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At least 127 records · Page 7Linked to original sources

Biogenesis and function of IgM: the role of the conserved mu-chain tailpiece glycans.

The tailpiece of secretory Ig-mu-chains (mu(s)tp) is highly conserved throughout evolution: in particular, a carboxy-terminal cysteine residue (Cys575) and a glycan linked to Asn563 are found in all species sequenced so far. Here we show that the mu(s)tp oligosaccharide moieties are important for the binding of J-chains and for the process of IgM polymerization. In the absence of the mu(s)tp glycans, pentamers cannot be assembled and polymers containing six or more subunits are secreted. Despite their increased valency, these molecules have a lower association rate with antigen than wild-type polymers. Unexpectedly, the C-terminal oligosaccharides also affect kinetic parameters on unpolymerized subunits. Thus, monomers lacking the C-terminal sugars because of either site-directed mutagenesis or selective enzymatic deglycosylation with endoglycosidase H, have a lower k(on) for the antigen. Taken together, our results indicate that the C-terminal mu-chain glycans can shape the structure of mu(s2)L2 subunits and their further assembly into polymers.

Animals↗

The shaping of the T cell repertoire.

By combining a TCRbeta transgene with a TCRalpha minilocus comprised of a single V and two J gene segments, we engineered a mouse line exhibiting ample but focused TCR diversity, restricted to CDR3alpha. Using single-cell PCR and high-throughput sequencing, we have exploited this system to scrutinize T cell repertoire selection and evolution. Some striking observations emerged: (1) thymic selection produces a repertoire that is very "bumpy," with marked overrepresentation of a subset of sequences; (2) MHC class I- and class II-restricted TCRs can be distinguished by minute, single-residue changes in CDR3alpha; and (3) homeostatic expansion and survival in the periphery can markedly remold the postselection repertoire, likely reflecting variability in the potential of cells displaying different TCRs to respond to homeostatic cues.

Animals↗

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↗

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↗

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↗

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↗

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↗

Longitudinal dynamics of gene expression and metabolomics in an aging population cohort.

Multiomic profiling provides a comprehensive physiological overview at the molecular level, but understanding of its spatiotemporal dynamics remains limited in human populations. We profiled longitudinal whole-blood gene expression and metabolite levels in 335 females over 8 years. Levels of 5061 genes and 181 metabolites changed over time, with individual trajectories often diverging from population-level trends. Longitudinally variable genes showed cell type specificity and enrichment for aging-relevant pathways, including cardiometabolic and neurodegenerative disorders. Longitudinal trajectories were further shaped by genetics, circadian rhythm, seasonality, and environmental pollutant exposures. Integrative analyses revealed extensive static and time-variable cross-omic connectivity. Longitudinal profiling offers insight into the temporal evolution of age-related conditions at the molecular level, and understanding individual variation within these longitudinal patterns will be essential for future precision medicine approaches.

Female↗

Comparison of vegetative anatomy of Piperales. II. Leaf.

Many characters of leaf (hair, hypodermal cells, palisade layers, intercellular space, distinction between spongy and palisade parenchyma, "palisade ratio", distribution of collenchyma and sclerenchyma, presence or absence of starch grains, calcium oxalate crystals, number, shape and arrangement of bundles of petiole) are useful distinguishing characters. Reduction of palisade layers seems to be the trend of evolution in Piper and Peperomia.

Plants↗

Plant profilins rescue the aberrant phenotype of profilin-deficient Dictyostelium cells.

To characterize the function of plant profilins in vivo, we expressed two pollen specific Zea mays (maize) profilin isoforms in profilin-minus Dictyostelium discoideum mutants. In maize, profilins exist as a multigene family containing 4 or more members which are highly similar to each other but substantially less similar to profilins from animals and lower eukaryotes. Previously we have shown that D. discoideum profilin-minus cells have an aberrant phenotype due to defects in cell shape, cytokinesis, and development. These defects could be rescued by introducing the pollen-specific profilins 1 or 2 from maize using a newly constructed expression vector. Expression of the heterologous profilins in Dictyostelium clones was assayed by affinity purification of the pollen profilins with poly-proline agarose and by immunoblotting with a polyclonal antiserum raised against maize pollen profilin. In contrast to the profilin-minus mutants, Dictyostelium cells expressing plant profilins showed normal cell shape, contained less F-actin, and were able to form fruiting bodies. These data provide genetic evidence that maize pollen profilins, even though they are specific for a distinct developmental stage, share functional properties with profilin from a lower eukaryote and apparently act as G-actin-sequestering proteins in this system.

Animals↗

A model of the early evolution of soma-to-germline feedback.

The V-genes of the immunoglobulin locus in vertebrates code for a part of the heavy and light chain variable regions of antibodies and are extremely variable. Steele (1979) has developed a theory that explains the evolution of adaptive immune response by a soma-to-germline flow of cDNAs derived from somatically mutated V-genes. Here we model the early evolution of soma-to-germline feedback in a population living in a changing viral environment in terms of the dynamics of an initially rare genetic modifier that controls transfer of V-genes to germ cells' DNA. It is shown that a modifier invades the population and creates a great variety of V-genes if the environment follows stepwise temporal changes, i.e. a soma-to-germline feedback machinery evolves in a population if newly derived V-alleles still play a role in protecting the population against foreign antigens in some following generations. The distribution of the age of V-genes evolves to a bell-shaped curve the width and the maximum of which depend mainly on selection strength. Two phases of modifier evolution are distinguished. In the first phase, the dynamics are slow while the number of different V-genes is small. In the second phase, when a sufficiently large number of different V-genes is created, the modifier increases faster in frequency. Linkage of V-genes and the modifier enhances the rate of evolution.

Animals↗

Contributions of the Mac-1 glycoprotein family to adherence-dependent granulocyte functions: structure-function assessments employing subunit-specific monoclonal antibodies.

MAb directed at the alpha-subunits of Mac-1 (alpha M), LFA-1 (alpha L), p150,95 (alpha X), or their common beta-subunit were used to characterize the contributions of the Mac-1 glycoprotein family to granulocyte adherence reactions. Inhibitory effects of these MAb in incubation experiments with normal granulocytes indicated distinct adhesive contributions of each subunit. Significantly greater adherence, and inhibition of adherence by anti alpha M, alpha X, and beta MAb, was observed under chemotactic conditions designed to "up-regulate" the surface expression of the alpha M beta and alpha X beta complexes. Adherence to protein-coated glass and binding of albumin-coated latex beads were significantly inhibited by anti-beta greater than anti-alpha M (OKM-10, M1/70, LM2/1.6 and OKM-1) greater than anti-alpha X greater than anti-alpha L MAb, but no effects of anti-HLA, AB, or anti-CR-1 MAb were evident. A similar rank order of inhibition was observed in granulocyte aggregation assays in response to C5a, PMA, or f-Met-Leu-Phe. Significant inhibition of directed migration by anti-beta or anti-alpha M (OKM-1 or OKM-10) MAb was observed in subagarose but not Boyden chemotaxis assays; inhibition was dependent on a continuous cell exposure to anti-Mac-1 alpha or beta during the assay, suggesting that a continuum of new Mac-1 expression is required for directed translocation. Phagocytosis of Oil-Red-O paraffin or zymosan selectively opsonized with C3-derived ligands was significantly inhibited by anti-alpha M MAb (OKM-10 greater than LM2/1.6 greater than M1/70 greater than OKM-1) or by combinations of anti-alpha M + anti-CR-1 MAb, but only minimal inhibitory effects of anti-beta MAb and no effects of anti-alpha L or anti-alpha X MAb were seen. Similarly, complement-dependent phagocytosis-associated lactoferrin release, ingestion, and intracellular killing of Staphylococcus aureus 502A, and binding of iC3b-opsonized SRBC, were significantly inhibited by anti-alpha M (OKM-10, M1/70) or combinations of anti-alpha M + anti-CR-1 MAb, but not by anti-beta, alpha L, or alpha X MAb. Notably, none of the anti-Mac-1 MAb demonstrated inhibitory effects in assays of adherence-independent functions including shape change, specific f-Met-Leu-3H-Phe binding, O-2 generation, chemiluminescence evolution, or lactoferrin release in response to PMA.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Salmonellosis: host immune responses and bacterial virulence determinants.

The lifestyle of bacterial pathogens requires them to establish infection in the face of host immunity. Upon entering a potential host, a variety of interactions are initiated, the outcome of which depends upon a myriad of attributes of each of the participants. In this review we discuss the interactions that occur between pathogenic Salmonella species and the host immune systems, but when appropriate to broaden perspective, we have provided a general overview of the interactions between bacterial pathogens and animal hosts. Pathogenic Salmonella species possess an array of invasion genes that produce proteins secreted by a specialized type III secretion apparatus. These proteins are used by the bacteria to penetrate the intestinal mucosa by invading and destroying specialized epithelial M cells of the Peyer's patches. This maneuver deposits the bacteria directly within the confines of the reticuloendothelial system. The host responds to these actions with nonspecific phagocytic cells and an inflammatory response as well as by activating specific cellular and humoral immune responses. Salmonella responds to this show of force directly. It appears that the bacteria invade and establish a niche within the very cells that have been sent to destroy them. Efforts are underway to characterize the factors that allow these intracellular bacteria to customize intracellular vacuoles for their own purposes. It is the constant play between these interactions that determines the outcome of the host infection, and clearly they will also shape the evolution of new survival strategies for both the bacterium and the host.

Animals↗