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Beauty and Complexity of Calcium Carbonate Precipitation: Optical Microscopy and <i>in situ</i> Raman Microspectroscopy Characterization
No full textCalcium carbonate is one of the most studied systems in several disciplines (chemistry, biology, geology, etc.). Its crystallization process has been highly debated, and contradicting claims can be found in the literature. The controversy may be attributed to various initial conditions (concentration, pH, with or without additives), different precipitation protocols among literature, and the methods adopted with a large gap in the length scale: electron microscopy at the nano- and spectroscopic means at the bulk scale. Here, we investigated calcium carbonate precipitation by combining optical microscopy with in situ Raman microspectroscopy as a mesoscopic length scale technique. The precipitation of calcium carbonate was performed by mixing CaCl2 and Na2CO3 from a wide range of supersaturations without stirring to screen all possible crystallization pathways. We categorized and characterized the initial precipitates observed upon mixing as gel, gel + amorphous calcium carbonate (ACC), ACC, crystal, and no precipitate. Calcite and vaterite were observed in all mixed solutions, while aragonite was observed in most of them. This study shows how complex and heterogeneous yet beautiful CaCO3 precipitation is, and it emphasizes the importance of studying the system at the length scale between nano and bulk as well as that of initial conditions in order for the debates to converge in the near future
Concept d’alignement coronal dans la prothèse totale de genou
No full textTotal knee arthroplasty (TKA) is one of the most performed orthopedic surgeries worldwide. For many years, TKA implants were positioned according to a systematic approach known as mechanical alignment, which prioritized implant survival over the restoration of a more physiological knee. A high dissatisfaction rate of 20% after knee prosthesis has led to a rethinking of coronal alignment and a move towards a more personalized approach. With improved instrumentation, new-generation implants and the advent of robotic surgery, it is now possible to better restore the patient's anatomy, to position implants more accurately and to optimize ligament balance in extension and flexion. The aim is to achieve greater patient satisfaction and the perception of a normal or forgotten knee after surgery, while preserving the long-term survival of implants.Pendant longtemps, les prothèses totales de genou ont été posées selon un alignement mécanique, privilégiant la survie des implants à une restauration plus physiologique du genou. Un taux important de patients non satisfaits, de l’ordre de 20 %, a conduit à développer des approches plus personnalisées. Avec l’amélioration de l’instrumentation, les implants de nouvelle génération, et avec l’avènement de la chirurgie robotique, il est aujourd’hui possible de restaurer plus finement l’anatomie du patient, avec un positionnement des implants permettant de préserver un équilibre ligamentaire « physiologique », avec des gestes de libération limités. L’objectif recherché est une plus grande satisfaction du patient, avec la sensation d’un genou considéré comme normal ou oublié après l’intervention, tout en préservant la survie des implants à long terme
Synthesis and Properties of Cationic and Neutral Radical Diaza[4]helicenes
No full textThis PhD describes the synthesis and characterization of various functionalized cationic diaza[4]helicenes based on dimethoxyquinacridine (DMQA) scaffolds. Based on organometallic catalysis, late-stage functionalization strategies are developed and applied to introduce a diversity of functional groups. Chapter 1 provides a general introduction of chirality in organic molecules and their interaction with circularly polarized light; generalities on helical dyes are also presented. In Chapter 2, a pH-sensitive helicene is functionalized via C-H insertions of electrophilic metal carbenes (Ru or Rh). Up to four malonate moieties are introduced and, through the study of the electronic and chiroptical properties of these malonate-functionalized helicenes, the stereoelectronic influence of the added moieties is elucidated. In Chapter 3, the core transformation of this manuscript is described. Thanks to Ir-catalyzed direct C-H borylation of DMQA, regioselective functionalization of the three positions in para to the formal positive charge is obtained for the first time. In this chapter, Ir-catalysis is coupled, in tandem, with Suzuki-Miyaura cross coupling reactivity to give a series of tris(arene) derivatives. Furthermore, in Chapter 4, after Ir-catalysis, PdII-catalyzed alkoxycarbonylation and hydroxylation reactions are performed. Thanks to these two transformations, functional groups with strong ED or EW character are introduced in para positions. An extensive tuning of the optical and electronic properties of the helical core is observed with para-EDGs and EWGs, with absorption and emission spectra covering a range of ≈ 300 nm. Derivatives with EDGs have blue-shifted optical properties with high fluorescence quantum yields up to 70%. On the contrary, derivatives with EWGs have red-shifted absorption and emission and are poor fluorophores. However, they present interesting electronic properties, mainly due to their facile first one-electron reduction that makes them good candidates for the production of neutral radical helicenes. The formation of neutral persistent radicals, via electrochemical or chemical (CoCp2) mono electron reductions, is described in Chapter 5. The reversibility of this redox process, the chiroptical properties of the obtained radicals, their EPR signatures, spin density delocalization and half-life values under air are described. Finally, in Chapter 6, a family of strongly fluorescent para-OMe derivatives, based on helical scaffolds bearing primary or secondary N-alkyl chains, is presented. These compounds are employed in two-photon excitation studies, showing good values of cross section at 810 nm. Additionally, two-photon excitation circularly polarized emission spectra are reported. Further reactions are briefly described in the conclusions to give a prospective on future projects.</p
Prise en charge de la fragilité osseuse du patient diabétique
No full textThe risk of fracture is increased in patients with type 1 and type 2 diabetes. Bone mineral density (BMD) tends to be decreased in type 1 diabetes and increased in type 2 diabetes. BMD and the fracture risk assessment tool (FRAX) underestimate the fracture risk in patients with type 2 diabetes, and specific adjustments may be required. Poor glycemic control is the main fracture risk predictor. Conventional treatments for osteoporosis have not been specifically evaluated in non-osteoporotic diabetic patients. However, they can be prescribed to diabetics at high risk for fractures if there are no contraindications. Preventing the risk of falls and optimizing muscle health are essential in older diabetic patients.Le risque de fracture est élevé chez les patients diabétiques de type 1 et 2. La densité minérale osseuse (DMO) est abaissée dans le diabète de type 1, mais augmentée dans le diabète de type 2. La DMO et l’outil d’évaluation du risque de fracture (FRAX) sous-estiment le risque de fracture chez les patients diabétiques de type 2, ce qui peut nécessiter des ajustements. Le déséquilibre du diabète est le principal prédicteur du risque de fracture. Les traitements classiques de l’ostéoporose n’ont pas été évalués chez les patients diabétiques non ostéoporotiques, mais peuvent être prescrits aux patients diabétiques à haut risque de fracture, sauf contre-indications. La prévention du risque de chute et l’optimisation de la santé musculaire sont également primordiales chez le patient âgé
From membrane microdomains to NPC: investigating the role of sterols during <i>Mycobacterium marinum</i> infection
No full textThe Mycobacterium genus comprises several pathogenic species that can infect a broad range of hosts, animal or human. The severity of the disease can range from skin lesions to pulmonary or brain infections. Mycobacterium marinum is a non-tuberculous mycobacteria inducing a disease similar to the human tuberculosis in freshwater and marine vertebrates. At the cellular level, the stages of M. marinum infection are highly similar to the ones of Mycobacterium tuberculosis. Once inside host cells, both bacteria manipulate the phagosome maturation process to reside in a non-degradative vacuole called Mycobacterium-containing vacuole (MCV). During this transition, M. marinum and M. tuberculosis induce membrane damage that is a major event in the infection cycle. Indeed, it leads to a battle with the host, which aims at constraining the bacteria inside the MCV by involving major repair processes such as the ESCRT machinery and the autophagy pathway. The MCV damaging ability of M. marinum and M. tuberculosis depends on one of their type VII secretion systems, ESX-1, and its secreted peptide, EsxA. Scattered in vitro experiments document that EsxA’s membranolytic activity depend on the host vacuole membrane composition. In addition, their infection cycle leads to the characteristic induction of lipid accumulation in their host cells. These lipids are required for their own metabolism and virulence.
This thesis aims at 1) deciphering the contribution of host membrane composition to M. marinum infection and at 2) investigating the role of sterol transporters, Niemann-pick C1type C1 (NPC1) in both the social amoeba Dictyostelium discoideum and murine microglial BV-2 cells.
1) We demonstrated that microdomain components, organiser proteins and sterols, gradually accumulate at the MCV at all stages and that microdomains are required for successful M. marinum infection. In addition, we show in vitro that microdomains are necessary for EsxA partitioning into membrane and in vivo that microdomain disruption leads to a decrease of M. marinum induced MCV damage and cytosolic access. Importantly, we demonstrate that this phenomenon is conserved in D. discoideum and BV-2 cells.
2) We showed that NPC1 localises and accumulates at the MCV and npc expression is modulated during M. marinum infection. In D. discoideum knockout of the two NPC1 homologs strongly affects intracellular growth of M. marinum. The underlying mechanisms are still to be elucidated.
This thesis highlights an evolutionary conserved role of host sterols during M. marinum infection with a major impact on bacterial virulence. </p
The knock-out of paracingulin attenuates hypertension through modulation of kidney ion transport
No full textHypertension is a major risk factor for human morbidity and mortality, and the junctional protein paracingulin (CGNL1, JACOP) is required for development of hypertension in a Dahl salt-sensitive rat model and is linked to human hypertension in genome-wide association studies. However, the mechanism through which CGNL1 may regulate hypertension is unknown. Here we address this question using a mouse model, where hypertension is induced by unilateral nephrectomy and angiotensin II infusion (N+A model). Although untreated WT and CGNL1-KO mice showed similar blood pressure, the N+A protocol induced hypertension in WT mice but not in CGNL1-KO mice. We show by immunolocalization and transcriptomic analysis that CGNL1 is expressed throughout the kidney tubules and in endothelium of blood vessels, but not in smooth muscle. The (N+A) protocol induced decreased potassium urinary excretion in wild-type (WT), but not CGNL1-KO mice. Immunoblot analysis shows that the KO of CGNL1 blunted the (N+A)-induced changes in the expression levels and activation of tubular ion transporters, including the Na/H exchanger 3 (NHE3) and the thiazide-sensitive Na-Cl cotransporter (NCC), and blunted the angiotensin II-dependent changes in the levels and/or activation of AMP38 activated protein kinase (AMPK), ERK and myosin light chain. In contrast, myography showed comparable vascular reactivity in thoracic aortas and mesenteric arteries isolated from WT or CGNL1-KO mice. Together, these results suggest the KO of CGNL1 attenuates hypertension by uncoupling angiotensin II signaling in kidney tubule cells, indicating a novel pathway of regulation of signaling by a junctional protein
Récolte de vestiges glaciaires au Col de la Forcle (Chamoson, Valais, 2542 m) : rapport d'intervention 2020
No full textLos paisajes en la literatura castellana medieval (siglos XIII y XIV)
No full textLa thèse analyse la fonction discursive du paysage dans la littérature castillane du Moyen Âge (XIIIe et XIVe siècles). Une première partie souligne les difficultés inhérentes à une étude basée sur un anachronisme lexical et débat de la possibilité de parler d'un "paysage" médiéval. Cette première partie se conclut sur une nouvelle proposition du paysage littéraire, en accord avec l'usage actuel. C'est sur la base de cette définition, qui insiste sur la mouvance du concept de "paysage", que se construit la deuxième partie, dédiée aux particularités du paysage littéraire médiéval. Elle revient sur plusieurs aspects-clés de l'époque, comme la valorisation des sens, l'allégorie, le symbolisme ou encore la rhétorique. Enfin, une troisième partie présente un catalogue analytique où l'auteure propose une étude de différents extraits de paysage de textes narratifs, organisée en fonction de l'espace décrit (forêt, montagne, désert, mer, espaces d'eau douce, bâtiments situés dans un écrin naturel, villes, vergers et champs de bataille)
Exploring the role of FKBP10 in lung and colorectal cancers
No full textLung cancer is first cause of cancer-related death worldwide, followed by colorectal cancer (CRC). There is an unmet need to explore novel cancer-specific targets involved in malignant phenotypes to improve current therapy. The objective of this thesis is to explore the role of peptidyl-prolyl-cis-trans-isomerase (PPIase) FK506-binding protein 10 (FKBP10) in lung and colorectal cancers. Herein, we report that FKBP10 is specifically expressed in human lung and colorectal cancer lesions, and absent in healthy lung parenchyma and colonic mucosa. Furthermore, FKBP10 expression negatively correlates with survival of lung cancer patients, and its expression is positively related to tumor grade and cancer recurrence of CRC patients. By investigating the therapeutic potential of targeting FKBP10 in a KRAS-driven lung tumorigenesis mouse model, we show that while in mice with intact FKBP10, the tumor volume continues to increase, FKBP10 ablation greatly reduces tumor burden in these animals. Our results from gain- and loss-of-function in vitro assays indicates that FKBP10 boosts cancer growth and stemness of lung and colorectal cancer cells via its PPIase activity. Further investigation revealed that FKBP10 interacts with ribosomes, and its silencing leads to a significant reduction of protein translation. Mechanistically, we uncovered that FKBP10 downregulation leads to a reduction of translation elongation at the beginning of open reading frames, in particular upon the insertion of proline residues, therefore, playing a role in translational reprogramming of cancer cells. Collectively, this project unveiled FKBP10 as a cancer-selective molecule exerting an important role in the regulation of protein translation, hence supporting cancer growth and stemness. Inhibiting FKBP10 may show promising therapeutic opportunity as a personalized medicine to increase the efficacy and safety of therapies against lung and colorectal cancers. </p