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On the space of subgroups of Baumslag-Solitar groups II : High transitivity
No full textA continuation of "On the space of subgroups of Baumslag-Solitar groups I: perfect kernel and phenotype", by Alessandro Carderi, Damien Gaboriau, François Le Maîitre, Yves Stalder (hal-03829832). 44 pages, 1 figureInternational audienceWe continue our study of the perfect kernel of the space of transitive actions of Baumslag-Solitar groups by investigating high transitivity. We show that actions of finite phenotype are never highly transitive, except when the phenotype is 1, in which case high transitivity is actually generic. In infinite phenotype, high transitivity is generic, except when |m|=|n| where it is empty. We also reinforce the dynamical properties of the action by conjugation on the perfect kernel that we had established in our first paper, replacing topological transitivity by high topological transitivity
Nivolumab in Metastatic Clear-cell Renal Cell Carcinoma: An Integrative Biomarker Analysis from the NIVOREN GETUG-AFU 26 Phase 2 Study
No full textInternational audienceNivolumab improved survival in patients with refractory metastatic clear-cell renal cell carcinoma (ccRCC), but no reliable biomarker of activity has been identified. We conducted a real-world phase 2 trial of nivolumab in patients progressing after one or more vascular endothelial growth factor (VEGF) receptor-directed therapies, which included an integrated translational programme. Candidate tissue and circulating biomarkers were assessed using immunoassays and gene expression profiling. Overall, 720 patients were treated, with activity and safety in line with pivotal trial data. Exploration of tissue architecture showed that the presence of tertiary lymphoid structures, CD8+ lymphocytes, and CD163+ macrophage infiltration at the invasive margin were all marginally associated with longer progression-free survival, similarly to PD-1 expression on immune cells. Expression of hypoxia-related marker VEGF on tumour cells was however strongly associated with shorter progression-free and overall survival. Recapitulation of microenvironment composition based on gene expression signatures showed that patients harbouring a high tumour lymphocyte infiltration, concomitantly to low infiltration of neutrophil and non-immune stromal cells, had improved response to nivolumab. Conversely, circulating cytokines related to protumoral inflammation interleukin (IL)-6 and IL-8 were independently associated with shorter progression-free and overall survival. Overall, immune and angiogenic features helped inform outcomes to nivolumab. Circulating factors were best potential predictors for immunotherapy activity in ccRCC
Towards robust probabilistic maps in Deep Brain Stimulation: exploring the impact of patient number, stimulation counts, and statistical approaches
No full textInternational audienceIntroduction Probabilistic Stimulation Maps (PSMs) are increasingly employed to identify brain regions associated with optimal therapeutic outcomes in Deep Brain Stimulation (DBS). However, their reliability and generalizability are challenged by the limited size of most patient cohorts and the inherent variability introduced by different statistical methods and input data configurations. This study aimed to investigate the geometrical variability of Probabilistic Sweet Spots (PSS) as a function of both the number of patients (nPat) and the number of stimulations per patient (nStim), and to model a stability boundary defining the minimum data requirements for obtaining geometrically stable PSS. Methods Three statistical approaches–Bayesian t -test, Wilcoxon test with False Discovery Rate (FDR) correction, and Wilcoxon test with nonparametric permutation correction–were applied to two patient cohorts: a primary cohort of 36 patients undergoing DBS for Parkinson’s Disease (PD), and a secondary cohort of 61 patients treated for Essential Tremor (ET), used to assess generalizability. Stimulation test data was collected intra-operatively for the first cohort and post-operatively for the second one. Geometric stability was evaluated based on variability in PSS volume extent and centroid location. Results The analysis revealed a non-linear trade-off between nPat and nStim to yield stable PSS. A stability boundary was defined, representing the minimum combinations of nPat–nStim required for anatomically robust PSS. Among the tested methods, the Bayesian t -test achieved stability with smaller sample sizes (∼15 patients) and demonstrated a consistent performance across both cohorts. In contrast, the Wilcoxon-based methods showed variable behavior between cohorts, which differed in symptom type and testing phase (intra-operative testing vs. post-operative screening). Discussion The proposed PSS stability boundary provides a practical reference for designing DBS studies and stimulation screening protocols aimed at probabilistic mapping. The Bayesian t -test emerged as a reliable method across both cohorts, supporting its potential in studies with limited sample sizes and scenarios where the method needs to be readily generalized to varying symptoms. These findings underscore the importance of considering both cohort size and stimulation count in probabilistic DBS mapping and call for further investigation into method-specific sensitivities to clinical and procedural factors
Parenting and empathy capabilities drive brain response to pain cues in baby cries
No full textInternational audienceThe ability of human caregivers to decode and respond to the distress information encoded in a baby's cries is essential for the baby's survival. What are the factors that influence this aptitude, and how is this represented in the brain? Although previous neuroimaging studies have shown that hearing cries activates a set of brain areas that drive caregiver response behaviors, they have mainly focused on adults with parenting experience, especially mothers, and have not explored how the level of pain expressed in the cry modulates caregiver brain activation. In this study, we combine fMRI studies on a large sample of parents and nonparents with ground-breaking voice resynthesis tools enabling us to systematically control the level of pain expressed by babies' cries. We show that pain cries induce more specialized brain activation in parents than in nonparents, with greater connectivity within and between networks involved in mentalizing, emotional regulation, and vigilance. Mothers show higher overall connectome activity than fathers. Yet, it is among parents with the greatest emotional empathy—both fathers and mothers—that vocal roughness (a marker of distress in baby cries) most actively recruits the parental vigilance brain network. By taking advantage of acoustic resynthesis, which allows precise control over sound stimuli, and by paying attention to the ability to understand the emotions of others rather than focusing solely on sex, our study highlights that parental status interacts with empathetic capabilities to modulate how the brains of human adults respond when a baby's cry signals distress
Experimental evaluation of literature-established delignification techniques on poplar wood
No full textInternational audienceTo minimize greenhouse gas emissions, the development of biobased building materials is gaining increasing priority. Wood's insulation performance can be enhanced by creating additional porosity through the removal of non-cellulosic substances. Although delignification techniques have been used in the pulping industry to produce cellulose pulp, they have evolved to produce cellulose nanofibers or cellulose scaffolds for functional materials. Various top-down delignification techniques have been suggested for solid wood, but most studies have focused on a single technique applied to a specific wood species, making it difficult to compare the effectiveness of different methods. This paper addresses this gap by presenting a comparative analysis of literature-established delignification techniques applied to solid wood pieces: soda pulping, alkaline sulfite pulping followed by hydrogen peroxide bleaching, and organosolv pulping followed by sodium chlorite bleaching. This study evaluated the impact of these techniques by examining the changes in mass loss, chemical constituents and FTIR spectra of French poplar wood planks of 100 cm 3 after treatment. The combination of organosolv pulping by alcoholysis and sodium chlorite bleaching was found to be the most effective method for complete lignin removal. Our findings reveal the strengths and limitations of these methods, providing insights into the selection of wood modification techniques for upscaling purposes. Further research on drying delignified wood is required to complete a preliminary study of the industrialization of insulating wood. These advancements promoted the sustainable use of wood as a mechanically strong thermal insulator to reduce building energy consumption and mitigate climate change
Design and synthesis of first-in-class stapled peptides targeting the E3 ligase MuRF1 to potentially prevent muscle wasting
No full textInternational audienceThis study focuses on developing stapled peptides that target the E3 ubiquitin ligase MuRF1 (TRIM63), a key player in muscle protein degradation and muscle wasting. MuRF1 is so far the only E3 involved in the degradation of contractile proteins in muscle tissue, making it a potential therapeutic target for conditions like cachexia, sarcopenia, and chronic disease-related muscle atrophy. We designed two stapled decapeptides mimicking a helical segment of MuRF1's coiled-coil domain, aiming at perturbating its structural organization. To enhance their α-helical structure, these peptides were stabilized using hydrocarbon stapling and were prepared using solid-phase peptide synthesis. Their binding affinities to MuRF1 were assessed using spectral shift and microscale thermophoresis (MST) assays. Stapled peptides bound efficiently to MuRF1 with equilibrium dissociation constants KD in the range 1.5–1.8 μM, whereas their unstapled counterparts showed little or no binding. This work represents an early promising step in targeting MuRF1, thus offering a potential therapeutic approach to prevent or reduce muscle wasting
MiCoReCa (Microbiome Community Resource Catalogue) - Towards Centralized Curation And Integration Of Microbiome Bioinformatics Resources
No full textThe rapid growth of microbiome research has led to the development of numerous bioinformatics tools and databases, but information about them remains fragmented across disparate, often outdated cataloging efforts, hindering resource discovery and utilization. To address this critical gap, the ELIXIR Microbiome Community proposes the development of MiCoReCa (Microbiome Community Resource Catalogue), a comprehensive, dynamic, open-access catalogue of microbiome-related bioinformatics resources (tools, workflows, training, standards, and databases). Leveraging our community's expertise, this initiative will utilize standardized ontologies like EDAM and cross-reference established platforms like bio.tools and WorkflowHub to create a centralized, findable inventory. A key feature is the community-driven process for identifying and curating missing ontological terms and metadata, ensuring MiCoReCa's accuracy and relevance in collaboration with partner platforms. Furthermore, the catalogue will integrate links to training materials from TeSS to support appropriate tool usage, and connect with OpenEBench for benchmarking capabilities. This project will not only provide a vital resource for the microbiome field, enhancing research efficiency and reproducibility, but will also establish a sustainable, adaptable infrastructure potentially applicable to other ELIXIR Communities. This effort represents a significant contribution by the ELIXIR Microbiome Community to streamline microbiome bioinformatics
