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L’individualisation des horizons culturels et la répartition verticale du mobilier des dépôts de bergerie
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Acceptor-Acceptor Diazo Reagents and Subsequent Metal Carbenes Toward New Oxaheterocyclic Chemistry
No full textWithin this thesis, the synthesis of highly functionalized enantioenriched macrocycles was attempted and applications in catalysis were undertaken. For this purpose, a three-step synthetic procedure was developed focusing on the deconjugative isomerization of endocyclic unsaturated amides. Also, care was taken to introduce strong hydrogen-bond donor groups such as squaramide moieties on the chiral platforms and study their activity in organocatalysis.
In other independent studies, the decomposition of diazo reagents and the subsequent reactivity of the derived metal carbenes were investigated using as substrates alkene-containing strained oxacycles to explore ring expansion or cascade transformations. First, the combination of 3-gem-dialkyl 2-vinyl-oxetanes and acceptor(-acceptor) diazo reagents under copper catalysis led to the formation of functionalized tetrahydro oxepines via [2,3]-Stevens rearrangement. Also, the dual reactivity of diazo malonate was studied, used both as 1,3-dipoles and carbene precursors, in presence of hetero benzonorbornadienes and under ruthenium catalysis, to prepare polycyclic pyrazolidines in a three-step synthetic sequence.
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Positive Party Cues, Negative Ones, and Policy Information: An Experiment on the Drivers of Voting Intention in the Swiss Direct Democracy context
No full textPositive Party Cues, Negative Ones, and Policy Information: An Experiment on the Drivers of Voting Intention in the Swiss Direct Democracy contex
Chirurgie urologique : ce qui a changé en 2023
No full textUrology continues its development in minimally invasive surgery, and the year 2023 is marked by important innovations in the different approaches such as endoscopy, laparoscopy, and open surgery. The following innovations are instruments or medical devices which are still being evaluated. What they have in common is a questioning of our current practices, on the technical side but also for some of them on the ecological vision of our profession with the eternal debate of single use or reusable. Even if the evaluation of new devices is primarily medical and medico-economic, it is actually no longer possible to ignore the ecological aspect and the impact on the environment of the various new products. New technologies also make it possible to think about smart connected prostheses and precision intraoperative imaging that can ultimately guide the surgeon's hand.L’urologie est une spécialité en constante évolution. L’année 2023 a été marquée par le développement de nouveautés en chirurgie minimalement invasive, tant en endoscopie qu’en laparoscopie ou chirurgie ouverte, principalement dans les domaines de la robotique, des technologies connectées, ainsi que dans les instruments médicaux réutilisables. Dans le domaine de l’imagerie, le TEP/CT peropératoire pourrait dans l’avenir guider le geste chirurgical afin d’améliorer les résultats oncologiques. Ces nouvelles technologies permettent le développement de nouveaux instruments ou dispositifs médicaux, dont l’évaluation doit se faire aujourd’hui tant sur le plan médical que socio-économique ou écologique
Unraveling the Neuroprotective Role of NATO3 in Dopaminergic Neurons
No full textParkinson’s disease (PD), the second most prevalent neurodegenerative disorder, is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta, leading to various motor and non-motor disabilities. Its high prevalence and significant impact on quality of life underscore the urgent need for innovative treatments.
This study investigated the post-developmental role of Nato3, a crucial transcription factor for midbrain DA neurogenesis, using a mouse model with conditional Nato3 ablation (Nato3 cKO) in differentiated DA neurons. Employing immunohistochemistry, electron microscopy, RNA-sequencing, and behavioral assays, we found that Nato3 cKO mice recapitulate PD-like symptoms, including progressive locomotor decline, loss of mitochondrial integrity, and autophagy defects.
Furthermore, human NATO3 overexpression ameliorated cellular phenotypes associated with PD pathology, suggesting NATO3's involvement in autophagy-lysosomal system dynamics and mitochondrial health. These findings provide insights into NATO3's role in PD pathology and potential therapeutic targets.</p
Sensing and modulating G protein-coupled receptor function using novel nanobody tools
No full textG protein-coupled receptors (GPCRs) represent a vast superfamily of transmembrane proteins that play critical roles in cellular signalling, regulate diverse physiological processes, and serve as key therapeutic targets. Opioid receptors (ORs), a subfamily of GPCRs, play a pivotal role as targets for pain medication, but their activation by opioid drugs can also trigger undesirable effects such as tolerance, dependence, and respiratory depression. Investigating the mechanisms underlying GPCR signalling and regulation, such as receptor activation, engagement of signalling partners, location-biased signalling and receptor phosphorylation/dephosphorylation, is essential for understanding the role of GPCRs in physiology and disease and requires suitable research tools.
Nanobodies (Nbs), the recombinant antigen-binding fragments of camelid heavy-chain-only antibodies, have emerged as innovative tools for studying GPCRs. Recent Nb-based biosensors have enabled real-time monitoring of GPCR activation at subcellular resolution, providing valuable insights into cellular GPCR actions. However, existing fluorescent sensors rely on single-cell confocal fluorescence microscopy for visualizing ligand-dependent biosensor re-localisation from the cytosol to the site of receptor activation, limiting their applicability to higher throughput assays. Beyond sensing GPCR activity, Nbs can also be employed to inhibit receptor function. While intracellular OR-blocking Nbs would pave the way for dissecting receptor function at the cellular and subcellular level, they have not yet been developed. My PhD research aimed to generate Nb-based tools to study ORs, and more broadly, GPCR function on a cellular and subcellular level, and to investigate the regulation of ligand-driven OR phosphorylation by phosphatases.
Overall, my PhD thesis work shows the successful development and characterization of high-affinity Nbs that effectively block OR signalling. As genetically encoded tools, the Nbs hold promise for dissecting OR signalling in individual cells and subcellular compartments. Expanding the toolkit further, we developed novel dark-to-light GPCR reporters that offer subcellular spatial and seconds temporal resolution and can be readily redesigned to probe a wide range of GPCRs. Furthermore, we make inroads into understanding OR dephosphorylation, holding implications for understanding receptor resensitisation. </p
Le simple conseil « manger moins, bouger plus » ne suffit pas pour perdre du poids
No full textLes raisons pour lesquelles les personnes en situation d’obésité souhaitent perdre du poids sont multiples. Souvent, ce sont les médecins qui demandent à leurs patients de perdre du poids pour éviter ou mieux contrôler les complications de l’obésité, maladie multifactorielle et chronique (par exemple, diabète, hypertension, hypercholestérolémie ou arthralgies). Une mauvaise image corporelle vécue par les patient-e-s constitue aussi une incitation fréquente à perdre du poids. Nous avons de plus en plus de moyens « techniques » pour induire la perte pondérale mais la question de la prévention de la reprise du poids reste au centre de nos préoccupations
La Réforme. Matin du monde moderne
No full textLa Réforme est vieille de cinq siècles. Elle date du matin du monde moderne. Elle est même, avec d'autres, comme l'humanisme, un acteur important de notre modernité, ne serait-ce que parce que les Réformateurs ont toujours défendu la responsabilité de l'individu face à Dieu et face aux institutions humaines. Mais n'allons pas trop vite en besogne : les hommes du XVIe siècle ne sont pas nos contemporains. Ils ont vécu dans un univers mental qui nous est à bien des égards incompréhensible, où l'Eglise ne pouvait par exemple se penser en dehors de l'Etat et où la société ne pouvait être que chrétienne. Comment donc les paroles, les écrits, les actions de Luther, de Calvin ou d'autres figures importantes du mouvement de la Réforme (comme Castellion, un marginal visionnaire) peuvent-ils encore résonner malgré l'épaisseur des siècles qui nous séparent d'eux