Explore the vast range of titles available.

The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells (LSCs), while the nontransparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human LSCs from the cornea and keratinocytes from the epidermis and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors (TFs) that define specific cell fates and established their regulatory hierarchy. Single-cell RNA-seq (scRNA-seq) analyses of the cornea and the epidermis confirmed these shared and cell type-specific TFs. Notably, the shared and LSC-specific TFs can cooperatively target genes associated with corneal opacity. Importantly, we discovered that FOSL2 , a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the LSC fate and its association with corneal opacity.

Management of the non-renewable resource phosphorus (P) is critical to agricultural sustainability. The global P cycle is currently disturbed beyond planetary boundaries, mostly due to large excess P use in the agriculture of industrialized countries, while P is lacking in the Global South. The trajectories of P management and their effects on future sustainable agriculture were investigated for the case of France from 1850 to 2015 based on empirical data and simulations of two coupled biogeochemical models. Here we show that while French cropland soils have accumulated significant amounts of P, mainly sourced from former colonies or protectorates, P reserves in grassland soils have been depleted. Scenario calculations indicate that current P reserves may on average allow for another 60 years of agricultural production without mineral P application. In the light of a possible upcoming P scarcity, this time frame offers an opportunity for a transition towards regionally closed P loops and enhanced sustainability, allowing for fairer international distribution of P resources in the future.

Background:The available data on the impact of JAK inhibitors (JAKi) on rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are currently limited.Objectives:This study aimed to examine the progression of RA-ILD in France among individuals treated with JAKi, utilizing the MAJIK-SFR registry.Methods:A prospective national multicenter observational study was conducted, identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were specifically collected from centers with at least one RA-ILD patient on JAKi, using a dedicated form. Data were gathered at JAKi initiation and follow-up visits (6, 12, and an average of 21 months post-inclusion), including chest high-resolution computed tomography (HRCT), pulmonary function tests (FVC and DLCO), acute exacerbations of ILD, respiratory infections, and lung cancers.Results:We enrolled 42 patients with RA-ILD initiating JAKi (18 baricitinib, 11 upadacitinib, 9 tofacitinib and 4 filgotinib). Patients (26 women, 62%) were aged 61±12 and had a disease duration of 16±10 years. 15 (35%) were active smokers, 37 (88%) had positive rheumatoid factors, 39 (95%) positive ACPAs and 29 (69%) bone erosions. Mean DAS28-CRP at JAKi initiation was 4.69±1.61. 41 patients were on csDMARDs, including 37 (88%) on methotrexate, and the mean number of prior targeted therapies was 3±2. Nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) accounted for 46% and 43% of the chest HRCT ILD patterns, respectively. The study observed no significant changes in FVC and DLCO during follow-up (FVC (L)/LDCO (%): 3.2 L/65% at inclusion; 3.12 L/63% at 12 months follow-up and 3.03 L/60% at end of follow-up). Chest HRCT lesions remained stable in 62% of patients. Regression of chest HRCT lesions (2 NSIP and one organized lung disease) was observed in 3 patients (7%), associated with an improvement of more than 5% in the initial FVC value at the last assessment. Progressive ILD was identified during follow-up in 8 patients (including 3 NSIP and 3 UIP) receiving JAKi (19%), defined by a progressive worsening of FVC by more than 5% during follow-up and worsening of ILD lesions on chest HRCT or of their respiratory symptoms. Three were treated with Nintedanib for fibrosis. This pulmonary progression contrasted with joint efficacy, with a decrease in median DAS28-CRP from 4.29 to 2.30 (p<0.001). Cox proportional hazards analyses identified higher age at diagnosis of ILD, active smoking and the presence of extra-articular involvement as predictive factors for progression of RA-ILD. With regard to pulmonary tolerance, 5 infectious pneumonia and one pulmonary tuberculosis were observed. Only one acute regressive exacerbation of ILD was noted, and no lung cancer was diagnosed during the 21-month follow-up period. No deaths occurred. JAKi was discontinued in 17 patients, 8 for joint inefficacy and 4 for intolerance. No discontinuation of JAKi was linked to a progression of ILD.Conclusion:The analysis indicates a neutral effect of JAKi on RA-ILD, contrasting with notable joint efficacy. JAKi demonstrated an expected safety profile, with no increased risk of acute exacerbation of ILD in this population.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Jérôme Avouac Abbvie, Lilly, Pfizer, Galapagos, Abbvie, Galapagos, Galapagos, Felicien Triboulet: None declared, Pierre-Antoine Juge: None declared, Marie-Elise Truchetet: None declared, Thao Pham: None declared, Nicolas Roux: None declared, René-Marc Flipo: None declared, Charles Leské: None declared, Christian Roux: None declared, Raphaèle Seror: None declared, André Basch: None declared, Olilvier Brocq: None declared, Pascal Chazerain: None declared, Fabienne Coury-Lucas: None declared, Richard DAMADE: None declared, Emmanuelle Dernis: None declared, Jacques-Eric Gottenberg: None declared, André Ramon: None declared, Adeline Ruyssen-Witrand: None declared, Jean-Hugues Salmon: None declared, Emilie SHIPLEY: None declared, Anne Tournadre: None declared, Clément Prati: None declared, Philippe Dieudé: None declared.

Dessert and cooking bananas are vegetatively propagated crops of great importance for both the subsistence and the livelihood of people in developing countries. A wide diversity of diploid and triploid cultivars including AA, AB, AS, AT, AAA, AAB, ABB, AAS and AAT genomic constitutions exists. Within each of this genome groups, cultivars are classified into subgroups that are reported to correspond to varieties clonally derived from each other after a single sexual event. The number of those founding events at the basis of the diversity of bananas is a matter of debate. We analysed a large panel of 575 accessions, 94 wild relatives and 481 cultivated accessions belonging to the section Musa with a set of 498 DArT markers previously developed. DArT appeared successful and accurate to describe Musa diversity and help in the resolution of cultivated banana genome constitution and taxonomy, and highlighted discrepancies in the acknowledged classification of some accessions. This study also argues for at least two centres of domestication corresponding to South-East Asia and New Guinea, respectively. Banana domestication in New Guinea probably followed different schemes that those previously reported where hybridization underpins the emergence of edible banana. In addition, our results suggest that not all wild ancestors of bananas are known, especially in M. acuminata subspecies. We also estimate the extent of the two consecutive bottlenecks in edible bananas by evaluating the number of sexual founding events underlying our sets of edible diploids and triploids, respectively. The attribution of clone identity to each sample of the sets allowed the detection of subgroups represented by several sets of clones. Although morphological characterization of some of the accessions is needed to correct potentially erroneous classifications, some of the subgroups seem polyclonal.

Coral reefs, some of the most important marine ecosystems, are mainly structured by interactions between corals and benthic algae. The outcome of these interactions varies depending on the types of corals and algae involved. However, human activities, associated mainly with eutrophication and overfishing of herbivorous organisms, strongly impact the outcome of algae-coral interactions by promoting progressive replacement of corals by algae. The present study aimed to firstly establish the first inventory of algae-coral interactions at the species level on the Bora Bora reefs, and then experimentally determine the role of herbivorous species (sea urchins and Trochus shells) in the regulation of these complex algae-coral interactions. Firstly, visual surveys showed that the outcome of algae-coral interactions varied significantly according to the length of the algae-coral interaction border, and among algae-coral couples. For example, unhealthy coral colonies with large interaction borders were associated with a higher percentage of negative interactions. Then, using experimental enclosures for 70 days, we showed that the sea urchin Tripneustes gratilla controlled the proliferation of algae and thus allowed a better growth of Acropora corals. Overall, the present study suggests that conservation programs should rely on grazer densities as a Nature-Based Solution to attenuate global shifts from coral- to algal-dominance.

The mechanisms by which a wetting, non-saturating liquid bestows macroscopic cohesion and strength to a granular material are usually not accessible to micromechanical investigations for saturations exceeding the pendular regime of isolated menisci, easily studied by discrete element models (DEM). The paper by Delenne et al. (J. Fluid Mech., 2015, vol. 762, R5) exploiting a multiphase lattice Boltzmann approach, pioneers the simulation of the micromorphology and of the mechanical effects on grains of an interstitial liquid, in equilibrium with its vapour, for the whole saturation range. Interestingly, in accordance with some experiments and phenomenological models, the results suggest that the mechanical effect of capillary forces is maximized for some intermediate saturation level (near 40 % in the model), well beyond the pendular range. In general, the proposed simulation technique opens the way to many studies of partially saturated granular assemblies, for different saturation or imbibition processes and histories.

• Background and Aims The production of triploid banana and plantain (Musa spp.) cultivars with improved characteristics (e.g. greater disease resistance or higher yield), while still preserving the main features of current popular cultivars (e. g. taste and cooking quality), remains a major challenge for Musa breeders. In this regard, breeders require a sound knowledge of the lineage of the current sterile triploid cultivars, to select diploid parents that are able to transmit desirable traits, together with a breeding strategy ensuring final triploidization and sterility. Highly polymorphic single sequence repeats (SSRs) are valuable markers for investigating phylogenetic relationships. • Methods Here, the allelic distribution of each of 22 SSR loci across 561 Musa accessions is analysed. • Key Results and Conclusions We determine the closest diploid progenitors of the triploid 'Cavendish' and 'Gros Michel' subgroups, valuable information for breeding programmes. Nevertheless, in establishing the likely monoclonal origin of the main edible triploid banana subgroups (i.e. 'Cavendish', 'Plantain' and 'Mutika-Lujugira'), we postulated that the huge phenotypic diversity observed within these subgroups did not result from gamete recombination, but rather from epigenetic regulations. This emphasizes the need to investigate the regulatory mechanisms of genome expression on a unique model in the plant kingdom. We also propose experimental standards to compare additional and independent genotyping data for reference.

Drained triaxial axisymmetric compression tests are performed on water-saturated short cylindrical samples of nearly monodisperse glass beads, initially assembled in a loose state by a moist tamping technique. Both deviator stress and volumetric strain , measured as functions of axial strain , for different strain rates, are affected by stick-slip events of very large amplitude, while the classical behavior of loose, contractant granular assemblies, approaching the critical state for large , corresponds to the upper envelop of the stress-strain behaviour. Those events consist in a very fast ( slip ) part in which a drop of coincides with a jump of (contraction), while loss of control of and generation of pore pressure signal a dynamic collapse of the material structure triggered by an instability; and then a quasi-static ( stick ) part in which the sample regains its strength and, over a short strain interval, behaves similarly to a denser system that dilates before reaching its critical state. A unique stress-dilatancy relation applies to all stick-slip events. Apparent internal friction angles and effects of strain rate and confining pressure are discussed, and it is argued that stick-slip instabilities originate in physico-chemical aging phenomena coupled to contact mechanics.

Patient education constitutes a relevant strategy to improve pain management. In the field of therapeutic patient education (TPE), we aimed 1) to assess pain impact in cancer patients, 2) to identify patients' educative needs in pain management, and 3) to refine research criteria for its future evaluation. Pain intensity, relief and interference were assessed in 75 cancer patients with unbalanced background pain. Self-assessment questionnaire evaluated i) patients' pain management and ii) their knowledge and needs in TPE. Most patients experienced pain for more than 6 months and 41.6% reported adequate pain relief. Understanding pain and pain management were major patients' preferences (>58%). Most patients declared they knew their pain treatments, but fewer than half of them were able to name them. However, education concerning pain treatment was considered as essential in <30% of patients. Almost all patients (97.1%) stated pain education as beneficial, with a preference for individualized sessions (41.2%). In addition, the assessment criteria for its future evaluation were refined. Targeted population mainly concerned patients with persistent pain. Only half of patients reported pain relief despite antalgics. Patient education was declared as beneficial for almost all participants. Tailoring a pain TPE on patients' needs has the potential to help them to optimally manage their pain daily.

Human skin homeostasis is partly maintained by a complex microscopic ecosystem known as the microbiota. Together, the skin host and microbiota form a synergistic evolutionary unit referred to as ‘skin holobiont’, which can be modulated by various stresses. By extracting organic wild yellow gentian roots enhanced through fermentation of a rare and resistant bacterium, Sphingomonas faeni, a cosmetic active ingredient was developed to rebalance the holobiont functions as well as hydric and lipidic skin content. Indeed, gentian-fermented extract (GFE) boosts hyaluronic acid (HA) biosynthesis in vitro, stimulates the HA receptor, CD44, and allows water storage and retention through its signaling cascade by epidermal reinforcement. Importantly, GFE also increases lipid synthesis by +147% in vitro, which was confirmed clinically on volunteers with dehydrated and dry skin who presented an increase in hydration and skin surface lipids after 28 days of treatment. Furthermore, a metaproteomic study highlighted that there is a slow-down of skin barrier and antioxidant proteins from both human and microbial origins, with age and dehydration, that can be reversed by GFE after 56 days. In conclusion, acting on the HA metabolism and specific microbiota species, GFE rebalances the skin holobiont for a reinforced and rehydrated skin with optimal lipid content.