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Inferring Population Dynamics During Past Expansion Events Using Spatiotemporal Molecular Patterns
No full textPopulation expansions have a major evolutionary impact on the genetic diversity of species. When a population expands into a new territory, it often encounters other populations of the same or closely related species. Interbreeding between the migrating population and the local one occurs can generate specific molecular patterns in both populations. These patterns can potentially be used to infer the migratory and demographic dynamics of the expansion. However, the effect of interbreeding during population expansions on the spatiotemporal patterns of molecular diversity in the involved populations has not been studied yet. In the present thesis, I used palaeogenomic data to investigate spatiotemporal patterns of molecular diversity that were created during past expansions of the species Homo sapiens, and I used these patterns to make inferences about these important evolutionary processes. The thesis mainly focused on patterns of genomic introgression. In Chapter 2, we used spatially explicit simulations to investigate the expected pattern of introgression after an expansion with interbreeding. We showed that the levels of introgression from the local population in the expanding one are expected to increase with distance from the source of the expansion, while the opposite cline is expected in the local population. We reported the existence of such empirical introgression patterns in various species that underwent an expansion with interbreeding, in accordance with our theoretical expectation. In Chapter 3, we used palaeogenomic data to investigate the spatiotemporal pattern of Neanderthal introgression in Eurasian anatomically modern human populations at different periods of time. In accordance with the theoretical expectations from Chapter 2, we found that during the expansion of modern humans in Eurasia, a spatial cline of Neanderthal introgression developed, increasing with distance from the Near East, and it persists until the present. In Chapter 4, we inferred the population dynamics of two human migrations that created the observed spatiotemporal pattern of Neanderthal introgression in Europe, by using a novel spatially explicit simulation framework of three populations. We showed that the observed cline of Neanderthal introgression is indicative of the direction from which the first humans arrived in Europe and that the reduction of Neanderthal introgression levels during the Neolithic transition can be explained by drift, and demographic and migratory processes. Lastly, in Chapter 5, we investigated in more depth the Neolithic transition in Europe, by following two different approaches and using two palaeogenomic datasets. Our results are compatible with a model of “demic diffusion with delayed admixture”, meaning that early farmer populations migrated into Europe from Anatolia and that the assimilation of local hunter-gatherers increased with time. Altogether, my thesis shows that population expansions with interbreeding create clear spatiotemporal patterns of local introgression in the migrating population, which can provide information both on the direction of past expansions and on the demography and interactions of the involved populations. Although focused on specific events of human evolution, our approach and results offer a framework for using the introgression levels in genomic data to study other instances of spatial processes between populations, in humans or other species.</p
Toutes nos différences…
No full textDans le diabète de type 2, des différences, jusqu'alors plus pressenties que démontrées, existent
Prise en charge de la douleur aiguë en ambulatoire
No full textLa prise en charge de la douleur aiguë se centre autour d’une approche multimodale intégrant des traitements pharmacologiques et non pharmacologiques. Ces dernières années, la prudence envers les opiacés s’est accrue, plusieurs études montrant qu’ils ne sont pas forcément plus efficaces que les non-opiacés face à la douleur musculosquelettique notamment, qui est le symptôme douloureux le plus fréquent en ambulatoire, et ont l’inconvénient d’apporter davantage d’effets indésirables et un risque de dépendance. Les traitements adjuvants et non pharmacologiques (comme la médecine manuelle, l’acupuncture, l’hypnose) gagnent en importance pour réduire l’escalade thérapeutique et améliorer la gestion de la douleur. Cette approche personnalisée vise à minimiser les risques tout en assurant un soulagement efficace de la douleur aiguë.The management of acute pain focuses on a multimodal approach integrating both pharmacological and non-pharmacological treatments. In recent years, caution towards opioids has increased, with several studies showing that they are not necessarily more effective than non opioid analgesics for pain relief for musculoskeletal pain, which is the most common painful symptom in outpatient settings, and have the disadvantages of more side effects and a risk of dependence. Adjuvant and non-pharmacological treatments (e.g. manual medicine, acupuncture, hypnosis) are gaining importance to reduce therapeutic escalation and improve pain management. This approach which can be more personalized, aims to minimize risks while ensuring effective relief of acute pain
Sarah Grimkés Bibel: eine Waffe im Kampf gegen die Sklaverei der Schwarzen und die Unterwerfung der Frauen
No full textAlerte au feu : des nanopompiers pour combattre les flammes de la polyarthrite rhumatoïde
No full textÇa chauffe dans les articulations ! De petits fragments d’ADN libérés dans les articulations induisent et entretiennent l’inflammation caractéristique de la polyarthrite rhumatoïde (PR). Selon un article paru dans sPNAS en août 2023, l’administration d’un nanogel conjugué à une enzyme permet la neutralisation et l’élimination de ces fragments d’ADN au sein des articulations touchées, dans un modèle murin.1 Mieux vaut éteindre les flammes avant qu’elles ne deviennent incontrôlables
Exploring the Impact of Amniotic Epithelial Cell Derivatives on Pancreatic Islet Cell Function and Viability for Type 1 Diabetes
No full textType 1 diabetes Mellitus (T1DM) is an autoimmune disease characterized by the destruction of the insulin-producing β-cells of the pancreatic islets of Langerhans. Allogeneic intraportal islet transplantation offers a promising treatment to restore insulin independence, yet post-transplant survival and function remain critically limited by hypoxia, inflammation, and poor vascularization. Therefore, addressing these challenges is crucial to improve long-term transplantation outcomes. Among various strategies, the use of accessory cells has shown promise in protecting and supporting islets and their function. In particular, human amniotic epithelial cells (AECs) have demonstrated cytoprotective effects on pancreatic islets under normal and stressful conditions such as hypoxia and inflammation, due to their anti-inflammatory, immunomodulatory, and regenerative properties. Recently, cell-free derivatives of stem cells such as secretome (conditioned medium, CM) and extracellular vesicles (EVs) have emerged as safer and scalable alternatives to live cell therapies. These derivatives harness the paracrine effects of stem cells by delivering bioactive molecules, including proteins, lipids, and nucleic acids, to target cells, while minimizing risks linked to cell transplantation such as immunogenicity and tumorigenicity. Notably, AEC-derived secretome and EVs (AEC-CM and AEC-EVs) have shown therapeutic potential in various regenerative contexts but remain unexplored in islet transplantation. Therefore, this thesis investigates the therapeutic potential of AEC derivatives on pancreatic islets.
The first aim was to assess the effect of AEC derivatives on the function and survival of pancreatic islets in normal, hypoxic, and inflammatory environments. We addressed this aim by dividing it into two parts. First, on an analytical level, by isolating and characterizing AEC-EVs from AEC-CM. We successfully isolated and characterized AEC-EVs. We also demonstrated that their cargo is rich in proteins related to the extracellular matrix, cell growth, and metabolic regulation, all of which may support islet survival and function. The second part was on a functional level, assessing the effects of AEC derivatives on islets. Our results demonstrated that AEC-CM significantly enhanced insulin secretion in islets under normoxic conditions. In contrast, the EV fraction confers a cytoprotective effect primarily under hypoxic stress, promoting enhanced islet function and mildly ameliorated survival, while showing limited benefit under inflammatory conditions.
The second aim was to elucidate the underlying mechanisms mediating beneficial effects on islets, focusing on AEC-EV treatment, which showed the most benefit under hypoxia following the first aim. We employed mass spectrometry to uncover proteomic changes in islets treated with or without AEC-EVs. We found that AEC-EVs mediate their cytoprotective effects on hypoxic islets by promoting the establishment of rich extracellular matrix protein levels and the regulation of different mechanisms, including pathways related to autophagy and insulin receptor signaling.
In summary, this work supports AEC derivatives as promising cell-free therapeutic strategies to enhance pancreatic islet survival and function. These insights open new avenues for improving graft survival and long-term clinical outcomes in T1DM patients undergoing islet transplantation.</p
Exploring environmental nanobiogeochemistry using field-flow fractionation and ICP-MS-based tools: background and fundamentals
No full textThe recent application of sophisticated instrumentation and novel experimental techniques to environmental systems has driven the study of natural nanoparticles and nanoparticle systems towards new horizons. Moving beyond the detection of engineered nanoparticles in natural systems, these technologies create new knowledge about the composition, behaviour, and functions of natural nanoparticles as individual entities and particle systems. In this tutorial review, we define the emerging field of environmental nanobiogeochemistry and describe the fundamentals, optimization, advantages, and disadvantages of field-flow fractionation and ICP-MS-based techniques for advancing our understanding of natural nanoscale particles and particle systems. The companion perspective Exploring environmental nanobiogeochemistry using field-flow fractionation and ICP-MS-based tools: progress and frontiers describes the progress and frontiers in this research area using case studies drawn from a range of published and unpublished data spanning diverse environmental systems. Thus, by combining necessary background with the most recent findings and key challenges, these contributions provide key knowledge for new and established researchers entering this exciting field and lay the groundwork for future researc
Characterisation of clathrin dynamics along the endocytic timeline in yeast
No full textClathrin-mediated endocytosis is a fundamental eukaryotic mechanism, involving the coordinated assembly of a complex protein coat at the plasma membrane. This coat is essential for the regulation of cargo recruitment and successful vesicle formation.
Clathrin is a coat protein whose structural properties are well characterised. Yet, many unanswered questions remain regarding its role in endocytic site maturation: its scaffolding nature places it at the centre of the interaction network governing vesicle formation, and its specific assembly properties hint at a regulatory function.
In this thesis, I characterise clathrin’s assembly properties over time at single endocytic sites. Using a combination of live fluorescence microscopy techniques in S. cerevisiae, I show that the Hsc70/Auxilin machinery mediates clathrin turnover during the early phase of endocytosis. The clathrin lattice is then stabilised by late-phase proteins Sla1 and Sla2. This two-step tuning of clathrin dynamics regulates endocytic coat size and ensures successful vesicle formation.</p
Local energy communities in rural Switzerland: national scalability under different incentives schemes and economic scenarios
No full textLocal Energy Communities (LECs), as a mechanism to incentivize production, self-consumption, storage, and selling of renewable energy, could be particularly interesting in agricultural regions, but the potential for rural LECs remains unexplored. This study models at high spatial and temporal resolution the portfolios of building-integrated solar photovoltaics (PV), agri-PV, wind power, biomass, hydropower, and batteries for forming LECs in all 730 rural Swiss municipalities. By focusing on the self-consumption benefits that often motivate LECs, including consumption for electrified heating, transport and agriculture, we evaluate the national scalability of LECs, as virtual microgrids, under various economic scenarios and incentive schemes. A key finding is that LECs in rural Swiss municipalities could generate up to 8 TWh/year of renewable electricity in 2035, contributing 23 % towards the new Swiss renewable electricity target of 35 TWh/year. However, this potential is contingent on suitable economic conditions (market prices, feed-in tariffs, and retail tariffs) and there is a risk that, under current incentives, LECs might prioritize self-consumption, leveraging only part of their renewable electricity potential and sidelining technologies that could more effectively meet national targets.</p