Biology subjects

Vallet, A.

Publications and source records attributed to Vallet, A..

9 recordsLinked to original sources

bioRxiv2026

How brain pulsations drive solute transport in thecranial subarachnoid space: insights from a toymodel

Cerebrospinal fluid (CSF) circulates around and through the brain, supporting neural homeostasis by regulating the extracellular chemical environment. Yet the physical mechanisms governing CSF-driven solute transport remain poorly understood, limiting the design of diagnostic and therapeutic strategies targeting brain clearance and drug delivery. Pulsatile CSF flow in the cranial subarachnoid space (cSAS), is driven by cardiac, respiratory, and sleep-related vasomotion. Over longer timescales weaker steady flows, such as inertial steady streaming, Stokes drift, and production-drainage flow, may contribute to solute transport, but their role and relative importance remain unclear. Here, we develop a simplified two-dimensional model of CSF flow and solute transport in the cSAS using lubrication theory. Through multiple-timescale and asymptotic analyses, we derive a reduced long-time transport equation in which advection is governed by the Lagrangian mean velocity, incorporating steady streaming, production-drainage flow, and Stokes drift. Analysing three physiologically relevant case studies, we show that steady flows can substantially reshape concentration profiles, enhance dispersion, and alter clearance efficiency. Our results clarify the mechanisms underlying CSF-mediated transport, predict distinct regimes in humans and mice, and highlight the importance of subject-specific physiological parameters when interpreting contrast-agent and intrathecal drug-delivery studies.

biophysics↗

bioRxiv2025

Disparities in climate risk-mitigation and recreation services in Grenoble (France)

Urban green spaces provide cultural and climate risk-mitigation ecosystem services (ES) critical for the well-being of urban residents. Yet these benefits are not equally shared across social groups, and environmental segregation - i.e., the spatial separation of population groups between areas of contrasted environmental quality - is common. For instance, environmental justice studies have shown that green space acreage and quality are typically lower in low-income neighbourhoods. However, more detailed assessments integrating a range of ES and the diverse needs of multiple groups are needed to effectively inform equitable urban planning. Here, we combine socio-demographic spatial data with ES modelling to assess social disparities in the distribution of three ES - heatwave mitigation, flood regulation, and urban recreation - in the Grenoble metropolitan area, France. Our results show that low-income households generally benefit from lower climate risk mitigation, but from equal or slightly greater urban recreation opportunities. We also identify mismatches between ES supply and demand from vulnerable groups, which are particularly acute in disadvantaged neighborhoods. These findings highlight the importance of integrating social needs and vulnerabilities into urban greening strategies. Policies that move beyond generic measures of green space provision and explicitly consider multiple ES can help ensure that urban green infrastructure delivers fair and effective benefits across diverse communities.

ecology↗

bioRxiv2025

Identification of uranyl-binding proteins in Arabidopsis thaliana cells exposed to uranium: Insights from a metalloproteomic analysis and characterization of Glycine-Rich RNA-binding Protein 7 (GRP7)

Uranium (U) is a naturally occurring radionuclide, chemotoxic for living organisms. To identify proteins that could be cellular targets for U in plants, we used metalloproteomic approaches combining column chromatographic fractionation analyses, protein identification by high-resolution mass spectrometry shotgun proteomics, and metal quantification by induced coupled plasma mass spectrometry. We identified 57 candidate proteins for uranyl (U(VI)) binding in cultured Arabidopsis thaliana cells. One of these proteins, the Glycine-Rich RNA-binding Protein 7 (GRP7) is a RNA-binding protein involved in various developmental processes and responses to biotic and abiotic stress. Recombinant GRP7 was purified from overproducing bacteria and subjected to further biochemical characterization. First, we showed that GRP7 binds U(VI) with a 1:2 (protein:metal) stoichiometry in vitro. Next, we analyzed its structural properties by solution-state nuclear magnetic resonance spectroscopy. This allowed us to gain insight into the molecular dynamics of the protein-metal interaction and to identify residues involved in U(VI)-binding in the two sites. Finally, we observed that U(VI) binding interferes with nucleic acid binding to the protein RNA-binding domain, suggesting that U(VI) binding to GRP7 contributes to U toxicity in plants. HIGHLIGHTSO_LI57 candidate uranyl-binding proteins were identified from Arabidopsis cells exposed to uranyl, of which the RNA-binding protein GRP7. C_LIO_LIIn vitro, recombinant GRP7 binds 2 uranyl ions within the RNA recognition motif domain. C_LIO_LIAmino acid residues involved in uranyl binding in both binding sites were identified. C_LIO_LICompetition between specific oligonucleotide and uranyl for binding suggests the implication of GRP7 in uranium toxicity, as a cellular target. C_LI

biochemistry↗

bioRxiv2025

Sensitivity analysis enlightens effects of connectivity in a Neural Mass Model under Control-Target mode

Biophysical models of human brain represent the latter as a graph of inter-connected neural regions. Building from the model by Naskar et al. [1], our motivation was to understand how these brain regions can be connected at neural level to implement some inhibitory control, which calls for inhibitory connectivity rarely considered in such models. In this model, regions are made of inter-connected excitatory and inhibitory pools of neurons, but are long-range connected only via excitatory pools (mutual excitation). We thus extend this model by generalizing connectivity, and we analyse how connectivity affects the behaviour of this model. Focusing on the simplest paradigm made of a Control area and a Target area, we explore four typical kinds of connectivity: mutual excitation, Target inhibition by Control, Control inhibition by Target, and mutual inhibition. For this, we build an analytical sensitivity framework, nesting up sensitivities of isolated pools, of isolated regions, and of the full system. We show that inhibitory control can emerge only in Target inhibition by Control and mutual inhibition connectivities. We next offer an analysis of how the model sensitivities depends on connectivity structure, depending on a parameter controling the strength of the self-inhibition within Target region. Finally, we illustrate the effect of connectivity structure upon control effectivity in response to an external forcing in the Control area. Beyond the case explored here, our methodology to build analytical sensitivities by nesting up levels (pool, region, system) lays the groundwork for expressing nested sensitivities for more complex network configurations, either for this model or any other one.

neuroscience↗

bioRxiv2025

A single domain intrabody as a novel tool to bias the subcellular trafficking of the follicle-stimulating hormone receptor

Intracellular variable fragments from heavy-chain only antibodies of camelids (intra-VHH) have been successfully used for their stabilizing properties to solve the 3D structure of active G protein-coupled receptors (GPCRs) bound to their cognate transducers. They also provide tools to link a given conformation of a GPCR to the signalling network engaged, thus allowing extensive structure/activity studies. Recently, they have been instrumental in tracking active GPCRs in various subcellular compartments. Here, we report the isolation and characterization of iPRC2, an intra-VHH recognizing the 1st and 3rd intracellular loops of the FSHR, but not of the luteinizing hormone/choriogonadotropin receptor close relative. Its expression in the cell decreases the cAMP production in response to hormone binding, and requires Gs for optimal interaction with the receptor. Importantly, iPRC2 increases the FSHR accumulation in the early endosomes, and consequently, diminishes its recycling to the cell surface. Hence, in contrast to previously described intra-VHH that disclose active GPCR intracellular location, iPRC2 provokes per se a location bias, through its ability to reroute the FSHR. Thus, it is an innovative tool to examine the functional consequences of GPCR accumulation in various sub-cellular compartments.

pharmacology and toxicology↗

bioRxiv2024

The plastid-encoded RNA polymerase structures a logistic chain for light-induced photosynthesis

The chloroplast is the semi-autonomous organelle of eukaryotes that performs photosynthesis. In higher plants, chloroplast biogenesis depends on a tight transcriptional coordination of both nuclear- and-plastid photosynthesis-associated genes. The plastid-encoded RNA-polymerase (PEP) is composed of a plastid-encoded catalytic core, similar to multi-subunit RNA polymerases, bound to fifteen nuclear-encoded PEP-associated proteins (PAPs). The binding of all the PAPs to the catalytic core is essential for plastid transcription of photosynthesis-associated genes. Our cryo-electron microscopy structure of the native 21-subunit PEP from Sinapis alba reveals the distinctive patterning of PAP interactions, which evolved upon the ancestral cyanobacterial catalytic core acting as a scaffold. Using PAP8 in planta as bait for affinity purification and proximity labeling, we provide the protein landscapes surrounding the PEP and other PAP8-interacting complexes at the transition from skotomorphogenesis to photomorphogenesis. The data highlight multiple functional couplings in which plastid transcription is at the beginning of a spatial logistic chain, extending from transcription to the assembly of the photosynthetic apparatus into the thylakoids. In addition, dark-specific interactions between photoreceptors and PAP8 establish a physical link between an integrated light signaling and plastid functions.

plant biology↗

bioRxiv2023

A single domain intrabody targeting the follicle-stimulating hormone receptor (FSHR) impacts FSH-induced G protein-dependent signalling

Intracellular variable fragments from heavy-chain antibody from camelids (intra-VHH) have been successfully used as chaperones to solve the 3D structure of active G protein-coupled receptors bound to their transducers. However, their effect on signalling has been poorly explored, although they may provide a better understanding on the relationships between receptor conformation and activity. Here, we isolated and characterized iPRC1, the first intra-VHH recognizing a member of the large glycoprotein hormone receptors family, the follicle-stimulating hormone receptor (FSHR). This intra-VHH recognizes the FSHR 3rd intracellular loop and decreases cAMP production in response to FSH, without altering Gs recruitment. Hence, iPRC1 behaves as an allosteric modulator and provides a new tool to complete structure/activity studies performed so far on this receptor.

pharmacology and toxicology↗

bioRxiv2023

Disulfide-bond-induced structural frustrationand dynamic disorder in a peroxiredoxin fromMAS NMR

Disulfide bond formation is fundamentally important for protein structure, and constitutes a key mechanism by which cells regulate the intracellular oxidation state. Peroxiredoxins (PRDXs) eliminate reactive oxygen species such as hydrogen peroxide by using a catalytic cycle of Cys oxidation and reduction. High molecular-weight assemblies of PRDXs have recently been shown to additionally act as molecular chaperones. The consequences of disulfide bonds on the dynamics of these large assemblies are poorly understood. We show that formation of disulfide bonds along the catalytic cycle induces extensive s time scale dynamics, as monitored by magic-angle spinning NMR of the 216 kDa-large Tsa1 decameric assembly and solution-NMR of a designed dimeric mutant. We ascribe the conformational dynamics to structural frustration, resulting from conflicts between the disulfide-constrained reduction of mobility and the desire to fulfil other favorable contacts.

biophysics↗

bioRxiv2022

Sleep cycle-dependent vascular dynamics enhance perivascular cerebrospinal fluid flow and solute transport

Perivascular spaces (PVS) are important highways for fluid and solute transport in the brain enabling efficient waste clearance during sleep. Using two-photon imaging of naturally sleeping mice we demonstrate sleep cycle-dependent PVS dynamics - slow, large-amplitude oscillations in NREM, a reduction in REM and an enlargement upon awakening at the end of a sleep cycle. By biomechanical modeling we demonstrate that these sleep cycle-dependent PVS dynamics drive fluid flow and solute transport.

neuroscience↗