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Publications

Sont listées ci-dessous, par année, les publications figurant dans l'archive ouverte HAL.

2025

  • Study on and off axis of levitation induced by a rotating permanent magnet
    • Schreckenberg Hugo
    • El Omari El Alaoui Zayneb
    • Gallot Guilhem
    , 2025. A slightly tilted permanent magnet rotating at high speed can induce a magnetic field capable of trapping another permanent magnet in a non-gravitational dependent levitated bound state, bypassing Earnshaw's theorem. During levitation, the floater magnet is locked in a conical orbit at the same frequency as the rotor. This rotation allows the sides of the same polarity of each magnet to face each other, which is responsible for the dynamic equilibrium of the floater magnet. Here, we theoretically explain the motion of the floater in-axis and off-axis and highlight levitation stability conditions and their dependence on the size of the floater and the speed of the rotor. We experimentally studied the levitation conditions with respect to the angular velocity of the rotor for different floater's sizes and shapes. We observed and analyzed the lower and upper limits of levitation. Finally, we explained the off-axis motion of the center of mass of the floater from its equilibrium position by an extension of the dipole moment model.
  • Consensus guidelines for cellular label-free optical metabolic imaging: ensuring accuracy and reproducibility in metabolic profiling
    • Georgakoudi Irene
    • Skala Melissa
    • Quinn Kyle
    • Stringari Chiara
    • Sorrells Janet
    • Heikal Ahmed
    • Li Lin
    • Xu He
    • You Sixian
    • Walsh Alex
    • Datta Rupsa
    • Samimi Kayvan
    • Gillette Amani
    • Eliceiri Kevin
    • Balu Mihaela
    • Boppart Stephen
    • Digman Michelle
    • Dunning Kylie
    • Evans Conor
    • Garcia Alba Alfonso
    • Houston Jessica
    • Hwang Wonsang
    • Lindley Matthew
    • Li Xingde
    • Liu Zhiyi
    • Marcu Laura
    • Murugkar Sangeeta
    • Nichols Michael
    • Niesner Raluca
    • Parekh Sapun
    • Rajaram Narasimhan
    • Ranjit Suman
    • Shen Keyue
    • Shi Lingyan
    • Torrado Belén
    • Vallmitjana Alexander
    • Wang-Evers Michael
    • Zemp Roger
    Journal of Biomedical Optics, Society of Photo-optical Instrumentation Engineers, 2025, 30 (S2), pp.S23901. Significance: Cellular metabolism plays a central role in health and disease, making its study critical for advancing diagnostics and therapies. Label-free optical metabolic imaging using endogenous fluorescence from reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and flavin adenine dinucleotide (FAD) provides nondestructive, high-resolution insights into metabolic function and heterogeneity from the sub-cellular to the tissue level. Standardized approaches are essential to ensure reproducibility and comparability across studies. Aim: We aim to establish a consensus framework for the acquisition, calibration, and reporting of microscopic imaging metabolic function assessments based on fluorescence intensity and lifetime measurements of NAD(P)H and FAD. Approach: We present best practices for calibrating, analyzing, and reporting fluorescence intensity-based optical redox ratios and fluorescence lifetime data using multiexponential fitting and phasor analysis. Guidelines for validation experiments and cross-system standardization are provided to improve accuracy and reproducibility. Results: We demonstrate the importance of calibration procedures and normalization strategies for intensity-based optical redox measurements. We highlight needed calibration, signal-to-noise ratio considerations, and the impact of distinct analytical approaches on fluorescence lifetime-based metabolic function metrics. Conclusion: We recommend a consistent, practical framework for reproducible, label-free, optical metabolic imaging, facilitating robust comparisons across studies and supporting the broader adoption of optical metabolic imaging technologies for biomedical research and clinical translation. (10.1117/1.JBO.30.S2.S23901)
    DOI : 10.1117/1.JBO.30.S2.S23901
  • ViT-based Local Volume Dwarf Galaxy Identification (VIDA) in the CSST survey
    • Qu Han
    • Yuan Zhen
    • Wei Chengliang
    • Liu Chao
    • Chang Jiang
    • Li Guoliang
    • Martin Nicolas F
    • Tsai Chaowei
    • Shao Shi
    • Luo Yu
    • Li Ran
    • Kang Xi
    • Xue Xiangxiang
    • Fan Zhou
    Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP): Policy P - Oxford Open Option A, 2025, 544, pp.1238 - 1254. <div><p>Identifying dwarf galaxies within the Local Volume is crucial for constraining the luminosity function of satellite galaxies in the nearby universe. We report the detection capabilities of dwarf galaxies within the Local Volume using the Chinese Space Station Telescope (CSST). Based on the simulated imaging data of CSST, we present VIDA, a ViT-based dwarf galaxy identification Algorithm designed for detecting Local Volume dwarf galaxies. The simulated Local Volume dwarf galaxies can be identified using a pre-processing method for 'extended source detection', followed by classification with a pretrained ViT-Base model. This pipeline achieves a true positive rate exceeding 85 per cent with a false positive rate of only 0.1 per cent. We quantify the detection completeness of Local Volume dwarf galaxies across a three-dimensional parameter space defined by absolute magnitude ( M V ), half-light radius ( R h ), and heliocentric distance, based on simulated single-exposure CSST wide-field imaging survey data. For unresolved or semiresolved dwarf galaxies, our method achieves a significantly deeper absolute magnitude detection limit compared to catalogue-based approaches, reaching M V = -7 within 10 Mpc with a surface brightness threshold μ ∼ 25 mag/arcsec 2 at 2-5 Mpc and ∼26 mag/arcsec 2 at 5-10 Mpc. While traditional matched-filter techniques based on stellar catalogues remain more effective for detecting fully resolved, extremely low surface brightness galaxies within 5 Mpc, our approach offers complementary strengths -particularly in identifying compact or more distant systems -making it a valuable tool for expanding the census of Local Volume dwarf galaxies.</p></div> (10.1093/mnras/staf1586)
    DOI : 10.1093/mnras/staf1586
  • Ultrafast photooxidation of semireduced flavin in fatty acid photodecarboxylase
    • Vos Marten
    • Balduzzi Elsa
    • Sorigué Damien
    • Aleksandrov Alexey
    Science Advances, American Association for the Advancement of Science (AAAS), 2025, 11 (38). The initial photoproduct of the natural photoenzyme fatty acid photodecarboxylase involves the flavin anion radical flavin adenine dinucleotide (FAD •– ). Using spectrally resolved ultrafast transient absorption spectroscopy, we demonstrate that FAD •– photoexcitation in the absence of substrate leads to the formation of the oxidized flavin FAD ox (the resting state in the catalytic cycle) within 100 femtoseconds. While this feature is similar to that occurring in flavoprotein oxidases, the ensuing photocycle is more complex. Upon excitation at the lowest-energy transition, the ejected electron is initially captured as a hydrated electron ( e – H ) before transferring to a secondary acceptor in 2.5 picoseconds and returning to the flavin in 37 picoseconds. This implies that e – H can be generated within a protein environment, an unprecedented finding. This assessment is supported by molecular dynamics simulations showing an expansion of the flavin-binding pocket without substrate, allowing water molecules to fill the void. Our results may pave the way to developing unconventional photocatalytic processes. (10.1126/sciadv.adz1904)
    DOI : 10.1126/sciadv.adz1904
  • Circular RNAs in Archaea
    • Becker Hubert
    • Ferreira-Cerca Sébastien
    , 2025, 1485, pp.451-464. Circular RNA molecules were first described more than 40 years ago. However, it is only recently that the broadness of their phylogenetic distribution has been revealed. Since their discoveries, numerous studies have characterized the molecular mechanisms and function underlying these peculiar molecules, mostly in diverse eukaryotic species. In contrast, studies focusing on the biology of circular RNAs in archaea remain relatively scarce. In this chapter, we provide an overview of the discovery of circular RNAs in archaea and summarize our knowledge of their biology, with an emphasis on circular pre-ribosomal RNAs and Box C/D RNAs. (10.1007/978-981-96-9428-0_26)
    DOI : 10.1007/978-981-96-9428-0_26
  • A Selective and Sensitive Method for Colistin Detection by G-Quadruplex Ligand Competition
    • Wei Shijiong
    • Qiu Dehui
    • Yan Xinrong
    • Liu Bin
    • Mergny Jean-Louis
    • Monchaud David
    • Ju Huangxian
    • Zhou Jun
    Analytical Chemistry, American Chemical Society, 2025, 97 (31), pp.16805. Colistin (COL) is a widely used antibiotic and is quite often used as a last-resort treatment option for treating multidrug-resistant Gram-negative bacterial infections. Due to its widespread use, COL accumulates in nature, which represents a novel ecological and health threat. However, there is currently no rapid and specific method available for titrating COL levels in collected samples. Herein, we report a simple chemiluminescence detection method based on the specific interaction between COL and a parallel G-quadruplex (G4). To this end, we exploit the catalytic properties of the G4/hemin DNAzyme, which is able to oxidize substrates to provide a readily monitored readout. The stronger affinity of G4 for COL versus hemin allows for the inactivation of the G4/hemin DNAzyme, which is used herein to quantify COL in solution. Through a series of optimizations, we identified the best G4 sequence (F3TC), oxidation substrate (luminol), and experimental conditions, which allow for the detection of COL over a broad concentration window, from 0.5 to 2,500 ng/mL, with a detection limit of 0.4 ng/mL and excellent selectivity against other antibiotics. Compared with existing methods, the proposed approach provides a simpler and label-free quantification of COL, which might serve as a valuable standard method for antibiotic detection, whose use was validated under real conditions herein (10.1021/acs.analchem.5c01733)
    DOI : 10.1021/acs.analchem.5c01733
  • Design, synthesis, biophysical and biological evaluation of original condensed pyrrolopyrimidine and pyrrolopyridine ligands as anti-SARS-CoV-2 agents targeting G4
    • Guillon Jean
    • Savrimoutou Solène
    • da Rocha Nicolas
    • Albenque-Rubio Sandra
    • Helynck Olivier
    • Durand Cyrielle
    • Chiaravalli Jeanne
    • Pinaud Noël
    • Ronga Luisa
    • Moreau Stéphane
    • Chirold Simon
    • Zangmo Tshering
    • Arab Melika
    • Lari Lindita
    • Mergny Jean‐louis
    • Munier-Lehmann Hélène
    • Lavigne Marc
    European Journal of Medicinal Chemistry, Elsevier, 2025, 292, pp.117655. The design and synthesis of novel bis[(substituted-aminomethyl)phenyl]phenyl pyrrolopyrimidines, pyrrolopyridines, pyrazolopyrimidines, imidazopyrimidines, and tris[(substituted-aminomethyl)phenyl]phenyl pyrrolopyrimidines are reported here. These original G-quadruplex (G4) ligands have been then subjected to a screening on SARS-CoV-2 using a competition HTRF assay by targeting the SUD-NM/TRF2 RNA G4 interaction. The more promising derivatives have been evaluated in vitro to determine their potential antiviral effect on two different cell lines infected by two SARS-CoV-2 strains. This study revealed a clear correlation between their antiviral property and their efficacy to prevent the SUD/G4 interaction. This correlation supports the choice of SUD/RNA G4 complexes formed during SARS-CoV-2 infection as new antiviral targets (10.1016/j.ejmech.2025.117655)
    DOI : 10.1016/j.ejmech.2025.117655
  • Chromium‐Doped Zinc Gallate Nanoparticles for Enhanced Enzyme‐Linked Immunosorbent Assay Sensitivity: Optimization of Synthesis and Functionalization Strategies for Ultra‐Low IgG Detection
    • Ferjaoui Zied
    • Liu Jianhua
    • Matuszewska Celina
    • Chanéac Corinne
    • Viana Bruno
    • Bouzigues Cédric
    • Scherman Daniel
    • Mignet Nathalie
    • Richard Cyrille
    Small Science, Wiley, 2025, 5 (10). The use of zinc gallate nanoparticles (ZnGa 2 O 4 :Cr 3+ ) (ZGO‐NPs) presents significant potential for improving the sensitivity in enzyme‐linked immunosorbent assays (ELISA). The persistent luminescence signal increase of these nanoparticles in the presence of hydrogen peroxide (H 2 O 2 ) offers advantages for the sensitive detection of biomolecules. Herein, different conditions of ZGO synthesis have been investigated by varying the hydrothermal reaction duration (6, 12, and 24 h) and examining its impact in the presence of H 2 O 2 . These nanoparticles have been integrated into ELISA assays, using as target antigen IgG. The lowest limit of detection (LOD) of 0.2 pg mL −1 is observed for ZGO‐NPs prepared during 12 h (ZGO2), and with a detection range from 1 to 1000 pg mL −1 . The impact of covalently functionalizing these nanoparticles has then been assessed. First using glucose oxidase (GOx) and the detection antibody (Ab D ) linked to PEGylated ZGO‐NPs, named ZGO‐GOx‐Ab D . Alternatively, only the detection antibody is linked to the PEG ZGO‐NPs, named ZGO‐Ab D . The results show a significant lowering of the LOD when using the functionalized ZGO2 NPs and also highlight the impact of the signal amplification by H 2 O 2 . Specifically, when using ZGO2‐GOx‐Ab D incubated with glucose to produce H 2 O 2 , or with ZGO2‐Ab D to which H 2 O 2 was added, the LODs are ≈98 and 56 fg mL −1 respectively, with detection ranges from 0.01 to 100 pg mL −1 . (10.1002/smsc.202500177)
    DOI : 10.1002/smsc.202500177
  • Design and biological evaluation of bioinspired Lipidic AlkynylCarbinols for anti-TB drug discovery
    • Mehalla Chérine
    • Mefoum Leïla
    • Bouvet Jon
    • Djaout Kamel
    • Joly Etienne
    • Baulard Alain
    • Maraval Valérie
    • Bernardes-Génisson Vania
    • Ballereau Stéphanie
    • Génisson Yves
    • Constant Patricia
    • Marrakchi Hedia
    , 2025.
  • Bioinspired Lipids as Leads for Developing New Anti-TB agents with a Unique Mechanism of Action
    • Mehalla Chérine
    • Bouvet Jon
    • Mefoum Leïla
    • Stella Alexandre
    • Britton Sébastien
    • Joly Etienne
    • Djaout Kamel
    • Baulard Alain
    • Daffé Mamadou
    • Maraval Valérie
    • Bernardes-Génisson Vania
    • Ballereau Stéphanie
    • Génisson Yves
    • Constant Patricia
    • Marrakchi Hedia
    • Mehalla Chérine
    • Bouvet Jon
    • Mefoum Leïla
    • Stella Alexandre
    • Britton Sébastien
    • Joly Etienne
    • Djaout Kamel
    • Baulard Alain
    • Daffé Mamadou
    • Maraval Valérie
    • Bernardes-Génisson Vania
    • Ballereau Stéphanie
    • Génisson Yves
    • Constant Patricia
    • Marrakchi Hedia
    , 2025.
  • In situ determination and matching of the refractive index of the Human cornea to improve polarization-resolved SHG imaging in depth
    • Nyembo Kasongo Poncia
    • Mahou Pierre
    • Sintès Jean-Marc
    • Latour Gaël
    • Schanne-Klein Marie-Claire
    Biomedical optics express, Optical Society of America - OSA Publishing, 2025, 16 (8), pp.3270-3282. <div><p>The human cornea is a highly organized tissue, which comprises hundreds of 1-3 µm thick stacked collagen lamellae. However, this microstructure is poorly characterized and requires further investigation. Polarization-resolved second harmonic generation (pSHG) microscopy is a powerful technique for this purpose because of its specificity for collagen and its sensitivity to its orientation. However, pSHG is prone to spatial resolution degradation with depth unless the immersion refractive index is matched to that of the sample, which is critical for corneas that are approximately 600 µm thick. In the absence of experimental data on the refractive index along the entire cornea, we propose a measurement method that applies to the entire cornea directly under the microscope objective. We then use an iodixanol solution to match the refractive index of the immersion medium to that of the cornea. Finally, we carefully characterize the pSHG orientation data obtained under these optimal conditions, and we show that they provide a better resolution along the entire thickness of the cornea and a better determination of the lamellae orientation.</p></div> (10.1364/boe.564209)
    DOI : 10.1364/boe.564209
  • Multiscale characterization of myelin distribution with polarized THG microscopy
    • Morizet Josephine
    • Olivier Nicolas
    • Aigrot Marie-Stephane
    • Mahou Pierre
    • Martin Elodie
    • Desmazieres Anne
    • Stankoff Bruno
    • Stringari Chiara
    • Beaurepaire Emmanuel
    Optica, Optical Society of America - OSA Publishing, 2025, 12 (7), pp.1122. Myelin is essential for axonal conduction and metabolic support. To better understand its role in health and disease, it is necessary to establish accurate methods for in situ mapping of myelin at scales ranging from submicrometer to centimeters. Third-harmonic generation (THG) microscopy has recently been proposed as an efficient label-free method to visualize myelin in thick and living tissue. However, the contrast mechanism of THG from myelinated axons is complex and poorly described, which has limited the development of THG as a quantitative probe of myelin distribution. Here, we present a systematic characterization and modeling of polarization-resolved THG (pTHG) signals from individual axons as a function of their diameter and myelin thickness, and we show that pTHG can be used to derive myelin scores in several biological systems. First, we confirm the sensitivity and specificity of the THG contrast for myelinated axons in mouse brain tissue and its ability to detect isolated micrometer-sized axons oriented both in-plane and out-of-plane. We then present a detailed characterization of the pTHG contrast of small and large axons in live zebrafish larvae at different developmental stages, and we demonstrate that pTHG detects early axon development in vivo. We show that classical models of coherent multiphoton microscopy fail to reproduce pTHG profiles of axons because they neglect myelin-induced optical aberrations, and we establish a numerical strategy based on finite-difference time-domain calculations that can accurately relate pTHG signal profiles to axonal diameter and myelin thickness. Finally, we illustrate the relevance of pTHG microscopy for characterizing myelin distribution at different scales in fixed mouse and human brain tissue. (10.1364/optica.562091)
    DOI : 10.1364/optica.562091
  • Editorial: The metabolic pathways of archaea
    • Myllykallio Hannu
    • Qin Wei
    • Berg Ivan
    Frontiers in Microbiology, Frontiers Media, 2025, 16. (10.3389/fmicb.2025.1648560)
    DOI : 10.3389/fmicb.2025.1648560
  • IgG detection in human serum employing non-functionalized chromium doped zinc gallate nanoparticles
    • Ferjaoui Zied
    • Zimmer Capucine
    • Matuszewska Celina
    • Chanéac Corinne
    • Viana Bruno
    • Bouzigues Cédric
    • Scherman Daniel
    • Mignet Nathalie
    • Richard Cyrille
    Next Nanotechnology, Elsevier, 2025, 8, pp.100199. Chromium-doped zinc gallate (ZnGa2O4:Cr3 +) nanoparticles (ZGO) show promising potential for antigen immunodetection using persistent luminescence, thereby reducing autofluorescence interference. Recently, we have shown that ZGO prepared by hydrothermal treatment at 120°C for 24 h can be used for in vitro biodetection in simple media such as phosphate-buffered saline. In this study, we investigated the effect of the protocol used to synthesize these ZGO nanoparticles, using a hydrothermal treatment at 220°C for different durations (6 h, 12 h, and 24 h), followed by calcination at 500°C. The nanoparticle size determined by transmission electron microscopy after grinding and centrifugation was found to be around 15 nm. The persistent luminescence signal of the ZGO nanoparticles varied with the hydrothermal synthesis conditions. Moreover, in the presence of H2O2, these nanoparticles show a signal enhancement dependent on the hydrothermal duration, with a 12 h treatment showing the highest 8-fold luminescence increase in the presence of H2O2 produced by glucose oxidase mediated glucose degradation. Based on these results, these non-functionalized nanoparticles were successfully used to develop a persistent luminescence-based sandwich immunoassay for autofluorescence-free detection of antigens in undiluted human serum samples, using rabbit IgG as a model antigen. This study highlights the promising potential for biosensing applications of persistent ZGO nanophosphors for IgG detection in a complex medium (undiluted human serum), with a linear range from 1 ng mL−1 to 104 ng mL−1 and a limit of detection of 0.01 ng mL−1. The present optimization of ZGO nanophosphor synthesis offers promising prospects for medical diagnostics due to their increased sensitivity and ability to eliminate autofluorescence interference, as well as their ease of use, since no functionalization of the ZGO NPs is required before use. (10.1016/j.nxnano.2025.100199)
    DOI : 10.1016/j.nxnano.2025.100199
  • Etude du rôle de la myosine II dans la migration cellulaire collective au cours de la gastrulation du poisson-zèbre Danio rerio
    • Elouin Amélie
    , 2025. La migration collective des cellules, où chaque cellule dépend de ses voisines pour se diriger, est un processus fondamental présent lors du développement embryonnaire, de la cicatrisation et dans certains processus métastatiques. La question de fond de cette thèse est : comment des cellules qui migrent en groupe s’orientent-elles ? Pour y répondre, cette thèse a utilisé un modèle de choix : la gastrulation de poisson-zèbre (Danio rerio). Lors de cette étape clé du développement embryonnaire, une structure dorsale appelée mésoderme axial s’étend vers le pôle animal, conduite par un groupe de cellules appelées polster. Ces cellules migrent en tête, et contribuent à l’allongement de l’embryon. Les travaux précédents ont montré que les cellules de polster sont guidées par leurs cellules suiveuses immédiates et que ce guidage repose sur de la mécanotransduction via l’α-caténine, qui adopte une conformation ouverte, suggérant que des tensions sont exercées entre les cellules du polster. Mais quelle est l’origine de ces tensions ? Cette thèse s’est concentrée sur le rôle de la myosine II non musculaire (myosine II), une protéine motrice bien connue pour générer des tensions intracellulaires. À l’aide de diverses approches techniques, telles que l’inhibition fonctionnelle de la myosine II par des formes dominantes négatives de kinases comme MLCK et ROCK, des traitements pharmacologiques et des transplantations cellulaires, cette thèse a démontré que l’inhibition de la myosine II est nécessaire à l’orientation des cellules de polster de manière non-autonome, c’est-à-dire par l’intermédiaire de ses effets sur les cellules voisines. Parallèlement, l’utilisation d’une lignée transgénique marquant la myosine II, combinée à un système d’imagerie in vitro, et à des ablations laser par microscopie à 2-photons, a révélé un rôle autonome de la myosine II dans la contractilité des protrusions, et en particulier dans le flux rétrograde d’actine. De plus, l’utilisation d’un anticorps sensible à la tension sur l’α-caténine a montré que la myosine II intervient également de manière non-autonome pour mettre sous tension les jonctions adhérentes. Ensemble, ces résultats soutiennent l’idée que les cellules suiveuses orientent les cellules meneuses en exerçant une traction via des protrusions contractiles, dépendantes de la myosine II. Ce mécanisme de guidage, fondé sur les forces exercées par les cellules arrière, permet une coordination efficace des mouvements collectifs sans avoir recours à des gradients chimiques préétablis. Ce travail positionne ainsi la myosine II comme un acteur clé dans la coordination mécanique des migrations collectives, avec des implications non seulement pour le développement embryonnaire, mais aussi pour des contextes pathologiques comme le cancer.
  • Laser driven FLASH radiobiology using a high dose and ultra high dose rate single pulse proton source
    • Flacco A
    • Bayart E.
    • Romagnani L
    • Cavallone M.
    • de Marzi L.
    • Fouillade C
    • Giaccaglia C.
    • Heinrich S.
    • Lamarre-Jouenne I.
    • Monzac J.
    • Parodi K.
    • Patriarca A
    • Rösch T
    • Schreiber J
    • Tischendorf L
    Scientific Reports, Nature Publishing Group, 2025, 15, pp.16511. Laser-driven proton sources have long been developed with an eye on their potential for medical application to radiation therapy. These sources are compact, versatile, and show peculiar characteristics such as extreme instantaneous dose rates, short duration and broad energy spectrum. Typical temporal modality of laser-driven irradiation, the so-called fast-fractionation, results from the composition of multiple, temporally separated, ultra-short dose fractions. In this paper we present the use of a high-energy laser system for delivering the target dose in a single nanosecond pulse, for ultra-fast irradiation of biological samples. A transport line composed by two permanent-magnet quadrupoles and a scattering system is used to improve the dose profile and to control the delivered dose-per-pulse. A single-shot dosimetry protocol for the broad-spectrum proton source using Monte Carlo simulations was developed. Doses as high as 20 Gy could be delivered in a single shot, lasting less than 10 ns over a 1 cm diameter biological sample, at a dose-rate exceeding 10 9 Gy s -1 . Exploratory application of extreme laser-driven irradiation conditions, falling within the FLASH irradiation protocol, are presented for irradiation in vitro and in vivo. A reduction of radiation-induced oxidative stress in vitro and radiation-induced developmental damage compatible with the onset of FLASH effect were observed in vivo, whereas anti-tumoral efficacy was confirmed by cell survival assay. (10.1038/s41598-025-01105-z)
    DOI : 10.1038/s41598-025-01105-z
  • Genome wide analyses reveal the role of mutator phenotypes in Mycobacterium tuberculosis drug resistance emergence
    • Zein-Eddine R.
    • Le Meur Adrien
    • Skouloubris S.
    • Jelsbak L.
    • Refrégier Guislaine
    • Myllykallio Hannu Hannu
    npj Antimicrobials and Resistance, Springer Nature, 2025, 3 (1), pp.35. Antimicrobial combination therapy is widely used to combat Mycobacterium tuberculosis (Mtb), yet resistance rates continue to rise. Mutator strains, with defects in DNA repair genes, drive resistance in other bacterial infections, but their role in Mtb remains unclear. Here, we study the contribution of single nucleotide polymorphisms (SNPs) in DNA Repair, Replication, and Recombination (3 R) genes to Mtb resistance. Through large-scale bioinformatics analysis of 53,589 whole-genomes, we identified 18 novel SNPs in lineages 2 and 4 linked to genotypic drug resistance in 3 R genes, covering 12.5% of clinical isolates with available genome sequences. Notably, a number of the detected SNPs were positively selected during Mtb evolution. Experimental tests showed that mutM, fpgg2, xthA, and nucS mutants had increased the mutation frequency compared to the wild type. Our findings highlight the role of 3 R gene mutations in resistance, emphasizing the need for surveillance to improve early detection and control strategies. (10.1038/s44259-025-00107-1)
    DOI : 10.1038/s44259-025-00107-1
  • Caractérisation et suivi physico-chimique du collagène lors de l’altération des parchemins par microscopie multiphoton résolue en polarisation
    • Galante Giulia
    , 2025. Le parchemin, issu de peaux animales non tannées, grattées et séchées sous tension, est composé à plus de 80% de collagène fibrillaire. Ce matériau est sensible aux changements importants de température et d’humidité. L’évaluation de l’état de dégradation du parchemin est nécessaire pour sa conservation et préalablement à sa restauration. La microscopie multiphoton, technique d’imagerie tridimensionnelle non-invasive et sans contact permet l’accès à des signaux endogènes dans ce matériau : la génération de second harmonique (SHG), spécifique du collagène fibrillaire, et la fluorescence excitée à 2 photon (2PEF), indiquant la présence de gélatine suite à la dénaturation du collagène. La microscopie SHG peut être résolues en polarisation (P-SHG) pour accéder à l’organisation des fibrilles de collagène dans le tissu. Le but de cette thèse est d’étudier si la dégradation peut être mesurée par deux paramètres multiphoton : le ratio des signaux 2PEF et SHG traduisant la proportion de collagène dégradé versus préservé et le paramètre d’anisotropie ρ, traduisant le désordre des fibrilles. Pour cela, divers types de parchemins sont soumis à divers types de vieillissements artificiels en chaleur sèche ou chaleur humide. Nous avons d’abord étudié le comportement du paramètre d’anisotropie avec l’organisation des fibrilles de collagène dans le parchemin pour déterminer les conditions pour que ce paramètre soit une mesure fiable de dégradation. Nous avons ensuite étudié la dégradation du collagène par microscopie P-SHG en fonction de la durée et de la méthode de vieillissement, en se référant à des mesures de température de dénaturation par DSC. Nous avons observé des différences entre parchemins modernes et anciens, mais aussi réussi à discriminer des dégradations en chaleur sèche et chaleur humide. Enfin des mesures sur des fibres de collagène isolées et sur deux cas d’étude sont décrits.
  • Genome-wide ribonucleotide detection in Archaea
    • Moalic Yann
    • Reveil Maurane
    • Kundnani Deepali L
    • Balachander Sathya
    • Yang Taehwan
    • Gombolay Alli
    • Ranjbarian Farahnaz
    • Brizard Raphael
    • Durand Patrick
    • Myllykallio Hannu
    • Jebbar Mohamed
    • Hofer Anders
    • Storici Francesca
    • Henneke Ghislaine
    , 2025. ABSTRACT Genome integrity is constantly challenged by the incorporation of ribonucleotides (rNMPs) during DNA synthesis. Covalently linked single and several consecutive rNMPs occur in the genome of a number of organisms. They are mainly introduced by DNA polymerases during DNA replication and repair. In general, cells evolved ribonucleases H (RNases H) specialized in the removal of rNMPs from DNA to avoid any detrimental consequences on genome stability. Here, we describe the involvement of types 1 and/or 2 RNases H in processing embedded rNMPs in the genome of two archaeal species Haloferax volcanii and Thermococcus barophilus . Using combined approaches that include alkaline DNA fragmentation, high-throughput ribose-seq DNA sequencing and nucleotide pool quantification, the distribution, identity, level and sequence context of genomic rNMPs are reported and discussed regards to the intracellular balances of dNTPs and rNTPs. Our results confirm the predominant role of type 2 RNase H in the removal of genomic rNMPs. They also reveal rNMP-base compositions, densities, locations, and variations of surrounding bases at rNMP-embedment for each mutant. The cellular roles of the different RNases H in processing rNMPs in the genome of Archaea are discussed. (10.1101/2025.03.17.643674)
    DOI : 10.1101/2025.03.17.643674
  • Two-dimensional infrared spectroscopy using a fast-scanning interferometer and chirped pulse up-conversion at 100 kHz
    • Jonušas Mindaugas
    • Bournet Quentin
    • Bonvalet Adeline
    • Natile Michele
    • Guichard Florent
    • Zaouter Yoann
    • Georges Patrick
    • Druon Frédéric
    • Hanna Marc
    • Joffre Manuel
    , 2024, pp.8020. We report on a 100-kHz two-dimensional infrared (2DIR) spectrometer in the pump-probe geometry, which we apply to the measurement of the 2DIR spectrum of carboxy-hemoglobin. The probe pulses are spectrally resolved by chirped-pulse upconversion (CPU) using a fast 2048-pixel linescan CMOS camera. The two-pulse pump sequence is generated using a conventional interferometer with a fast-scanning mechanical delay line allowing to achieve a scanning frequency of 2 Hz. The resulting modulation frequency of 3.1 kHz is large enough to shift the relevant signal away from the low-frequency noise of the laser source. The combined use of an interferometer on the pump side and of CPU on the probe side opens the way to an improved spectral resolution in both pump and probe dimensions, as compared to currently-available 100-kHz 2DIR spectrometers based on pulse shapers and Mercury-Cadmium Telluride (MCT) detector arrays. (10.1364/OE.515291)
    DOI : 10.1364/OE.515291
  • Ultra-Specific G-Quadruplex–Colistin Interaction for Efficient Transcriptome-Wide G4 Mapping
    • Wei Shijiong
    • Zhang Xiaobo
    • Feng Yilong
    • Tao Shentong
    • Qiu Dehui
    • Yan Xinrong
    • Li Guangming
    • Guittat Lionel
    • Zhang Wenli
    • Monchaud David
    • Mergny Jean-Louis
    • Ju Huangxian
    • Zhou Jun
    Journal of the American Chemical Society, American Chemical Society, 2025, 147, pp.9962 - 9971. G-quadruplexes (G4s) are challenging targets for chemical biology interventions, notably because of their dynamic topological polymorphism. We found that the antibiotic smallmolecule colistin (COL) interacts specifically with a single subtype of G4 structures, the so-called parallel G4s. This interaction triggers the aggregation of the G4/COL complexes in a structure-specific manner, which can thus be separated from the bulk solution by centrifugation. This unprecedented mode of affinity-precipitation was exploited here to design the COL-induced RNA G4 precipitation and sequencing (CoRP-seq) protocol, which allows for the assessment of the prevalence of RNA G4s in the transcriptome of human cells in a straightforward manner. CoRP-seq shines by its ultraspecificity, simplicity, and practical convenience, which thus advances G4 mapping further and addresses unmet needs in the field of G4omics. (10.1021/jacs.5c01172)
    DOI : 10.1021/jacs.5c01172
  • Increasing the Accuracy and Robustness of the CHARMM General Force Field with an Expanded Training Set
    • Croitoru Anastasia
    • Kumar Anmol
    • Lambry Jean-Christophe
    • Lee Jihyeon
    • Sharif Suliman
    • Yu Wenbo
    • Mackerell Alexander
    • Aleksandrov Alexey
    Journal of Chemical Theory and Computation, American Chemical Society, 2025, 21 (6), pp.3044-3065. <div><p>Small molecule empirical force fields (FFs), including the CHARMM General Force Field (CGenFF), are designed to have wide coverage of organic molecules and to rapidly assign parameters to molecules not explicitly included in the FF. Assignment of parameters to new molecules in CGenFF is based on a trained bond-angledihedral charge increment linear interpolation scheme for the partial atomic charges along with bonded parameters assigned based on analogy using a rules-based penalty score scheme associated with atom types and chemical connectivity. Accordingly, the accuracy of CGenFF is related to the extent of the training set of available parameters. In the present study that training set is extended by 1,390 molecules selected to represent connectivities new to CGenFF training compounds. Quantum mechanical (QM) data for optimized geometries, bond, valence angle, and dihedral angle potential energy scans, interactions with water, molecular dipole moments, and electrostatic potentials were used as target data. The resultant bonded parameters and partial atomic charges were used to train a new version of the CGenFF program, v5.0, which was used to generate parameters for a validation set of molecules, including drug-like molecules approved by the FDA, which were then benchmarked against both experimental and QM data. CGenFF v5.0 shows overall improvements with respect to QM intramolecular geometries, vibrations, dihedral potential energy scans, dipole moments and interactions with water. Tests of pure solvent properties of 216 molecules show small improvements versus the previous release of CGenFF v2.5.1 reflecting the high quality of the Lennard-Jones parameters that were explicitly optimized during the initial optimization of both the CGenFF and the CHARMM36 force field. CGenFF v5.0 represents an improvement that is anticipated to more accurately model intramolecular geometries and strain energies as well as non-covalent interactions of drug-like and other organic molecules.</p></div> (10.1021/acs.jctc.5c00046)
    DOI : 10.1021/acs.jctc.5c00046
  • Nance-Horan-Syndrome-like 1b controls mesodermal cell migration by regulating protrusion and actin dynamics during zebrafish gastrulation.
    • Escot Sophie
    • Hassanein Yara
    • Elouin Amélie
    • Torres-Paz Jorge
    • Mellottee Lucille
    • Ignace Amandine
    • David Nicolas B
    Communications Biology, Nature Publishing Group, 2025, 8 (1), pp.328. Cell migrations are crucial for embryonic development, wound healing, the immune response, as well as for cancer progression. In most cells, the RAC1/Arp2/3/WAVE signalling pathway induces branched actin polymerisation, which protrudes the membrane and allows migration. Fine-tuning the activity of the RAC1/Arp2/3/WAVE complex modulates protrusion lifetime and migration persistence. Recently, NHSL1, a novel interactor in this complex has been identified as a negative regulator of cell migration in vitro. We here analysed its function in vivo, during zebrafish gastrulation, as nhsl1b is specifically expressed in migrating mesodermal cells. Loss and gain of function experiments revealed that nhsl1b is required for the proper migration of the mesoderm, controlling cell speed and migration persistence. Consistent with a role in regulating actin dynamics, Nhsl1b localises to the tip of actin-rich protrusions. However, in contrast to the in vitro situation, it appears to be a positive regulator of migration, with its loss of function reducing the length and lifetime of protrusions, whereas overexpression has the opposite effect. These results reveal that the effects of actin modulators depend on the cellular context, and highlight the importance of analysing their function in physiological contexts. (10.1101/2023.01.28.526006)
    DOI : 10.1101/2023.01.28.526006
  • Fast and Efficient Red‐absorbing Photoswitching Proteins Based on Flavin–Ligand Charge Transfer Complexes
    • Zhuang Bo
    • Liebl Ursula
    • Vos Marten
    • Sliwa Michel
    ChemPhotoChem, Wiley, 2025. Recently a novel class of reversible protein photoswitches has been discovered that is based on a charge transfer (CT) complex composed of the flavin cofactor and a substrate‐analogue inhibitor molecule in the family of sarcosine oxidase flavoproteins. Here, excitation of the CT band results in barrierless dissociation of the CT complex on the femtosecond timescale followed by its thermally activated reformation, on the timescale of a few nanoseconds at ambient temperature. The photoreaction is thought to involve a well‐defined isomerization of the inhibitor without its dissociation from the protein. This reaction occurs with an unusually high quantum yield (~80%), is initiated by absorption in the red part of the visible absorption spectrum, and leads to a photoproduct absorbing in the blue spectral region (negative photochromism). Therefore, this class of photoswitches can be considered a promising template for developing a new class of fast negative photochromic compounds for Life Science applications provided the lifetime of the photoproducts (‘light state’) can be prolonged. Potential future developments will be discussed. (10.1002/cptc.202500012)
    DOI : 10.1002/cptc.202500012
  • Understanding the key challenges in tuberculosis drug discovery: what does the future hold?
    • Zein-Eddine Rima
    • Ramuz Masoud
    • Refrégier Guislaine
    • Lutzeyer Johannes F
    • Aleksandrov Alexey
    • Myllykallio Hannu
    Expert Opinion on Drug Discovery, Informa Healthcare, 2025, 20 (9), pp.1115-1130. Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health concern. It spreads through airborne droplets and has a high mortality rate, particularly without treatment. Drug resistance is rising, with treatments against multidrug-resistant TB (MDR-TB) showing poor treatment success rates. The thick, lipid-rich wall of Mtb and its slow growth reduce antibiotic effectiveness, requiring long treatment courses of 4-6 months. Current therapies often fail against drugresistant strains, highlighting the urgent need for new, short-course treatment, affordable, and combination-friendly drugs. Areas covered: Within this perspective, the authors review and comment on the following topics regarding Mtb resistance emergence and treatment strategies: i) Existing treatment ii) Resistance evolution in Mtb; iii) Key challenges in drug discovery targeting Mtb; iv) emerging strategies and recent advances in Mtb drug discovery, and v) Next-generation approaches. Literature was identified through a search of PubMed, google scholar, and web of science, from January 2010 to March 2025. Expert opinion: AI is accelerating the discovery of bioavailable and safe preclinical drug candidates for TB, though data limitations and biological complexity remain challenging. Future progress requires multi-modal models, open-access datasets, and interdisciplinary collaboration. (10.1080/17460441.2025.2531229)
    DOI : 10.1080/17460441.2025.2531229