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Riviere, B.

Publications and source records attributed to Riviere, B..

3 recordsLinked to original sources

Quantitative Comparison of 3D-1D Vascular Coupling Models: Lateral Average versus Sphere of Influence Methods

Computational models coupling one-dimensional vascular networks with three-dimensional tissue domains are widely used for predicting blood flow distribution in tumor perfusion, drug delivery, and therapeutic planning. Two prominent coupling paradigms have emerged: the Lateral Average Model (LAM) which implements distributed transmural exchange via a vessel wall conductivity parameter{gamma} (m Pa-1 s-1), and the Sphere of Influence (SOI) model, which employs localized terminal coupling via a source sphere radius{varepsilon} (m). Despite their broad application, systematic quantitative comparisons of their parametric behavior and predictive equivalence remain lacking. We compare LAM and SOI in 3D-1D simulations on a benchmark vascular network and a porcine liver study with a hepatic arterial network reconstructed from CT arteriography. Across a benchmark vascular network under three sink configurations, the LAM net flow rate rose smoothly with{gamma} and saturated at a plateau, while the SOI net flow rate increased with{varepsilon} without saturating; as a result, global-flow equivalence between the two formulations exists only for particular boundary geometries, and not at all within the tested parameter range for one of the three configurations examined. Despite this partial agreement in total flow, the two models diverged substantially in regional perfusion: in a porcine hepatic arterial network reconstructed from CT arteriography, SOI predicted stable perfusion fractions to two regions of interest across its full tested parameter range, whereas LAM predictions for the same regions varied several-fold with vessel wall permeability and, at low permeability, could invert which region received more flow. These results indicate that the choice of coupling model has limited consequence for predicted total organ flow but substantial consequence for predicted local drug delivery, and we provide guidance for selecting between the two formulations depending on the clinical or research question being asked. Author SummaryWhen doctors plan treatments for liver cancer, they often rely on computer simulations to predict how blood flows through the liver and how well a drug will reach the tumor. These simulations depend on mathematical models that describe how blood moves from vessels into surrounding tissue. Two commonly used approaches exist for building these models, but researchers have generally chosen between them based on habit or convenience rather than on a principled understanding of how their predictions differ. In this work, we directly compared these two approaches, one that spreads blood exchange continuously along the vessel wall, and one that delivers blood from the vessel tips into a surrounding spherical zone, using both a simple test network and a realistic pig liver reconstructed from medical imaging. We found that the two approaches can agree on the total amount of blood reaching the liver, but disagree substantially on where that blood goes within the tissue. This distinction matters enormously for treatment planning: a model that predicts the right total blood flow but delivers it to the wrong region of the liver could lead to an inaccurate forecast of drug concentration at the tumor site. Our results provide practical guidance for researchers on which approach to use depending on what information is available and what question is being asked.

biophysics↗

Microbiome composition and function vary with depth in the Mediterranean gorgonian Eunicella singularis

BackgroundThe Gorgonian coral, Eunicella singularis, is one of the main components of Mediterranean marine animal forests, whose canopies play a key role in Mediterranean sublittoral ecosystems due to their capacity to provide shelter, food, and nursery ground to several species. Like other gorgonian species, E. singularis faces environmental threats with potential repercussions on the associated biodiversity. This photophilic octocoral, spanning the Western Mediterranean, Adriatic, and Aegean Seas at depths of 10-70m, engages in symbiosis with Symbiodiniaceae dinoflagellates, thereby influencing their resilience in nutrient-poor habitats. However, mesophotic populations ([~]60m depth) are characterized by very low Symbiodiniaceae density, prompting questions regarding metabolic adaptations. The associations of corals with specific bacteria that differ from those in the surrounding seawater suggest a role in host health and physiology. In particular, in mesophotic colonies, bacteria may perform activities that Symbiodinium typically carries out in shallow colonies. Here, we applied metagenomics techniques to analyze the changes in the microbiome of Eunicella singularis with depth, analyzing DNA samples from shallow (12m) and mesophotic (57m) colonies in the Northwestern Mediterranean Sea. ResultsHigh-coverage metagenomes (ca. 80 Gb per sample) were generated from E. singularis colony samples. We observed significant changes in the relative abundance of prokaryotic and microbial eukaryotic symbionts with depth. Mesophotic samples exhibited higher levels of symbiotic prokaryotes, dominated by Endozoicomonas and Bermanella, whereas shallow samples were enriched with the symbiotic dinoflagellate Symbiodiniaceae. The metabolic potential of the microbiome also varied with depth. The shallow microbiome showed a prevalence of photosynthesis and carbon fixation pathways. In turn, the mesophotic microbiome exhibited a higher abundance of metabolic functions related to vitamin biosynthesis, energy metabolism, especially carbon metabolism, as well as pathways associated with carbohydrates, amino acids, and cofactors. ConclusionsOur results indicate that the structure and metabolic function of the microbiome of Eunicella singularis change with depth. In the absence of symbiotic dinoflagellates, associated bacteria seem to use different sources of carbon, in addition to cycling nutrients and vitamins, which could influence coral health. These findings gain significance in the context of global change, as shifts in oceanic conditions may affect the coral microbiome.

ecology↗

FGF19 and its analog Aldafermin cooperate with MYC to induce aggressive hepatocarcinogenesis

FGF19 hormone has pleiotropic metabolic functions, notably the modulation of insulin sensitivity, glucose/lipid metabolism and energy homeostasis. On top of its physiological metabolic role, FGF19 has been identified as a potentially targetable oncogenic driver, notably in hepatocellular carcinoma (HCC). Nevertheless, FGF19 remained an attractive candidate for treatment of metabolic disease, prompting the development of analogs uncoupling its metabolic and tumor-promoting activities. Using pre-clinical mice models of somatic mutation driven HCC, we assessed the oncogenicity of FGF19 in combination with frequent HCC tumorigenic alterations: p53 inactivation, CTNNB1 mutation, CCND1 or MYC overexpression. Our data revealed a strong oncogenic cooperation between FGF19 and MYC. Most importantly, we show that this oncogenic synergy is conserved with a FGF19-analog Aldafermin (NGM282), designed to solely mimic the hormones metabolic functions. In particular, even a short systemic treatment with recombinant proteins triggered rapid appearance of proliferative foci of MYC-expressing hepatocytes. The fact that FGF19 analog Aldafermin is not fully devoid of the hormones oncogenic properties raises concerns in the context of its potential use for patients with damaged, mutation-prone liver.

cancer biology↗