Biology subjects

Pons, V.

Publications and source records attributed to Pons, V..

4 recordsLinked to original sources

bioRxiv2026

Inter-unit variability and rapid depletion of 2,3-diphosphoglycerate in stored red blood cells: implications for transfusion practice in neurocritical care

Red blood cell (RBC) transfusion aims to restore tissue oxygen delivery, yet a stored unit's capacity to unload oxygen depends on 2,3-diphosphoglycerate (2,3-DPG), the principal allosteric modulator of hemoglobin-oxygen affinity. Randomized trials comparing fresher with older units have been consistently null, and all have used storage duration as the exposure variable. We asked whether storage age reflects the metabolic state of individual units. Twenty-four leukodepleted packed RBC units were sampled serially from day 3 to day 42 of standard cold storage. 2,3-DPG was quanti-fied by liquid chromatography-mass spectrometry (LC-MS) with isotopically labelled internal standards, pH was measured in parallel, and trajectories were modelled by linear mixed effects with unit-level random intercepts. At day 3, 2,3-DPG spanned a twenty-fold range across units of identical age (0.8-14.7 mol/g Hb; median 4.8): some were already near-depleted at the earliest sampled timepoint, while others retained near-physiological concentrations. This heterogeneity collapsed rapidly - median val-ues fell to 27% of day-3 levels by day 7 and by more than 90% by day 14 ({beta} = -0.298 mol/g Hb per day, p < 0.001) - and were below the limit of detection in most units af-ter day 17. pH declined monotonically to 6.40 {+/-} 0.04 by day 42 ({beta} = -0.0163 units per day, p < 0.001). Units of identical storage age therefore differ markedly in the metabo-lite that governs oxygen unloading, and virtually all are depleted long before the 42-day expiry, indicating that storage-age dichotomies misclassify the exposure they are intended to represent.

biochemistry↗

bioRxiv2026

The constitutive androstane receptor protects against metabolic dysfunction-associated steatotic liver disease through sex specific interactions with the gut microbiota

Background: The gut-liver axis is involved in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), but the host molecular actors involved in such dialogue have not yet been fully characterized. Objective: We investigated the sex-dependent role of the Constitutive Androstane Receptor (CAR) as a hepatic sensor of microbial signals in MASLD pathophysiology. Design: Male and female Car+/+ and Car-/- mice were fed a western diet (WD) for 4, 14 or 35 weeks. We performed plasma biochemistry, liver histology, bile acid and cholesterol quantification, untargeted multi-omics approach combining liver RNA-sequencing and 16S rRNA sequencing, together with co-housing, fecal microbiota transplantation and analysis of publicly available transcriptomics data in human cohorts. Results: Short-term WD revealed CAR-dependent protection against steatosis, together with perturbations in the transcriptional signatures of multiple transcription factors involved in hepatocyte identity in males. After 14 weeks, CAR deletion increased WD-induced liver damage, inflammation and fibrosis, and disrupted bile acid, cholesterol and gut microbiota homeostasis, in males only. Co-housing and fecal microbiota transplantations revealed that a Car+/+ gut microbiota protected against WD-induced liver damage, while a Car-/- microbiota was reshaped by a Car+/+ host. No CAR-dependent phenotype was observed in females. Finally, in human cohorts, hepatic CAR expression decreased in advanced clinical stages of MASLD. Conclusion: CAR is a sex-dependent protective nuclear receptor against MASLD progression, acting both as a transcriptional regulator of hepatocyte identity and as a mediator of the host-microbiota crosstalk.

physiology↗

bioRxiv2023

Ongoing convergent evolution of a selfing syndrome threatens plant-pollinator interactions

O_LIPlant-pollinator interactions evolved early in the angiosperm radiation. Ongoing environmental changes are however leading to pollinator declines that may cause pollen limitation to plants and change the evolutionary pressures shaping plant mating systems. C_LIO_LIWe used resurrection ecology methodology to contrast ancestors and contemporary descendants in four natural populations of the field pansy (Viola arvensis) in the Paris region (France), a depauperate pollinator environment. We combine population genetics analysis, phenotypic measurements and behavioural tests on a common garden experiment. C_LIO_LIPopulation genetics analysis reveals 27% increase in realized selfing rates in the field during this period. We documented trait evolution towards smaller and less conspicuous corollas, reduced nectar production and reduced attractiveness to bumblebees, with these trait shifts convergent across the four studied populations. C_LIO_LIWe demonstrate the rapid evolution of a selfing syndrome in the four studied plant populations, associated with a weakening of the interactions with pollinators over the last three decades. This study demonstrates that plant mating systems can evolve rapidly in natural populations in the face of ongoing environmental changes. The rapid evolution towards a selfing syndrome may in turn further accelerate pollinator declines, in an eco-evolutionary feedback loop with broader implications to natural ecosystems. C_LI

evolutionary biology↗

bioRxiv2019

Ephrin-B1 blocks adult cardiomyocyte proliferation and heart regeneration

AimsDeciphering the innate mechanisms governing the blockade of proliferation in adult cardiomyocytes (CMs) is challenging for mammalian heart regeneration. Despite the exit of CMs from the cell cycle during the postnatal maturation period coincides with their morphological switch to a typical adult rod-shape, whether these two processes are connected is unknown. Here, we examined the role of ephrin-B1, a CM rod-shape stabilizer, in adult CM proliferation and cardiac regeneration.\n\nMethods and resultsTransgenic- or AAV9-based ephrin-B1 repression in adult mouse heart led to substantial proliferation of resident CMs and tissue regeneration to compensate for apex resection, myocardial infarction (MI) and senescence. Interestingly, in the resting state, CMs lacking ephrin-B1 did not constitutively proliferate, indicative of no major cardiac defects. However, they exhibited proliferation-competent signature, as indicated by higher mononucleated state and a dramatic decrease of miR-195 mitotic blocker, which can be mobilized under neuregulin-1 stimulation in vitro and in vivo. Mechanistically, the post-mitotic state of the adult CM relies on ephrin-B1 sequestering of inactive phospho-Yap1, the effector of the Hippo-pathway, at the lateral membrane. Hence, ephrin-B1 repression leads to phospho-Yap1 release in the cytosol but CM quiescence at resting state. Upon cardiac stresses (apectomy, MI, senescence), Yap1 could be activated and translocated to the nucleus to induce proliferation-gene expression and consequent CM proliferation\n\nConclusionsOur results identified ephrin-B1 as a new natural locker of adult CM proliferation and emphasize that targeting ephrin-B1 may prove a future promising approach in cardiac regenerative medicine for HF treatment.\n\nSignificanceThe mammalian adult heart is unable to regenerate due to the inability of cardiomyocytes (CMs) to proliferate and replace cardiac tissue lost. Exploiting CM-specific transgenic mice or AAV9-based gene therapy, this works identifies ephrin-B1, a specific rod-shape stabilizer of the adult CM, as a natural padlock of adult CM proliferation for compensatory adaptation to different cardiac stresses (apectomy, MI, senescence), thus emphasizing a new link between the adult CM morphology and their proliferation potential. Moreover, the study demonstrates proof-of-concept that targeting ephrin-B1 may be an innovative therapeutic approach for ischemic heart failure.

physiology↗