HAL Portal ESPCI (Ecole Supérieure de Physique et de Chimie Industrielles)
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Spatio-temporal dynamics of macroglial cell organisation and proximity to blood vessels during postnatal development
No full textAbstract Brain cortical development results from the proliferation, differentiation, migration and maturation of many cell types. While neuronal development is well characterized, the mechanisms regulating macroglial cells (oligodendrocytes and astrocytes) development remain largely unknown. Recent works suggest that the vascular system plays a key, yet under-evaluated role in this process. To investigate this, we developed VeCell , a Fiji plugin designed to analyse the spatial organization of macroglial cells relative to blood vessels. Using immunolabeling for Sry-box transcription factor (Sox) 9 (macroglial progenitors and astrocytes) and Sox10 (oligodendrocyte lineage), we determined macroglia density, distribution and proximity to blood vessels from postnatal day (P) 1 to P60 in the somatosensory cortex. We showed that Sox9+ cells were evenly distributed across cortical layers with regular intercellular spacing. In contrast, Sox10+ cells concentrated in deeper cortical layers, and exhibited a random distribution. Vascular density and branching increased markedly between P5 and P15 and macroglial cells were closer to blood vessels from P15 onward. As a proof of concept, we used Vecell to show that astrocyte cortical distribution is preserved in MLC1-deficient mice, a model of Megalencephalic leukoencephalopathy with subcortical cysts, in which astrocyte perivascular coverage is altered. Thus, VeCell is a powerful tool to characterize and quantify macroglial cell distribution in the brain and in relation to the vasculature. It revealed distinct distribution and postnatal development patterns for astrocytes and oligodendrocytes. Table of Contents Entry VeCell: quantification of macroglial cell density, distribution, and proximity to blood vessels From P5, Sox9⁺ cells are evenly distributed, unlike Sox10⁺ cells From P15, Sox9⁺ cells are located closer to blood vessels than Sox10⁺ cells Abstract Figur
Interactions of the LINE-1 encoded ORF1p with proteins and chromatin converge on a role in neuronal physiology
No full textInternational audienceRetrotransposons are emerging as novel regulators of embryonic and brain development. We recently demonstrated that the LINE-1–encoded protein ORF1p is abundantly expressed in adult mouse and human neurons, although its function remains unclear. Here, we characterize the ORF1p interactome in differentiated mouse and human neurons using mass spectrometry and identify novel partners implicated in gene regulation and neuron-specific processes. ORF1p localizes not only to neuronal nuclei, where it associates with chromatin under steady-state conditions, but also to neurites, supporting a role in neuronal physiology. To further explore its nuclear functions, we sorted human post-mortem neurons with high or low nuclear ORF1p levels and performed ORF1p knockdown in cultured human neurons, followed by chromatin accessibility assays. Both approaches revealed consistent patterns of differential chromatin accessibility dependent on ORF1p. Loss of ORF1p also led to the downregulation of long, neuron-specific genes and altered neurite morphology. Together, these findings point to a physiological role of ORF1p in post-mitotic neurons, mediated through converging interactions with proteins and chromatin
Synthesis of 2‐(Trifluoromethyl)Azetidines by Strain‐Release Reactions of 2‐(Trifluoromethyl)‐1‐Azabicyclo[1.1.0]Butanes
No full textInternational audienceSubstituted azetidines are privileged heterocyclic scaffolds in medicinal chemistry and have become synthetic targets of high interest in recent years. With the goal of developing a new access to azetidines incorporating the pharmaceutically relevant trifluoromethyl group, the reactivity of 2‐(trifluoromethyl)‐1‐azabicyclo[1.1.0]butanes was investigated in polar strain‐release reactions. By using benzyl chloroformate or trifluoroacetic anhydride as reacting partners, diversely substituted 3‐chloroazetidines, 3‐substituted azetidines and azetidin‐3‐ols bearing a trifluoromethyl group at C2 could be readily synthesized. In addition, palladium‐catalyzed hydrogenolysis reactions provided an entry to cis‐ 3‐aryl‐2‐trifluoromethyl azetidines
Detection and characterization of targets in complex media using fingerprint matrices
No full textInternational audienceWhen waves propagate through a complex medium, they undergo several scattering events. This phenomenon is detrimental to imaging, as it causes full blurring of the image. Here we describe a method for detecting, localizing and characterizing any scattering target embedded in a complex medium. We introduce a fingerprint operator that contains the specific signature of the target with respect to its environment. When applied to the recorded reflection matrix, it provides a likelihood index of the target state. This state can be the position of the target for localization purposes, its shape for characterization or any other parameter that influences its response. We demonstrate the versatility of our method by performing proof-of-concept ultrasound experiments on elastic spheres buried inside a strongly scattering granular suspension and on lesion markers, which are commonly used to monitor breast tumours, embedded in a foam mimicking soft tissue. Furthermore, we show how the fingerprint operator can be leveraged to characterize the complex medium itself by mapping the fibre architecture within muscle tissue. Our method is broadly applicable to different types of waves beyond ultrasound for which multi-element technology allows a reflection matrix to be measured
Sound offset responses become highly informative in the auditory cortex
No full textInternational audienceThe entire auditory system downstream of the cochlea features pronounced offset responses that follow the termination of sounds. Because of their ubiquity, it remains an unsolved question whether offset responses are generated early in the auditory system and subsequently propagated downstream or recomputed at each processing stage. Here, we analysed large-scale sound response datasets acquired in the cochlear nucleus, inferior colliculus, medial geniculate nucleus and auditory cortex of awake mice. All brain regions showed a significant proportion of offset responses, often combined with onset and sustained responses in the same neuron. However, using population activity decoders, we observed that neural representations after the sound offset show a three-fold increase in sound encoding accuracy in the cortex relative to subcortical areas. This result indicates that cortical offsets encode a more precise short-term memory of the elapsed sound than subcortical offsets and that they probably result from specific computational steps
Dynamic quantum spin Hall effect for light
No full textInternational audienceQuantum Hall effects are prominent phenomena in condensed matter physics that consist in a precisely quantized electrical transport along sample edges [1]. Optical analogs of these effects have been proposed and realized experimentally [2]. We demonstrate that electromagnetic waves not only allow for mimicking these condensed-matter physics phenomena but also add a new dimension to their study. In particular, dynamical aspects of transport phenomena in quantum Hall effects can be studied in optical and microwave experiments whereas these aspects are hardly accessible for electrical transport experiments in solid-state setups. Our experiments use microwaves propagating in carefully designed two-dimensional photonic crystals to demonstrate topologically protected transport of the optical orbital momentum along an interface between two topologically distinct crystals or along crystal edges [3]. This is analogous to the quantum spin Hall effects (QSHE) with the optical orbital momentum playing the role of electron spin (intrinsic angular momentum). Signals carrying orbital angular momenta of opposite signs propagate in opposite directions. Together with the sensitivity of the band structure to the properties of the photonic crystal boundary (an interface with another photonic crystal or with the free space), this allows for controlling the direction of signal propagation by choosing the position of the source and tuning its frequency. The emitted pulse propagates at a speed that is two orders of magnitude slower than the speed of light in the free space and goes around obstacles without backscattering. The last property is due to the topological protection resulting from the topologically nontrivial band structure of our photonic crystals. Although our experiments are performed in the microwave frequency range, they can be readily scaled to optical wavelengths. This opens new opportunities for studying questions of fundamental importance as well as for routing optical signals in photonic applications.This work was funded by the Agence Nationale de la Recherche (Grant No. ANR-20-CE30-0003 LOLITOP).[1] S. Oh, Science 340, 153 (2013)[2] T. Ozawa et al., Rev. Mod. Phys. 91, 015006 (2019)[3] L.A. Razo López, P. Wulles, G. J. Aubry, S.E. Skipetrov, F. Mortessagne, arXiv:2502.2091
Effect of enhanced foaming capacities of binary liquid mixtures on vertical two-phase flow regimes
No full textInternational audienceThis study focuses on the regimes of gas-liquid vertical flows in stagnant liquids displaying foaming properties. The liquids investigated are binary mixtures of miscible oils, that exhibits foaming properties without any surfactant. These foaming properties have recently been studied in our laboratories and ascribed to an enhanced stability of the thin liquid films separating bubbles. The present study aims at highlighting the effect of those foaming abilities on the vertical two-phase flow regimes, usually studied on non-foaming pure liquids or aqueous solutions. The gas-liquid flows are generated by injecting nitrogen through a sinter at the bottom of a glass column, in an original setup derived from the classical Bikerman method, broadly used for measuring the foamability of liquids. In the first place, gas-liquid flows with pure, non-foaming liquids are investigated through several parameters, namely the initial liquid height inserted, the generated bubble sizes, and the column’s diameter. Secondly, the effect of the liquid’s foamability on the flow regimes is investigated, the adjustment of the molar fractions of each components allowing us to tune the foaming properties of the system on a wide range (Fig.1.A). In our first experiments on foaming gas-liquid flows, we observed that the addition of small molar fractions of the second miscible liquid in the binary mixture leads to new flow regimes in which large gas pockets coexist with liquid slugs with numerous small bubbles (Fig. 1.B). In practical applications, where liquids are often mixtures, we believe that our results will have important implications, notably in predicting the gas-liquid flow regimes
Rapid C-S+ Bond Cleavage via 1,6-Benzyl Elimination for Traceless Modification of Bioactive Peptides
No full textInternational audiencePeptides and proteins are invaluable therapeutics and biological tools, where stimuli-responsive and fully reversible conjugation chemistry is essential to advances in drug delivery systems and chemical biology. However, methods that allow precise conjugation, efficient regulation of biochemical functions, and customized recovery of parent peptides remain underdeveloped. Here, we introduce a straightforward yet powerful reversible chemical strategy targeting methionine (Met), a widespread yet low abundance amino acid in peptides and proteins. By selectively alkylating Met-containing peptides under weakly acidic conditions, we form a stable C–S+ bond, which can be cleaved rapidly via 1,6-benzyl elimination upon stimulus. This versatile chemistry is demonstrated in diverse applications: (i) PEGylated prodrugs of antimicrobial peptides with reduced toxicity and enhanced enzymatic stability, (ii) esterase-responsive peptide–peptide inhibitor conjugates (PPICs) with improved cell membrane permeability and therapeutic effects, (iii) reversibly stapled peptides with switchable conformations for targeting both intra- and extracellular sites, and (iv) bioorthogonal control of C-terminal Met-caged neuropeptides. Overall, this work describes, for the first time, a valuable traceless modification strategy that promises to greatly benefit the peptide community and advance the field of chemical biology
Sequential and Time-Controlled Sol-Gel Transitions by the Mechanical Switching of Molecular Tweezers
No full textInternational audienceControlling the motion of molecular machines to influence higher-order structures is well-established in biological systems but remains a significant challenge for synthetic analogs. Herein, we aim to harness the mechanical switching of switchable molecular tweezers to modulate their self-assembly and produce stimuli-responsive organogels. We report a series of terpy(Pt-salphen)2 molecular tweezers functionalized with alkyl chains that act as low-molecular-weight gelators (LMWGs) in their open conformation. The resulting organogels were thoroughly characterized by SEM, cryo-TEM, SAXS, and rheology. The macroscopic transition from gel to solution was achieved by the cation-induced closing of the tweezers, which triggers their substantial structural reorganization. Reversible sol-gel transitions were achieved through the sequential addition of chemical stimuli or by a decomposable acid in a time-controlled operation. Such transient disassembly process regulated by a chemical fuel enables multiple gelation cycles with minimal waste while maintaining stable rheological properties. These results underscore the potential of switchable molecular tweezers in creating advanced stimuli-responsive materials
High-triplet-energy polymers via RAFT polymerization: Synthesis and properties
No full textInternational audienceRAFT polymerization of a series of styrene-type dibenzoheterocyclic monomers bearing carbazole, phenoxazine, 9,9-dimethylacridane and phenothiazine moieties using S-dodecyl-S′-(α,α′-dimethyl-α′′-acetic acid)trithiocarbonate as a chain transfer agent has been investigated. The corresponding polymers with the controlled molar mass of up to 30,000 g mol -1 with low to moderate dispersity (Đ = 1.2-1.6) were synthesized. The thermal, photophysical and electrochemical properties of the prepared polymers have been investigated using their solutions, films and in silico to establish the structure-properties relationship. The synthesized polymers were characterized by high values of HOMO (up to -5 eV), singlet (up to 3.8 eV) and triplet (up to 3.2 eV) energies, which are responsible for their unique properties such as formation of excimers with CHCl3 and dichloromethane or the ability to undergo coupling via electrooxidation in case of poly(9,9-dimethyl-10-(4-vinylphenyl)-9,10dihydroacridan). Subsequently, two series of OLEDs based on the synthesized polymers were fabricated in order to study the charge-injecting and charge-transporting properties of these materials as well as to evaluate their performance in solution-processable diodes