Global ETD Search

1	Les mécanismes de la neuropathie auditive AUNA1 / Mechanisms of the auditory neuropathy AUNA1 Surel, Clément 19 December 2016 (has links) La neuropathie auditive est une forme de surdité caractérisée par une atteinte des cellules ciliées internes (qui détectent les ondes sonores et les transforment en message nerveux) et/ou des neurones afférents primaires (qui véhiculent les messages nerveux jusqu'au noyau cochléaire), associée à une activité normale des cellules ciliées externes (qui amplifient les ondes sonores). AUNA1 est la première neuropathie auditive héréditaire à avoir été décrite. Elle est causée par une mutation ponctuelle située dans le promoteur du gène DIAPH3, résultant en une surexpression de DIAPH3. La protéine DIAPH3, un membre de la famille des formines, est connue pour promouvoir la nucléation et l’élongation des filaments d’actine ainsi que la stabilisation des microtubules. Nous avons étudié les mécanismes d’AUNA1 à partir d’un modèle murin transgénique surexprimant le gène diap3, l’orthologue murin de DIAPH3. Les souris transgéniques développent une surdité dont les caractéristiques sont semblables à celles d’AUNA1. Cette surdité est due à une perte d’activité des cellules ciliées internes. L’activité synaptique et les courants potassiques de ces cellules ne sont pas altérés. En revanche, la microscopie électronique révèle une fusion des stéréocils (expansions cytoplasmiques qui permettent la détection des ondes sonores) et une déformation de la plaque cuticulaire (plateforme qui assure l’ancrage des stéréocils). Par la technique d’immunomarquage, nous avons mis en évidence une invasion de la plaque cuticulaire par des microtubules. Enfin, nous avons démontré que la protéine Diap3 est localisée dans la plaque cuticulaire des cellules ciliées internes, suggérant ainsi que la surexpression de diap3 provoque un remodelage du réseau de microtubule des cellules ciliées internes, à l’origine de la surdité AUNA1. / Auditory neuropathy is a type of deafness characterized by an alteration of the inner hair cells (which detect the acoustic waves and transform them into neural messages) and/or of the primary afferent neurons (which conduct the neural messages to the cochlear nucleus), associated with a normal activity of the outer hair cells (which amplify the acoustic waves).AUNA1 is the first hereditary auditory neuropathy which has been described. It is caused by a point mutation in the promoter of the DIAPH3 gene, resulting in an overexpression of DIAPH3. The DIAPH3 protein, a formin family member, is known to promote the actin filament nucleation and elongation and to stabilize the microtubules.We studied the AUNA1 mechanisms using a transgenic mouse model which overexpresses the diap3 gene, the mouse homologue of DIAPH3. Transgenic mice develop a deafness whose characteristics are similar to the ones of AUNA1. The hearing loss is due to a defect in the inner hair cell activity. The synaptic activity and the potassium currents of these cells are not altered. However, electron microscopy reveals a fusion of the stereocilia (cytoplasmic expansions which detect the acoustic waves) and a disruption of the cuticular plate (plateform which maintains stereocilia). By immunolabeling, we showed an invasion of the cuticular plate by microtubules. Eventually, we demonstrated that Diap3 is located in the inner hair cell cuticular plate, suggesting that the overexpression of diap3 provokes a remodeling of the inner hair cell microtubule network, underlying the AUNA1 deafness. Surdité Cochlée Cellule ciliée interne Diaphanous Microtubule Deafness Cochlea Inner hair cell Diaphanous Microtubule
2	Investigation into the molecular mechanisms governing Drosophila embryonic hemocyte migration in vivo Comber, Kate January 2014 (has links) Accumulating evidence highlights the importance of studying the migration of cells within the context of their natural environment as manipulating the substrate on which a cell is migrating can have a dramatic impact on the mode/mechanisms employed by cells during migration. Central to this phenomenon is the requirement of adhesion to the ECM in order to gain traction during migration. Integrins constitute the main family of cell receptors involved in mediating cell-ECM interactions during motility. Whilst traditionally two-dimensional cell culture studies have placed emphasis on the importance of these receptors for spreading and migration, it has become evident that within more confined environments these receptors, at least for some cell types, are less crucial. In this research we utilise Drosophila embryonic hemocytes as an in vivo model for cell migration. We show that whilst hemocytes migrate within confined environments in vivo, these cells depend on integrins for powering both developmental and inflammatory migrations. Given the close association between these receptors and the actin cytoskeleton we were surprised to discover that removal of the main β integrin subunit, Myospheroid, did not affect cell spreading in vivo and had only a small impact on lamellipodial structure and dynamics. Furthermore we discovered that, in contrast to other cell types previously analysed, removal of this integrin subunit in hemocytes was not accompanied by an increase in the rate of actin retrograde flow within the protrusions, which we believe could reflect abrogation of a positive feedback between Rho, ROCK and Myosin II contraction. Instead, we discover a key role for integrins in regulating the microtubule cytoskeleton, in the maintenance of a polarised microtubule bundle, termed a ‘microtubule-arm’. Although the molecular mechanisms by which this stabilisation is coordinated have yet to be identified, this provides important insight into the co-regulation of adhesion and microtubule cytoskeleton important for the migratory behaviour of these cells. Cell migration reflects the complex and integrated regulation of the actin cytoskeleton by diverse families of actin regulatory proteins. Using hemocytes as a model system, we also explore the regulatory interactions between two main actin regulatory proteins, Diaphanous and Enabled, in vivo. Whilst the function of these proteins in the formation of filopodial protrusions is overlapping, recent research has highlighted the ability of these proteins to regulate the activity of one another. We find that co-expression of Enabled in hemocytes is able to rescue the morphological and migratory defects resulting from overexpression of active Diaphanous. Thus, data here presents Enabled as a negative regulator of Diaphanous, which may play an important role in the migration of hemocytes in vivo. 571.6
3	Une peinture volumique diaphane / A diaphanous volume paint Casado, Richard 23 November 2017 (has links) Résumé. Le sujet de ce mémoire d'arts plastiques est d'étudier « le branle du statut de l'image » selon l'expression d' Anca Vasiliu , mais d'une image contemporaine par le biais d'une peinture de recherche. Cette étude passe par le paradigme de l'aura Benjaminienne puis son application rapportée à la notion de matrice (chôra Platonicienne) en condition de lumière particulière (le diaphane). Une forme sans forme, celle d'une « chôra diaphane » , comme volumétrie transparente du tableau est déduite et s'agrège autour d'un volume reformulant son percept.C'est ainsi que l'analyse étudie les propriétés d’un subjectile devenu biface pour le plasticien et le regardeur où la couleur incorpore la rétention lumineuse singulière d’un châssis. L'étude débouche sur un constat plastique, celui d'un dispositif cathartique hybride nécessitant un travail de synthèse : la percolation du feuil peint par le regard où des plans (toiles) complexes sont explorés. La conclusion se porte alors sur l'évolution du médium Peinture en direction de ce subjectile à l'aura reformulée dans l'ensemble du champ dit « postmoderne ». / Abstract. The subject of this visual arts dissertation is to study "the motion of the status of the image", a contemporary image through a painting of research. This study goes through the paradigm of the Benjaminian aura and its application related to the notion of matrix (platonic chôra) in particular light condition (diaphanous). A formless form, that of a « diaphanous chôra », as a transparent volumetry of the painting is deduced and aggregates around a volume reformulating its percept. This is how the analysis studies the properties of a substrate that has become biface for the visual artist and the viewer where color incorporates the singular luminous retention of a frame. The study leads to a plastic finding, that of a hybrid cathartic device requiring a synthesis : the percolation of the film painted by the look where complex plans (canvases) are explored. The conclusion then turns on the evolution of the painting medium in the direction of this substrate to the reformulated aura throughout the "postmodern" field. Diaphane Volume Voluminosité Peinture
4	La formine Diaphanous est essentielle pour l’organisation et la maturation de l’anneau contractile pendant la cytokinèse Ruella, Yvonne 12 1900 (has links) Une cellule se divise en deux par le processus de cytokinèse. Elle requiert la coordination de plusieurs composants pour éviter la formation des cellules potentiellement cancéreuses. Premièrement, un anneau contractile (AC) dépendant de l’actine et de Rho-GTP diminue le diamètre de la cellule jusqu’à la formation d’une structure plus stable indépendante de l’actine, l’anneau du midbody (AM) qui guide l’éventuelle séparation des cellules sœurs. Diaphanous (Dia) est une formine dépendante de Rho responsable de l’agencement des filaments d’actine non ramifiés qui se localise à l’AC et est essentielle à la cytokinèse. Nous avons étudié le rôle de Dia pendant la cytokinèse par microscopie de haute résolution en temps réel pour suivre le comportement dynamique des protéines fluorescentes (PF) dans des cellules de Drosophile S2. Une construction fonctionnelle de Dia-PF est recrutée à l’AC et l’AM indépendamment de l’actine mais est absente dans l’AM mature. Dia quitte l’AM au même temps où l’AM dévient indépendant d’actine. La déplétion de Dia par ARN interférant ralentit la constriction de l’AC, augmente les oscillations et, dans 70% des cas, les cellules échouent la cytokinèse pendant la constriction, suggérant que Dia a un rôle dans l’organisation de l’AC. LifeAct-PF, une sonde pour F-actine, dévoile une diminution des filaments d’actine spécifique à l’AC des cellules dépourvues de Dia pendant que Anilline-PF et Myosine-PF sont recrutées en puncta. Ces résultats soutiennent un modèle où Dia nuclée des filaments d’actine qui permettent l’organisation dynamique de l’AC et la perte de Dia régule la transition à l’AM stable indépendant d’actine. / Cytokinesis is the intricate process by which eukaryotic cells divide in two. It involves the coordination of many components in order to avoid the formation potentially cancerous cells. Initially, a Rho GTPase- and actomyosin-dependent contractile ring (CR) drives constriction at the cell equator until a stable actin-independent midbody ring (MR) forms and ultimately guides the separation of the two sister cells. Diaphanous (Dia), is a Rho-dependent formin that nucleates unbranched actin filaments, localises to the cleavage furrow and is required for cytokinesis. We have examined the role of Dia during cytokinesis by time lapse video microscopy of Drosophila S2 cells expressing markers tagged with fluorescent proteins (FPs). A functional Dia-FP was recruited to the CR independently of actin and stayed in the nascent MR, but was absent from the mature MR. The timing of its disappearance coincided with the transition of the MR to an actin-independent structure. RNAi-mediated depletion of Dia slowed furrow ingression, enhanced furrow oscillations and, in 70% of the failures, prevented furrow completion, consistent with a role for Dia in CR organization. The F-actin probe, LifeAct-FP, revealed a decrease in F-actin in Dia-depleted cells specifically at the CR while Anillin-FP and Myosin-FP were aberrantly recruited in punctate structures. Our findings are consistent with a model in which Dia nucleates actin filaments at the CR to maintain the dynamic organization of the actin-dependent CR and that the regulated loss of Dia from the nascent MR guides the formation of the stable, actin-independent MR. Diaphanous Cytokinèse Actine Anneau contractile Anneau du midbody Cytokinesis Actin Contractile ring Midbody ring
5	Extracellular S100A4 induces human thyroid cancer cell migration Medapati, Manoj Reddy 28 August 2013 (has links) Human thyroid cancer is the most commonly occurring cancer of the endocrine gland having good survival rate, but some patients show recurrence with an invasive phenotype and treatment failures. The mechanisms behind this invasive phenotype are not well understood in TC. Previously our group has identified a pro-migratory role of relaxin-like peptides in thyroid cancer that is mediated by S100A4. We have observed in human TC cells that extracellular S100A4 induces migration and activates ERK1/2, JNK/SAPK and NFkB signaling pathways. Employing immunohistochemistry and immunofluorescence we have identified the expression of RAGE in human TC primary cells, cell lines, and in tumor tissues but not in normal thyroid tissues. We showed that S100A4 binds to RAGE in TC cells and that RAGE and its cytoplasmic partner Dia-1 mediate the S100A4-induced migration of TC cells. This study identified a crucial role of RAGE in TC cell migration induced by S100A4. TC Thyroid Cancer RAGE DM Distant Metastasis Dia-1 Diaphanous-1
6	Extracellular S100A4 induces human thyroid cancer cell migration Medapati, Manoj Reddy 28 August 2013 (has links) Human thyroid cancer is the most commonly occurring cancer of the endocrine gland having good survival rate, but some patients show recurrence with an invasive phenotype and treatment failures. The mechanisms behind this invasive phenotype are not well understood in TC. Previously our group has identified a pro-migratory role of relaxin-like peptides in thyroid cancer that is mediated by S100A4. We have observed in human TC cells that extracellular S100A4 induces migration and activates ERK1/2, JNK/SAPK and NFkB signaling pathways. Employing immunohistochemistry and immunofluorescence we have identified the expression of RAGE in human TC primary cells, cell lines, and in tumor tissues but not in normal thyroid tissues. We showed that S100A4 binds to RAGE in TC cells and that RAGE and its cytoplasmic partner Dia-1 mediate the S100A4-induced migration of TC cells. This study identified a crucial role of RAGE in TC cell migration induced by S100A4. TC Thyroid Cancer RAGE DM Distant Metastasis Dia-1 Diaphanous-1
7	Transparency and learning spaces Finau, Emily 08 April 2011 (has links) This thesis explores the various meanings and implications of transparency in architecture and in learning environments in particular. Architectural transparency, achieved through choice of materials and principles of formal composition, creates a diversity of relationships and can facilitate visual, conceptual, and functional clarity as well as offering simultaneous perception of different spaces. It offers a range of phenomenological qualities and so provides an opportunity to explore and complicate such dichotomies as translucency and opacity, openness and closure, and public space and private space. While celebrated throughout modern and contemporary architecture, transparency raises issues of privacy and safety even as it breaks down hierarchies and social boundaries. The research-based design of transparency in a school building necessitates careful planning to achieve a balance between the access to views, natural light, fresh air, and social interaction that transparency may bring and the continuing obligation to provide a safe, secure environment for schoolchildren. Design Expanded meshes Metal fabrics Netherlands Embassy in Berlin Polycarbonate Multi-cinema Rotterdam Koen van Velsen School size Phoenix Union Bioscience High School Oslo International School Betty H. Fairfax High School Blythewood High School Diaphanous metals Fabric Aerogel Schematic Spatial projection Classroom design Patterned carpet Carpet floor plan Rem Koolhaas OMA Plastic Glass Transparent materials School program School design Security Transparent security Two-way One-way Health Safety Activity levels Hormone patterns Attendance Visual Surface Phenomenal Learning environment Classroom Daylighting Ventilation School High school Small school Small school initiative Small learning community High school transformation Therrell High School Atlanta Public Schools Teen depression Blood pressure Transparency in architecture School facilities

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