106 research outputs found

    Genetic survey of shallow populations of the Mediterranean red coral [ Corallium rubrum (Linnaeus, 1758)]: new insights into evolutionary processes shaping nuclear diversity and implications for conservation

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    International audienceCombined action from over-harvesting and recent mass mortality events potentially linked to ongoing climate changes has led to new concerns for the conservation of shallow populations (5-60 m) of Corallium rubrum, an octocorallian that is mainly found in the Mediterranean Sea. The present study was designed to analyse population structure and relationships at different spatial scales (from 10s of meters to 100s of kilometres) with a focus on dispersal pattern. We also performed the first analysis of the distribution of genetic diversity using a comparative approach between regional-clusters and samples. Forty populations dwelling in four distinct regions between 14 and 60 m in depth were genotyped using 10 microsatellites. Our main results indicate (i) a generalized pair-sample differentiation combined with a weak structure between regional-clusters; (ii) the occurrence of isolation by distance at the global scale, but also within two of the three analysed regional-clusters; (iii) a high level of genetic diversity over the surveyed area with a heterogeneous distribution from regional-cluster to sample levels. The evolutionary consequences of these results are discussed and their management implications are provided

    CD98hc facilitates B cell proliferation and adaptive humoral immunity.

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    The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

    Regional and local environmental conditions do not shape the response to warming of a marine habitat-forming species

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    The differential response of marine populations to climate change remains poorly understood. Here, we combine common garden thermotolerance experiments in aquaria and population genetics to disentangle the factors driving the population response to thermal stress in a temperate habitatforming species: the octocoral Paramuricea clavata. Using eight populations separated from tens of meters to hundreds of kilometers, which were differentially impacted by recent mortality events, we identify 25 degrees C as a critical thermal threshold. After one week of exposure at this temperature, seven of the eight populations were affected by tissue necrosis and after 30 days of exposure at this temperature, the mean % of affected colonies increased gradually from 3 to 97%. We then demonstrate the weak relation between the observed differential phenotypic responses and the local temperature regimes experienced by each population. A significant correlation was observed between these responses and the extent of genetic drift impacting each population. Local adaptation may thus be hindered by genetic drift, which seems to be the main driver of the differential response. Accordingly, conservation measures should promote connectivity and control density erosion in order to limit the impact of genetic drift on marine populations facing climate change

    CD98 Increases Renal Epithelial Cell Proliferation by Activating MAPKs

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    CD98 heavy chain (CD98hc) is a multifunctional transmembrane spanning scaffolding protein whose extracellular domain binds with light chain amino acid transporters (Lats) to form the heterodimeric amino acid transporters (HATs). It also interacts with β1 and β3 integrins by its transmembrane and cytoplasmic domains. This interaction is proposed to be the mechanism whereby CD98 mediates cell survival and growth via currently undefined signaling pathways. In this study, we determined whether the critical function of CD98-dependent amino acid transport also plays a role in cell proliferation and defined the signaling pathways that mediate CD98-dependent proliferation of murine renal inner medullary collecting duct (IMCD) cells. We demonstrate that downregulating CD98hc expression resulted in IMCD cell death. Utilizing overexpression studies of CD98hc mutants that either lacked a cytoplasmic tail or were unable to bind to Lats we showed that CD98 increases serum-dependent cell proliferation by a mechanism that requires the CD98hc cytoplasmic tail. We further demonstrated that CD98-dependent amino acid transport increased renal tubular epithelial cell proliferation by a mechanism that does not require the CD98hc cytoplasmic tail. Both these mechanisms of increased renal tubular epithelial cell proliferation are mediated by Erk and p38 MAPK signaling. Although increased amino transport markedly activated mTor signaling, this pathway did not alter cell proliferation. Thus, these studies demonstrate that in IMCD cells, the cytoplasmic and extracellular domains of CD98hc regulate cell proliferation by distinct mechanisms that are mediated by common MAPK signaling pathways

    High Refractive Index Silicone Gels for Simultaneous Total Internal Reflection Fluorescence and Traction Force Microscopy of Adherent Cells

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    Substrate rigidity profoundly impacts cellular behaviors such as migration, gene expression, and cell fate. Total Internal Reflection Fluorescence (TIRF) microscopy enables selective visualization of the dynamics of substrate adhesions, vesicle trafficking, and biochemical signaling at the cell-substrate interface. Here we apply high-refractive-index silicone gels to perform TIRF microscopy on substrates with a wide range of physiological elastic moduli and simultaneously measure traction forces exerted by cells on the substrate

    The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

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    Background: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. Methods: SLC3A2 was assessed at the genomic level, using METABRIC data (n=1,980), and proteomic level, using immunohistochemistry on TMA sections constructed from a large well-characterised primary BC cohort (n=2,500). SLC3A2 expression was correlated with clinicopathological parameters, molecular subtypes, and patient outcome. Results: SLC3A2 mRNA and protein expression were strongly correlated with higher tumour grade and poor Nottingham prognostic index (NPI). High expression of SLC3A2 was observed in triple negative (TN), HER2+, and ER+ high proliferation subtypes. SLC3A2 mRNA and protein expression were significantly associated with the expression of c-MYC in all BC subtypes (p<0.001). High expression of SLC3A2 protein was associated with poor patient outcome (p<0.001)), but only in the ER+ high proliferation (p=0.01) and triple negative (p=0.04) subtypes. In multivariate analysis SLC3A2 protein was an independent risk factor for shorter breast cancer specific survival (p<0.001). Conclusions: SLC3A2 appears to play a role in the aggressive BC subtypes driven by MYC and could act as a potential prognostic marker. Functional assessment is necessary to reveal its potential therapeutic value in the different BC subtypes

    Neue linguistische Methoden und arbeitstechnische Verfahren in der Erschliessung der ägyptischen Grammatik

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    15 páginas, 1 tabla, 6 figuras.Does diversity beget diversity? Diversity includes a diversity of concepts because it is linked to variability in and of life and can be applied to multiple levels. The connections between multiple levels of diversity are poorly understood. Here, we investigated the relationships between genetic, bacterial, and chemical diversity of the endangered Atlanto-Mediterranean sponge Spongia lamella. These levels of diversity are intrinsically related to sponge evolution and could have strong conservation implications. We used microsatellite markers, denaturing gel gradient electrophoresis and quantitative polymerase chain reaction, and high performance liquid chromatography to quantify genetic, bacterial, and chemical diversity of nine sponge populations. We then used correlations to test whether these diversity levels covaried. We found that sponge populations differed significantly in genetic, bacterial, and chemical diversity. We also found a strong geographic pattern of increasing genetic, bacterial, and chemical dissimilarity with increasing geographic distance between populations. However, we failed to detect significant correlations between the three levels of diversity investigated in our study. Our results suggest that diversity fails to beget diversity within a single species and indicates that a diversity of factors regulates a diversity of diversities, which highlights the complex nature of the mechanisms behind diversityResearch funded by grants from the Agence Nationale de la Recherche (ECIMAR), from the Spanish Ministry of Science and Technology SOLID (CTM2010-17755) and Benthomics (CTM2010-22218-C02-01) and the BIOCAPITAL project (MRTN-CT-2004-512301) of the European Union. This is a contribution of the Consolidated Research Group ‘‘Grupo de Ecologı´a Bento´nica,’’ SGR2009-655.Peer reviewe

    Measurements of Elastic Moduli of Silicone Gel Substrates with a Microfluidic Device

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    Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM). Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the device to gels with elastic moduli in a range from 0.4 to 300 kPa that are all prepared by mixing two components of a transparent commercial silicone Sylgard 184. The elastic modulus is measured by tracking beads on the gel surface under a wide-field fluorescence microscope without any other specialized equipment. The measurements have small and simple to estimate errors and their results are confirmed by conventional tensile tests. A master curve is obtained relating the mixing ratios of the two components of Sylgard 184 with the resulting elastic moduli of the gels. The rigidity of the silicone gels is less susceptible to effects from drying, swelling, and aging than polyacrylamide gels and can be easily coated with fluorescent tracer particles and with molecules promoting cellular adhesion. This work can lead to broader use of silicone gels in the cell biology laboratory and to improved repeatability and accuracy of cell traction force microscopy and rigidity sensing experiments

    Human Endometrial CD98 Is Essential for Blastocyst Adhesion

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    BACKGROUND: Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. METHODS AND PRINCIPAL FINDINGS: Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. CONCLUSIONS: These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window
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