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Synthesis and Properties of Chalcogen and Carbon-bridged Cationic [6]Helicenes: A Comparative Study
No full textDuring the course of this PhD Thesis supervised by Professor J. Lacour at the Organic Chemistry Department of the University of Geneva, the synthesis and study of novel cationic [6]helicenes were performed.
In fact, the derivatives previously reported by our group were bearing oxygen or nitrogen atoms as bridging units of the carbon skeleton. They displayed remarkable (chir)optical properties based on the delocalisation of the positive charge through their conjugated π-system, as well as very different chemical and configurational stabilities. However, these features were hard to rationalise so far. Herein, the scope of such derivatives is expanded via the synthesis and study of novel cationic and neutral [6]helicenes bearing sulfur or selenium bridging atoms in Chapter 1.
In a second chapter, the scope of novel derivatives is expanded via the introduction of an isopropyl staple motif, and the synthesis of both the cationic and anionic variants is described.
In a third chapter, this manuscript also presents the efforts towards the preparation of phosphorus-containing cationic [6]helicenes, and several synthetic strategies are described. However, despite all the attempts, the synthesis of such compounds was not successful so far.
Finally, in the last chapter, a comparative study of the properties of the novel derivatives is presented. It includes an original discussion of their structural features via the correlation of the increase of the helical pitch with the distortion induced by the bridging units. Somehow related to these structural features, the aromaticity of some of the novel derivatives is commented via advanced density functional theory (DFT) calculations. A study of the chemical stability of these compounds is also globally presented via the correlation of their pKR+ values with their reduction potentials, indicating that their chemical stability depends only on the electronic effects of the various substituents. Finally, the configurational stability of some of the novel derivatives is studied. The absence of correlation with their structural features led to the reevaluation of the postulated racemization pathway for such compounds. In fact, the racemization barriers globally follow the order of chemical stabilities. An alternative mechanism is thus proposed, involving first the formation of sp3-neutral adducts, favoured for the most electron-poor compounds, and the racemization of these intermediates instead of the cationic variants.</p
New methods to investigate the viral-like trans-synaptic transmission mechanism of Alzheimer’s Disease
No full textAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the progressive spread of pathological proteins throughout the brain in a stereotypical manner, following specific neuronal networks. Recent work suggests that pathological proteins may spread via vesicular viral-like trans-synaptic transmission. While this mechanism has been studied in preclinical models, it has never been directly investigated in the human brain. This study aims at developing and optimizing new methods to explore the vesicular viral-like transsynaptic transmission of AD patients using postmortem brain samples from the Geneva Brain Bank (GBB). We successfully implemented a 4x Expansion Microscopy (ExM) protocol on formalin-fixed paraffin-embedded (FFPE) brain sections, achieving uniform tissue expansion while preserving structural integrity, including samples stored since 1998, thus enabling high-resolution imaging of synaptic markers. In parallel, an RNA extraction protocol was optimized for FFPE tissues by extending lysis and final elution incubations times and introducing a chemical cross-link reversal step, which significantly improved RNA yield. Notably, RNA extraction yielded satisfactory results even from samples preserved for over a decade. Importantly, we demonstrated for the first time the feasibility of performing RNA sequencing (RNA-seq) on FFPE brain samples from the GBB. Together, these new tools will actively contribute to advancing the molecular and histological characterization of AD pathology in human tissues, promoting human-based investigations and opening new perspectives for translational research in AD, thereby strengthening future translational studies in the field
Living among blacksmiths? Preliminary archaeological results of the 2023 campaign at the Kpeta 2 settlement (Benin)
No full textSilver Nanoparticles in Freshwater Ecosystems: Biointeractions, Toxicity Mechanisms, and Adverse Outcome Pathway Development in Gastropods
No full textThe increasing use of nanomaterials and the release of nanoparticles (NPs) into the environment raise concerns about their ecological impacts. This thesis investigates the biological responses of freshwater gastropods to silver nanoparticles (AgNPs), aiming to support the development of Adverse Outcome Pathways (AOPs). Combining approaches from physical chemistry, ecotoxicology, molecular biology, and ecology, it focuses on how AgNPs physicochemical properties and exposure routes affect uptake, transformation, and biological effects in Lymnaea stagnalis. The proposed AOP begins with citrate-coated AgNPs undergoing aggregation and limited dissolution in freshwater. Following uptake, their interaction with plasma proteins leads to dynamic bio-corona formation (MIE), triggering oxidative stress, altered glutathione metabolism, and energy imbalance. These molecular disruptions activate antioxidant and immune responses, increase lipid peroxidation, and suppress hemocyte counts. Tissue-level effects include AChE inhibition and energy imbalances in the hepatopancreas. Organism-level outcomes involve reduced reproduction, delayed development, and lower condition indices, persisting into the next generation. Trophic transfer and route-specific detoxification further illustrate how AgNPs toxicity propagates across biological levels, informing nanoparticle risk assessment in freshwater invertebrates
Impact de la consommation de viande rouge pendant la grossesse. Enjeux, risques et alternatives nutritionnelles
No full textExcessive consumption of red meat is harmful to our health (cardio-vascular disease, cancer, diabetes) and to the environment. However, its effects on pregnancy are still poorly understood. The aim of this literature review was to examine the effects of a diet rich in red meat or, on the contrary, a vegetarian diet, on the course of pregnancy and fetal development. A correlation was found between a high intake of red meat and the risk of developing gestational diabetes, while a vegetarian diet, although associated with a risk of vitamin B12 and iron deficiency, does not appear to pose a risk if it is well balanced. However, current data on this subject is insufficient and should be further developed, especially in the context of the climate crisis.La surconsommation de viande rouge est nocive pour notre santé (maladie cardiovasculaire, cancer, diabète) et celle de l’environnement. Néanmoins, son impact sur la grossesse reste peu étudié. Cet article a pour objectif d’examiner les effets d’une alimentation riche en viande rouge ou, à l’opposé, végétarienne, sur l’évolution de la grossesse et le développement fœtal. Elle retient une corrélation entre une consommation élevée de viande rouge et le risque de développer un diabète gestationnel ; alors que le régime végétarien, bien que comportant un risque de carence en vitamine B12 et en fer, ne semble pas présenter de danger s’il est bien équilibré. Mais les données actuelles à ce sujet sont insuffisantes, et devraient être développées, surtout dans un contexte de crise climatique
Oncologie. Conjugués anticorps-médicaments : une avancée pleine de défis
No full textNew therapeutic agents in oncology are emerging rapidly, both in terms of the number of approved drugs and the technological and biological innovation of new treatments. Antibody-drug conjugates (ADC) offer a promising cancer therapy by specifically targeting tumor cells. ADC are composed of a monoclonal antibody recognizing the tumor cell via specific antigens, coupled with a potent cytotoxic agent that resembles classical chemotherapy. This mechanism of action aims to deliver the cytotoxic agent directly to the tumor cell and spare healthy cells. However, important toxicities have been reported. On the one hand, these toxicities are related to the cytotoxic agents that, once delivered locally, spread to other parts of the body. On the other hand, there are specific toxicities associated with these ADC, which we address in this article.L’arsenal thérapeutique oncologique ne cesse de croître, que ce soit par le nombre de produits approuvés ou par l’innovation technologique et biologique des nouveaux médicaments. Les conjugués anticorps-médicaments constituent une approche innovante, qui cible spécifiquement les cellules tumorales afin de délivrer localement une charge cytotoxique. Ces molécules sont composées d’un anticorps reconnaissant la cellule tumorale grâce à un antigène spécifique, conjugué à un traitement cytotoxique – des molécules semblables aux chimiothérapies classiques. Leur force réside dans cette spécificité. Toutefois, cela n’exclut pas des effets collatéraux, liés à la toxicité du médicament cytotoxique qui, une fois délivré localement, va se propager dans le reste du corps, mais aussi à des toxicités spécifiques que nous abordons
L'utilisation de services <i>cloud </i>par des responsables du traitement privés
No full textCet article a pour objectif de mettre en lumière certains des enjeux juridiques liés au recours, par des entreprises, à des services de type cloud dans la perspective du droit de la protection des données. Après avoir rappelé les contours du champ d'application de la loi sur la protection des données (RS 235.1 ; LPD) (chap. II.), les auteurs traitent de deux problématiques caractéristiques de l'utilisation de services cloud, soit le recours à des sous-traitants (chap III.) et le transfert de données personnelles à l'étranger (chap. IV.). Ils abordent aussi le recours à un prestataire de services cloud basé aux États-Unis ou présentant certains liens avec les États-Unis (chap. V.). Avant de conclure, ils évoquent brièvement d'autres normes dont il convient de tenir compte, dans certains secteurs de l'économie, dans le cadre du lancement de projets d'utilisation de cloud (chap. VI.)
Enfance et adolescence sénégalaises transnationales : enchevêtrements moraux au fil d’une double socialisation entre pays d’accueil et Sénégal
No full textCet article traite des pratiques de confiage d’enfants et d’adolescents vivant dans des familles transnationales dont les membres résident au Sénégal et en Autriche. L’analyse se fonde sur des récits biographiques, des entretiens et des phases d’observation directe portant sur un cas contextualisé. Elle explore les points de tension et les enjeux de la double socialisation de ces jeunes en se focalisant sur leurs vécus et leurs points de vue, particulièrement leur apprentissage et leur usage de valeurs sénégalaises, à savoir la retenue (kersa), la discrétion (sutura) et l’embellissement (rafetal). Ces jeunes sont discriminés tant en Autriche qu’au Sénégal. L’appel à une réciprocité future qu’instiguent les dons de membres de leur famille provoque des tensions. Les efforts consentis à la socialisation transnationale des premiers-nés portent aussi l’enjeu de leur exercice futur du rôle de chef de maison.This article focuses on child and adolescent fostering within transnational families whose members reside in Senegal and Austria. The analysis is based on biographical accounts, interviews and direct observation of a contextualized case. It explores the points of tension and the issues at stake in the dual socialization of these young people, concentrating on their experiences and points of view, especially the ways in which they learn and use Senegalese values such as restraint (kersa), discretion (sutura) and embellishment (rafetal). These young people are discriminated against in both Austria and Senegal. The call for future reciprocity instigated by gifts from family members causes occasional tensions. The considerable efforts put in to socialize a first-born in a transnational setting point also to their future role as head of household
Communauté de pratique : collaborer entre médecins de famille et psychiatres
No full textMental disorders affect 13 % of the world's population. These disorders are mostly treated on an outpatient basis. In Switzerland, 8 % of the population received mental health care in 2022. In primary care, mental health management is often challenging, with many barriers documented in the literature. The Barriers to Depression Care Questionnaire has been developed to identify these barriers. Collaboration between primary care physicians and psychiatrists is the most common difficulty in our population. Solutions, including the creation of a community of practice between primary care physicians and psychiatrists, are proposed in this article.Les troubles de santé mentale touchent 13 % de la population mondiale. Leur prise en charge est majoritairement ambulatoire. En Suisse, 8 % de la population a reçu des soins en santé mentale en 2022. En médecine de famille, répondre aux besoins de santé mentale est souvent difficile, avec de nombreuses barrières décrites dans la littérature. Le Barriers to Depression Care Questionnaire est un questionnaire développé pour identifier ces barrières. La difficulté la plus fréquemment retrouvée dans nos populations concerne la collaboration entre médecins de famille et spécialistes en psychiatrie. Cet article propose des solutions, parmi lesquelles la constitution d’une communauté de pratique entre médecins de famille et psychiatres