Biology subjects

Chretien, A.

Publications and source records attributed to Chretien, A..

3 recordsLinked to original sources

bioRxiv2026

GL-0001, a first-in-class dual GIP/GLP-2 analogue, reduces bone fragility by enhancing bone material properties in a murine model of type III osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a severe heritable skeletal disorder characterized by bone fragility, short stature, and increased fracture risk. Currently, no pharmacological treatment has been approved for OI, and bisphosphonates are commonly used off label. While bisphosphonates increase bone mass, their effects on bone quality and fracture reduction remain limited. GL-0001, a first-in-class dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-2 (GLP-2) compound that targets bone material properties, may offer alternative skeletal benefits. We evaluated the effects of 9 weeks of GL-0001 treatment in the oim/oim murine model of severe OI, a well-established model carrying a homozygous Col1a2 mutation resulting in abnormal type I collagen formation and compared outcomes with zoledronic acid (100 g/kg) or saline. Analyses included longitudinal growth, fracture incidence, bone biomechanics, microarchitecture, turnover markers, and bone material properties. OI mice exhibited reduced body weight, impaired femoral growth, severe trabecular and cortical deficits, altered bone turnover, and compromised biomechanical properties compared with WT controls. GL-0001 increased femur length by 5% (p=0.015) and reduced spontaneous fracture incidence by 90% (p=0.004), whereas zoledronic acid had no significant effect on fracture burden. Bone microarchitecture was not significantly altered by GL-0001, whereas zoledronic acid improved trabecular and cortical parameters. At the tissue level, GL-0001 improved bone strength, increasing ultimate stress (+26%, p=0.022) and yield stress (+30%, p=0.014), and reducing brittleness (-32%, p=0.002). These changes were associated with increased collagen maturity (+12%, p<0.001). In contrast, zoledronic acid had limited effects on bone material properties. These findings demonstrate that GL-0001 improves skeletal fragility in the oim/oim murine model of severe OI through mechanisms primarily involving enhancement of bone material properties and longitudinal growth, rather than changes in bone mass or microarchitecture. GL-0001 may therefore represent a novel therapeutic strategy targeting bone quality in OI.

physiology↗

bioRxiv2025

Preventing unintentional bat captures in canopy traps used for insect surveys

There is growing interest in deploying insect traps in forest canopies for ecological research, invasive species surveillance, and biodiversity monitoring. However, forest canopies also harbor a diverse and abundant bat community, which may be incidentally trapped and killed by these devices. In this study, we investigated the impact of flight interception traps and multi-funnel traps deployed in oak canopies on incidental bat captures, and evaluated whether trap modifications could reduce this bycatch. We also examined how these modifications influenced the species richness, abundance, and mean body size of several beetle taxa, including Buprestidae, Cerambycidae, Cetoniinae, and Scolytinae. Both trap types captured bats. Flight interception traps accidentally caught seven species - Myotis bechsteinii, Myotis daubentonii, Myotis mystacinus, Nyctalus noctula, Nyctalus leisleri, Plecotus auritus, and Pipistrellus pipistrellus - with an average of 0.42 bats per trap. Multi-funnel traps primarily caught males of P. pipistrellus, with an average of 0.29 bats per trap. Adding a 13-mm mesh above the collection container significantly reduced bat bycatch to 0.02 and 0.05 bats per trap in flight interception traps and multi-funnel traps, respectively. This modification had no significant effect on insect species richness or mean body size, although it did reduce Cerambycidae and Scolytinae abundance in black multi-funnel and flight interception traps, respectively. This was likely due to more frequent clogging by twigs and leaves. We recommend modifying flight interception and multi-funnel traps deployed in forest canopies to prevent unintentional harm to protected bat species.

ecology↗

bioRxiv2023

Light-induced Trpin/Metout switching during BLUF domain activation in ATP-bound photoactivatable adenylate cyclase OaPAC

The understanding of signal transduction mechanisms in photoreceptor proteins is essential for elucidating how living organisms respond to light as environmental stimuli. In this study, we investigated the ATP binding, photoactivation and signal transduction process in the photoactivatable adenylate cyclase from Oscillatoria acuminata (OaPAC) upon blue light excitation. Structural models with ATP bound in the active site of native OaPAC at cryogenic as well as room temperature are presented. ATP is found in one conformation at cryogenic- and in two conformations at ambient-temperature, and is bound in a non-productive conformation. However, FTIR spectroscopic experiments confirm that the non-productive conformation is the native binding mode in dark state OaPAC and that transition to a productive conformation for ATP turnover only occurs after light activation. A combination of time-resolved crystallography experiments at synchrotron and X-ray Free Electron Lasers sheds light on the initial events around the Flavin Adenine Dinucleotide (FAD) chromophore in the light-sensitive BLUF domain of OaPAC. Initial changes involve the highly conserved amino acids Tyr6, Gln48 and Met92. Crucially, the Gln48 side chain performs a 180{degrees} rotation during activation, leading to the stabilization of the FAD chromophore. Cryo-trapping experiments allowed us to investigate a late light-activated state of the reaction and revealed significant conformational changes in the BLUF domain around the FAD chromophore. In particular, a Trpin/Metout transition upon illumination is observed for the first time in the BLUF domain and its role in signal transmission via -helix 3 and 4 in the linker region between sensor and effector domain is discussed.

biochemistry↗