HAL Portal ESPCI (Ecole Supérieure de Physique et de Chimie Industrielles)
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Mise en évidence de la connectivité fonctionnelle des réseaux d'astrocytes grâce à AstroNet, un algorithme de reconstruction de graphes couplé au traitement d'images.
No full textInternational audienceAstrocytes form extended intercellular networks, displaying complex calcium activity. However, the specific organization of these astrocytic networks and the precise extent of their functional connectivity in different brain areas remain unexplored. To unveil the functional architecture of astrocytic networks, we developed, using a datadriven methodology, a novel algorithm called AstroNet that uses two-photon calcium imaging to map temporal correlations in activation events among neighboring astrocytes. Our approach involves reconstructing functional astrocytic networks by organizing individual astrocyte activation events chronologically. This chronological order creates activity paths that enable the extraction of local astrocyte functional correlations. Ultimately, by tallying the occurrences of direct co-activations between pairs of cells along these pathways, we construct a graph that mirrors the underlying astrocyte functional network. By applying this method to two distinct brain regions (CA1 hippocampus and motor cortex), we identified notable differences in local network organizations in sub-regions of around 20-40 astrocytes. Specifically, the cortex exhibited a lower connectivity, while astrocytes in the hippocampus displayed stronger connections. Moreover, we found that in both regions, astrocytic networks consist of smaller, tightly connected sub-networks embedded within a larger, more loosely connected one. Altogether, our innovative method enables the identification of activation paths among astrocytes, facilitates the characterization of local network functional connectivity, and quantifies distinct connectivity patterns among astrocytes from different brain regions. This approach sheds light on the heterogeneous functional organization of astrocytic networks within the brain, pointing to region-specific astrocyte connectivity
Viral and immune dynamics of genital human papillomavirus infections in young women with high temporal resolution
No full textInternational audienceHuman papillomavirus (HPV) infections drive one in 20 new cancer cases, exerting a particularly high burden on women. Most anogenital HPV infections are cleared in less than two years, but the underlying mechanisms that favour persistence in around 10% of women remain largely unknown. Notwithstanding, it is precisely this information that is crucial for improving treatment, screening, and vaccination strategies. To understand viral and immune dynamics in non-persisting HPV infections, we set up an observational longitudinal cohort study with frequent on-site visits for biological sample collection. We enrolled 189 women aged from 18 to 25 and living in the area of Montpellier (France) between 2016 and 2020. We performed 974 on-site visits for a total of 1,619 months of follow-up. We collected data on virus load, local immune cell populations, local concentrations of cytokines, and circulating antibody titres. Using hierarchical Bayesian statistical modelling to simultaneously analyse the data from 164 HPV infections from 76 participants, we show that in two months after infection, HPV viral load in non-persisting infections reaches a plateau that lasts on average for 13 to 20 months (95% credibility interval) and is then followed by a rapid clearance phase. This first description of the dynamics of HPV infections comes with the identification of immune correlates associated with infection clearance, especially gamma-delta T cells and CXCL10 concentration. A limitation of this study on HPV kinetics is that many infection follow-ups are censored. Furthermore, some immune cell populations are difficult to label because cervical immunity is less well characterised than systemic immunity. These results open new perspectives for understanding the frontier between acute and chronic infections, and for controlling HPV-associated diseases, as well as for research on human cancers of infectious origin. Trial Registration: This trial was registered is registered at ClinicalTrials.gov under the ID NCT02946346 . This study has been approved by the Comité de Protection des Personnes (CPP) Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/ AR1612278, decision number DR-2016–488), by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007)
Mechanism and Optimization of Ruthenium-Catalyzed Oxalamide Synthesis Using DFT
No full textInternational audienceThe oxalamide skeleton is a common structural motif in many biologically active molecules. These scaffolds can be synthesized via ruthenium pincer complex-catalyzed acceptorless dehydrogenative coupling of ethylene glycol and amines...
Comparison between modulated-pulsed and continuous wave laser powder bed fusion on an Inconel 625 alloy
No full textInternational audienceUsing pulsed or modulated laser irradiation for laser powder bed fusion (L-PBF) manufacturing can be an attractive solution for better controlling heat input, mastering geometry, and tuning microstructures of built samples. A comparison was made between a continuous wave (CW) and a modulated pulsed wave (PW) L-PBF process, considering high pulse frequencies (50 kHz), various duty cycles, and an Inconel 625 powder. In the first step, considering the precise shape of laser pulses, the peak powers were adjusted to provide similar mean powers between PW and CW and analyze the specific effect of the pulse regime at constant mean power. In the second step, single L-PBF beads were considered. The PW regime was shown to reduce the process window on (P, V) maps, increase powder-denudated widths around scan tracks, and slightly reduce the dimensions (depth, width, area) of fusion beads. In the third step, 3D samples were manufactured with PW (with duty cycles of 0.9 and 0.7 ) and CW regimes. The PW regime was shown to slightly increase the porosity rate, reduce the mean grain size by 30-40 %, and modify the crystallographic texture
Tuning the size of poly(butylene oxide) nanoparticles by microfluidic-assisted nanoprecipitation
No full textInternational audienceMicrofluidic-assisted nanoprecipitation provides precise control over formulation conditions, enabling for the design of nanoparticles with highly tunable properties. This study explores the influence of channel geometry, flow dynamics, and polymer concentration on the size and polydispersity of poly(butylene oxide) (PBO) nanoparticles. PBO is a hydrophobic polymer with a low glass transition temperature (Tg = –71 °C) that typically forms large nanoparticles (>176 nm) via bulk nanoprecipitation, as well as aggregates ranging from 3000–5000 nm. Using a hydrodynamic flow-focusing Ψ-geometry, we demonstrate that higher total flow rates increase convective mixing, reduce mixing times, and produce smaller, more monodisperse PBO nanoparticles. A comparative analysis of Ψ- and T-channel geometries across various dimensions revealed that Ψ-geometries consistently outperformed T-geometries due to their superior mixing efficiency. Decreasing the channel dimensions to 20 µm further improved mixing by shortening diffusion lengths and accelerating solvent–antisolvent interdiffusion. Using the Ψ-geometry, nanoparticles as small as 66 nm were achieved, whereas T-geometries produced significantly larger particles (>500 nm). A linear trend between particle size and total flow was observed, best described by a power-law relationship, linking flow rate—and by extension, Reynolds number—to mixing speed and nanoparticle size. These findings highlight the pivotal role of microfluidic design and flow control in tailoring nanoprecipitation for low-Tg, hydrophobic polymers such as PBO. This approach shows promising potential for the encapsulation and delivery of hydrophobic drugs
Incomplete lytic cycle of a widespread Bacteroides bacteriophage leads to the formation of defective viral particles
No full textInternational audienceAdvances in metagenomics have led to the identification of new intestinal temperate bacteriophages. However, their experimental characterization remains challenging due to a limited understanding of their lysogenic-lytic cycle and the common lack of plaque formation in vitro. In this study, we investigated the hankyphage, a widespread transposable phage of prominent Bacteroides symbionts. Hankyphages spontaneously produced virions in laboratory conditions even in the absence of inducer, but virions did not show any evidence of infectivity. To increase virion production and raise the chances of observing infection events, we identified a master repressor of the hankyphage lytic cycle, RepC HP , whose silencing amplified hankyphage gene expression, and enhanced replicative transposition and virion production. However, attempts to infect or lysogenize new host cells with different capsular types remained unsuccessful. Transmission electron microscopy and capsid DNA sequencing revealed an abnormal virion morphology and incomplete DNA packaging of the hankyphage, suggesting that it cannot complete its assembly in laboratory conditions for reasons that are yet to be identified. Still, metavirome and phylogenetic analyses were suggestive of hankyphage horizontal transmission. We could also detect the activity of diversity-generating retroelements (DGRs) that mutagenize the hankyphage tail fiber, and likely contribute to its broad host range. This study sheds light on the life cycle of this abundant intestinal bacteriophage and highlights important gaps in our understanding of the factors required for the completion of its life cycle. Elucidating this puzzle will be critical to gain a better understanding of the hankyphage biology and ecological role
Microwells as Minimalistic Niches to Study Heterotypic Interactions of Stromal and Hematopoietic Stem Cells
No full textInternational audienceHematopoietic stem and progenitor cells (HSPCs) can migrate and reside within the bone marrow in distinct microenvironments or niches. The niches organize around specific stromal cells, such as endothelial cells at the capillary or sinusoid walls, and osteoblasts along the bone matrix. Within each niche, a specific combination of external cues, including secreted and diffusible factors, cell-matrix, and cell-cell interactions, controls HSPCs behavior and fate. Deciphering the interplay between HSPCs and stromal cells of the niches is challenging: in vivo, it is hindered by the opacity of the bone matrix; in vitro, classical co-culture models only poorly recapitulate essential features of the physiological niches. The difficulty is moreover amplified by the exceptional migration capacity of HSPCs.In this chapter, we present a method to overcome these limitations by producing arrays of microwells designed to mimic bone marrow niches in a functional manner. These "microniches" promote a long-term interaction between the HSPC and a stromal cell of interest. We describe their microfabrication based on a maskless photolithography method allowing the production of arrays of microwells with reproducible volume and geometry, and the iterative improvement of the geometric design of the wells. We describe the loading and culture of stromal cells with HSPCs. We discuss the potentiality of microwells, in basic and applied research, as a platform to investigate molecular mechanisms involved in direct cell-cell interactions and local effects of diffusible factors, for any adherent and non-adherent cells of interest
Self‐Photosensitizing Cobalt Complexes for Photocatalytic CO<sub>2</sub> Reduction Coupled with CH<sub>3</sub>OH Oxidation
No full textInternational audienceThe use of metal complexes as homogeneous molecular catalysts has attracted considerable attention regarding photocatalytic CO2 reduction. Enhancing these complexes with photosensitivity and photooxidation capabilities, aiming to create multifunctional molecular devices, presents significant challenges. In response to these challenges, we successfully designed and synthesized three innovative metal complexes. The complexes demonstrate a remarkable ability to perform CO2 photoreduction in tandem with methanol photooxidation, allowing for the simultaneous production of formic acid without requiring additional photosensitizers and electron sacrificial reductants. An optimal turnover number (TON) value of 855 was obtained under simulated sunlight. Even under natural sunlight, the TON can reach 207, much higher than the value of the physical mixture of the photocatalytic reductive and oxidative moieties. Spectroscopic studies and density functional theory (DFT) calculations revealed that integrating reduction and oxidation sites in one molecular catalyst can promote charge transfer kinetics and enhance activity for CO2 reduction and methanol oxidation. This is the first report that non‐noble metal homogeneous catalysts can simultaneously possess photosensitivity, photoreduction, and photo‐oxidation functions, offering new insights into designing homogeneous catalysts for artificial photosynthesis
SARS-CoV-2 epidemiology, kinetics, and evolution: A narrative review
No full textInternational audienceSince winter 2019, SARS-CoV-2 has emerged, spread, and evolved all around the globe. We explore 4 y of evolutionary epidemiology of this virus, ranging from the applied public health challenges to the more conceptual evolutionary biology perspectives. Through this review, we first present the spread and lethality of the infections it causes, starting from its emergence in Wuhan (China) from the initial epidemics all around the world, compare the virus to other betacoronaviruses, focus on its airborne transmission, compare containment strategies ("zero-COVID" vs. "herd immunity"), explain its phylogeographical tracking, underline the importance of natural selection on the epidemics, mention its within-host population dynamics. Finally, we discuss how the pandemic has transformed (or should transform) the surveillance and prevention of viral respiratory infections and identify perspectives for the research on epidemiology of COVID-19
Conception de films photomagnétiques ultra-minces par électrodéposition de complexes Fe 4 Co 4 pontés au cyanure commutables
No full textInternational audiencePreparing thin-films of molecular polymetallic materials remains one of the current limitations in the implementation of polymetallic complexes into devices. The hurdle was tackled here using an electrochemical route for depositing the cyanido-bridged polymetallic complex {Tl[Fe II (2-TPhTp)(CN) 3 ] 4 [Co III (Tp)] 3 [Co II (Tp)]}(1) (where 2-TPhTp = [4-(2thienyl)Phenyl]tris(pyrazol-1-yl)borate ; and Tp = hydrotris(pyrazol-1-yl)borate), functionalized with thiophene groups, on conductive surface (Pt/mica). Cyclic voltammograms show that the electrochemical pattern of the cubic units is maintained in the electropolymerized film, notably with four quasi reversible successive Fe III /Fe II redox events. Assessing the morphology and the chemical composition of the resulting thin-film by Atomic Force Microscopy (AFM) and X-ray Photoelectron Spectroscopy (XPS) experiments respectively, reveal a homogenous deposition (thickness of ca. 20 nm) showing the expected metallic ratio. More importantly, X-ray Absorption Spectroscopy (XAS) and X-ray Magnetic Circular Dichroism (XMCD) measurements demonstrate that the photo-induced metal-metal electron transfer is preserved in the film. XMCD signals of Fe and Co atoms at their L 2,3 absorption edges both indicate an equivalent conversion of Fe II -CN-Co III diamagnetic pairs into Fe III -CN-Co II paramagnetic ones under laser light irradiation below 62 K. As for the photomagnetic complex, the phenomenon is reversible: the metastable Fe III -CN-Co II paramagnetic pairs thermally relax to the diamagnetic ground state upon heating to room temperature.La préparation de couches minces de matériaux polymétalliques moléculaires reste l'une des limitations actuelles dans la mise en œuvre de complexes polymétalliques dans des dispositifs. Cet obstacle a été abordé ici en utilisant une voie électrochimique pour déposer le complexe polymétallique ponté cyanido {Tl[Fe II (2-TPhTp)(CN) 3 ] 4 [Co III (Tp)] 3 [Co II (Tp)]}(1) (où 2-TPhTp = [4-(2thiényl)phényl]tris(pyrazol-1-yl)borate ; et Tp = hydrotris(pyrazol-1-yl)borate), fonctionnalisé avec des groupes thiophène, sur une surface conductrice (Pt/mica). Les voltampérogrammes cycliques montrent que le motif électrochimique des unités cubiques est maintenu dans le film électropolymérisé, notamment avec quatre événements redox Fe III /Fe II successifs quasi réversibles. L'évaluation de la morphologie et de la composition chimique du film mince obtenu, par microscopie à force atomique (AFM) et spectroscopie de photoélectrons X (XPS), révèle un dépôt homogène (épaisseur d'environ 20 nm) présentant le rapport métallique attendu. Plus important encore, les mesures de spectroscopie d'absorption des rayons X (XAS) et de dichroïsme circulaire magnétique des rayons X (XMCD) démontrent que le transfert d'électrons métal-métal photo-induit est préservé dans le film. Les signaux XMCD des atomes de Fe et de Co à leurs seuils d'absorption L 2,3 indiquent tous deux une conversion équivalente des paires diamagnétiques Fe II -CN-Co III en paires paramagnétiques Fe III -CN-Co II sous irradiation laser à une température inférieure à 62 K. Concernant le complexe photomagnétique, le phénomène est réversible : les paires paramagnétiques métastables Fe III -CN-Co II se relaxent thermiquement et reviennent à l'état fondamental diamagnétique lors du chauffage à température ambiante