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Sponge Morphology of Osteosarcoma Finds Origin in Synergy Between Bone Synthesis and Tumor Growth
No full textInternational audienceOsteosarcoma is medically defined as a bone-forming tumor with associated bone-degrading activity. There is a lack of knowledge about the network that generates the overproduction of bone. We studied the early stage of osteosarcoma development with mice enduring a periosteum injection of osteosarcoma cells at the proximal third of the tibia. On day 7 (D7), tumor cells activate the over-synthesis of bone-like material inside the medulla. This overproduction of bone is quickly (D13) followed by degradation. Samples were characterized by microfocus small-angle X-ray scattering (SAXS), wide-angle X-ray scattering (WAXS), optical and electron microscopies, and micro-indentation. This intramedullary apatite–collagen composite synthesis highlights an unknown network of bone synthesis stimulation by extramedullary osteosarcoma cells. This synthesis activation mechanism, coupled with the well-known bone induced osteosarcoma growth activation, produces a rare synergy that may enlighten the final osteosarcoma morphology. With this aim, a 3D cellular automaton was developed that only included two rules. Simulations can accurately reproduce the bi-continuous sponge macroscopic structure that was analyzed from mice tumor micro-tomography. This unknown tumor activation pathway of bone synthesis, combined with the known bone activation of tumor growth, generates a positive feedback synergy explaining the unusual sponge-like morphology of this bone cancer. From a biomaterials point of view, how nature controls self-assembly processes remains an open question. Here, we show how the synergy between two biological growth processes is responsible for the complex morphology of a bone tumor. This highlights how hierarchical morphologies, accurately defined from the nanometer to the centimeter scale, can be controlled by positive feedback between the self-assembly of a scaffold and the deposition of solid material
Unconformity-related mineralization and fluid transfers in the northern Aquitaine Basin (France) revealed by fluid inclusions and S-Sr isotopes studies
No full textInternational audienceIn sedimentary basins, unconformity between basement and sediments is the ideal site where fluids from different sources can flow and mix, initiating the formation of ore deposits. In western Europe there are numerous F-Pb-Zn-Ba (±Ag, Ge) basin-hosted deposits located near the unconformity between Mesozoic Basins and the Variscan basement as for example the deposits of the Vendée Coast (France) containing fluorite, baryte, pyrite and quartz. Here, microthermometric data on the primary fluid inclusions of these minerals indicate salinity ranging from 1 to 20 wt% eq. NaCl and homogenization temperatures between 100 and 390 °C. We interpret these data as resulting of a fluids circulation in the ore deposit zone, with an early incursion of basin brines expelled by the leaching of Hettangian evaporites buried several tens of kilometers away, followed by an ascent of basement-derived fluids and, finally, a recharge of seawater. In other French deposits, the δ34S isotopes of baryte are also consistent with a source of fluids from buried evaporites. The 87Sr/86Sr ratio of baryte demonstrates a crustal source of elements associated with brines-leached base metals and Fsingle bondBa. The process of buried-derived evaporites brines altering the basement along the unconformity is ubiquitous in all unconformity deposits in France.With our results, we confirm that the basin deposits in the Southeastern Massif Central occur along structures formed during Tethys rifting at around 200 Ma, whereas in the Western part they form at ca. 145 Ma in link with the opening of the Bay of Biscay. This highlights that these basin-hosted deposits are preferentially formed during extensional activity in rifting settings, rather than in compressive settings
Veille
No full textNational audienceVeille normative et juridique janvier 2025: Mayotte, catastrophe naturelle, stress test à l'ACP
Blood-borne sphingosine 1-phosphate maintains vascular resistance and cardiac function
No full textInternational audienceG protein-coupled receptors (GPCRs) are key regulators of cardiovascular function that provide targets for the treatment of cardiovascular disease. Sphingosine 1-phosphate (S1P) is an erythrocyte- and platelet-derived lipid mediator with cognate GPCRs on endothelial cells (EC), vascular smooth muscle cells (VSMC) and cardiomyocytes. S1P circulates in plasma bound to apolipoprotein M (ApoM)-containing high-density lipoproteins (HDL) and to albumin. Circulating S1P levels correlate positively with systolic blood pressure in hypertension and negatively with severity in septic shock and with left ventricular (LV) function in coronary heart disease. In mice, impaired S1P binding to HDL or signaling to EC both trigger hypertension, supporting an essential role for HDL-S1P in supporting endothelial function. The roles of albumin-S1P and myocyte S1PRs in cardiovascular homeostasis remain incompletely defined. Contrasting isolated HDL-S1P deficiency, we report that non-selective depletion of circulating S1P pools in mice impairs LV contractile function and induces hypotension and resistance to the spontaneous increase in blood pressure with age. Cardiac output was preserved in naïve S1P deficient mice by compensatory LV dilation, but cardiac reserve reduced in a dobutamine stress test. These phenotypes tracked with hematopoietic cell S1P production and were partially or fully reversed by erythrocyte transfusion. Hypotension was accompanied by reduced peripheral resistance, and S1P infusion dose-dependently increased vascular resistance in isolated perfused kidneys from wild-type mice but not mice with compound deficiency in S1PR2&3. Epistatic analysis supported a critical role for S1PR3 in S1P-dependent blood pressure regulation and pointed to a distinct origin of the cardiac phenotype. Although circulating S1P is elevated in hypertensive mice and humans, increasing circulating S1P was not sufficient to induce hypertension in naive mice. These observations suggests that albumin-S1P crosses the endothelium in resistance arteries to gain access to contractile VSMC S1P receptors, and that myocyte S1PR signaling is essential for vascular resistance and blood pressure maintenance in mice. They also highlight the role for plasma chaperones in specifying vascular responses to S1P and the relevance of S1P as a biomarker and potential therapeutic target for blood pressure regulation and heart failure
La chicorée, un remède pour assainir les sols viticoles
No full textInternational audienceL’utilisation de la bouillie bordelaise contre le mildiou provoque une contamination des sols et un dysfonctionnement des écosystèmes viticoles. Pour limiter ses effets toxiques et dans une perspective d’économie circulaire, le projet Vitalicuivre expérimente la culture de la chicorée qui extrait le cuivre de ces sols pollués pour le recycler en alimentation animale
High-throughput screening to identify endocrine disruptors: Contribution of low-resolution tandem MS and high-resolution MS
No full textInternational audienceTelomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells. Simulations of yeast populations, where cells with varying proliferation capacities compete against each other, show that the distribution of telomere lengths of the initial population shapes population growth, especially through the distribution of cells’ shortest telomere lengths. We also quantified how factors influencing cell viability independently of telomeres can impact senescence rates. Overall, we demonstrate a temporal evolution in the composition of senescent cell populations—from a state directly linked to critically short telomeres to a state where senescence onset becomes stochastic. This population structure may promote genome instability and facilitate senescence escape
(Se) jouer de la coopération intercommunale. Normes juridiques et stratégies de sauvegarde d’une capacité politique des villes thermales en milieu rural
No full textInternational audienceFollowing the failure of the Marcellin law (1971), the legislator identified in inter-municipal groupings as a compromise to merger. For several decades, he encouraged (politically and economically) local elected representatives to come together in more integrated groupings with their own tax status. However, a new institutional phase began in 2010, aiming to simplify the ‘territorial mille-feuille’ and ‘reshape the geography of local authorities and their establishments’. As a result of the battles waged by representatives of the Association of mayors of France and the Association of French communities, the legislator took a more directive stance (forcing the last remaining municipalities to join a public inter-municipal cooperation body), while respecting the freedom of local elected representatives and promoting the preservation of municipal interests. However, when the reform was implemented, this paradox led to a distortion between the stated objectives of the reform and the results achieved. Far from being a simple administrative and routine process, the implementation of a reform constitutes a profoundly political sequence, reopening the game to a local level and giving rise to new controversies, mobilisations, resistance and negotiations. To test the hypothesis that local elected officials exploit these flexibilities to adapt these new legislative rules to their advantage, thermal towns are an ideal object of study. Although they are well-equipped with services and have a greater political and financial capacity than their counterparts of the same size, the majority of them remains small, sparsely populated towns. Given this specificity, which limits their leadership in the local governance, the obligation to join an EPCI may be perceived more as a constraint than an opportunity. Therefore this article analyses the strategies used by local elected officials to circumvent the rule in order to enhance their town’s political capacity, to the detriment of the stated objectives of rationalisation.Suite à l’échec de la loi Marcellin (1971), le législateur identifie dans le regroupement intercommunal un compromis à la fusion. Pendant plusieurs décennies, il incite (politiquement et économiquement) les élus locaux à se rassembler dans des groupements à fiscalité propre plus intégrés. Une nouvelle séquence institutionnelle s’ouvre toutefois à partir de 2010 avec l’objectif de simplifier le « mille-feuille territorial » et de « redimensionner la géographie des collectivités territoriales et de leurs établissements ». Sous l’effet de luttes que se livrent les représentants de l’Association des Maires de France et de l’Association des Communautés de France, le législateur se montre plus directif tout en essayant de ménager l’autonomie des élus locaux. Cet article souligne ainsi combien les subtilités et contradictions offertes par ces différentes lois permettent à ces derniers d’instrumentaliser ces institutions, au profit de leur capacité politique mais au détriment des objectifs de rationalisation affichés.Plan1. Introduction2. Une capacité politique construite à l’échelle communale3. Un rapport ambigu à la coopération intercommunale - 3.1. Instrumentaliser l’échelon intercommunal - 3.2. Le redécoupage des intercommunalités comme accélérateur des dissensions4. La commune nouvelle ou l’opportunité de préserver capacité et autonomie politique - 4.1. Conserver son autonomie politique - 4.2. La commune nouvelle comme alternative au jeu intercommunal5. Conclusion</b
WISER: an innovative and efficient method for correcting population structure in omics-based selection and association studies
No full textThis work introduces WISER (whitening and successive least squares estimation refinement), an innovative and efficient method designed to enhance phenotype estimation by addressing population structure. WISER outperforms traditional methods such as least squares (LS) means and best linear unbiased prediction (BLUP) in phenotype estimation, offering a more accurate approach for omics-based selection and association studies. Unlike existing approaches which correct for population structure, WISER offers a generalized framework that can be applied across diverse experimental setups, species, and omics datasets, such as single nucleotide polymorphisms (SNPs), near-infrared spectroscopy (NIRS), and metabolomics. Within its framework, WISER extends classical methods that use eigen-information as fixed-effect covariates to correct for population structure, by relaxing their assumptions and implementing a true whitening matrix instead of a pseudo-whitening matrix. This approach corrects fixed effects (e.g., environmental effects) for the genetic covariance structure embedded within the experimental design, thereby removing confounding factors between fixed and genetic effects. To support its practical application, a user-friendly R package named wiser has been developed. The WISER method has been employed in analyses for genomic prediction and heritability estimation across four species and 33 traits using multiple datasets, including rice, maize, apple, and Scots pine. Results indicate that genomic predictive abilities based on WISER-estimated phenotypes consistently outperform the LS-means and BLUP approaches for phenotype estimation, regardless of the predictive model applied. This underscores WISERs potential to advance omics analyses and related research fields by capturing stronger genetic signals
Veille
No full textNational audienceVeille doctrinale et normative en droit de la responsabilité et des assurances: catastrophe naturelle
New members of Alternaria (Pleosporales, Pleosporaceae) collected from Apiaceae in Algeria
No full textInternational audienceAlternaria species have often been reported as plant pathogens and are commonly isolated from diseased plant hosts. During an investigation of this genus in Algeria, seven Embellisia -like isolates were collected from Apiaceae. Phylogenetic analysis using sequences at four loci, the internal transcribed spacer of the rDNA region (ITS), glyceraldehyde-3-phosphate dehydrogenase ( gpd ), translation elongation factor 1-alpha (tef1), and RNA polymerase second largest subunit (rpb2), revealed that these isolates grouped into three sections, namely Embellisia , Embellisioides , and Eureka . Four isolates had significant differences with their closest species and were determined to be new species, namely Alternaria longiformis and A. radicicola spp. nov. The three other isolates of section Eureka were identified as A. eureka and A. hungarica , the latter species being described as a new record in Algeria. Detailed descriptions of new species are provided based on colony color, aspect, diameter, conidial size, septa, sporulation patterns and compared with other relevant Alternaria species within same sections. All these species were weakly pathogenic on carrot, coriander, and fennel under greenhouse experiments. Apiaceae may constitute a reservoir of Alternaria species that could represent potential pathogens for other plant families