intertubular spaces. In the medulla, these cells extend thick processes horizontally along the basal surfaces of the thin limbs or vasa recta, reinforcing their attenuate walls. The horizontal processes connect with each other at their terminals, compartmentalizing the interstitial space into thin layers. The medullary sustentacular cells contain abundant small lipid droplets. The network of sustentacular cells houses vasa recta, keeping them in parallel position to each other and to the tubules. The arterial vasa recta are accompanied by pericytes, which frequently contain lipid droplets larger in size than those in the sustentacular cells. Venous vasa recta extend numerous basal microvilli, which anchor the venous wall to adjacent tubules or vessels. Numerous free cells, round in shape, are found in the sustentacular cell network, especially in the cortex. They consist of macrophages and occasional lymphocytes. Some macrophages extend long pseudopodia, while others make intimate contact with lymphocytes, suggesting their high level of activity.

Animals↗

The effect of cytochalasin B on chick mesoderm cells as studied by scanning electron microscopy.

The effects of cytochalasin B (CCB) on chick mesoderm cells in vivo was examined by scanning electron microscopy (SEM). The embryos were mounted for New Culture and the mesoderm exposed by dissecting off the endoderm. Cytochalasin B was suspended in saline and the embryos flooded with the suspension. Control embryos were treated with saline alone. The embryos were reincubated for varying times at 37 degrees C. In the treated embryos the mesoderm cells were rounded and separated from each other. Many had long branched processes and rough surfaces. These changes became more pronounced as treatment time was increased. They were also reversible on reincubating treated embryos in the absence of cytochalasin B. The morphological changes produced by CCB are thought to be due to an effect on the cytoskeleton, either a direct disruptive effect or detachment of skeletal microfilaments from the cell membrane. There may also be a direct removal of cell surface materials leading to the observed surface roughening of treated cells.

Animals↗