Biology subjects

Bureau, C.

Publications and source records attributed to Bureau, C..

8 recordsLinked to original sources

bioRxiv2025

Hepatocyte ERα orchestrates sex-specific liver adaptation to fasting and feeding states

Sex differences in hepatic physiology are thought to influence individual susceptibility to chronic liver diseases including Metabolic-Associated Steatotic Liver Disease (MALSD). Previous studies demonstrated the central contribution of estrogens which primarily influence liver biology through the activation of Estrogen Receptor alpha (ER). However, how ER signaling in hepatocyte modulates liver functions according to the nutritional status, a critical determinant of hepatic metabolism, remains to be characterized. The present study first reveals the nycthemeral expression profile of liver ER, which peaks during the feeding period (ZT16) in both male and female mice. ER expression is altered by reprogramming the hepatic circadian clock in response to inverted food intake, highlighting the influence of feeding on liver ER expression patterns. As ER is mainly expressed in hepatocytes both in human and mouse livers, the functional role of hepatocyte ER during fasting or feeding state was then delineated, using mice harboring ER hepatocyte-specific deletion (ERhep-/-) compared with their wild-type littermates (ERhep+/+). Transcriptomic analyses reveal significant sex differences in the adaptation of liver functions to this contrasted nutritional status, as well as the sex-specific regulatory effects of hepatocyte ER. In such physiological settings, hepatocyte ER deletion does not influence liver transcriptomic profiles in males but significantly alters gene expression in female livers, both fed and fasted conditions. Hepatocyte ER more specifically controls genes associated with inflammatory responses and fatty acid metabolic pathways in females, modulating the ChREBP and PPAR pathways in feeding or fasting states, respectively. Thus, hepatocyte ER is integral to liver metabolic adaptations to fasting and feeding in females but not in males, thus exhibiting both sex-specific and diet-dependent actions. Further characterizing sex differences in liver metabolic flexibility, these results provide new information to develop sex-based strategies for the prevention and management of MASLD.

physiology↗

bioRxiv2025

Teleost-specific ictacalcins exhibit similar structural organization, cation-dependent activation and transcriptional regulation as human S100 proteins

S100 proteins are highly versatile calcium-binding proteins from vertebrates. Following extracellular release, they become instrumental in immune and antimicrobial defenses, initiating the inflammatory response through receptor signaling and providing direct control of bacterial invaders via nutritional immunity. While mammalian S100s have been extensively studied, very little is known about the more recently discovered S100 proteins from teleost fish, including those with no strict orthologs in mammals. Comparable functioning between both clades would allow to expand their study into the highly popular zebrafish model, particularly suited for live imaging and mechanistic exploration of immune and inflammatory processes. To fill the gap of knowledge on teleost S100s, we here provide a detailed structural and biochemical characterization of S100i1 and S100i2 from Danio rerio, two teleost-specific S100s absent in mammals. We demonstrate that they nevertheless share conserved tertiary and quaternary organization with mammalian S100s. In addition, they exhibit comparable calcium binding properties and undergo a similar calcium-dependent activation mechanism. Furthermore, they display analogous expression pattern, being enriched in tissues highly exposed to the environment like gills and skin, the latter constituting an important reservoir of S100 proteins in mammals. Finally, our results show, for the very first time, that s100i2/i2 gene expression is differentially modulated in sterile disease conditions associated with sustained inflammation or high hypoxic state. Altogether, these findings underline the strong parallelism existing between mammalian and teleost-specific S100 proteins despite their divergent evolution, opening up new avenues to explore their biology in the zebrafish model.

immunology↗

bioRxiv2025

A deeper study on propionic acid-related inhibition during anaerobic digestion: insights on methane production and identification of biomarker candidates for an early warning

Propionic acid (HPr) accumulation is a major indicator of anaerobic digestion (AD) dysfunction, yet the relative contributions of acidity, undissociated HPr, and propionate ions (Pr-) to process inhibition remain poorly understood. We investigated these effects in mesophilic batch AD microcosms fed with municipal sewage sludge, using a comparative design involving HPr, sodium propionate (NaPr), NaCl, and HCl treatments across two series of experiments. While 20 mM HPr caused a 22% reduction in the maximal methane production rate, 81 mM HPr led to complete inhibition, with the initial pH dropping to 5.1. By contrast, 81 mM NaPr reduced methane production rate by only 40%, and 81 mM NaCl caused no inhibition, demonstrating that acidity is the dominant inhibitory factor, with Pr- exerting a secondary concentration-dependent effect. 16S rRNA gene amplicon sequencing revealed strong, compound-specific shifts in microbial community composition, affecting key functional groups including syntrophs and methanogenic archaea. The proportion of methanogens dropped from 2-3% in control reactors to less than 0.2% under 81 mM HPr, consistent with the observed methane production inhibition. Under HPr81, over 100 ASVs were differentially abundant compared to controls, a pattern largely shared with HCl-treated reactors, further confirming the predominant role of acidity. The number of differentially abundant ASVs was negatively correlated with methane production rates (R{superscript 2} = 0.97), underscoring the link between community reshaping and process impairment. These results provide a unifying framework for propionate inhibition in AD and suggest that microbial community profiling could serve as an early warning tool for process imbalance detection.

bioengineering↗

bioRxiv2024

Curcumin-mediated NRF2 induction limits inflammatory damage in preclinical models of cystic fibrosis

Overactive inflammation is directly correlated with airway damage and early death in individuals with cystic fibrosis (CF), a genetic disorder caused by mutation in the CFTR gene. Reducing the impact of inflammatory damage is therefore a major concern in CF. Several studies indicate that a decrease in the nuclear factor erythroid 2-related factor-2 (NRF2) signaling in people with CF may hamper their ability to alleviate oxidative stress and inflammation, although the role of NRF2 in CF inflammatory damage has not been determined. Therefore, we examined whether the phytochemical curcumin, an activator of NRF2, might provide a beneficial effect in the context of CF. Herein, combining Cftr-depleted zebrafish larvae as innovative biomedical model with CF patient-derived airway organoids (AOs), we sought to understand how NRF2 dysfunction leads to abnormal inflammatory status and impaired tissue remodeling, and determine the effects of curcumin in reducing inflammation and tissue damage in CF. We demonstrate that NFR2 is instrumental in efficiently regulating inflammatory and repair processes in vivo, thereby preventing acute neutrophilic inflammation and tissue damage. Importantly, curcumin treatment restores NRF2 activity in both CF zebrafish and AOs. Curcumin reduces neutrophilic inflammation in CF context, by rebalancing the production of epithelial ROS and pro-inflammatory cytokines. Furthermore, curcumin alleviates CF-associated tissue remodeling and allows tissue repair to occur. Our findings demonstrate that curcumin reduces inflammatory damage by restoring normal NRF2 activity, since disruption of Nrf2 pathway abrogated the effect of treatment in CF zebrafish. This work highlights the protective role of NRF2 in limiting inflammation and injury, and show that therapeutic strategies to normalize NRF2 activity using curcumin might simultaneously reduce inflammation and enhance tissue repair, and thus prevent infectious and inflammatory lung damage in CF.

immunology↗

bioRxiv2023

Camouflaging Endovascular Stents with an Endothelial Coat Using CD31 Domain 1-mimetic Peptides

BackgroundEndovascular stents and flow diverters have become widely used for the treatment of vascular diseases; however, their effectiveness is often limited by the deposition and activation of blood platelets and leukocytes. The foreignness of these devices often triggers pathologic local reactions that impede their integration and compromise their efficacy. In this study, we developed a method to camouflage endovascular stents and flow diverters by coating them with a surface that mimics healthy endothelium, in order to promote more effective device integration and prevent the activation of blood cells. MethodsWe designed peptides using domain 1 and/or domain 2 of human CD31 and synthesized the chosen peptide to coat clinical-grade nitinol flow diverters and cobalt chromium balloon expandable stents. The coated stents were implanted in adult rabbits and included control groups of uncoated devices and drug-eluting CoCr stents. The rabbits were monitored for 60 days, during which we assessed the integration of the devices under a physiologic confluence of endothelial cells. ResultsOur results demonstrated that the stents coated with the CD31-Domain 1 mimicking peptide promoted a smooth integration of the devices under a physiologic confluence of endothelial cells. By day 7, the coated stents were entirely covered by a smooth endothelium, unlike bare-metal and drug-eluting stents which remained largely exposed to the flowing blood. By day 60, the coated stents demonstrated superiority over both bare-metal and drug-eluting stents, as they resulted in the formation of a "neo-arterial" wall at the entrance of the aneurysmal sac. ConclusionOur method provides a promising step towards the development of more effective and biocompatible endovascular devices. The CD31 domain 1 coating prevented the pathologic local reaction at the site of stent implantation and promoted faster and more effective device integration. Further studies are necessary to investigate the efficacy and safety of CD31 domain 1 coatings on a larger scale, as well as their long-term durability and potential clinical applications.

bioengineering↗

bioRxiv2021

Endoglin deficiency elicits hypoxia-driven congestive heart failure in zebrafish.

Hereditary hemorrhagic Telangiectasia (HHT) is a rare genetic disease relying on mutations affecting components of Bone Morphogenetic Protein and Transforming Growth Factor-{beta} (BMP/TGF-{beta}) signaling pathway in endothelial cells. This disorder is characterized by arterio-venous malformations prone to rupture. and ensuing hemorrhages are responsible for iron deficiency anemia. Along with Activin receptor-like kinase ALK1, Endoglin is involved in the vast majority of HHT cases. In this report, we characterized zebrafish endoglin locus and demonstrated that it produces two phylogenetically conserved protein isoforms using a distinctive alternative splicing mechanism. Functional analysis of a Crispr/Cas9 zebrafish Endoglin mutant revealed that Endoglin deficiency results in massive death during the course from juvenile stage to adulthood. Endoglin deficient fish develop a cardiomegaly resulting in heart failure and hypochromic anemia which both stem from chronic hypoxia. Histological analysis and confocal imaging evidenced structural alterations of the developing gill and its underlying vascular network that tally with hypoxia. Finally, phenylhydrazine treatment demonstrated that lowering hematocrit/blood viscosity alleviates heart failure and enhances survival of Endoglin deficient fish. Altogether, our data indicate that Endoglin is crucial for gill vascular development and that further studies using zebrafish in general and this endoglin mutant in particular will provide crucial hints regarding the molecular and cellular events altered in HHT for the development of new therapeutic strategies. Summary StatementEndoglin deficiency in zebrafish recapitulates critical aspects of Hereditary Hemorrhagic Telangiectasia (HHT) and will thus constitute a valuable model in large scale screens for HHT-active drugs.

developmental biology↗

bioRxiv2020

Integrative analyses to investigate the link between microbial activity and molecules degradation during anaerobic digestion

Anaerobic digestion (AD) is a promising biological process which converts waste into sustainable energy. To fully exploit ADs capability, we need to deepen our knowledge of the microbiota involved in this complex bioprocess. High-throughput methodologies open new perspectives to investigate AD process at the molecular level, supported by recent data integration methodologies to extract relevant information. In this study, we investigated the link between microbial activity and substrate degradation in a lab-scale anaerobic co-digestion experiment, where bioreactors were fed with 9 different mixtures of three co-substrates (fish waste, sewage sludge, and grass). Samples were profiled using 16S rRNA sequencing and untargeted metabolomics. In this article, we propose a suite of multivariate tools to statistically integrate these data and identify coordinated patterns between groups of microbial and metabolic profiles specific of each co-substrate. Five main groups of features were successfully evidenced, including cadaverine degradation found to be associated with the activity of microorganisms from the order Clostridiales and the genus Methanosarcina. This study highlights the potential of data integration towards a comprehensive understanding of AD microbiota.

bioengineering↗

bioRxiv2019

Upscaling of Microbial Electrolysis Cell Integrating Microbial Electrosynthesis: Insights, Challenges and Perspectives

Recent development of microbial electrochemical technologies has allowed microbial electrosynthesis (MES) of organic molecules with microbial electrolysis cell treating waste organic matter. An electrolytic cell with a MES cathode (ME-ME cell) can produce soluble organic molecules with higher market price than biomethane, and thus satisfy both economic and environmental interest. However, the sustainability of bioanode activity could become a major concern. In this work, a 15-liter ME-ME reactor was designed with specific electrode configurations. An electrochemical model was established to assess the feasibility and possible performance of the design, considering the \"aging\" effect of the bioanode. The reactor was then built and operated for performance evaluation as well as bioanode regeneration assay. Biowaste from an industrial deconditioning platform was used as substrate for bioanode. The COD removal rate in the anodic chamber reached 0.83 g day-1 L-1 of anolyte and the anodic coulombic efficiency reached 98.6%. Acetate was produced with a rate of 0.53 g day-1 L-1 of catholyte, reaching a maximum concentration of 8.3 g L-1. A potential difference was applied between the bioanode and biocathode independent of reference electrodes. The active biocathode was dominated by members of the Genus Pseudomonas, rarely reported so far for MES activity.

microbiology↗