18 research outputs found

    The Development of Linguistic Competences for Employability: A Training Project for Teachers

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    AbstractEmployability is a new concept that has just appeared in the Spanish educational system. Its rising importance is due to European Union educational policies which aim to provide young people with training that enables them to take part successfully in the present and future working world.This paper argues for the need to develop employability from the very start of formal education, and within this, we highlight the importance of developing linguistic competence among pre-school and primary pupils as a key element for favouring employability.To be able to do so, the teaching staff must be trained using quality education to enable them to work effectively on this competence. In this paper we present how a training program, with a specific European dimension, has been designed by a state school from the Valencian Community, to serve as a model for other schools concerned about the development of a linguistic competence that helps to improve both teachers’ and pupils’ employability

    Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer

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    The accumulation of senescent cells in the tumor microenvironment can drive tumorigenesis in a paracrine manner through the senescence-associated secretory phenotype (SASP). Using a new p16-FDR mouse line, we show that macrophages and endothelial cells are the predominant senescent cell types in murine KRAS-driven lung tumors. Through single cell transcriptomics, we identify a population of tumor-associated macrophages that express a unique array of pro-tumorigenic SASP factors and surface proteins and are also present in normal aged lungs. Genetic or senolytic ablation of senescent cells, or macrophage depletion, result in a significant decrease in tumor burden and increased survival in KRAS-driven lung cancer models. Moreover, we reveal the presence of macrophages with senescent features in human lung pre-malignant lesions, but not in adenocarcinomas. Taken together, our results have uncovered the important role of senescent macrophages in the initiation and progression of lung cancer, highlighting potential therapeutic avenues and cancer preventative strategies

    Scube3 Is Expressed in Multiple Tissues during Development but Is Dispensable for Embryonic Survival in the Mouse

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    The vertebrate Scube family consists of three independent members Scube1-3; which encode secreted cell surface-associated membrane glycoproteins that share a domain organization of at least five recognizable motifs and the ability to both homo- and heterodimerize. There is recent biochemical evidence to suggest that Scube2 is directly involved in Hedgehog signaling, acting co-operatively with Dispatched to mediate the release in soluble form of cholesterol and palmitate-modified Hedgehog ligand during long-range activity. Indeed, in the zebrafish myotome, all three Scube proteins can subtly promote Hedgehog signal transduction in a non-cell autonomous manner. In order to further investigate the role of Scube genes during development, we have generated mice with targeted inactivation of Scube3. Despite a dynamic developmental expression pattern, with transcripts present in neuroectoderm, endoderm and endochondral tissues, particularly within the craniofacial region; an absence of Scube3 function results in no overt embryonic phenotype in the mouse. Mutant mice are born at expected Mendelian ratios, are both viable and fertile, and seemingly retain normal Hedgehog signaling activity in craniofacial tissues. These findings suggest that in the mouse, Scube3 is dispensable for normal development; however, they do not exclude the possibility of a co-operative role for Scube3 with other Scube members during embryogenesis or a potential role in adult tissue homeostasis over the long-term

    Expression of <i>Scube3</i> and <i>Shh</i> in the early craniofacial region.

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    <p>Radioactive <i>in situ</i> hybridization on frontal sections. (A–D) <i>Scube3</i> expression. (A, B) At E10.5, expression is seen primarily in early ectoderm of the facial processes with transcripts also dispersed within the underlying mesenchyme; (C, D) At E11.5, expression is seen throughout the oral ectoderm, including early thickenings of the developing tooth germs, and in the craniofacial mesenchyme. (E–H) <i>Shh</i> expression. Regions of overlap between <i>Shh</i> and <i>Scube3</i> transcription are indicated by red arrows and include: (E, F) At E10.5, ectoderm of the medial nasal and maxillary processes in the midline; (G, H) At E11.5, ectoderm at the base of the nasal pits and early ectoderm of the developing teeth. fnp, fronto-nasal process; lnp, lateral nasal process; md, mandibular process; mdi, mandibular incisor tooth germs; mnp, medial nasal process; mx, maxillary process; mxm, maxillary molar tooth germs; np, nasal pit; oe, oral ectoderm.</p

    Craniofacial development in wild type and <i>Scube3<sup>−/−</sup></i> mice.

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    <p>Histological comparison of the developing craniofacial region in wild type and <i>Scube3<sup>−/−</sup></i> mice at E13.5 and E15.5. (A–C) E13.5 wild type; (D–F) E13.5 mutant; (G–I) E15.5 wild type; (J–L) E15.5 mutant. All sections are orientated in the frontal plane and stained with Haematoxylin and Eosin. Orientation is through the primary palate (left panels), central region (middle panels) and posterior region (right panels) of the secondary palate. mdi, mandibular incisor tooth germs; mdm, mandibular molar tooth germs; mxi, maxillary incisor tooth germs; mxm, maxillary molar tooth germs; nc, nasal cavity; ns, nasal septum; ps, palatal shelf; t, tongue; vi, vibrissae; vno, vomeronasal organ.</p

    Expression of <i>Scube3</i> and <i>Shh</i> at later stages of craniofacial development.

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    <p>Radioactive <i>in situ</i> hybridization on frontal sections. (A–E) <i>Scube3</i> expression. (A, B) At E13.5, expression is seen in ectoderm of the bud stage tooth buds, early palatal shelves and tongue; (C) At E14.5, expression is intense in the cap stage tooth germ; (D, E) At E15.5, strong expression continues in ectodermal tissues of the developing teeth, the vibrissae and cartilaginous condensations of the nasal cavity. (F–J) <i>Shh</i> expression. Regions of overlap are between <i>Shh</i> and <i>Scube3</i> are indicated by red arrows and include: (F, G) At E13.5, ectoderm of the early tooth buds and palatal shelves; (H) At E14.5, cells of the enamel knot within the cap stage tooth germs; (I–J) At E15.5, within the internal enamel epithelium of the bell stage tooth germs and the vibrissae. mdi, mandibular incisor tooth germs; mdm, mandibular molar tooth germs; mxi, maxillary incisor tooth germ; mxm, maxillary molar tooth germs; nc, nasal capsule; ps, palatal shelf; t, tongue; vi, vibrissae.</p

    Hedgehog signaling in wild type and <i>Scube3<sup>−/−</sup></i> mice.

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    <p>Comparison of <i>Ptch1</i> expression in the developing craniofacial region of wild type and <i>Scube3<sup>−/−</sup></i> mice at E14.5 assayed by <i>in situ</i> hybridization on frontal sections. (A–D) Wild type; (G–H) <i>Scube3<sup>−/−</sup></i>. Orientation is through the primary palate (A, E), central region (B, F) and posterior region (C, G) of the secondary palate. Red square in B, F highlights <i>Ptch1</i> expression in the cap stage maxillary molar teeth shown in D, H (red hatched line outlines the enamel organ).</p

    Scube gene function in tooth development.

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    <p>(A–I) <i>Scube</i> gene expression in the developing first molar at E14.5–16.5 assayed by <i>in situ</i> hybridization on frontal sections. (A–C) <i>Scube2</i>; (D–F) <i>Scube1</i>; (G–I) <i>Scube3</i>. (J–O) Ultra-structural view of incisor tooth development in wild type and <i>Scube3<sup>−/−</sup></i> mice at P18. In the incisor, amelogenesis commences apically and proceeds in an coronal direction, demonstrating (J, M) Secretion; (K, N) Maturation; (L, O), Post-maturation. These different stages of amelogenesis all show a characteristically normal morphology in wild-type and <i>Scube3<sup>−/−</sup></i> mice. a, ameloblasts; em, enamel matrix.</p
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