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At least 217 records · Page 12Linked to original sources

Non-linear model of cancer growth and metastasis: a limiting nutrient as a major determinant of tumor shape and diffusion.

A new approach for modelling the spatio-temporal evolution of tumors is presented. To test its validity, a very basic model is considered, which, in spite of its simplicity, is capable of generating a multiplicity of morphologies and growth and migration rates. From an in-vivo scenario of basic life processes, cancer cell proliferation is described as a competition for basic nutrients. The chosen mathematical treatment and simulation techniques permit a direct implementation of the local nonlinear couplings existing between the various cell populations and the free and bound nutrient concentration. A discussion of the results and proposed improvements and applications of the model is also presented.

Cell Division↗

[Cranial fasciitis of childhood].

INTRODUCTION: A nodule of the scalp in a child of less than eleven years should evoke a cranial fasciitis among other serious diagnoses. OBSERVATION: A four-month old infant had a firm and pink nodule at the left parietal level, exhibiting a slow growth since two months. It was excised. The pathologic sample showed spindle-shaped cells within a myxoïde matrix, with a strong reactivity for smooth muscle actin (immunohistochemical analysis). Diagnosis of cranial fasciitis was made. Due to the results of pathology, it was possible to rule out the diagnosis of sarcoma, therefore, no complementary work-up was performed. Evolution was favorable. DISCUSSION: Cranial fasciitis is a diagnosis to be considered when confronted with a firm nodule of the scalp in a infant or a young child, with or without bone involvement. This is a benign lesion but worrying pathological signs may exist, making diagnosis of benignity difficult. Exeresis of the lesion, even incomplete, protects the child from possible recurrence. Evolution is always good.

Fasciitis↗

Three-dimensional conformal radiotherapy for lung cancer: promises and pitfalls.

Lung cancer represents a major source of morbidity and mortality. Despite recent advances, long-term survival remains elusive in most patients with locally advanced cancer. A substantial proportion of these patients experience a relapse at the original site of disease within the thorax, making radiotherapy an important component of treatment. Of several approaches investigated to improve the therapeutic ratio in radiotherapy, three-dimensional conformal radiotherapy holds the most promise, primarily because it allows higher doses to be delivered to the target by improved shaping of radiation portals and conformal avoidance of normal structures. The rationale and evolution of this technology and its potential pitfalls are presented in this review.

Carcinoma, Non-Small-Cell Lung↗

Ecological and evolutionary forces shaping microbial diversity in the human intestine.

The human gut is populated with as many as 100 trillion cells, whose collective genome, the microbiome, is a reflection of evolutionary selection pressures acting at the level of the host and at the level of the microbial cell. The ecological rules that govern the shape of microbial diversity in the gut apply to mutualists and pathogens alike.

Animals↗

The evolution of bacterial transformation: sex with poor relations.

Bacteria are the only organisms known to actively take up DNA and recombine it into their genomes. While such natural transformation systems may provide many of the same benefits that sexual reproduction provides eukaryotes, there are important differences that critically alter the consequences, especially when recombination's main benefit is reducing the mutation load. Here, analytical and numerical methods are used to study the selection of transformation genes in populations undergoing deleterious mutation. Selection for transformability depends on the shape of the fitness function against mutation. If the fitness function is linear, then transformation would be selectively neutral were it not for the possibility that transforming cells may take up DNA that converts them into nontransformable cells. If the selection includes strong positive (synergistic) epistasis, then transformation can be advantageous in spite of this risk. The effect of low quality DNA (from selectively killed cells) on selection is then studied analytically and found to impose an additional cost. The limited data available for real bacterial populations suggest that the conditions necessary for the evolution of transformation are unlikely to be met, and thus that DNA uptake may have some function other than recombination of deleterious mutations.

Bacteria↗

Association of developmental regulatory genes with the development of different molar tooth shapes in two species of rodents.

While the evolutionary history of mammalian tooth shapes is well documented in the fossil record, the developmental basis of their tooth shape evolution is unknown. We investigated the expression patterns of eight developmental regulatory genes in two species of rodents with different molar morphologies (mouse, Mus musculus and sibling vole, Microtus rossiaemeridionalis). The genes Bmp-2, Bmp-4, Fgf-4 and Shh encode signal molecules, Lef-1, Msx-1 and Msx-2, are transcription factors and p21CIP1/WAF1 participates in the regulation of cell cycle. These genes are all known to be associated with developmental regulation in mouse molars. In this paper we show that the antisense mRNA probes made from mouse cDNA cross-hybridized with vole tissue. The comparisons of gene expression patterns and morphologies suggest that similar molecular cascades are used in the early budding of tooth germs, in the initiation of tooth crown base formation, and in the initiation of each cusp's development. Furthermore, the co-localization of several genes indicate that epithelial signalling centres function at the three stages of morphogenesis. The earliest signalling centre in the early budding epithelium has not been reported before, but the latter signalling centres, the primary and the secondary enamel knots, have been studied in mouse. The appearance of species-specific tooth shapes was manifested by the regulatory molecules expressed in the secondary enamel knots at the areas of future cusp tips, whilst the mesenchymal gene expression patterns had a buccal bias without similar species-specific associations.

Animals↗

Bottlenecks and broomsticks: the molecular evolution of Mycobacterium bovis.

Mycobacterium bovis is the cause of tuberculosis in cattle and is a member of the Mycobacterium tuberculosis complex. In contrast to many other pathogenic bacterial species, there is little evidence for the transfer and recombination of genes between cells. The clonality of this group of organisms indicates that the population structure is dominated by reductions in diversity, caused either by population bottlenecks or selective sweeps as entire chromosomes become fixed in the population. We describe how these forces have shaped not only the phylogeny of this group but also, at a very local level, the population structure of Mycobacterium bovis in the British Isles. We also discuss the practical implications of applying this knowledge to understanding the spread of infection and the development of improved vaccines and diagnostic tests.

Animals↗

Activation of a slow outward current by the calcium released during contraction of cultured rat skeletal muscle cells.

A slow outward current, activated during depolarization, which induced contraction in whole-cell patch-clamped rat skeletal muscle cells in primary culture [10], was extensively characterized in the present study. This current, Io, was simultaneously recorded with the contraction as a slow outward current during the test pulse, and a slow outward bell-shaped tail after repolarization. Io never appeared below the threshold potential for contraction, and the tail amplitude displayed a similar evolution with peak contraction amplitude as a function of membrane potential. This feature is consistent with the fact that Io was suppressed when contraction was blocked by 5 microM nifedipine [10], and it suggests that Io was dependent on calcium released during contraction. This was confirmed by the fact that the presence of 10 mM EGTA in the patch pipette prevented the development of both contraction and Io, and that Io could be activated during caffeine-induced contractures without applying depolarizations. Io could be carried by K+ or Cs+ ions, but not by Na+. The pharmacology of Io was different from that of Ca(2+)-dependent BK and SK channels, since it was resistant to tetraethylammonium (135 mM), charybdotoxin (25 nM) and apamin (50 nM). Io was also insensitive to 4-aminopyridine (1 mM) but blocked by 5 mM Ba2+ without change to contraction. It was concluded that rat cultured myoballs exhibit a Cs+ permeation through an atypical K+ channel type, which is activated by the calcium released during contraction.

4-Aminopyridine↗

Nonindependence of mammalian dental characters.

Studies of mammalian evolution frequently use data derived from the dentition. Dental characters are particularly central for inferring phylogenetic relationships of fossil taxa, of which teeth are often the only recovered part. The use of different aspects of dental morphology as phylogenetic signals implies the independence of dental characters from each other. Here we report, however, that, at least developmentally, most dental characters may be nonindependent. We investigated how three different levels of the cell signalling protein ectodysplasin (Eda) changed dental characters in mouse. We found that with increasing expression levels of this one gene, the number of cusps increases, cusp shapes and positions change, longitudinal crests form, and number of teeth increases. The consistent modification of characters related to lateral placement of cusps can be traced to a small difference in the formation of an early signalling centre at the onset of tooth crown formation. Our results suggest that most aspects of tooth shape have the developmental potential for correlated changes during evolution which may, if not taken into account, obscure phylogenetic history.

Animals↗

The neurons of the medial geniculate body in the mustached bat (Pteronotus parnellii).

The neurons in the medial geniculate body were studied in Golgi preparations from adult mustached bats (Pteronotus parnellii). Their somatic and dendritic configurations were compared with those of cells in other, nonecholocating mammals. A second goal was to use the thalamic nuclear subdivisions derived from Golgi material to integrate the findings in parallel studies of cytoarchitecture, immunocytochemistry, and tectothalamic connections. Three primary divisions are defined. The ventral division is large and has a stereotyped neuronal organization. Medium-sized perikarya (about 10 microns in diameter) represent tufted neurons; the fibrodendritic plexus forms laminae in the lateral part along which midbrain axons terminate. A smaller, possibly intrinsic, neuron with thin, sparse dendrites is rarely impregnated. Neurons in the larger, medial part, which represents frequencies of 60 kHz and higher, have more spherical dendritic fields; their branching pattern remains tufted, and the laminar organization was less evident. The dorsal division is about equal in size, and it has many nuclei and a corresponding neuronal diversity. These neurons are medium-sized except in the suprageniculate nucleus, where many cells are larger. Four dorsal division nuclei are recognized. Each has neurons with radiate or weakly tufted dendritic arbors. Superficial dorsal nucleus neurons are oriented from medial to lateral, imparting a slightly laminated appearance to the neuropil. A few smaller, stellate neurons with modest dendritic domains are present. Suprageniculate nucleus neurons have radiating dendritic fields that project spherically; they have fewer branches than dorsal nucleus neurons. The posterior limitans nucleus is dorsomedial to the suprageniculate nucleus; it has small neurons with long, sparsely branched dendrites. The rostral pole nucleus, included in the dorsal division on cytoarchitectonic grounds, had too few neurons impregnated to reveal its neuronal architecture. The medial division, the smallest of the main parts, is one nucleus with at least six types of cells, including the magnocellular, bushy tufted, disc-shaped, medium-sized multipolar, elongated, and small stellate neurons. There is no laminar arrangement. Many of the neurons resemble those in rodent, marsupial, carnivore, and primate auditory thalamic nuclei. Despite such morphological correspondences, functional differences, such as the evolution of combination sensitivity, suggest that structurally comparable auditory thalamic neurons may subserve diverse physiological representations.

Animals↗

Fine structure of the ordinary lateral line organ. II. The lateral line canal organ of spotted shark, Mustelus manazo.

The lateral line organ of the spotted shark is characterized by its semi-cylindrical shape. Each organ (neuromast) is so closely apposed to the next that the individual neuromasts are almost continuous. The neuromast is composed of receptor cells, supporting cells and mantle cells. The receptor cells bear one kinocilium and up to 40 stereocilia. Bi-directional arrangement of the receptor cells as occurs in teleosts was demonstrated. Afferent and efferent nerve endings were found at the base of the receptor cells. The supporting cells extend from the basal lamina to the free surface. Long microvilli and a cilium-like "ciliary rod" project from the top of each supporting cell. The cell contains relatively few elements of the Golgi apparatus and little rough endoplasmic reticulum, but mitochondria and filaments are abundant. The mantle cell limits the lateral margin of the neuromast. It is distinguished from the supporting cell because of its long crescent-shaped nucleus and scarce, short microvilli. Myelinated nerve fibres are found in the subepithelial connective tissue but not in the epithelium. The fine structure of the shark lateral line organ suggests that this organ is in an intermediated step of evolution between that of lamphrey and teleost.

Animals↗

[Sarcomatoid spindle-cell epithelioma. Anatomicoclinical study of 15 cases].

Sarcomatoid spindle cell carcinoma, which is a rather rare cancer, is of epithelial origin, but histologically resembles a connective spindle cell sarcoma. It remains subject to controversy, especially concerning the reality of epitheliomesenchymatous transformation of the neoplastic cells which, indeed, take on not only the shape but also the behaviour of connective cells. The debate is of both a dogmatic and practical nature, dogmatic in that it has bearing on the question of cellular specificity, and practical in that histological transmutation has repercussions on the macroscopic aspect of the tumor, its clinical evolution and even its behaviour vis-a-vis radiation therapy. The preferred, but not the only, sites of such tumors are the upper respiratory and digestive tracts. In many cases, they occur in subjects who many years previously had undergone radiological treatment, with the tumor appearing in the irradiated area. The problems raised by these unusual cancers explain and seem to justify the publication over the last few years of isolated cases or series of reports made in various centers. The present work concerns 15 anatomoclinical cases observed at the Institut Curie.

Adult↗

Intra-puff CO and CO2 measurements of cigarettes with iron oxide cigarette paper using quantum cascade laser spectroscopy.

The objective of this research was to apply Fourier transform infrared spectroscopy (FTIR) and tunable infrared laser differential absorption spectroscopy (TILDAS) for measuring selected gaseous constituents in mainstream (MS) and sidestream (SS) smoke for experimental cigarettes designed to reduce MS CO using iron oxide cigarette papers. These two complimentary analytical techniques are well suited for providing per puff smoke deliveries and intra-puff evolution profiles in cigarette smoke respectively. The quad quantum cascade (QC) laser high resolution infrared spectroscopy system has the necessary temporal and spectral resolution and whole smoke analysis capabilities to provide detailed information for CO and CO(2) as they are being formed in both MS and SS smoke. The QC laser system has an optimal data rate of 20 Hz and a unique puffing system, with a square wave shaped puff, that allows whole smoke to enter an 18 m, 0.3 L multi-pass gas cell in real time (0.1s cell response time) requiring no syringe or Cambridge filter pad. Another similar multi-pass gas cell with a 36 m pathlength simultaneously monitors the sidestream cigarette smoke. The smoke from experimental cigarettes manufactured with two types of iron oxide papers were compared to the smoke from cigarettes manufactured similarly without iron oxide in the paper using both instrument systems. The delivery per puff determined by the QC laser method agreed with FTIR results. MS CO intra-puff evolution profiles for iron oxide prototype cigarettes demonstrated CO reduction when compared to cigarettes without iron oxide paper. Additionally, both CO and CO(2) intra-puff evolution profiles of the cigarettes with iron oxide paper showed a significant reduction at the initial portion of the 2 s puff not observed in the non-iron oxide prototype cigarettes. This effect also was observed for ammonia and ethylene, suggesting that physical parameters such as paper porosity and burn rate are important. The SS CO and CO(2) deliveries for the experimental cigarettes evaluated remained unaffected. The iron oxide paper technology remains under development and continues to be evaluated.

Carbon Dioxide↗

[hScrib: a potential novel tumor suppressor].

Establishment and maintenance of epithelial cell polarity rely on finely tuned protein networks comprising cell surface molecules, cytoplasmic adaptors, and enzymes connected to the actin cytoskeleton. Oncogenes and tumor suppressors promote cell proliferation and resistance to apoptosis and, in many cases, alter some of these molecular scaffolds, and profoundly affect the epithelial cytoarchitecture. Reciprocally, loss of central actors of epithelial polarity unleashes normally repressed signaling pathways and perturb the shape and functions of epithelial tissues. Among the newcomers impacting on epithelial integrity, Scribble is a scaffold protein of a remarkable importance that furthermore displays a tumor suppressing activity in Drosophila melanogaster. Together with Discs Large (Dlg) and Lethal Giant Larvae (Lgl), two known tumor suppressors, Scribble acts on the correct positioning of epithelial junctions required to organize functional epithelial sheets. Scribble, Dlg and Lgl proteins are well conserved during evolution at the molecular and subcellular level implying their potential role in cell polarity and tumorigenesis in humans. Recent findings on hScrib, the human orthologue of Scribble, are discussed here.

Animals↗

Diverse evolutionary mechanisms shape the type III effector virulence factor repertoire in the plant pathogen Pseudomonas syringae.

Many gram-negative pathogenic bacteria directly translocate effector proteins into eukaryotic host cells via type III delivery systems. Type III effector proteins are determinants of virulence on susceptible plant hosts; they are also the proteins that trigger specific disease resistance in resistant plant hosts. Evolution of type III effectors is dominated by competing forces: the likely requirement for conservation of virulence function, the avoidance of host defenses, and possible adaptation to new hosts. To understand the evolutionary history of type III effectors in Pseudomonas syringae, we searched for homologs to 44 known or candidate P. syringae type III effectors and two effector chaperones. We examined 24 gene families for distribution among bacterial species, amino acid sequence diversity, and features indicative of horizontal transfer. We assessed the role of diversifying and purifying selection in the evolution of these gene families. While some P. syringae type III effectors were acquired recently, others have evolved predominantly by descent. The majority of codons in most of these genes were subjected to purifying selection, suggesting selective pressure to maintain presumed virulence function. However, members of 7 families had domains subject to diversifying selection.

Base Composition↗

Comparative analysis of ribosomal proteins in complete genomes: an example of reductive evolution at the domain scale.

A comprehensive investigation of ribosomal genes in complete genomes from 66 different species allows us to address the distribution of r-proteins between and within the three primary domains. Thirty-four r-protein families are represented in all domains but 33 families are specific to Archaea and Eucarya, providing evidence for specialisation at an early stage of evolution between the bacterial lineage and the lineage leading to Archaea and Eukaryotes. With only one specific r-protein, the archaeal ribosome appears to be a small-scale model of the eukaryotic one in terms of protein composition. However, the mechanism of evolution of the protein component of the ribosome appears dramatically different in Archaea. In Bacteria and Eucarya, a restricted number of ribosomal genes can be lost with a bias toward losses in intracellular pathogens. In Archaea, losses implicate 15% of the ribosomal genes revealing an unexpected plasticity of the translation apparatus and the pattern of gene losses indicates a progressive elimination of ribosomal genes in the course of archaeal evolution. This first documented case of reductive evolution at the domain scale provides a new framework for discussing the shape of the universal tree of life and the selective forces directing the evolution of prokaryotes.

Animals↗

CEACAMs: their role in physiology and pathophysiology.

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) belong to a group of mammalian immunoglobulin-related glycoproteins. They are involved in cell-cell recognition and modulate cellular processes that range from the shaping of tissue architecture and neovascularization to the regulation of insulin homeostasis and T-cell proliferation. CEACAMs have also been identified as receptors for host-specific viruses and bacteria in mice and humans, respectively, making these proteins an interesting example of pathogen-host co-evolution. Forward and reverse genetics in the mouse now provide powerful novel models to elucidate the action of CEACAM family members in vivo.

Animals↗

Research on red cell membrane permeability in arterial hypertension.

Arterial hypertension, including the elucidation of hypertension pathogenic mechanisms involving elements in the composition of the blood, continues to represent a topical research area. Recent work, such as nuclear magnetic resonance studies looking into red cell permeability, illustrates the presence of modifications of red cell permeability to water (RCPW) related to the stage of arterial hypertension. The identification of a significant increase of RCPW compared to that present in the population with normal arterial pressure values can be useful both in early diagnosis and in warning about a possible predisposition for this condition. At the same time, the dynamic investigation of protonic relaxation time of both intra- and extra-erythrocytic water, the assessment of proton exchange time across the red cell and the calculation of permeability to water enable one not only to diagnose arterial hypertension but also to ascertain the evolution of the disease, its complications and the effectiveness of anti-hypertensive medication. Our studies have also proven the existence of a correlation between the values of systolic arterial pressure and red cell permeability to water. The curve describing the interdependence of the two values has the shape of a bell, in the case of males. The peak of the curve is reached for a systolic pressure of 160 mmHg and gets below the values of the control group in the case of systolic pressures above 200 mmHg. The RCPW test can also be considered a valuable indicator in evaluating the risk of stroke in hypertensive patients. In the chronic therapy of arterial hypertension with various types of anti-hypertensive drugs, one can note differences in the RCPW values related to the effectiveness of the respective medication, to the clinical form and stage of the disease, the sex of the patient as well as to the existence of cerebro-vascular complications.

Adrenergic alpha-Agonists↗