Caractérisation moléculaire du rôle de Lhx2 dans le développement de l'oeil et du cerveau

Le développement du système nerveux central (SNC) chez les vertébrés est un processus d'une extrême complexité qui nécessite une orchestration moléculaire très précise. Certains gènes exprimés très tôt lors du développement embryonnaire sont d'une importance capitale pour la formation du SNC. Parmi ces gènes, on retrouve le facteur de transcription à Lim homéodomaine Lhx2. Les embryons de souris mutants pour Lhx2 (Lhx2-/-) souffre d'une hypoplasie du cortex cérébral, sont anophtalmiques et ont un foie de volume réduit. Ces embryons mutants meurent in utero au jour embryonnaire 16 (e16) dû à une déficience en érythrocytes matures. L'objectif principal de cette thèse est de caractériser le rôle moléculaire de Lhx2 dans le développement des yeux et du cortex cérébral. Lhx2 fait partie des facteurs de transcription à homéodomaine exprimé dans la portion antérieure de la plaque neurale avec Rx, Pax6, Six3. Le développement de l'oeil débute par une évagination bilatérale de cette région. Nous démontrons que l'expression de Lhx2 est cruciale pour les premières étapes de la formation de l'oeil. En effet, en absence de Lhx2, l'expression de Rx, Six3 et Pax6 est retardée dans la plaque neurale antérieure. Au stade de la formation de la vésicule optique, l'absence de Lhx2 empêche l'activation de Six6 (un facteur de transcription également essentiel au développement de l'œil). Nous démontrons que Lhx2 et Pax6 coopèrent en s'associant au promoteur de Six6 afin de promouvoir sa trans-activation. Donc, Lhx2 est un gène essentiel pour la détermination de l'identité rétinienne au niveau de la plaque neurale. Plus tard, il collabore avec Pax6 pour établir l'identité rétinienne définitive et promouvoir la prolifération cellulaire. De plus, Lhx2 est fortement exprimé dans le télencéphale, région qui donnera naissance au cortex cérébral. L'absence de Lhx2 entraîne une diminution de la prolifération des cellules progénitrices neurales dans cette région à e12.5. Nous démontrons qu'en absence de Lhx2, les cellules progénitrices neurales (cellules de glie radiale) se différencient prématurément en cellules progénitrices intermédiaires et en neurones post-mitotiques. Ces phénotypes sont corrélés à une baisse d'activité de la voie Notch. En absence de Lhx2, DNER (un ligand atypique de la voie Notch) est fortement surexprimé dans le télencéphale. De plus, Lhx2 et des co-répresseurs s'associent à la chromatine de la région promotrice de DNER. Nous concluons que Lhx2 permet l'activation de la voie Notch dans le cortex cérébral en développement en inhibant la transcription de DNER, qui est un inhibiteur de la voie Notch dans ce contexte particulier. Lhx2 permet ainsi la maintenance et la prolifération des cellules progénitrices neurales.Central nervous system (CNS) development in vertebrates is an extremely complex process that requires tight molecular control. Some very early expressed genes during embryonic development are of tremendous importance for CNS development. Among those, we find the LIM homeodomain protein Lhx2. Embryos that lack Lhx2 (Lhx2-/-) suffer from cerebral cortex hypoplasia, are anophtalmic and have smaller liver. The mutant embryos die in utero at embryonic day 16 (e16) due to a deficit in mature erythrocytes. The principal objective of this thesis was to characterize the molecular function of Lhx2 in eye and cerebral cortex development. Lhx2 is a part of the homeodomain transcription factors expressed in the anterior neural plate along with Rx, Pax6 and Six3. Eye development starts by a bilateral evagination of this region. We show here that Lhx2 expression is crucial for the first steps of eye formation. Indeed, in absence of Lhx2, Rx, Six3 and Pax6 expression is delayed in the anterior neural plate. At the optic vesicle stage, Lhx2 mutation precludes the initiation of Six6 expression (an homeodomain transcription factor essential for eye development). We demonstrate that Lhx2 and Pax6 bind to Six6 promoter and cooperate for its trans‐activation. So, Lhx2 is essential for retinal identity determination in the neural plate. Later on, it cooperates with Pax6 to establish definitive retinal identity and promote cell proliferation. Lhx2 is strongly express in the telencephalon, the embryonic region that will give rise to cerebral cortex. Lhx2 ablation causes a decrease in neural progenitor cells proliferation in this region. We show that the lack of Lhx2 causes a premature differentiation of the radial glia cells into intermediate progenitors and post‐mitotic neurons. These phenotypes correlate with a decrease activity of the Notch pathway. In Lhx2-/- telencephalon, the atypical Notch‐ligand DNER is strongly overexpressed. Furthermore, Lhx2 and co‐repressors associate at the DNER promoter region. We conclude that Lhx2 allows Notch pathway activation in the developing cerebral cortex. It does so by inhibiting DNER transcription, which is a Notch pathway repressor in this particular context. Thus, Lhx2 allows the maintenance and the proliferation of neural progenitor cells

Grandir, un chemin ardu

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Intercultural Experiences Prior to the Educational Program: Occupational Therapy and Social Work Students

In the health and social professions, including occupational therapy and social work, interactions and exchanges with people are essential. Populations encountered by professionals in these fields are becoming increasingly diverse in terms of age, origin, language, health status, and socio-economic background. Sometimes, professionals can have potential misinterpretations regarding intentions and actions, health beliefs and practices, or verbal and non-verbal communication. To overcome obstacles related to practice in a context of diversity, universities must develop students’ intercultural competence. Scientific literature stresses the importance of encountering diversity to improve awareness and sensitivity and to bring attention to biases and prejudices. Considering students’ intercultural experiences before their formation could be a basis to achieve this educational goal. The present study aims to document this topic. Semi-structured interviews with 51 first-year students from two educational institutions in French-speaking Switzerland were conducted to capture the participants’ descriptions of these experiences in private or professional contexts. The interviews were transcribed and submitted to a thematic analysis approach. A thematic map was generated and three main themes emerged: (1) perception of diversity; (2) communication challenges; and (3) transformation of attitudes toward the “Other.” They are described and discussed in terms of developing intercultural competence. Recommendations regarding intercultural education emerge from these findings

Comment favoriser l'intervention interculturelle ?

Disponible sur le site internet REISO, Revue d'information sociale, mis en ligne le 5 septembre 2019, https://www.reiso.org/document/4867Les réflexions et les recommandations présentées dans cet article proviennent de multiples échanges lors d’ateliers avec des intervenant·e·s, des professeur·e·s et des étudiant·e·s des domaines de la santé et du social. Il vise à identifier des stratégies à mettre en place dans les milieux de pratique pour favoriser l’implantation d’une intervention interculturelle efficace auprès de leurs clientèles diversifiées

Directional wetting in anisotropic inverse opals

Porous materials display interesting transport phenomena due to the restricted motion of fluids within the nano- to micro-scale voids. Here, we investigate how liquid wetting in highly ordered inverse opals is affected by anisotropy in pore geometry. We compare samples with different degrees of pore asphericity and find different wetting patterns depending on the pore shape. Highly anisotropic structures are infiltrated more easily than their isotropic counterparts. Further, the wetting of anisotropic inverse opals is directional, with liquids filling from the side more easily. This effect is supported by percolation simulations as well as direct observations of wetting using time-resolved optical microscopy

The Effect of Hole Transport Material Pore Filling on Photovoltaic Performance in Solid-State Dye-Sensitized Solar Cells

A detailed investigation of the effect of hole transport material (HTM) pore filling on the photovoltaic performance of solid-state dye-sensitized solar cells (ss-DSCs) and the specific mechanisms involved is reported. It is demonstrated that the efficiency and photovoltaic characteristics of ss-DSCs improve with the pore filling fraction (PFF) of the HTM, 2,2’,7,7’-tetrakis-( N, N-di-p-methoxyphenylamine)9,9’-spirobifluorene(spiro-OMeTAD). The mechanisms through which the improvement of photovoltaic characteristics takes place were studied with transient absorption spectroscopy and transient photovoltage/photocurrent measurements. It is shown that as the spiro- OMeTAD PFF is increased from 26% to 65%, there is a higher hole injection efficiency from dye cations to spiro-OMeTAD because more dye molecules are covered with spiro-OMeTAD, an order-of-magnitude slower recombination rate because holes can diffuse further away from the dye/HTM interface, and a 50% higher ambipolar diffusion coefficient due to an improved percolation network. Device simulations predict that if 100% PFF could be achieved for thicker devices, the efficiency of ss-DSCs using a conventional ruthenium dye would increase by 25% beyond its current value

Tunable anisotropy in inverse opals and emerging optical properties

Using self-assembly, nanoscale materials can be fabricated from the bottom up. Opals and inverse opals are examples of self-assembled nanomaterials made from crystallizing colloidal particles. As self-assembly requires a high level of control, it is challenging to use building blocks with anisotropic geometry to form complex opals, which limits the realizable structures. Typically, spherical colloids are employed as building blocks, leading to symmetric, isotropic superstructures. However, a significantly richer palette of directionally dependent properties are expected if less symmetric, anisotropic structures can be created, especially originating from the assembly of regular, spherical particles. Here we show a simple method to introduce anisotropy into inverse opals by subjecting them to a post-assembly thermal treatment that results in directional shrinkage of the silica matrix caused by condensation of partially hydrated sol-gel silica structures. In this way, we can tailor the shape of the pores, and the anisotropy of the final inverse opal preserves the order and uniformity of the self-assembled structure, while completely avoiding the need to synthesize complex oval-shaped particles and crystallize them into such target geometries. Detailed X-ray photoelectron spectroscopy (XPS) and infrared (IR) spectroscopy studies clearly identify increasing degrees of sol-gel condensation in confinement as a mechanism for the structure change. A computer simulation of structure changes resulting from the condensation-induced shrinkage further confirmed this mechanism. As an example of property changes induced by the introduction of anisotropy, we characterized the optical spectra of the anisotropic inverse opals and found that the optical properties can be controlled in a precise way using calcination temperature

Efficient Near-Infrared-Transparent Perovskite Solar Cells Enabling Direct Comparison of 4-Terminal and Monolithic Perovskite/Silicon Tandem Cells

Combining market-proven silicon solar cell technology with an efficient wide band gap top cell into a tandem device is an attractive approach to reduce the cost of photovoltaic systems. For this, perovskite solar cells are promising high-efficiency top cell candidates, but their typical device size (<0.2 cm2), is still far from standard industrial sizes. We present a1cm2 near-infrared transparent perovskite solar cell with 14.5% steady- state efficiency, as compared to 16.4% on 0.25 cm2. By mechanically stacking these cells with silicon heterojunction cells, we experimentally demonstrate a 4-terminal tandem measurement with a steady-state efficiency of 25.2%, with a 0.25 cm2 top cell. The developed top cell processing methods enable the fabrication of a 20.5% efficient and 1.43 cm2 large monolithic perovskite/silicon heterojunction tandem solar cell, featuring a rear-side textured bottom cell to increase its near-infrared spectral response. Finally, we compare both tandem configurations to identify efficiency-limiting factors and discuss the potential for further performance improvement

XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia

XRCC1 is a molecular scaffold protein that assembles multi-protein complexes involved in DNA single-strand break repair1,2. Here we show that biallelic mutations in the human XRCC1 gene are associated with ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia. Cells from a patient with mutations in XRCC1 exhibited not only reduced rates of single-strand break repair but also elevated levels of protein ADP-ribosylation. This latter phenotype is recapitulated in a related syndrome caused by mutations in the XRCC1 partner protein PNKP3,4,5 and implicates hyperactivation of poly(ADP-ribose) polymerase/s as a cause of cerebellar ataxia. Indeed, remarkably, genetic deletion of Parp1 rescued normal cerebellar ADP-ribose levels and reduced the loss of cerebellar neurons and ataxia in Xrcc1-defective mice, identifying a molecular mechanism by which endogenous single-strand breaks trigger neuropathology. Collectively, these data establish the importance of XRCC1 protein complexes for normal neurological function and identify PARP1 as a therapeutic target in DNA strand break repair-defective disease