Biomedical subjects

Laurent David

Publications and source records attributed to Laurent David.

8 recordsLinked to original sources

PubMed2026

The transformative impact of stem cell core facilities in biomedical research.

Over the past three decades, advances in human pluripotent stem cell (hPSC) technologies, including induced pluripotent stem cells, gene editing, and 2D/3D models, have transformed biomedical research. These powerful tools have revolutionized disease modeling, drug discovery, and the development of advanced therapy medicinal products (ATMPs), while driving the establishment of stem cell core facilities. By providing specialized expertise, standardized workflows, and access to advanced technologies, these facilities support both fundamental and translational research, promote rigor and reproducibility, and foster collaboration. This manuscript highlights their role as hubs of excellence and discusses current challenges and future opportunities for the global stem cell community.

Humans↗

PubMed2025

HUMESS: integrating quantitative transcriptomic analysis and metabolic modeling to unveil condition-specific gene signatures.

SUMMARY: Transcriptomic analysis is a key tool for exploring gene expression, but the complexity of biological systems often limits its insights. In particular, the lack of intermodal or multi-layered analysis hinders the ability to fully capture key cellular functions such as metabolism from transcriptomic data alone. Here, we introduce a novel approach that informs transcriptomic data analysis with metabolic network modeling to address this. Unlike traditional methods, HUman MEtabolism Specific Signature (HUMESS) uses genome-scale metabolic modeling and flux analysis to highlight reactions and involved genes based on their metabolic significance, offering a deeper understanding of transcriptomic data. Our computational pipeline, supported by a user-friendly Rshiny application, enhances gene expression analysis by uncovering metabolic phenotypic signatures. AVAILABILITY AND IMPLEMENTATION: HUMESS is open source and available under GitLab https://gitlab.univ-nantes.fr/bird_pipeline_registry/humess with the complete documentation available at https://gitlab.univ-nantes.fr/bird_pipeline_registry/humess/-/wikis/Home. A zenodo archive is also available at the following DOI: https://doi.org/10.5281/zenodo.15487717. An RShiny application has been developed to facilitate the exploration and analysis of HUMESS's results. The app is available online at the following address: https://shiny-bird.univ-nantes.fr/app/shinymess but can also be installed locally, available under GitLab https://gitlab.univ-nantes.fr/pare-l/shinymess.

Humans↗

PubMed2006

Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells.

ALK1 is an endothelial-specific type I receptor of the TGFbeta receptor family whose heterozygous mutations cause hereditary hemorrhagic telangiectasia type 2. Although TGFbeta1 and TGFbeta3 have been shown to bind ALK1 under specific experimental conditions, they may not represent the physiological ligands for this receptor. In the present study, we demonstrate that BMP9 induces the phosphorylation of Smad1/5/8 in microvascular endothelial cells, and this phosphorylation lasts over a period of 24 hours. BMP9 also activates the ID1 promoter-derived BMP response element (BRE) in a dose-dependent manner (EC50 = 45 +/- 27 pg/mL), and this activation is abolished by silencing ALK1 expression or addition of ALK1 extracellular domain. Overexpression of endoglin increases the BMP9 response, whereas silencing of both BMPRII and ActRIIA expressions completely abolishes it. BMP10, which is structurally close to BMP9, is also a potent ALK1 ligand. Finally, we demonstrate that BMP9 and BMP10 potently inhibit endothelial cell migration and growth, and stimulate endothelial expression of a panel of genes that was previously reported to be activated by the constitutively active form of ALK1. Taken together, our results suggest that BMP9 and BMP10 are two specific ALK1 ligands that may physiologically trigger the effects of ALK1 on angiogenesis.

Activin Receptors, Type II↗

PubMed2006

Morphology and mechanical properties of chitosan fibers obtained by gel-spinning: influence of the dry-jet-stretching step and ageing.

The morphology and mechanical properties of chitosan fibers obtained by gel-spinning are reported. The objectives were both to understand how the microstructure of the fibers could be modified and how the mechanical properties were improved by means of a dry-jet-stretching step. A highly deacetylated chitosan (degree of acetylation=2.7%) from squid-pens, with a high weight-average molecular weight (M(w)=540,000g/mol) was dissolved in an aqueous acetic acid solution, spun using gaseous ammonia as the coagulant, and then directly dried under hot air. A "post-drying" of 1week was necessary to stabilize the fibers in ambient atmosphere. A dry-jet-stretching ratio applied during the monofilament coagulation (maximal value of 4.3) allowed us to increase the density and favor the orientation of chains along the fiber axis. This allowed us to improve the mechanical properties of the fibers (Young's modulus of 82g/denier and tenacity of 2g/denier). The ageing in ambient atmosphere played an important role in the crystalline microstructure in relation to: the kinetics of ammonium acetate hydrolysis, the formation of a weak fraction of the anhydrous allomorph of chitosan, and an increase of the crystallinity index, whereas the Young's modulus was increased and the tenacity was slightly lowered. In addition, gel-jet-stretched or dry-jet-stretched fibers could be stored at least 3months in ambient atmosphere without any significant degradation.

Acetic Acid↗

PubMed2006

Synthesis of polymer latex particles decorated with organically-modified laponite clay platelets via emulsion polymerization.

We report a new route to colloidal nanocomposites consisting of polymer latex particles covered with Laponite clay nanoplatelets. These composite particles are prepared by seeded emulsion (co)polymerization of styrene and butyl acrylate from Laponite clay suspensions previously functionalized by ion exchange using either a free radical initiator: 2,2-azobis (2-methylpropionamidine) hydrochloride (AIBA) or a cationic vinyl monomer: 2-(methacryloyloxy) ethyl trimethyl ammonium chloride (MADQUAT). The successful intercalation of the cationic reactive molecules was confirmed by elemental analysis, FTIR, 13C solid-state NMR and WAXD. The organically-modified clays were dispersed into water with the help of tetrasodium pyrophosphate and an anionic surfactant. stable latexes, produced under different experimental conditions, were successfully obtained from the clay suspensions. Cryo-TEM images of the resulting latexes showed spherical composite particles with diameters in the 50-250 nm range with clay sheets located on their surface. This paper reports on the effect of the processing conditions on the particle morphology and latex stability, and describes the mechanism of formation of the nanocomposite particles.

Aluminum Silicates↗

PubMed2004

Reticulated hyaluronan hydrogels: a model for examining cancer cell invasion in 3D.

The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation and proliferation, and contributes to the invasiveness of human cancers. The roles of HA cell surface receptors and hyaluronidases (HAses) in this process are still controversial. In order to investigate their involvement in cancer pathogenesis, we developed a reticulated HA hydrogel, a three-dimensional matrix in which cells can invade and grow. We have studied thirteen cell lines, from primary tumors or metastases, that migrated into the HA hydrogel and proliferated giving rise to clusters and colonies. The number of colonies, which reflects tumor cell invasiveness, ranged from 7 to 193 after 5 days of culture. Invasion was dependent on the production of HAse as well as other factors. Optimal colonization occurred when cells released HAse, lacked HA-binding sites and did not secrete HA. Moreover, we describe for the first time a HAse activity at physiological pH that may be responding to the confinement of the enzyme in a three-dimensional structure. We show here that this reticulated matrix provides a three-dimensional model for investigating mechanisms involved in malignant invasion.

Binding Sites↗

PubMed2002

Accelerated Poisson-Boltzmann calculations for static and dynamic systems.

We report here an efficient implementation of the finite difference Poisson-Boltzmann solvent model based on the Modified Incomplete Cholsky Conjugate Gradient algorithm, which gives rather impressive performance for both static and dynamic systems. This is achieved by implementing the algorithm with Eisenstat's two optimizations, utilizing the electrostatic update in simulations, and applying prudent approximations, including: relaxing the convergence criterion, not updating Poisson-Boltzmann-related forces every step, and using electrostatic focusing. It is also possible to markedly accelerate the supporting routines that are used to set up the calculations and to obtain energies and forces. The resulting finite difference Poisson-Boltzmann method delivers efficiency comparable to the distance-dependent dielectric model for a system tested, HIV Protease, making it a strong candidate for solution-phase molecular dynamics simulations. Further, the finite difference method includes all intrasolute electrostatic interactions, whereas the distance dependent dielectric calculations use a 15-A cutoff. The speed of our numerical finite difference method is comparable to that of the pair-wise Generalized Born approximation to the Poisson-Boltzmann method.

Algorithms↗

PubMedDate not supplied

Parametrization of a force field for metals complexed to biomacromolecules: applications to Fe(II), Cu(II) and Pb(II).

Although techniques for the simulation of biomolecules, such as proteins and RNAs, have greatly advanced in the last decade, modeling complexes of biomolecules with metal ions remains problematic. Precise calculations can be done with quantum mechanical methods but these are prohibitive for systems the size of macromolecules. More qualitative modeling can be done with molecular mechanical potentials but the parametrization of force fields for metals is often difficult, particularly if the bonding between the metal and the groups in its coordination shell has significant covalent character. In this paper we present a method for deriving bond and bond-angle parameters for metal complexes from experimental bond and bond-angle distributions obtained from the Cambridge Structural Database. In conjunction with this method, we also introduce a non-standard energy term of gaussian form that allows us to obtain a stable description of the coordination about a metal center during a simulation. The method was evaluated on Fe(II)-porphyrin complexes, on simple Cu(II) ion complexes and a number of complexes of the Pb(II) ion.

Computer Simulation↗