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„[D]ie Hinwendung zur Armut“ : Lukas Bärfussʼ Bamberger Poetikvorlesung und die Mittel der Literatur
No full textIn seiner ersten Bamberger Poetikvorlesung schreibt der Schweizer Dramatiker und Schriftsteller Lukas Bärfuss, die Literatur verfüge über ein „Mittel“ gegen die vorherrschende „Illusionslosigkeit“ der westlichen Gesellschaften des 21. Jahrhunderts und dieses liege in der „Hinwendung zur Armut“. Bärfuss begründet diese These im Dialog mit Charles Baudelaires Gedichtband Le Spleen de Paris (1869) und Walter Benjamins kulturkritischem Essay Erfahrung und Armut (1933). Der vorliegende Beitrag geht der Frage nach, was mit dieser „Hinwendung zur Armut“ gemeint sein könnte und wie Bärfuss seine These über den intertextuellen Dialog mit Baudelaire und Benjamin entwickelt. Es wird gezeigt, wie sich diese (literarische) Hinwendung zur Armut als eine mögliche ‚Idee der Reparatur‘ erweisen kann
Burden-shifting, encroaching and shirking: Federalism in a pandemic crisis
No full textResponding to a novel pandemic took many governments unaware, and especially in federal countries the interplay among executives at different levels proved difficult and illustrated the inherent tensions in federations. Drawing on data covering the temporal evolution of the epidemiological, economic and political situation at the cantonal level in Switzerland, we assess how federations dealt with the crisis situation. We find that while the federal government was in various instances accused of encroaching on the prerogatives of the cantonal governments, our empirical analysis of the latter's pandemic responses suggests that cantons equally engaged in burden-shifting and shirking. Our findings also suggest that non-pharmaceutical measures affected the fiscal measures taken by cantonal governments
The interplay between structure and function in the neural organization of working memory
No full textWorking memory (WM) plays a central role in many cognitive functions, such as decision-making and planning. This thesis aims to deepen our understanding of its neural bases by combining lesion analysis and functional connectivity approaches in both healthy individuals and patients with brain injuries. Three complementary studies are presented. The first study demonstrates that focal lesions in the right hemisphere (RH) significantly impair WM, regardless of modality (verbal or visuospatial), involving a distributed network that includes frontal, parietal, and temporal regions, as well as associated white matter tracts. The second study reveals that a stroke affecting the RH leads to a reduction in intra-hemispheric connectivity and a simultaneous increase in inter-hemispheric connectivity, suggesting the existence of adaptive mechanisms for functional reorganization. Finally, the third study, conducted in healthy participants, shows that WM relies on the integrity of fronto-parietal and sensorimotor networks, which are engaged in executive functions such as the active manipulation of information. Together, these studies contribute to refining our understanding of the brain substrates of working memory and open promising avenues for neuropsychological assessment and rehabilitation.La mémoire de travail (MdT) joue un rôle central dans de nombreuses fonctions cognitives, telles que la prise de décision et la planification. Cette thèse vise à en approfondir les bases neuronales en combinant des approches d’analyses lésionnelles et de connectivité fonctionnelle, chez des individus sains et des patients cérébrolésés. Trois études complémentaires sont présentées. La première met en évidence que des lésions focales de l’hémisphère droit (HD) altèrent significativement la MdT, indépendamment de la modalité (verbale ou visuospatiale), en impliquant un réseau distribué incluant les régions frontales, pariétales et temporales, ainsi que les faisceaux de substance blanche associés. La deuxième étude révèle qu’un accident vasculaire cérébral (AVC) affectant le HD entraîne une réduction de la connectivité intra-hémisphérique et une augmentation concomitante de la connectivité inter-hémisphérique, suggérant l’existence de mécanismes adaptatifs de réorganisation fonctionnelle. Enfin, la troisième étude, conduite chez des participants sains, montre que la MdT repose sur l’intégrité de réseaux fronto-pariétaux et sensorimoteurs, mobilisés dans les fonctions exécutives telles que la manipulation active de l’information. Ensemble, ces travaux contribuent à affiner la compréhension des substrats cérébraux de la mémoire de travail et ouvrent des perspectives prometteuses pour l’évaluation et la réhabilitation neuropsychologique.</p
Human RecQL helicases in DNA replication and repair
No full textRecQL helicases represent a unique family of conserved proteins. The five human family members share the characteristic helicase core domains that confer the 3’-5’ DNA helicase activity. Non-conserved domains provide substrate specificity, different protein interactions and ultimately result in the varying functions of each homolog. In this thesis we focus on the synthetic lethal interaction of WRN in the context of microsatellite instability and the role of RECQL4 helicase in DNA origin firing.
Genetic loss or inhibition of WRN leads to severe reduction in viability of cancer cells exhibiting Microsatellite Instability (MSI). Studies point to the helicase activity of WRN as the contributing factor of MSI cell survival. Mechanistically, WRN is required for the resolution of putative secondary DNA structures associated with the expansion of DNA microsatellite elements. Such structures pose a significant threat to DNA replication, acting as ‘roadblocks’ to replisomes and leading to the generation of DNA damage and chromosomal instability. Yet, the existence of MSI cell lines insensitive to WRN inhibition implies that additional functions of WRN may contribute to the synthetic lethality. In this study we demonstrate that WRN is suppressing the generation of DNA damage both in and out of the S-phase in MSI cells. We show that WRN-sensitive and -insensitive MSI cells exhibit different patterns of DNA damage upon inhibition of WRN. In addition, we describe the unique nature of the cell cycle checkpoint activated in MSI cells treated with WRN inhibitors and identify similarities with the putative TOPOII-related DNA decatenation checkpoint. Furthermore, we showcase the different response of WRN-sensitive and -insensitive MSI cells to concomitant inhibition of WRN and TOPOII, suggesting the relevance of the interplay of WRN and TOPOII in MSI cells. Altogether, we reveal that different cellular functions of WRN are responsible for the synthetic lethality of WRN in MSI cells, paving the way for the identification of novel therapeutic targets.
The unique N-terminal domain of RECQL4 shares sequence similarity with the yeast Sld2 protein, an essential factor for DNA origin firing. A number of studies describe the implication of RECQL4 homologs from different organisms in DNA replication initiation. Yet, the exact functions of human RECQL4 in origin firing remain elusive. In our study we demonstrate that human RECQL4 WT and CRISPR-Cas9-generated knock-out (KO) cells exhibit similar S-phase entry kinetics and unaltered patterns in origin firing. Single-molecule experiments show that RECQL4 affects replication fork progression in a dominant negative manner, with KO clones displaying no defects in fork speed, while helicase-dead mutants exhibit slower fork progression rates. Interestingly, EdU-seq experiments revealed the genome-wide increase in mobility of the replication front in KO cells upon recovery from hydroxyurea, suggesting that RECQL4 might indirectly affect the progression of DNA replication under conditions of replication stress. Lastly, we show that RECQL4 does not participate in MiDAS, a BIR repair pathway responsible for rescuing under-replicated DNA regions in mitosis. Collectively, we provide evidence that RECQL4 has a dispensable role in DNA replication initiation under physiological conditions, while it regulates fork progression rates, showcasing its functional divergence from yeast Sld2.</p
Transformer des instruments pour enseigner la compréhension : un album de littérature de jeunesse et un article encyclopédique numérique participatif
No full textMetaproteomics as a Powerful Tool for an Extensive Characterization of Ambient Bioaerosols
No full textBioaerosols are of great health and environmental concern. Current techniques for their characterization are generally designed to detect individual species or oppositely unspecific molecular tracers. Metaproteomics on the other hand features the possibility to cover a broad range of taxonomies in a single analysis. This work presents a successful application of metaproteomics to characterize the biological fraction of airborne particulate matter (PM). A bottom-up proteomic strategy was employed, including protein extraction by ultrasonication in aqueous buffer, in-solution tryptic digestion, and nanoflow liquid chromatography-high-resolution mass spectrometry analysis. Extraction parameters were optimized to enhance proteins' recovery. The method was validated on Escherichia coli extracts before its application on ambient PM10 samples collected over 12 weeks in Strasbourg, France. A total of 1,087 peptides were detected across all samples, with a weekly average of 223 ± 104 peptides corresponding to 111 ± 40 proteins. Peptides from species belonging to animals, plants, fungi, bacteria, and archaea kingdoms were inventoried. Many of them proved to be very relevant, as they were related to human allergens and pathogens, plant pathogens, or ecological indicators. In this work, the major benefits of metaproteomics, yet rather unexploited, as well as its pitfalls and challenges for a broader application in atmospheric chemistry, are discussed
Terthiophene Photophysics Revisited: Independence of the Triplet Quantum Yield on the Excitation Wavelength
No full textA significant part of our understanding of the excited-state properties of polythiophenes comes from studies of smaller oligothiophenes, which have a better-defined structure. Among them, terthiophene (3T ) was reported to have an excitation-wavelength dependent triplet quantum yield, ΦT . This was explained by the opening of a second intersystem crossing (ISC) pathway upon the high-energy excitation of distorted molecules. Here, we reinvestigate the excited-state dynamics of 3T in solvents of various viscosity and in a polymer film. Our results reveal that, although different subpopulations are excited upon high- and low-energy irradiation, the ISC dynamics, and hence ΦT , are the same. We show that the distorted molecules excited at short wavelength undergo rapid planarization independent of the viscosity of the environment before significant ISC takes place. The apparent increase of ΦT with increasing excitation wavelength reported earlier can be explained by the neglect of the early relaxation dynamics
Time to exercise ! Boosting exercise performance via AMPK signaling
No full textBody physiology follows the daily rhythm driven by the circadian system, which underlies the emerging concept of chrono-medicine. In this issue, Chen et al. report that feeding timing modulates adipocyte AMP-activated protein kinase (AMPK) α2 signaling to enhance exercise performance in mice, paving the way for chronotherapeutic approaches of AMPK activators such as metformin.
Refers to : Chen J, Xiang J, Zhou M, Huang R, Zhang J, Cui Y, Jiang X, Li Y, Zhou R, Xin H, Li J, Li L, Lam SM, Zhu J, Chen Y, Yang Q, Xie Z, Shui G, Deng F, Zhang Z, Li MD. Dietary timing enhances exercise by modulating fat-muscle crosstalk via adipocyte AMPKα2 signaling. Cell Metab. 2025 Jun 3;37(6):1364-1380.e6. doi: 10.1016/j.cmet.2025.02.007. Epub 2025 Mar 14. PMID: 40088888.</p
Efficacité clinique des traitements de l’ostéoporose
No full textOsteoporosis therapy includes antiresorptive drugs of varying efficacy (estrogens, raloxifene, bisphosphonates, denosumab) and osteoanabolic agents capable of stimulating bone formation through various mechanisms (teriparatide, abaloparatide, romosozumab). This results in notable differences in bone mineral density gain and antifracture efficacy. Several comparative studies and meta-analyses have demonstrated the superiority of osteoanabolic agents over antiresorptive agents, particularly in high-risk women. For all treatments, the risk of severe adverse events remains very low. However, the reversibility of the effects of most osteoporosis treatments, except for bisphosphonates, makes it essential to consolidate their effects with a bisphosphonate.Les traitements de l’ostéoporose incluent d’une part les antirésorptifs (œstrogènes, raloxifène, bisphosphonates, dénosumab) et d’autre part les agents anaboliques osseux capables de stimuler la formation osseuse (tériparatide, abaloparatide, romosozumab). Le gain de densité minérale osseuse et l’efficacité antifracturaire varient en fonction du traitement. Plusieurs études comparatives ainsi que des méta-analyses ont démontré la supériorité des agents anaboliques osseux par rapport aux traitements antirésorbeurs, notamment chez les femmes à haut risque. Pour tous les traitements, le risque d’événement indésirable sévère demeure très faible. Toutefois, la réversibilité des effets de la plupart des traitements de l’ostéoporose, hormis les bisphosphonates, rend indispensable la prise d’un bisphosphonate pour consolider leurs effets