Publications

2026

• Characterization of Thermal Recovery Activation in Fast Photochromic Flavoprotein Charge-Transfer Complexes.
  
  • Mounya Gharbi Amira
  • Antonucci Laura
  • Bonvalet Adeline
  • Solinas Xavier
  • Lambry Jean-Christophe
  • Joffre Manuel
  • Monari Antonio
  • Zhuang Bo
  • Aleksandrov Alexey
  • H. Vos Marten
  • Sliwa Michel
  , 2026. A promising fast, negative, red-absorbing photochromic system based on an intra-protein intermolecular charge transfer (CT) complex between a flavin cofactor and a substrate-analogue inhibitor MXA (methylthioacetate or methylselenoacetate; X=S, Se) within monomeric sarcosine oxidase (MSOX) displays MXA-independent, barrierless, high-yield femtosecond photo-activation associated with CT-interaction disruption coupled to MXA isomerization. Assessing the origin of the known MXA-dependence of the nanosecond thermal recovery requires a very precise determination of activation energy barriers. Here, a newly developed visible pump-probe setup employing two Ti:sapphire femtosecond lasers spanning the picosecond to microsecond timescale was used. Whereas the room temperature thermal recovery time for MSeA is more than double for MTA (7.5 ns vs 2.9 ns), the dissociation rate, the quantum yield (0.85), and recombination activation enthalpy (21 kJ⋅mol−1) are MXA-independent. Quantum mechanical calculations rationalize this value as the intrinsic enthalpic barrier for MXA isomerization. The observed variation in thermal recovery is due to the activation entropy, which is negative (on the order of -15 J⋅mol−1⋅K−1) and MXA-dependent. This dependence is attributed to differently ordered transition state. Implications for the design and application of this class of photochromic systems are discussed.
• The Nance-Horan syndrome protein NHS regulates cell migration persistence by organizing WAVE and N-WASP nucleation-promoting factor complexes
  
  • Tsydenzhapova Ekaterina
  • Fokin Artem
  • David Nicolas
  • Rocques Nathalie
  • Polesskaya Anna
  • Haddad Iman
  • Vinh Joëlle
  • Guérois Raphaël
  • Gautreau Alexis
  Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2026, pp.113443. The function of the NHS gene that is responsible for the Nance-Horan Syndrome has remained elusive at the cellular level. Using CRISPR/Cas9, we inactivated the NHS gene in MCF10A cells and characterized the isoforms expressed in these cells. NHS KO cells displayed reduced migration persistence, a phenotype that was fully rescued by the long isoform 1 (i1) that contains a N-terminal WAVE Homology Domain (WHD), but only partially rescued by the short isoform 2 (i2), which does not. Patient mutations resulting in NHS proteins truncated at their C-terminus also reduced the ability of NHS i1 to rescue migration persistence. Using Tandem Affinity Purification (TAP) of NHS i1 and mass spectrometry, we identified as major NHS partners, all subunits of the WAVE Regulatory Complex (WRC) except WAVE subunits themselves, indicating that the WHD of NHS assembles a WAVE Shell Complex (WSC). The Arp2/3 complex and the Nucleation Promoting Factor (NPF) WAVE that activates it are critical for migration persistence. To investigate the role of the NHS-containing WSC, we performed TAP of the ABI1 subunit in parental and NHS KO cells and identified differential partners associated with ABI1 only in parental cells, but not in NHS KO cells. The most abundant of these were the WIPF2/N-WASP complex, which together with the kinase ABL2, was also critical for migration persistence. These results suggest that NHS controls cell migration by remodeling NPF complexes and their higher order assembly. (10.1016/j.jbc.2026.113443)
  DOI : 10.1016/j.jbc.2026.113443
• Advanced optical polarimetric microscopy reveals spatio-temporal dynamics of cervix remodeling during gestation
  
  • Abdelsayed V.
  • Pei J.
  • Ajmal A.
  • Giammattei D.
  • Mahou P.
  • Latour G.
  • Ramella-Roman J C
  • Schanne-Klein M.-C.
  APL Photonics, AIP Publishing LLC, 2026, 11 (8). Polarimetric microscopy is a powerful tool for assessing fiber orientation and reorganization during various biological processes. Collagen fiber remodeling in the uterine cervix is a vital process in pregnancy that enables timely fetal delivery, yet the spatio-temporal details of this process remain poorly understood. In this study, we measured collagen fiber reorganization at different stages of murine gestation and at various cervical depths. We employed two polarization-sensitive techniques, polarization-resolved Second Harmonic Generation (p-SHG) microscopy to specifically detect fibrillar collagen and analyze its orientation with sub-micrometer resolution, and Mueller matrix microscopy to achieve a large field of view but low-resolution imaging of the uterine cervix. Whole cervical transverse sections were imaged, and an analysis pipeline was implemented to quantify collagen distribution. p-SHG results show, for the first time, that collagen content is higher in the lower cervix and increases significantly throughout gestation. We also observed a notable increase in pore size and density during gestation, especially in the upper cervix. Most importantly, by analyzing polarimetric orientation maps, we found that collagen fiber disorganization occurs progressively, starting from the lower cervix at gestation day 12 and extending throughout the entire cervix by day 15. In addition, we demonstrated that the temporal dynamics of disorganization could also be tracked using Mueller matrix imaging, a method suitable for clinical deployment that has substantially lower spatial sensitivity. These findings highlight the potential of advanced polarimetric imaging to enhance our understanding of fibrous tissue remodeling and open new avenues for diagnosing gestation-related issues, such as premature birth. (10.1063/5.0335573)
  DOI : 10.1063/5.0335573
• Role of Neural Crest Cells in Establishing Corneal Transparency During Embryonic Development in Mice
  
  • Ghoubay Djida
  • Vidal Cécile
  • Rappeneau Quentin
  • Emini Jasmina
  • Gitton Yorick
  • Fouquet Stéphane
  • Schanne-Klein Marie-Claire
  • Plamann Karsten
  • Latour Gaël
  • Borderie Vincent
  Journal of Cellular Physiology, Wiley, 2026, 241 (8). ABSTRACT Corneal transparency emerges during embryogenesis through the coordinated organization of neural crest–derived cells (NCCs) and extracellular matrix (ECM), yet the temporal and structural basis of this process remains incompletely defined. Here, we provide a multimodal, spatiotemporal analysis of mouse corneal development from embryonic Day 10 (E10) to birth (P0), combining whole‐mount and sectioned immunofluorescence, tissue clearing with three‐dimensional (3D) imaging, second harmonic generation (SHG) microscopy, full‐field optical coherence microscopy (FFOCM), and transmission electron microscopy (TEM). We show that early periocular mesenchyme is characterized by broad expression of neural crest‐associated markers (Sox9, HNK1), followed by progressive spatial restriction and downregulation as cells populate the corneal stroma. Sox10‐positive cells remain primarily associated with developing nerves and are largely excluded from the stromal compartment. Concomitantly, stromal cells undergo marked morphological transitions, from rounded to progressively flattened and elongated phenotypes, accompanying stromal expansion. Collagen deposition is first detected in the subepithelial region around E12 and increases thereafter, with SHG and TEM analyses revealing progressive organization and compaction of fibrillar networks. Quantitative ultrastructural analysis indicates dynamic changes in interfibrillar spacing during development, consistent with ongoing ECM remodeling. The emergence of a posterior‐to‐anterior gradient in cell morphology and matrix organization suggests a spatially coordinated maturation process across the stroma. Together, these findings provide an integrated structural framework linking NCCs dynamics, stromal cell differentiation, and ECM organization during murine corneal development. This work establishes a quantitative and multiscale atlas of corneal morphogenesis that informs how tissue architecture compatible with transparency is progressively established in vivo. (10.1002/jcp.70215)
  DOI : 10.1002/jcp.70215
• Fgfr3–Wnt signaling crosstalk is involved in maintaining cranial suture integrity
  
  • Pereur Rachel
  • Marc Yvan
  • Lim Yuliya
  • Schmitt Alain
  • Malbouyres Marilyne
  • Chessel Anatole
  • Ruggiero Florence
  • Schanne-Klein Marie-Claire
  • Legeai-Mallet Laurence
  • Dambroise Emilie
  Bone Research, Springer Nature, 2026, 14 (1), pp.76. Abstract Cranial suture formation is a dynamic process that requires precise cellular and molecular coordination to regulate bone growth and maintain suture homeostasis. The Fibroblast Growth Factor Receptor 3 (FGFR3) signaling pathway is among the major pathways disrupted in craniosynostosis; however, its precise role during cranial suture formation is still unknown. Using a relevant fgfr3 LoF zebrafish model exhibiting abnormal suture morphology, we demonstrated for the first time that Fgfr3 plays a pleiotropic role in both the formation and maintenance of cranial sutures. Transmission electron microscopy and second harmonic generation imaging revealed that Fgfr3 is essential for the proper organization of the collagen network within the suture. Using specific transgenic reporter lines, we showed that Fgfr3 is crucial for regulating osteogenesis in this region. Specifically, Fgfr3 limits the number of osteoprogenitors at the osteogenic front and promotes osteoblast maturation at the suture edge. RNAscope analyses further revealed that loss of Fgfr3 led to significant upregulation of fgf18 expression. Finally, our findings show that loss of Fgfr3 results in the activation of the canonical Wnt pathway, and possibly the BMP pathway, within cranial sutures. Pharmacological inhibition of canonical Wnt signaling during suture development using the β-catenin inhibitor XAV939 restored fgf18 expression, partially normalized levels of the BMP antagonist grem1 , reduced SMAD1/5 phosphorylation, and produced a significant improvement in cranial suture morphology. In conclusion, these findings position Fgfr3 as a central regulator of cranial suture formation and homeostasis, acting through intricate cross-talk between the FGF, canonical Wnt, and possibly BMP signaling pathways. These data offer new insights into the biology of cranial suture and FGFR3-related craniosynostoses. (10.1038/s41413-026-00558-w)
  DOI : 10.1038/s41413-026-00558-w
• Collagen-producing eye cell atlas reveals distinct fibroblast fates in early injury vs. fibrotic subretinal disease
  
  • Ozaki Ema
  • Aktas Said
  • Mulfaul Kelly
  • Brennan Kiva
  • Roubeix Christo
  • Palko Sarah
  • Robb Katie
  • Ou Tai-Hsien
  • Schanne-Klein Marie-Claire
  • Toidze Anna
  • Watson Avril
  • Cahill Mark
  • Westenskow Peter
  • Feenstra Derrick
  • Doyle Sarah L
  • Ferrara Napoleone
  Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2026, 123 (26). Fibrosis is the end-stage of a maladaptive process that occurs when the body’s normal wound-healing strategy becomes dysregulated. Subretinal fibrosis is the end stage of neovascular age-related macular degeneration (nAMD), the most common cause of central vision loss in people over the age of 50. The cellular sources of excess extracellular matrix (ECM) contributing to subretinal fibrosis are unknown, as is the heterogeneity of cells involved in the fibrotic process. Here we identify cells contributing to subretinal fibrosis by using Col1a1 -YFP reporter mice to noninvasively image collagen production in real-time in vivo in two disease models, 1) a resolving retinal injury model and 2) a fibrotic model of subretinal disease. We create a collagen-producing eye cell atlas for subretinal injury and demonstrate subretinal fibroblast heterogeneity in healthy, resolving, and fibrotic tissue. We identify distinct molecular characteristics of general repair/resolving fibroblast populations versus pathogenic pro-fibrotic collagen-producing fibroblasts. Integration of this collagen-producing eye cell atlas with a published collagen-producing lung cell atlas shows conserved pro-fibrotic fibroblasts in both organs, yet also uncovers tissue-specific fibroblast populations unique to subretinal fibrosis. A Fap + Fgl2 + fibroblast population significantly expands in subretinal fibrosis that expresses the highest levels of collagens and distinctively expresses ECM components Periostin , Col15a1 and Col6a5 . Immunolabeling of mouse and human-donor eye tissue support the fibroblastic expression and perivascular location of periostin as clearly distinguishing between bona fide fibrosis and early disease in nAMD. Our collagen-producing eye cell atlas is a valuable resource for studying distinct fibroblast subsets in homeostasis, early injury, and fibrosis. (10.1073/pnas.2519056123)
  DOI : 10.1073/pnas.2519056123
• 2,4-Bis{4-[(dialkylaminoalkyl)aminomethyl]phenyl}-7-substituted-7H-pyrrolo[2,3-d]pyrimidine Derivatives: Synthesis and Biological Evaluation as Novel Antiprotozoal Agents by Potentially Targeting G-Quadruplex
  
  • Guillon Jean
  • Savrimoutou Solène
  • Agnamey Patrice
  • Milano Vittoria
  • Damiani Céline
  • Ronga Luisa
  • Hanot Marie
  • Albenque Sandra
  • Zangmo Tshering
  • Monic Sarah
  • Pinaud Noël
  • Lari Lindita
  • Marchivie Mathieu
  • Moreau Stéphane
  • Mergny Jean-Louis
  • Moukha Serge
  • Dozolme Pascale
  • Boudot Clotilde
  • Courtioux Bertrand
  • Cohen Anita
  • Sonnet Pascal
  Scientia Pharmaceutica, MDPI, 2026, 94 (2), pp.48. <p>A series of substituted pyrrolo[2,3-d]pyrimidines was designed, synthesized, and evaluated in vitro against two protozoan parasites: Plasmodium falciparum and Trypanosoma brucei brucei. Pharmacological studies revealed antiprotozoal activity with IC50 values in the submicromolar to micromolar range. Additionally, the in vitro cytotoxicity of these new compounds was assessed using human HepG2 cells. Among them, the pyrrolopyrimidine derivative 1d emerged as the most potent antimalarial compound, exhibiting a selectivity index (SI) of 600.81 against the P. falciparum chloroquine-resistant W2 strain. For the chloroquine-sensitive 3D7 strain, the most notable selectivity index (SI) was observed for pyrrolo[2,3-d]pyrimidine 1c, with a value of approximately 123. Furthermore, compound 1b demonstrated the most interesting activity against Trypanosoma brucei brucei, with an SI of 39.52, marking it as a promising trypanocidal agent. FRET melting assays confirmed that these nitrogen-containing heterocyclic compounds bind to telomeric G-quadruplexes in P. falciparum and Trypanosoma. However, no clear correlation was found between G-quadruplex binding and antiparasitic activity or selectivity, suggesting that G-quadruplex targeting is unlikely to be the main mechanism underlying cytotoxicity.</p> (10.3390/scipharm94020048)
  DOI : 10.3390/scipharm94020048
• Two-photon light-sheet live imaging at kilohertz frame rate using birefringence-based pulse splitting
  
  • Zhu Lei
  • Gottlieb Dale
  • Maioli Vincent
  • Hubert Antoine
  • Druon Frédéric
  • Mahou Pierre
  • Beaurepaire Emmanuel
  • Supatto Willy
  Optica, Optical Society of America - OSA Publishing, 2026, 13 (6), pp.1086. Multiphoton microscopy is widely used for imaging live and intact tissues. Its imaging speed, however, remains constrained by fluorophore emission rates and photodamage thresholds. In order to increase the effective pixel rate of a two-photon microscope beyond a few megahertz (MHz), multi-point acquisition schemes have been proposed. Two-photon (2P) light-sheet microscopy emerges as a particularly effective approach for high-speed multiphoton imaging of live specimens, as it enables parallelized excitation while minimizing the required increase in laser power. However, optimizing the signal-to-photodamage ratio in 2P light-sheet microscopy necessitates precise control over illumination parameters, including both wavelength and laser pulse repetition rate. Since conventional femtosecond laser sources generally do not allow independent modulation of these parameters, the development of low-cost, efficient, and robust strategies to modulate the temporal excitation profile is essential to fully exploit the advantages of 2P light-sheet microscopy. Here, we introduce a compact pulse-splitting scheme that meets these criteria. Our approach uses cascaded birefringent crystals to convert each excitation laser pulse into an adjustable sequence of collinear sub-pulses. We demonstrate its effectiveness in optimizing 2P light-sheet imaging of live zebrafish embryos. We analyze the impact of pulse splitting on photobleaching, nonlinear photodamage, and imaging performance. Additionally, we demonstrate high-speed 2P imaging of the beating heart and brain calcium dynamics using red fluorophores in live embryos. We achieve a kilohertz imaging frame rate, reaching more than 150 MHz pixel rates with fluorescent signal levels above 10photons⋅pixel −1 using a laser mean power and a peak intensity in the range of 100 mW and 0.1TW⋅cm −2 at the sample, respectively. This compact and adjustable pulse-splitting scheme allows full advantage to be taken of light-sheet illumination for fast in vivo 2P imaging. More generally, it facilitates the optimization of illumination parameters in multiphoton microscopy. (10.1364/OPTICA.588084)
  DOI : 10.1364/OPTICA.588084
• How nonlinear photodamage arises in multiphoton light-sheet microscopy: insights from numerical simulation and live imaging
  
  • Bing Xue
  • Zhu Lei
  • Mahou Pierre
  • Olivier Nicolas
  • Beaurepaire Emmanuel
  • Supatto Willy
  , 2026, 14094, pp.40. High-speed multiphoton microscopy enables the imaging of fast biological processes in vivo. In the case of multiphoton light-sheet microscopy, parallelized illumination with a single weakly focused beam enables fast imaging with reduced laser peak intensity, low mean power, and long pixel dwell times. However, we found that the nonlinear photodamage threshold in multiphoton light-sheet microscopy is lower than expected compared to point-scanning systems that use tightly focused beams. To explain this counter-intuitive result, we hypothesized that cells can act as micro-lenses that locally focus the beam, a phenomenon related to photonic jets from dielectric microspheres. When illuminating biological tissue with a weakly focused beam, the peak intensity can increase far beyond the expected level. We investigated this effect by using live imaging of zebrafish embryos and numerical simulations. Our findings suggest that cellular lensing can induce unexpected nonlinear photodamage when weakly focused beams are used with multiphoton microscopy. (10.1117/12.3097950)
  DOI : 10.1117/12.3097950
• Structural basis of the two-photon photoactivation mechanism of orange carotenoid protein
  
  • Munro Rory
  • Andreeva Elena
  • Hartmann Elisabeth
  • Goor Quentin
  • El Zein Hosni
  • Nizinski Stanislaw
  • Wilson Adjélé
  • de Zitter Elke
  • Effantin Gregory
  • Coquelle Nicolas
  • Zala Ninon
  • Appleby Martin
  • Bar-Zvi Shira
  • Bacellar Camila
  • Beale Emma
  • Bignon Emmanuelle
  • Brutscher Bernhard
  • Byrdin Martin
  • Cirelli Claudio
  • Dworkowski Florian
  • Foucar Lutz
  • Gotthard Guillaume
  • Gorel Alexander
  • Grünbein Marie Luise
  • Hilpert Mario
  • Johnson Philip J.M.
  • Kloos Marco
  • Knopp Gregor
  • Nass Karol
  • Kovacs Gabriela Nass
  • Ozerov Dmitry
  • Milne Christopher
  • Burdziński Gotard
  • Chipot Christophe
  • Karami Yasaman
  • Dehez François
  • Weik Martin
  • Doak R. Bruce
  • Shoeman Robert
  • Schirò Giorgio
  • Sliwa Michel
  • Kirilovsky Diana
  • Schlichting Ilme
  • Colletier Jacques-Philippe
  , 2026. Abstract Cyanobacteria have produced Earth’s oxygen for 2.4 billion years by adapting to fluctuating irradiance. This adaptation relies on orange carotenoid protein (OCP), which mediates light-intensity– dependent photoprotective energy dissipation using a unique two-photon absorption mechanism. Photon absorption by ground-state OCP (OCP O ) generates a metastable intermediate (OCP 1hν ) that either relaxes thermally or, upon absorption of a second photon within ∼1 s, converts to the active photoprotective state (OCP R ). By integrating static and time-resolved crystallography, cryo-EM, computation, spectroscopy and biochemistry, we assign the structure of OCP 1hν , establish its functional relevance and capture structural snapshots along the OCP O →OCP 1hν and OCP 1hν →OCP R photochemical pathways. We elucidate the molecular mechanism of OCP, which serves as a unique biological circuit breaker protecting the photosynthetic machinery from high light flux. One Sentence Summary Snapshots of a biological light intensity sensor reveal intermediates in consecutive two photon driven reactions. (10.64898/2026.04.21.718960)
  DOI : 10.64898/2026.04.21.718960
• Effect of tissue thickness on epidetection of backscattered third harmonic generation signals in mouse brain tissue
  
  • Prudhomme Solène
  • Blanc Hugo
  • Le Yannou Chloé
  • Le Dréau Gwenvaël
  • Livet Jean
  • Stankoff Bruno
  • Desmazières Anne
  • Stringari Chiara
  • Mahou Pierre
  • Beaurepaire Emmanuel
  , 2026, 14095, pp.16. Third-harmonic generation (THG) microscopy can be used to highlight myelin-rich regions in fixed mouse brain tissue in a label-free manner. Combining THG contrast with automated serial microscopy is an attractive strategy for large-scale structural imaging of brain tissue. However, THG is a forward-directed coherent process most efficiently detected in transmission geometry, whereas serial imaging requires epi-detection, raising the question of whether THG contrast can be reliably detected in this configuration. Here, we investigate the feasibility of epi-detected THG imaging in the context of serial multiphoton microscopy of mouse brain tissue. By analyzing epi-THG signal levels from samples of different thicknesses and the consequences of inserting a reflector beneath the sample, we confirm that epidetected THG is the result of backscattering towards the objective of forwardemitted coherent harmonic light by tissue located after the focal plane. We show that efficient epi-THG imaging is possible when the tissue thickness after the imaging plane reaches approximately 200 µm, ensuring efficient backscattering of forward-emitted THG photons toward the objective. This condition is typically met in serial multiphoton acquisitions. We illustrate that epidetected THG in this geometry is an effective contrast modality for large-scale mapping of myelin distribution in mouse brain tissue. (10.1117/12.3098299)
  DOI : 10.1117/12.3098299
• Photo-switching Quantum Yield of Reversibly Switchable Fluorescent Proteins depends on Wavelength and Temperature
  
  • Fu Xingjie
  • Uriarte Lucas Martinez
  • Mittelheisser Cédric
  • Devos O.
  • Laurent Guillaume
  • Sliwa Michel
  , 2026. Reversibly switchable fluorescent proteins (RSFPs) enable super-resolved bio-imaging by leveraging the photo-switching between their On-and Off-forms. The photoswitching quantum yield (φ) is the key parameter that characterizes the switching efficiency of RSFPs, yet reported values vary widely. Although, the quantum yield of molecular organic photo-switches is known to depend on both temperature and excitation wavelength, these dependencies have often been overlooked in studies of RSFPs. To study the modulation of φ, the wild type rsEGFP2 as well as two of its variants were selected. The wild type rsEGFP2 is a representative RSFP that has been reported multiple times in the literature of nanoscopy, and exibits up to four-fold variation in the reported values of φ. We measured the dependence of values on temperature (from 10 to 35°C) and on irradiation wavelength (408 and 480 nm) across variants, revealing evidence of distinct cis-trans excited state isomerization pathways. These results suggest that temperature-and wavelength-dependence are general properties of RSFPs and may offer new insights into their photo-switching mechanisms, enabling the development of novel temperature-and color-modulated imaging strategies.
• Self-Supervised Learning for Single Cell Large Scale Neuroimaging
  
  • Giraud M.
  • Blanc H.
  • Mahou P.
  • Kaddour G.
  • Caporal C.
  • Dréau G. Le
  • Livet J.
  • Beaurepaire E.
  • Chessel A.
  , 2026. We conduct a systematic evaluation of self-supervised learning (SSL) approaches to address label scarcity in single neuron analysis from large scale microscopy imaging. Our comprehensive study reveals that DINOv2 significantly outperforms both supervised ResNet and other SSL methods in low-data regimes, achieving 82% accuracy with only 32 training images compared to 65% for ResNet-50. Crucially, we identify partial fine-tuning as the optimal strategy. For segmentation, we demonstrate that with only 4 training images, multiple approaches achieve competitive performance: U-Net (0.677 IoU), pseudo-label refinement (0.639 IoU), and frozen backbone with lightweight decoder (0.570 IoU). Notably, standard DINOv3 features provide excellent out-of-thebox performance, establishing minimal supervision as sufficient for high-quality neuron segmentation. Code and data are made readily available, providing a new benchmark dataset for those methods. (10.1109/isbi61048.2026.11515940)
  DOI : 10.1109/isbi61048.2026.11515940
• Non-invasive quantitative investigation of varnish stratigraphy in historical artifacts using line-field confocal OCT
  
  • Galante Giulia
  • Vilbert Maëlle
  • Desvois Laetitia
  • Le Corre Diane
  • Archambault Lou
  • Robinet Laurianne
  • Saumagne Nicolas
  • Schanne-Klein Marie-Claire
  • Latour Gaël
  npj Heritage Science, Springer Nature, 2026, 14, pp.193. Optical Coherence Tomography (OCT) is a powerful non-destructive and non-invasive 3D imaging technique for cultural heritage artifacts. It provides morphological information, such as in-depth layer mapping and particle presence. Line-field Confocal OCT (LC-OCT) combines OCT with confocal microscopy to achieve improved spatial resolution (~1 µm) and fast imaging, while maintaining a similar penetration depth to standard OCT. LC-OCT combined with automated data processing is used to map varnish layers and characterize their removal during conservation treatments. It is applied to a 17th century painting, to document previous restorations, and to a 17th century violin by the renowned Italian violin-maker Nicolo Amati, to assess the presence of its unique original varnish and optimize the conservation process for the selective removal of the overlying non-original varnish. This demonstrates the effectiveness of LC-OCT as a new technique for the quantitative characterization and conservation guidance of varnished cultural heritage artifacts. (10.1038/s40494-026-02460-4)
  DOI : 10.1038/s40494-026-02460-4
• Revealing the whole photomechanism from femtoseconds to sub-milliseconds via multiple-probing transient absorption spectroscopy
  
  • Balanikas Evangelos
  • Solinas Xavier
  • Antonucci Laura
  • Bonvalet A.
  • Prouteau Matthieu
  • Sanchez Iris
  • Colasson Benoit
  • Abe Jiro
  • Changenet-Barret, Pascale
  • Sliwa Michel
  • Joffre Manuel
  , 2026. Deciphering complex photochemical mechanisms requires multiple-timescale methods capable of resolving dynamics from femtoseconds to milliseconds. We demonstrate that Arbitrary Detuning Asynchronous Optical Sampling (ADASOPS) can be combined with the technique known as multiple probing. By integrating a 1-kHz Titanium:Sapphire and a 125-kHz Ytterbium femtosecond amplifier, we control the time delay on a shot-by-shot basis and perform fast scanning over 8 decades with 500-fs resolution. We validate this method by resolving intersystem crossing in copper phenanthroline complexes, capturing dynamics from 700 fs to 40 ns, and reveal photomechanisms in a fast photochromic molecule, including picosecond bond dissociation and microsecond thermal recovery. Requiring no laser modifications, our approach should accelerate the widespread adoption of multiple-timescale multiple-probing spectroscopy.
• Multimodal AFM-IR nanospectroscopy and non-linear optical microscopy for detecting collagen matrix alterations
  
  • Mathurin Jérémie
  • Latour Gaël
  • Mosser Gervaise
  • Dazzi Alexandre
  • Schanne-Klein Marie-Claire
  • Deniset-Besseau Ariane
  Analyst, Royal Society of Chemistry, 2026, 151, pp.1881 - 1888. Correlative photothermal infrared nanospectroscopy (AFM-IR) and non linear optical microscopy analyses reveal that the emergence of a 1730 cm -1 IR band in collagen arises from local, thermally induced esterification. This band serves as a marker of irreversible molecular alteration, associated with structural destabilisation and chemical changes within the collagen matrix. (10.1039/d5an01298h)
  DOI : 10.1039/d5an01298h
• Structural and chemical characterization of slough in chronic wounds
  
  • Nurlybayeva Assem
  • Tang Ellie
  • Moguelet Philippe
  • Schanne-Klein Marie-Claire
  • Deniset-Besseau Ariane
  • Colboc Hester
  Vascular Diseases, Elsevier, 2026, 51 (1), pp.29. Correlative photothermal IR nanospectroscopy (AFM-IR) and non-linear optical microscopy analyses reveal that the emergence of a 1730 cm −1 band in collagen arises from local, thermally induced chemical alteration. (10.1016/j.vasdi.2026.01.100)
  DOI : 10.1016/j.vasdi.2026.01.100
• Archaeal G-quadruplexes: a novel model for understanding unusual DNA/RNA structures across the tree of life
  
  • Aktary Zackie
  • Sorg Kate
  • Cucchiarini Anne
  • Vesco Guglielmo
  • Noury Dorian
  • Zhang Rongxin
  • Jourdain Thomas
  • Verga Daniela
  • Mahou Pierre
  • Olivier Nicolas
  • Bohálová Natália
  • Porubiaková Otília
  • Brázda Václav
  • Bouvier Marie
  • Kwapisz Marta
  • Clouet-D’orval Béatrice
  • Allers Thorsten
  • Lestini Roxane
  • Mergny Jean-Louis
  • Guittat Lionel
  Nucleic Acids Research, Oxford University Press, 2026, 54 (4). Archaea, a domain of microorganisms found in diverse environments, including the human microbiome, represent the closest known prokaryotic relatives of eukaryotes. This phylogenetic proximity positions them as a relevant model for investigating the evolutionary origins of nucleic acid secondary structures such as G-quadruplexes (G4s) which play regulatory roles in transcription and replication. Although G4s have been extensively studied in eukaryotes, their presence and function in archaea remain poorly characterized. In this study, a genome-wide analysis of the halophilic archaeon Haloferax volcanii identified over 5800 potential G4-forming sequences. Biophysical validation confirmed that many of these sequences adopt stable G4 conformations in vitro. Using G4-specific detection tools and super-resolution microscopy, G4 structures were visualized in vivo in both DNA and RNA across multiple growth phases. Comparable findings were observed in the thermophilic archaeon Thermococcus barophilus. Functional analysis using helicase-deficient H. volcanii strains further identified candidate enzymes involved in G4 resolution. These results establish H. volcanii as a tractable archaeal model for G4 biology. (10.1093/nar/gkag067)
  DOI : 10.1093/nar/gkag067
• Selective Disruption of Plasmodium falciparum mitochondrial DNA via G-Quadruplex-Binding Ligand RHPS4 Provides a Novel Antimalarial Strategy
  
  • Salim Mariam
  • Paloque Lucie
  • Reyser Thibaud
  • Nardella Flore
  • Augereau Jean-Michel
  • Luo Yu
  • Britton Sébastien
  • Mergny Jean-Louis
  • Gervais Virginie
  • Benoit-Vical Françoise
  • Gomez Dennis
  , 2026. ABSTRACT Malaria caused by Plasmodium falciparum remains a major health threat, killing over 600,000 people annually. The spread of resistance to all major antimalarials, including artemisinins, highlights the urgent need for new drugs with distinct mechanisms of action. Here we show that the G-quadruplex ligand RHPS4, an acridine derivative, displays strong antiplasmodial activity against both drug-sensitive and -resistant P. falciparum strains and clinical isolates. RHPS4 primarily targets the trophozoite stage and induces major mitochondrial alterations, including reduction of mitochondrial DNA (mtDNA) and transcriptional dysfunctions. Bioinformatic analyses identified at least eight putative G4-forming sequences within the parasite’s mtDNA. Biophysical studies confirmed G4 folding of at least one sequence and its interaction with RHPS4. These findings indicate that RHPS4 disrupts P. falciparum mitochondrial metabolism through G4 stabilization, leading to parasite death, and establish mtDNA G4 structures as novel therapeutic targets for antimalarial development. (10.64898/2026.01.07.698092)
  DOI : 10.64898/2026.01.07.698092
• Pentanucleotide guanine-rich WGGGW repeats, including CANVAS AGGGA repeats, form a variety of noncanonical structures
  
  • Wang Jiawei
  • Qiu Dehui
  • Zhou Jun
  • Mergny Jean-Louis
  • Alberti Patrizia
  Nucleic Acids Research, Oxford University Press, 2026, 54 (3). Abstract Short tandem repeats (STRs) are an important component of the human genome as they contribute to genetic diversity and can influence gene expression and disease susceptibility. STRs are important in the context of CANVAS (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome) genetic disease as expansions of AGGGA repeats within the RFC1 gene are associated with the development of this neurodegenerative disorder. Interestingly, the RFC1 expanded motifs are pentanucleotides that differ from the nonpathogenic AGAAA pentanucleotide motif present in reference genomes. The molecular mechanisms underlying the pathogenicity of the mutated pentanucleotide expansion in CANVAS are still unknown. Several groups have shown that DNA and RNA containing AGGGA repeats fold into G-quadruplexes (G4s) under physiological K⁺ conditions. In this study, we reveal a more complex than expected behavior, in which DNA WGGGW motifs (where W is A or T) may adopt different G4 and non-G4 structures depending on sequence, repeat number and ionic conditions. These findings are relevant as they may help explain the genomic instability and pathogenicity specifically associated with AGGGA repeats among the WGGGW motifs. (10.1093/nar/gkag051)
  DOI : 10.1093/nar/gkag051
• Collagen microarchitecture from polarized light imaging: a biomechanics perspective
  
  • Kunz Miriam Bohlmann
  • Lee Po-Yi
  • Latour Gaël
  • Yang Bin
  • Schanne-Klein Marie-Claire
  • Kurokawa Kazuhiro
  • Sigal Ian A
  Journal of Biomedical Optics, Society of Photo-optical Instrumentation Engineers, 2026, 31 (1), pp.010902. Significance: Collagen, the main load-bearing component in tissue, is present in all animals and forms a variety of networks from the fibrils, fibers, bundles, and lamellae into which it self-assembles. The collagen microstructure is different among tissue types, and the different microstructures give rise to tissue-specific mechanical properties. Therefore, methods for visualizing collagen fibers and their orientation are essential for understanding the biomechanical properties of tissue. Aim: Our aim in this review is to provide the basis for understanding the methodology of polarized light imaging methods and how they can be used to characterize collagen microstructure. Approach: We begin with a description of collagen microstructure and its relationship to tissue biomechanics, a basic formalism of polarized light, and how collagen interacts with polarized light. We then describe polarized light microscopy and its various forms, particularly instant polarized light microscopy, then polarizationsensitive optical coherence tomography, and last, polarization-resolved secondharmonic generation microscopy. Results: We describe methods for imaging collagen microstructure with polarized light from in vivo methods to high-resolution volumetric imaging of tissue sections. Conclusions: We intend to help those interested in using polarized light to image and understand the relationship between collagen microstructure and biomechanics. (10.1117/1.jbo.31.1.010902)
  DOI : 10.1117/1.jbo.31.1.010902
• Resonant third harmonic generation in biological pigments
  
  • Dees Stella
  • Ferrer Ortas Júlia
  • Mahou Pierre
  • Supatto Willy
  • Olivier Nicolas
  • Beaurepaire Emmanuel
  APL Photonics, AIP Publishing LLC, 2026, 11 (8), pp.086116. Third harmonic generation (THG) microscopy provides label-free structural contrast of biological tissues. While the THG process can be enhanced by electronic transitions in absorbing molecules, knowledge of the third-order nonlinear properties of biological pigments is limited, and the potential of THG imaging for chemically selective imaging remains underutilized. In this study, we investigated resonant THG in pigments by performing nonlinear microspectroscopy in situ on three representative absorbers: hemoglobin in red blood cells, pteridines in xanthophores, and melanin in human hair. We measured THG spectra in the 1120–1300 nm excitation range. We observed a wavelength-dependent signal enhancement ranging from 10 to 100 times in these pigmented structures, depending on their respective absorption properties. We developed a numerical model of THG from interfaces, including resonant and non-resonant contributions, to interpret these observations. Our calculations reproduce key experimental trends, including resonance-induced enhancement factors and spectral properties. Finally, we demonstrate that third-order sum-frequency generation (TSFG) imaging provides spectroscopic contrast capable of distinguishing red blood cells from xanthophores in live zebrafish larvae. These results suggest that THG/TSFG is a promising approach to label-free, pigment-specific multiphoton imaging. (10.1063/5.0341777)
  DOI : 10.1063/5.0341777
• Corvis ^ST biomechanical indices in the diagnosis of corneal stromal and endothelial disorders: an artificial intelligence-based comparative study
  
  • Borderie Vincent Michel
  • Georgeon Cristina
  • Louissi Nassim
  • Memmi Benjamin
  • Hamrani Malika
  • Bouheraoua Nacim
  • Chessel Anatole
  British Journal of Ophthalmology, BMJ Publishing Group, 2026, 110, pp.396-402. Aims: To analyse the value of the Corvis ST indices in diagnosing corneal stromal and endothelial disorders (CSEDs). Methods: This institutional retrospective case-control study included 903 eyes with a CSED and 597 normal eyes (controls), assessed with Corvis ST and MS39. Main outcome measures: Corvis ST indices. The collected data were divided into a training set (70%) and a test set (30%). Artificial intelligence frameworks were used to distinguish each disorder from controls and to classify corneas into seven groups: keratoconus, highrisk corneas for keratoconus, laser corneal refractive surgery (LCRS), endothelial disorders, stromal opacities, glaucoma corneas and normal corneas. Results: Stress-strain index (SSI) significantly increased with age in the control group. Compared with controls matched for age/sex, keratoconus was associated with Corvis Biomechanical Index (CBI) &gt;0.51 (area under the curve, 0.99), Ambrósio's relational thickness horizontal (ARTh) &lt;425.5 (0.97), deflection amplitude at the time of the first applanation (SPA-A1) &lt;96.3 (0.97) and Pachy&lt;522.4 µm (0.91); high-risk corneas with a difference in CBI between fellow eyes (CBI SYM) &gt;0.14 (0.98), (L2) &lt;1.95 (0.83) and Pachy&lt;549.7 µm (0.71); LCRS with ARTh&lt;455.1 (0.93) and CBI&gt;0.35 (0.83); corneal endothelial disorders with Pachy SYM&gt;19.7 µm (0.83), Pachy&gt;569.1 µm (0.82) and CBI SYM&gt;0.14 (0.77); stromal opacities with SPA-A1 SYM&gt;11.8 (0.92), ARTh&lt;569.9 (0.89), SSI SYM&gt;0.14 (0.89) and CBI&gt;0.22 (0.86). A logistic regression function using all indices reached an area under the receiver operating characteristic curve of 0.81 for glaucoma diagnosis. The TabPFN model provided the best accuracy (88.7%) for diagnosing the seven corneal conditions. SSI, SPA-A1, CBI and Pachy correlated with keratoconus grade. Keratoplasty for keratoconus improved but failed to restore normal corneal biomechanics. Conclusions: Corvis ST indices are relevant for diagnosing CESDs and distinguishing various disorders from each other. (10.1136/bjo-2025-327855)
  DOI : 10.1136/bjo-2025-327855
• Self-referenced terahertz time-domain ATR spectroscopy of solutions
  
  • Lordon Blandine
  • Giraldo Betancur Susana
  • Gallot Guilhem
  Applied Physics Letters, American Institute of Physics, 2026, 128 (22), pp.221107. Terahertz spectroscopy and imaging have emerged as sophisticated, nondestructive tools for material analysis in physical and biomedical sciences, owing to their sensitivity to molecular vibrations. However, the high absorption of terahertz radiation by water raises a significant challenge for studying liquids and biological samples. This work introduces a novel self-referenced time-domain attenuated total reflection (ATR) spectroscopy technique that overcomes this limitation by simultaneously recording both sample and reference terahertz waveforms. The method is based on ATR geometry, along with two time-delayed, synchronized sub-waveforms. This configuration enables precise differential measurements, thereby significantly improving detection sensitivity and long-term stability by mitigating environmental fluctuations and laser noise. The technique makes possible the direct extraction of both amplitude and phase information from the ATR reflection coefficient. The potential of this approach is demonstrated by measuring the relative power and phase spectra of NaCl, ATP, and saccharose solutions at various concentrations. The results obtained from this study indicate the presence of distinct spectral signatures for each molecule. This advancement opens novel prospects for high-fidelity spectral analysis, particularly in biomedical applications such as real-time monitoring of biochemical processes and cellular responses. (10.1063/5.0332458)
  DOI : 10.1063/5.0332458
• On the origins and variation of nucleotide skews of archaeal genomes
  
  • Paravel Adrien
  • Mottez Clémence
  • Puech Romain
  • Flament Didier
  • Becker Hubert F
  • Myllykallio Hannu
  Frontiers in Microbiology, Frontiers Media, 2026, 17, pp.1727296. We have used nucleotide skews as the proxy to understand the evolution of archaeal genomes. Our genome-wide studies using substantial datasets suggest that translational selection and the nature of the genetic code are universally conserved determinants of asymmetric guanine and cytosine distributions. We propose that in the case of the majority of bacterial chromosomes, mutational processes and/or DNA repair also result in the strand-specific nucleotide skews. This is in stark contrast to what we observe for archaeal chromosomes and plasmids, and reveals that archaea have a greatly reduced ability to create mutations and/or repair DNA damage in a strand-specific manner. We suggest that in the future, the described computational and statistical approach will help to understand the evolutionary dynamics of the archaeal chromosomes through the tree of life. (10.3389/fmicb.2026.1727296)
  DOI : 10.3389/fmicb.2026.1727296