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Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells
No full textInternational audienceMitosis is a critical phase of the cell cycle and a vulnerable point where cancer cells can be disrupted, causing cell death and inhibiting tumor growth. Challenges such as drug resistance persist in clinical applications. During mitosis, mRNA translation is generally downregulated, while non-canonical translation of specific transcripts continues. Here, we show that mitotic cancer cells redistribute ribosomes toward the 5′ untranslated region (5′ UTR) and beginning of the coding sequence (CDS), enhancing translation of thousands of upstream open reading frames (uORFs) and upstream overlapping open reading frames (uoORFs). This mitotic induction of uORF/uoORF enriches human leukocyte antigen (HLA) presentation of non-canonical peptides on the surface of cancer cells after mitotic inhibitor treatment. Functional assays indicate these epitopes provoke cancer-cell killing by T cells. Our findings highlight the therapeutic potential of targeting uORF/uoORF-derived epitopes with mitotic inhibitors to enhance immune recognition and tumor cell elimination
Le chevalier Antar : Pierre Pocorull et Robert Lesbounit à la raffinerie de Donges (1958-1961)
No full textInternational audienceThis article tells the story of an exemplary collaboration between an artist, Robert Lesbounit, and an architect, Pierre Pocorull, to decorate buildings at the Donges oil refinery (Loire-Atlantique, France) in 1958. The story originates from the vision of a modernist manager, Jacques Riboud, who, like others at the time, believed that art could contribute to the humanization of the factory. It is also based on the close relationship between the artist—who had given up easel painting in favor of monumental art intended for the general public—and the architect, who had been his student. However, the correspondence found between the artist and the architect reveals the obstacles faced by those who, in the post-war decades, aspired to democratize art by integrating it into new urban neighborhoods and even into workplaces themselves.Cet article relate une histoire exemplaire de collaboration entre un artiste, Robert Lesbounit, et un architecte, Pierre Pocorull, pour la décoration de bâtiments au sein de la raffinerie de pétrole de Donges (Loire-Atlantique) en 1958. L’histoire a pour origine la volonté d’un patron moderniste, Jacques Riboud qui, comme d’autres à l’époque, pensait que l’art pouvait contribuer à l’humanisation de l’usine. Elle s’appuie aussi sur la relation étroite entre l’artiste qui avait renoncé à la peinture de chevalet pour l’art monumental à l’intention du plus grand nombre et l’architecte qui avait été son élève. La correspondance retrouvée entre l’artiste et l’architecte témoigne pourtant des obstacles rencontrés par ceux qui, dans les décennies d’après-guerre, avaient l’ambition de démocratiser l’art en l’installant dans les nouveaux quartiers urbains et jusqu’au sein même des espaces de travail
Fluorescent Nanodiamond-based delivery systems for mitochondrial targeting of bioactive molecules
No full textInternational audienc
Continuous self-repair protects vimentin intermediate filaments from fragmentation
No full textInternational audienceIntermediate filaments are key regulators of cell mechanics. Vimentin, a type of intermediate filament expressed in mesenchymal cells and involved in migration, forms a dense network in the cytoplasm that is constantly remodeling through filament transport, elongation/shortening, and subunit exchange. While it is known that filament elongation involves end-to-end annealing, the reverse process of filament shortening by fragmentation remains unclear. Here, we use a combination of in vitro reconstitution, probed by fluorescence imaging and atomic force microscopy, with theoretical modeling to uncover the molecular mechanism involved in filament breakage. We first show that vimentin filaments are composed of two populations of subunits, half of which are exchangeable and half immobile. We also show that the exchangeable subunits are tetramers. Furthermore, we reveal a mechanism of continuous filament self-repair, where a soluble pool of vimentin tetramers in equilibrium with the filaments is essential to maintain filament integrity. Filaments break due to local fluctuations in the number of tetramers per cross-section, induced by the constant subunit exchange. We determine that a filament tends to break if approximately four tetramers are removed from the same filament cross-section. Finally, we analyze the dynamics of association/dissociation and fragmentation to estimate the binding energy of a tetramer to a complete versus a partially disassembled filament. Our results provide a comprehensive description of vimentin turnover and reveal the link between subunit exchange and fragmentation
Structurally defined synthetic heparin oligosaccharides reveal unique signatures for nanopore structural analysis of GAGs
No full textInternational audienceEfforts to fully understand the structure-to-function relationships of glycosaminoglycans (GAGs) have been hampered by the complexity and polydispersity of GAGs and, more importantly, by the need for sensitive analytical techniques to discern their subtle structural motifs. Conventional analytical methods often fail to provide information on the sparse motifs of GAGs. Concurrently, nanopore-based analysis has shown great potential in GAGs structural analysis. Still, until now, it has been limited by the difficulty of relating ionic current changes to specific motifs. To address this, the present study allowed for obtaining reference signals by employing carefully designed synthetic sulfated tetra- to dodecasaccharides to allow precise sequence control and purity. Reference signals were obtained for specific motifs, paving the way for accurate motif recognition. The outcomes of the study demonstrated unequivocal recognition of specific GAG structures by monitoring the evolution of nanopore signals in response to the translocation of synthetic heparin (HP)-like oligosaccharides with controlled structures, allowing extensive structural discrimination. The findings highlight the nanopore's capability to detect subtle structural features, such as differences in sulfation patterns and epimerization of uronic acid. These results open the way to establishing detailed heparin (HP)-specific reference signals and to nanopore fingerprinting and sequencing of GAGs
Organisations alternatives : faire face aux injonctions contradictoires
No full textInternational audienceSession thématique ouverte.Cette session vise à mettre en lumière et enrichir l’analyse des tensions contradictoires qui peuvent traverser les organisations dites « alternatives » (société à mission, entreprise de l’ESS, associations, etc.) : autonomie vs. contrôle, financiarisation vs. logique de long terme, réindustrialisation vs. concurrence des territoires, soutenabilité forte vs. greenwashing, etc.• Est-il possible de faire émerger une typologie de ces injonctions contradictoires ?• Quels outils conceptuels transdisciplinaires pour les éclairer ? Comment les tensions que l’on peut théoriser au niveau macro sont-elles concrètement vécues par les acteurs ?• Comment les organisations alternatives inventent de nouvelles pratiques pour y faire face
Faire avec : une expérimentation de gestion des déchets avec une communauté pauvre en Bolivie
No full textFNEGE 3International audienceFaced with the major challenges that threaten us, such as the accumulation of waste, one way forward could be to learn to 'work with' (Citton, 2021): to work with and from waste, and to work with and within poor communities in the Global South. Drawing on concepts from Simondon's philosophy, we present an experiment in waste management in a Bolivian community. Neither social entrepreneurship nor community entrepreneurship, the approach initiated a movement that spread throughout the community. Rather than imposing a model, it is like a minor gesture that the community extends and propagates, towards a supplement of relational autonomy.Face aux grands défis qui nous menacent, à l'image de l'accumulation des déchets, une des directions pourrait être d'apprendre à « faire avec » (Citton, 2021) : faire avec et à partir des déchets, faire avec et auprès des communautés pauvres du Sud Global. En nous inspirant de concepts issus de la philosophie de Simondon, nous présentons une expérimentation de gestion des déchets dans une communauté bolivienne. Ni entrepreneuriat social ni entrepreneuriat communautaire, l'approche a initié un mouvement qui s'est propagé dans l'ensemble de la communauté. Plutôt qu'imposer un modèle, elle s'apparente à un geste mineur que le milieu prolonge et propage, favorisant une certaine autonomie relationnelle
An aeroponic system to characterize maize root exudates in relation to N nutrition and arbuscular mycorrhizal symbiosis
No full textInternational audienceRoot exudates play major roles in the recruitment of plant microbiota. The metabolic composition of root exudates varies according to plant developmental stage, nutrient availability, (a)biotic stresses and interaction with the root-associated microbiota, including arbuscular mycorrhizal fungi (AMF), which play a key role in plant mineral nutrition and stress tolerance. While it is well established that AMF can perceive plant root exudate compounds, little is known about plant root exudate modifications in response to AMF inoculation. Here, we developed an aeroponic-based culture system suitable for the analysis of maize root exudates during symbiosis with the AMF Rhizophagus irregularis while controlling nutrient availability.We validated the functionality of the system by monitoring both maize root colonization by the AMF and the expression profile of symbiotic root marker genes. We then investigated the composition of root exudates (strigolactones and specialized metabolites) from mycorrhizal and non-mycorrhizal plants grown under different N and P regimes. Comparisons of specialized metabolite profiles from root exudates, root tissues, and fungal extracts allowed us to identify candidate metabolic features specifically accumulating in mycorrhizal root exudates. Thus, we provide an innovative method to better understand the role of root exudate metabolites in shaping the microbiota of mycorrhizal plants.</p
Role of AI driven Internet of Things (IoT) and Wireless Sensor Networks in developing Smart Cities
No full textInternational audienceThe Wireless Sensor Networks and IoT are evolving technologies in the paradigm of Smart Cities. Interconnection among smart devices is to be done to provide the ease of communication using these technologies. Sensors are deployed in smart devices and embedded systems which are further integrated with Internet of Things to impart advanced facilities for developing smart cities. This paper explores the transformative role of Artificial Intelligence (AI) in enhancing Internet of Things (IoT) and Wireless Sensor Networks (WSNs) for smart city development. By leveraging AI-driven data analytics, predictive modeling, and automation, IoT and WSNs can optimize urban resource management, improve infrastructure efficiency, and support sustainable growth in smart cities. The Internet of Things are capable of bridging the physical objects by using actuator networks, sensors and then they control these components. It is the most crucial area of research in the field of wireless sensor networks that can be combined with IoT to work in developing Smart Cities. The main focus of writing this paper is on how smart devices can be deployed in various locations to collect the required information, how this collected data is to be analyzed and how it helps the Smart Cities. In this paper, our main objective is to discuss the technologies, concepts, various issues and challenges in developing Smart Cities using these intelligent IoT and WSNs
Leveraging Large Language Models for the Generation of Stochastic Models in System Availability and Reliability Analysis
No full textInternational audienceThis paper investigates the ability of large language models (LLMs) such as ChatGPT, Gemini, Claude, and Mistral to generate and expand Stochastic Petri Net (SPN) models specifically for system availability and reliability analysis. The study evaluates how LLMs can assist in automating the expansion of formal models in these domains, following a structured methodology: (a) modeling a basic availability and reliability system in Mercury-script; (b) providing detailed prompts to guide the extension of the model; (c) obtaining the expanded models from LLMs; (d) validating the generated models in Mercury for syntactic correctness, semantic accuracy, and dependability metrics; and (e) conducting a comparative analysis of the results across the different LLMs. The findings reveal the strengths and limitations of LLM-generated models regarding availability and reliability, providing insights into the potential of AI-assisted formal modeling for improving the efficiency and accuracy of system dependability evaluations