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Fine structure of podocytes in the bovine renal corpuscle.

Thick primary processes issued from the hemispherical or plate-like cell bodies of podocytes in bovine renal corpuscles. These processes branched into secondary and tertiary ones, but no fine pedicels were observed on the outer surface of the podocytes by scanning electron microscopy, because each primary process closely interdigitated with those of adjacent cells. Many pedicels, however, were observed under the processes by using the freeze-fractograph and a transmission electron microscope.

Aging↗

The pig synovium. I. The intact synovium in vivo and in organ culture.

1. The normal synovium of the metacarpophalangeal joints of young pigs was examined by light and electron microscopy with special reference to the superficial layer (intima). 2. Cells of the macrophage-like or A-type (Barland et al. 1962) constituted only a small proportion of the intimal synoviocytes; the majority were of the intermediate and B-types. 3. Synovial villi were explanted on Millipore filters and maintained as organ cultures. The intimal cells in contact with the Millipore formed long branched processes which penetrated deeply into the substrate; these cells, which had a very well-developed endoplasmic reticulum, resembled those of the B-type. The synoviocytes at the upper (free) surface of the villus withdrew their long processes, acquired lamelliform pseudopodia, and their endoplasmic reticulum regressed; they were similar in appearance to the A-type. 4. In the organ cultures the highly branched cells (B-type) next to the Millipore were less phagocytic than the rounded cells (A-type) at the free surface of the villus.

Animals↗

Detailed morphology and distribution of gap junction protein associated with cells from the intra-articular disc of the rat temporomandibular joint.

The present study details structural aspects of the cells of the rat intra-articular disc (IAD) of the temporomandibular joint. At the light and electron microscope level, the outline of the cells varied, although a number appeared oval/rounded. Ultrastructurally, the cells contained moderate amounts of the intracellular organelles associated with protein synthesis. Cell processes were not a prominent feature seen using these techniques. However, using confocal microscopy, phalloidin staining revealed the presence of numerous, actin-rich, long, thin, branching processes emanating from the cell membranes. Double staining for connexin 43 revealed that the cell processes showed dense, punctate positive staining for this gap junction protein along their whole length. These observations provide the basis for a transport mechanism for nutritive molecules from the periphery of the IAD (where blood vessels are present) to the central portions of the disc (where blood vessels are absent).

Actins↗

[Phenotypes of dendritic cells in central lymph of healthy rabbits and during correction of experimental atherosclerosis].

Dendritic cells of central lymph of rabbits have been identified according to the form of the cell body, characteristics of formation and branchiness of its processes in health, in atherosclerosis, its correction with radon, polyphenol preparations made of Sanguisorba officinalis and in combination of the latter. Two main types of dendritic cells have been distinguished. Type I is characterized by a rounded body with clear outlines, protrusions and one compact process. Such cells are often found in lymph of intact animals. Type II has a cell body of various forms with two and more compact or branching processes. This type is mainly detected in atherosclerosis and its correction. The prevalence of the above phenotypes of dendritic cells is attributed to the response of the immune system to atherosclerosis and its correction.

Animals↗

Complex morphogenesis of surfaces: theory and experiment on coupling of reaction-diffusion patterning to growth.

Reaction-diffusion theory for pattern formation is considered in relation to processes of biological development in which there is continuous growth and shape change as each new pattern forms. This is particularly common in the plant kingdom, for both unicellular and multicellular organisms. In addition to the feedbacks in the chemical dynamics, there is then another loop linking size and shape changes with the reaction-diffusion patterning of growth controllers in the growing region. In studies by computation, the codes must incorporate, alongside the usual solvers of the partial differential dynamic equations, a versatile growth code, to express any kind of shape change. We have found that regulation of shape change in particular ways (e.g. to make narrow-angle branchings) demands new features in our chemical mechanisms. Our growth algorithm is for a surface growing tangentially, but moving outward and changing shape to accommodate the extra area. This is potentially applicable both to the tunica layer of multicellular plant meristems and to the growing tip of the cell surface, e.g. in the morphogenesis of single-celled chlorophyte algae which display branching processes: whorl formation in Acetabularia (Dasycladales) and repeated dichotomous branching in Micrasterias (Desmidiaceae). For computational studies, a hemispherical shell is a reasonable idealization of the initial shape. We describe results of two types of study: (1) Pattern formation by three reaction-diffusion models, with contrasted nonlinearities, on the hemispherical shell, particularly to find conditions for robust formation of annular pattern or pattern for dichotomous branching, both of which are common in plants. (2) Sequential dichotomous branchings in a system growing and changing in shape from the hemispherical start.

Journal Article↗

Mathematical modeling of the loss of telomere sequences.

hortening of telomeres is one of the supposed mechanisms of cellular aging and death. An important question related to this so-called "end-replication" hypothesis is whether it can explain in quantitative detail the dynamic of cell sensescence in vitro and in vivo. A natural way to answer this question is to use mathematical modeling. In this paper, the models were successfully fitted to data on cultured fibroblasts from two different sources assuming that after reaching the Hayflick checkpoint on a single chromosome cells cease to proliferate. The main conclusion is that the end-replication hypothesis provides an explanation for the cell aging process which is quantitatively consistent with the data. As a secondary outcome, estimates were obtained of the rate of shortening of telomeres and several interesting mathematical results for branching processes with infinite type spaces arise.

Animals↗

The medial axis branch point in the human mandible.

The medial axis method was applied to radio-cephalometric images of the mandible in 20 adults and 18 children and to panoramic X-ray images of these children, and also directly to 50 halves of dry mandibles. It was found that the location of the posterior branch point coincided almost invariably with the mandibular foramen/lingula. The foramen may be regarded as the posterior limit of the mandibular body, from which the condylar and coronoid processes branch off. The medial axis appears to reflect the developmental and functional anatomy of the human mandible.

Adult↗

[Labeled mitosis curve in the presence of different states of cell proliferation kinetics. IV. Additional remarks on the method of a posteriori modeling].

Using the conditional probability density function of phase duration--h (a, t), defined for a cell just completing a given phase of the mitotic cycle at the moment t it is possible to construct a mathematical description of the fraction labeled mitoses curve. The function h (a, t) defined for any separate phase can be described by means of a certain mathematical expression which is applicable even in the presence of transient processes in cell kinetics and serves as an appropriate generalization of the same result from the theory of exponentially growing cell populations (the model of age-dependent branching process). When the sum of r successive phases with stochastically dependent durations is under consideration and the age of a cell is measured from the start of phase r, it is necessary to find out the expression for the function hr (ar, t). The derivation of such an expression is given.

Cytological Techniques↗

Morphological differentiation of neuropeptide Y neurons in aggregate cultures of dissociated fetal cortical cells: a model system for glia-neuron paracrine interactions.

The temporal changes in the morphological profiles of neuropeptide Y (NPY) neurons and their topographical relationship with glial cells (astrocytes) were characterized in aggregate cultures derived from fetal cortical tissue using immunocytochemical procedures. On day 6 of culture, structures labelled with NPY antibodies were small and uneven in size but many resembled neuronal cell bodies. On day 14, neuronal perikarya were well defined and several morphological types of NPY neurons could be distinguished most of which gave rise to beaded processes: unipolar or multipolar bitufted neurons whose processes branch in close proximity to the cell body; bipolar neurons; and multipolar neurons. On day 23, heavily punctate and asymmetrically labelled cell bodies were dispersed throughout the aggregate; neuronal processes were less conspicuous. At 14 and 23 days, cells expressing glial fibrillary acidic protein (GFAP) and neuronal specific enolase (NSE) were abundantly distributed throughout the aggregate. Using a double immunoreaction on 14-day-old aggregates revealed that GFAP+ cells and their processes were in close apposition to and engulfing the NPY neurons. Thus, dissociated fetal NPY neurons undergo morphological differentiation in culture along with astrocytes (GFAP+) and other neuronal cell types (NSE+). Based on the topographical association of astrocytes and neurons, particularly NPY neurons, we propose that the aggregate culture system can serve as a model to study the role of paracrine interactions in the regulation of the expression of NPY.

Animals↗

Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis.

A mutation was targeted to the murine alpha3 integrin gene. Homozygous mutant mice survived to birth, but died during the neonatal period. The mutation caused abnormal kidney and lung development. Mutant kidneys displayed decreased branching of the medullary collecting ducts, although the number of nephrons was not altered. Proximal tubules exhibited two distinct subsets of abnormalities, with the epithelial cells either containing excess lysosomes or becoming microcystic. In addition, glomerular development was markedly affected. In mutant kidneys, the extent of branching of glomerular capillary loops was decreased, with capillary lumina being wider than normal. The glomerular basement membrane was disorganized and glomerular podocytes were unable to form mature foot processes. Branching of the bronchi in lungs of mutant mice was also decreased and the large bronchi extended to the periphery. These results indicate a role for integrin receptors in basement membrane organization and branching morphogenesis.

Animals↗

Rod photoreceptor neurite sprouting in retinitis pigmentosa.

In animal models for retinitis pigmentosa (RP), rod photoreceptors show abnormal distribution of rhodopsin prior to undergoing cell death. To elucidate the steps in degeneration of human photoreceptors, immunocytochemistry was performed on donor retinas from 15 RP patients and five normal subjects. Rhodopsin immunolabeling in the normal retinas was restricted to the rod outer segments. In the RP retinas, rhodopsin was present in shortened rod outer segments and in the surface membranes of the rod inner segments and somata. In regions of photoreceptor death, the surviving rods had sprouted rhodopsin-positive neurites that were closely associated with gliotic Müller cell processes and extended to the inner limiting membrane. Rods and cones in the RP maculas did not form neurites, but the axons of peripheral cones were abnormally elongated and branched. Double immunofluorescence labeling showed that the rod neurites bypassed the horizontal and rod bipolar cells that are normally postsynaptic to rod axons. To our knowledge, this is the first report of rod neurite sprouting in vivo. We were unable to find neurites on degenerate rods in old rds mice, an animal model for RP. The rod neurites in the human RP retinas resemble the long, branched processes formed by rods cultured on Müller cells or purified N-CAM. Neurite growth by surviving rods in the RP retinas may be a response to neurotrophic factor upregulation, loss of inhibitory factors, or changes in molecules associated with reactive Müller cells. Such changes in the retinal microenvironment may impede functional integration of transplanted photoreceptors. The contributions of the rhodopsin-positive rod neurites and abnormal cone axons to the functional abnormalities observed in RP are unknown.

Adult↗

Distribution of the largest aftershocks in branching models of triggered seismicity: theory of the universal Båth law.

Using the epidemic-type aftershock sequence (ETAS) branching model of triggered seismicity, we apply the formalism of generating probability functions to calculate exactly the average difference between the magnitude of a mainshock and the magnitude of its largest aftershock over all generations. This average magnitude difference is found empirically to be independent of the mainshock magnitude and equal to 1.2, a universal behavior known as Båth's law. Our theory shows that Båth's law holds only sufficiently close to the critical regime of the ETAS branching process. Allowing for error bars +/- 0.1 for Båth's constant value around 1.2, our exact analytical treatment of Båth's law provides new constraints on the productivity exponent alpha and the branching ratio n: 0.9 approximately < alpha < or =1. We propose a method for measuring alpha based on the predicted renormalization of the Gutenberg-Richter distribution of the magnitudes of the largest aftershock. We also introduce the "second Båth law for foreshocks:" the probability that a main earthquake turns out to be the foreshock does not depend on its magnitude rho.

Journal Article↗

The multifractal structure of arterial trees.

Fractal properties of arterial trees are analysed using the cascade model of turbulence theory. It is shown that the branching process leads to a non-uniform structure at the micro-level meaning that blood supply to the tissue varies in space. From the model it is concluded that, depending on the branching parameter, vessels of a specific size contribute dominantly to the blood supply of tissue. The corresponding tissue elements form a dense set in the tissue. Furthermore, if blood flow in vessels can get obstructed with some probability, the above set of tissue elements may not be dense anymore. Then there is the risk that, spread out over the tissue, nutrient and gas exchange fall short.

Animals↗

Pattern analysis in branching and axillary flowering sequences.

In the architectural approach to the study of plants, a major issue is to analyse branching and axillary flowering patterns. Due to the structured expression of the branching process and the noisy character of the observed patterns, we propose an analysis framework which is both structural and probabilistic. Data take the form of sequences which naturally represent the underlying structural information of branching and axillary flowering patterns and allow the application of a large number of methods ranging from exploratory analysis to stochastic modeling. The primary aim of the proposed analysis methods is to reveal patterns not directly apparent in the data, and thus to deepen our biological understanding of the underlying mechanisms that control the branching and the axillary flowering of plants over time and space. The proposed approach is illustrated using a set of examples corresponding to different plant species and different biological or agronomic objectives.

Models, Biological↗

Mutation-replication statistics of polymerase chain reactions.

The variability of the products of polymerase chain reactions, due to mutations and to incomplete replications, can have important clinical consequences. Sun (1995) and Weiss and von Haeseler (1995) modeled these errors by a branching process and introduced estimators of the mutation rate and of the efficiency of the reaction based, for example, on the empirical distribution of the mutations of a random sequence. This distribution involves a noncanonical branching Markov chain which, although easy to describe, is not analytically tractable except in the infinite-population limit. These authors for the infinite-target limit, and Wang et al. (2000) for finite targets, solved the infinite-population limit. In this paper, we provide bounds of the difference between the finite-target finite-population case and its finite-target infinite-population approximation. The bounds are explicit functions of the efficiency of the reaction, the mutation rate per site and per cycle, the size of the target, the number of cycles, and the size of the initial population. They concern every moment and, what might be more surprising, the histogram itself of the distributions. The bounds for the moments exhibit a phase transition at the value 1 - 1/N = 3/4 of the mutation rate per site and per cycle, where N = 4 is the number of letters in the encoding alphabet of DNA and RNA. Of course, in biological contexts, the mutation rates are much smaller than 3/4.

Base Sequence↗

Supraependymal neurons overlying the periventricular region of the third ventricle of the guinea pig: a correlative scanning--transmission electron microscopic study.

The frequency of occurrence, distribution and morphology of supraependymal neurons associated with the third ventricular wall of the guinea pig were investigated by correlative scanning and transmission electron microscopy. Each of the specimens was located on the ciliated ventricular wall between the inferior border of the thalamus and the non-ciliated ependyma associated with the median eminence. Prominent clusters of neuronal perikaria in association with massive process bundles were observed in 7 of the 31 specimens examined. In those specimens lacking prominent neuronal networks a more diffuse array of independent nerve fibers was sometimes seen on the ependymal surface. Neuronal perikaria exhibited numerous surface protrusions and were covered by a rich meshwork of crisscrossing, varicosed fibers. Many of these cells were associated with multiple processes of varying diameters and lengths which either coursed independently over the ventricular surface or formed fasciculated bundles. As process bundles traversed the ependymal surface, individual processes branched off and either terminated within the ventricular lumen or penetrated the subjacent ependymal lining. Fibers also made contact with adjacent supraependymal neuronal elements. Correlative transmission electron microscopic observations indicate that both the perikaria and processes of such supraependymal networks possess ultrastructural features characteristic of neurons. The morphological characteristics of the intraventricular neuronal networks suggest that they may be engaged in functional interactions with the cerebrospinal fluid, with adjacent supraependymal neuronal elements and with the subjacent neuropil.

Animals↗

Cyclic AMP induces morphological changes of vascular smooth muscle cells by inhibiting a Rac-dependent signaling pathway.

Cyclic AMP (cAMP) is a pleiotropic second messenger that regulates numerous cellular processes. In vascular smooth muscle cells (VSMCs), these include cell proliferation, migration, and contractility. Here we show that cAMP-elevating agents induce dramatic morphological changes in VSMCs, characterized by cell rounding and formation of long branching processes. The stellate morphology is associated with disassembly of actin stress fibers and lamellipodia, loss of focal adhesions, and the formation of small F-actin rings. Because of the importance of Rho family GTPases in regulating actin dynamics, we analyzed their individual roles in the cAMP phenotype. We found that pharmacological or genetic inhibition of Rac mimics cAMP effect in inducing a stellate morphology of VSMCs. Expression of activated Rac1 prevents forskolin-induced cAMP stellation, suggesting that cAMP affects cell morphology by inhibiting Rac function. Consistent with this, treatment with forskolin inhibits agonist-stimulated Rac activation in VSMCs. We further show that activated Rac1 containing the F37A effector loop substitution fails to rescue the cAMP phenotype. Our results suggest that cAMP modulates the morphology of VSMCs by inhibiting a Rac-dependent signaling pathway.

Animals↗

Differentiation of photoreceptors and horizontal cells in the embryonic mouse retina: an electron microscopic, serial section analysis.

The early differentiation of photoreceptors and horizontal cells in the mouse retina has been studied with serial thin sections and reconstructions in embryos on the fifteenth and seventeenth days of gestation (E15 and E17). The following developmental sequences have been inferred. At E15 photoreceptors develop from ventricular cells when a long vitreal process fails to develop following mitosis, and the end of the ventricular process forms a bulbous enlargement (the future inner segment) which contains a pair of centrioles and a cilium and extends into the optic ventricle. This future inner segment is considerably larger at E17, but otherwise the photoreceptors resemble those seen at E15. At E15 horizontal cells develop from ventricular cells when a long vitreal process fails to develop following mitosis, and the end of the ventricular process detaches from the junctional complex at the ventricular surface. By E17 future horizontal cells are located in the middle of the ventricular layer (neuroblastic layer) and have developed from bipolar shaped cells into cells with multiple branching processes, predominantly radially arranged but rarely with a more tangential orientation. These relatively advanced cells at E17 resemble closely the earliest stage of horizontal cell formation described previously in silver studies by Cajal. A scheme is proposed which explains the initial differentiation of several of the major cell types in the retina in terms of two key features: whether or not the call remains attached to the junctional complex and whether or not a vitreal process grows into the ganglion cell layer. By independent variations in these two features, four classes of cells are produced that, by virtue of their differing environments, differentiate into four cell types: ganglion (and amacrine) cells, horizontal cells, photoreceptors, and Müller cells.

Animals↗