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Land surface model underperformance tied to specific meteorological conditions
No full textInternational audienceThe exchange of carbon, water, and energy fluxes between the land and the atmosphere plays a vital role in shaping global change and extreme events. Yet our understanding of the theory of this surface-atmosphere exchange, represented via land surface models (LSMs), continues to be limited, highlighted by marked biases in model-data benchmarking exercises. Here, we leveraged the PLUMBER2 dataset of observations and model simulations of terrestrial sensible heat, latent heat, and net ecosystem exchange fluxes from 153 international eddy-covariance sites to identify the meteorological conditions under which land surface models are performing worse than independent benchmark expectations. By defining performance relative to three sophisti-cated out-of-sample empirical models, we generated a lower bound of performance in turbulent flux prediction that can be achieved with the input information available to the land surface models during testing at flux tower sites. We found that land surface model performance relative to empirical models is worse at edge conditions -that is, LSMs underperform in timesteps where the meteorological conditions consist of coinciding relative extreme values. Conversely, LSMs perform much better under "typical" conditions within the centre of the meteorological variable distributions. Constraining analysis to exclude the edge conditions results in the LSMs outperforming strong empirical benchmarks. Encouragingly, we show that refinement of the performance of land surface</div
Building a Standardised Statistical Reporting Toolbox in an Academic Oncology Clinical Trials Unit: The grstat R Package
No full textAcademic Clinical Trial Units frequently face fragmented statistical workflows, leading to duplicated effort, limited collaboration, and inconsistent analytical practices. To address these challenges within an oncology Clinical Trial Unit, we developed grstat, an R package providing a standardised set of tools for routine statistical analyses.Beyond the software itself, the development of grstat is embedded in a structured organisational framework combining formal request tracking, peer-reviewed development, automated testing, and staged validation of new functionalities. The package is intentionally opinionated, reflecting shared practices agreed upon within the unit, and evolves through iterative use in real-world projects. Its development as an open-source project on GitHub supports transparent workflows, collective code ownership, and traceable decision-making.While primarily designed for internal use, this work illustrates a transferable approach to organising, validating, and maintaining a shared analytical toolbox in an academic setting. By coupling technical implementation with governance and validation principles, grstat supports efficiency, reproducibility, and long-term maintainability of biostatistical workflows, and may serve as a source of inspiration for other Clinical Trial Units facing similar organisational challenges.</p
Tissue-Specific Expression and Regulation of the Mineralocorticoid Receptor During Development
No full textInternational audienceThis review summarizes current knowledge on the mineralocorticoid receptor (MR), a nuclear receptor encoded by the NR3C2 gene, and its ligand aldosterone. In epithelial tissues like the kidney, colon, salivary glands and skin, particularly within the sweat glands, the MR plays a key role in regulating sodium reabsorption. In non-epithelial tissues such as the brain, adipose tissue, and heart, glucocorticoids are the main physiological MR ligands due to the absence of the 11βhydroxysteroid dehydrogenase type 2. MR expression begins during development with tissuespecific patterns. In the kidney, MR levels peak mid-gestation, decrease at birth then increase postnatally. Loss of MR function, as observed in pseudohypoaldosteronism type 1 causes saltwasting syndrome. Similar patterns are seen in the heart and brain, especially the hippocampus, where it influences stress regulation. On the contrary, MR expression is maintained at birth in the lung for neonatal fluid clearance via epithelial sodium channels. It is also present in tissues like skin, retina, and gastrointestinal tract, indicating broad physiological roles. MR expression during fetal development correlates with adaptations to extra-uterine life, like changes in amniotic fluid osmolality and aldosterone levels. MR gene expression and activity are tightly regulated through multiple mechanisms. These include transcriptional control via two promoters, posttranscriptional regulation involving RNA-binding proteins and microRNAs, and post-translational modifications such as phosphorylation, sumoylation, and ubiquitination. These regulatory levels ensure appropriate MR function across different tissues and developmental stages and may have implications for conditions such as hypertension and heart failure.</div
Identification of transdiagnostic phenomena among patients, the general population, relatives, and mental health professionals using topic modeling techniques
No full textInternational audienceIntroduction Recent research has highlighted the limitations of the categorical approach to mental disorders and has increasingly supported the development of a transdiagnostic perspective. This emerging approach focuses on common distal factors (circumstantial, biological, and social) and psychological processes that contribute to psychological suffering across a range of disorders, as well as on the resulting psychological symptoms. The present study aims to identify transdiagnostic distal factors, psychological processes, and symptoms by analyzing narratives through topic modeling—an unsupervised machine learning technique, specifically within Natural Language Processing (NLP). Topic modeling enables the automatic extraction of latent themes from unstructured text, making it possible to identify psychological patterns grounded in patients’ lived experiences. Methods We recruited four groups of participants: Patients diagnosed with a psychiatric disorder ( N = 445), Individuals from the general population ( N = 570), Relatives of patients with psychiatric disorders ( N = 354), and Mental health professionals ( N = 131). Participants answered open-ended questions exploring the causes of psychological suffering, their wishes for change, and their previous experiences with psychotherapy. Results We identified 258 topics, which were organized into 12 overarching themes. The most prominent topics concerned Emotional and Psychological Difficulties , Family and Social Relationships , and Therapeutic Processes . Each theme showed a comparable prevalence across the different diagnostic categories, supporting the transdiagnostic nature of these phenomena. Conclusion Topic modeling can be used effectively to identify transdiagnostic distal factors, psychological processes, and symptoms from diverse narratives. This approach tends to provide a novel means of supporting the relevance and validity of the transdiagnostic perspective
Connecting mitochondrial metabolism and mitotic fidelity to control vulnerability of high grade serous ovarian cancer patients to taxane-based chemotherapy
No full textHigh-grade serous ovarian carcinoma (HGSOC), which accounts for approximately 75% of ovarian cancer cases, is associated with poor clinical outcome. Although most patients initially achieve a complete response to conventional chemotherapy, HGSOC almost invariably develops chemoresistance. There is therefore an urgent need to identify predictive biomarkers of treatment response. Here, through integrative analyses of molecular and clinical data from HGSOC patient cohorts, we identify syntabulin (SYBU), a microtubule-associated protein originally described as a regulator of mitochondrial transport along neuronal microtubules, as a critical determinant of chemosensitivity in HGSOC. Low SYBU expression in tumors correlates with higher tumor grade and increased aggressiveness, yet paradoxically with enhanced sensitivity to chemotherapy. SYBU-deficient cancer cells display impaired oxidative phosphorylation and a metabolic shift toward glycolysis characteristic of the Warburg effect, together with mitotic defects such as chromosome lagging that promote aneuploidy. Mechanistically, syntabulin forms a complex with the mitochondrial outer membrane porin VDAC1 and the inner membrane protein MIC60, a major regulator of mitochondrial cristae organization. Functionally, the syntabulin-MIC60 axis controls cristae architecture and mitotic fidelity, thereby connecting mitochondrial metabolism to cell division. These findings highlight new therapeutic vulnerabilities to overcome chemoresistance in ovarian cancer. SIGNIFICANT STATEMENT Ovarian cancer remains the deadliest gynecologic malignancy, largely due to the systematic emergence of resistance to chemotherapy. Identifying molecular mechanisms involved in response to treatment is therefore a major clinical challenge. Here, we uncover an unexpected role for the mitochondrial protein syntabulin in regulating chemotherapy sensitivity in high-grade serous ovarian cancer. We demonstrate that syntabulin coordinates cancer cell mitotic progression with mitochondrial structure and metabolism through interactions with cristae-shaping proteins. These findings reveal a previously unrecognized link between mitotic regulation and mitochondrial architecture, and identify syntabulin as a potential therapeutic target in ovarian cancer to induce vulnerability to taxane-based chemotherapy
Enterobacter sp. SA187 boosts high‐affinity nitrate transporters expression, ethylene signaling, and plant growth under low nitrate
No full textInternational audienceSummary Sustainable crop production demands solutions to reduce the overuse of synthetic nitrogen (N) fertilizers, and plant‐growth‐promoting bacteria offer a promising strategy by enhancing nutrient acquisition. This study investigated the ability of a nondiazotrophic bacterium, Enterobacter sp. SA187 (SA187), in enhancing Arabidopsis growth under low‐nitrate conditions and the underlying mechanisms. Arabidopsis seedlings were grown under different nitrate concentrations with or without SA187 inoculation. Growth traits were quantified alongside shoot and root nitrate and total N contents, and C : N ratios. Transcriptomic profiling (RNA‐seq) and qRT‐PCR were used to assess modified gene expression. Functional validation was conducted using ethylene‐insensitive ( ein2‐1 ) and high‐affinity nitrate transporter (HATS) mutants ( nrt2.5 , nrt2.6 ). SA187 significantly enhanced fresh weight, primary root length, and lateral root density under low nitrate, with benefits increasing as nitrate availability decreased. SA187 improved nitrate accumulation and shoot N allocation, reducing shoot C : N ratios. SA187 regulated expression of HATS and hormone‐responsive genes. The growth‐promoting effects were abolished in ein2‐1 , nrt2.5 , and nrt2.6 mutants, and SA187‐induced regulation of NRT2.5 occurred downstream of ethylene signaling, while NRT2.6 was partly ethylene independent. SA187 promotes growth under low nitrate possibly through ethylene‐mediated and HATS‐dependent reprogramming of nitrate accumulation and N allocation, supporting its use as a microbial solution for low‐input agriculture
Tet2 deficiency promotes IgG1+ B‐cell expansion and differentiation blockade through deregulation of the Nfkbia –c‐Rel axis
No full textInternational audienceThe germinal center (GC) reaction is essential for orchestrating humoral immunity by producing plasma cells (PCs) and memory B cells (MBCs). TET2, an α‐ketoglutarate‐dependent dioxygenase, plays a critical role in B‐cell exit from the GC and in plasma cell differentiation. Moreover, TET2 functions as a tumor suppressor in diffuse large B‐cell lymphoma (DLBCL), with mutations frequently observed in the ST2 DLBCL subgroup, which is marked by elevated NF‐κB and PI3K signaling and predominant expression of IgG B‐cell receptors (BCRs). We used a combination of in vivo mouse models and in vitro differentiation systems to investigate the effects of Tet2 deficiency on IgG1+ GC B‐cells. We performed flow cytometry, gene expression, and DNA methylation analysis to assess differentiation, proliferation, and molecular alterations. Tet2 ‐deficient IgG1+ GC B‐cells displayed impaired differentiation into both PCs and MBCs, accompanied by enhanced proliferation. These cells exhibited hypermethylation and repression of the Nfkbia locus, increased activation of the NF‐κB subunit c‐Rel, and sustained high levels of surface IgG1. Upon recall immunization, Tet2 ‐deficient IgG1+ MBCs failed to efficiently differentiate into PCs, resulting in their accumulation and further GC expansion. These findings demonstrate that Tet2 is essential for balancing proliferation and terminal differentiation of IgG1+ GC B‐cells during the humoral response. The impaired regulation of this balance due to Tet2 loss provides mechanistic insight into a contributory pathway that may facilitate DLBCL transformation in TET2 ‐mutated cases
SAIL: Self-supervised Learning of Lighting-Invariant Representations from Real Images with Latent Diffusion
No full textInternational audienceIntrinsic image decomposition aims at separating an image into its underlying albedo and shading components, isolating the base color from lighting effects to enable downstream applications such as virtual relighting and scene editing. Despite the rise and success of learning-based approaches, intrinsic image decomposition from real-world images remains a significantly challenging task due to the scarcity of labeled ground-truth data. Most existing solutions rely on synthetic data as supervised setups, limiting their ability to generalize to real-world scenes. Self-supervised methods, on the other hand, often produce albedo-like maps that contain reflections and lack consistency under different lighting conditions. To address this, we propose SAIL, an approach designed to estimate illumination-invariant representations from single-view real-world images to specifically target plausible relighting. We repurpose the prior knowledge of a latent diffusion model for unconditioned scene relighting as a surrogate objective for learning light-invariant estimates. To this end, we introduce a novel intrinsic image decomposition fully formulated in the latent space. To guide the training of our latent diffusion model, we introduce regularization terms that constrain both the lighting-dependent and -independent components of our latent image decomposition. Through our experiments, we demonstrate that SAIL produces stable albedo-like representations under varying lighting conditions and generalizes to multiple scenes, using only unlabeled multi-illumination data available online
Measurement of the Higgs boson total decay width using the H WW e decay channel in proton-proton collisions at = 13 TeV
No full textInternational audienceThe Higgs boson (H) decay width is determined from the ratio of off- and on-shell production of H WW e using proton-proton collision data corresponding to an integrated luminosity of 138 fb collected at = 13 TeV by the CMS experiment at the LHC. The off-shell signal strength is measured as = 1.2. The Higgs boson total decay width is = 3.9 MeV, in agreement with the standard model prediction. The uncertainty in this result represents a factor of three improvement over the previous CMS result in this decay channel
Sine-Liouville gravity as a Vertex Model on Planar Graphs
No full textInternational audienceWe investigate the universal behaviour of a one-parameter generalisation of the six-vertex model on planar graphs, which we refer to as the 7-vertex model (7vM). The 7vM is characterised by a temperature coupling and its continuum limit is characterised by a massive, dilute and dense phases similarly to the loop model. We compute the sphere and disk partition functions of the 7vM from the spectral curve of the dual matrix model, abbreviated here as 7vMM. The disk partition function for fixed length is expressed in terms of an uncharted deformation of the K-Bessel functions. We argue that 7vMM and Matrix Quantum Mechanics (MQM) provide two complementary non-perturbative realisations of sine-Liouville gravity. Specifically, we find that the continuum limit of 7vMM and the MQM share the same classical spectral curve but describe two different types of branes in sine-Liouville gravity. The 7vMM precisely covers the range of parameters where the Minkowskian MQM lacks a simple interpretation in terms of multiple tachyon scattering. We investigate the flow relating the dilute and the dense phases and argue that this flow is the gravitational analogue of the massless flow in the sine-Gordon model with imaginary mass coupling. The two extremities of the flow are described by a free boson coupled to Liouville gravity and compactified at circles with two different radii