Publications

2025

• 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
• In vivo autofluorescence lifetime imaging of the Drosophila brain captures metabolic shifts associated with memory formation
  
  • Roussel Philémon
  • Zhou Mingyi
  • Stringari Chiara
  • Preat Thomas
  • Plaçais Pierre-Yves
  • Genovesio Auguste
  eLife, eLife Sciences Publication, 2025. Abstract Neuronal energy regulation is increasingly recognized as a critical factor underlying brain functions and their pathological alterations, yet the metabolic dynamics that accompany cognitive processes remain poorly understood. As a label-free and minimally invasive technique, fluorescence lifetime imaging (FLIM) of coenzymes NADH and NADPH (collectively referred to as NAD(P)H) offers the possibility to resolve cellular metabolic profiles with high spatial precision. However, NAD(P)H FLIM’s capacity to detect subtle changes in neuronal metabolism associated with cognition has not been demonstrated. In this study, we applied NAD(P)H FLIM to map the metabolic profiles of Drosophila neurons in vivo across multiple scales, focusing on the primary centers for associative memory: the mushroom bodies (MBs). At a broad scale, we obtained an overview of the metabolic signatures of the main brain tissue and identified a marked difference between neuropil and cortex areas. At a finer scale, our findings revealed notable heterogeneity in the basal metabolic profiles of distinct MB neuron subtypes. Measurements performed after associative olfactory learning also uncovered a subtype-specific metabolic shift associated with memory formation, demonstrating the utility of NAD(P)H FLIM in detecting physiology-driven changes linked to brain function. These results establish a promising framework for studying cerebral energy dynamics in vivo. (10.7554/eLife.106040.1)
  DOI : 10.7554/eLife.106040.1
• Épisode 3 : Cyndie & la création de projets innovants : des térahertz aux initiatives éco-responsables
  
  • Elouin Amélie
  • Poulin Cyndie
  , 2025. Pour clôturer ce mois des droits de la femme, Amélie Elouin interviewe Cyndie Poulin, consultante en stratégie de l’innovation et docteure en physique des matériaux dans le domaine des térahertz depuis 2018. Elle revient sur son parcours, ses projets menés après son doctorat, notamment en entrepreneuriat et en innovation. Fondatrice d’une maison d’édition engagée en faveur du développement durable et vice-présidente de la Jeune Chambre Économique de Montpellier, Cyndie Poulin partage également un message fort aux jeunes filles dans les domaines scientifiques et au-delà. Elle les encourage à oser, à croire en leurs projets et à ne pas se laisser freiner par les doutes extérieurs. - enregistrement et montage des interviews par les doctorants du Laboratoire d'Optique et Biosciences. - dépôt sur MediHal par Elsa BALDUZZI
• Épisode spécial : Interview de Maïlie Saint-Hilaire par Amélie Elouin : chlordécone, science & santé caribéenne
  
  • Elouin Amélie
  • Saint-Hilaire Maïlie
  , 2025. À l’occasion du mois des femmes, Amélie Elouin interviewe Maïlie Saint-Hilaire, une scientifique inspirante originaire de la Martinique. Maïlie a soutenu sa thèse en France métropolitaine et dirige aujourd’hui un laboratoire de chimie à l’Institut Pasteur de Guadeloupe. Dans cette interview, elle nous partage son parcours, ses recherches sur la chlordécone, ainsi que son rôle de responsable de laboratoire. Passionnée par la valorisation des talents scientifiques caribéens, elle a créé le podcast Caribéenne & Scientifique. Elle accompagne également les doctorants grâce à un programme en ligne, PhD BOOST, qui les aide à aborder leur thèse avec confiance et sérénité. - enregistrement et montage des interviews par les doctorants du Laboratoire d'Optique et Biosciences. - dépôt sur MediHal par Elsa BALDUZZI
• 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
• Episode 1: Ayah &amp; the plasma-semiconductor frontier
  
  • Soundous Taihi Ayah
  • Bing Xue
  , 2025. In this episode Xue receives Ayah and she will tel us about her PhD-thesis: the plasma-semiconductor frontier. Her research focuses on surface semiconducting barrier discharges, a type of plasma that propagates on a silicon surface. She aims to understand the physics behind this phenomenon, which has potential industrial applications. Ayah finds the PhD challenging, especially due to the difficulty of maintaining work-life balance. Don’t be scared, she will explain everything! - Recording and editing of the interviews by the PhD students of the Laboratory of Optics and Biosciences. - Upload to MediHal by Elsa BALDUZZI
• 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
• Épisode 2 : Poncia &amp; la microstructure de la cornée humaine
  
  • Sidi Abdel Jelil Aïchata
  • Nyembo Kasongo Poncia
  , 2025. Dans cet épisode, Aïchata reçoit le doctorant Poncia ! Poncia nous fait découvrir sa thèse : l’étude de la microstructure de la cornée humaine. Son objectif est d’analyser l’organisation des lamelles de collagène au sein des cornées. Son travail pourrait permettre d’améliorer le diagnostic précoce des maladies cornéennes et la compréhension de leur évolution. - enregistrement et montage des interviews par les doctorants du Laboratoire d'Optique et Biosciences. - dépôt sur MediHal par Elsa BALDUZZI
• 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
• G-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing
  
  • Esnault Cyril
  • Zine El Aabidine Amal
  • Robert Marie-Cécile
  • Cucchiarini Anne
  • Magat Talha
  • Pigeot Alexia
  • Bouchouika Soumya
  • Garcia-Oliver Encar
  • Gawron Kevin
  • Basyuk Eugénia
  • Karpinska Magdalena A
  • Kozulic-Pirher Alja
  • Luo Yu
  • Verga Daniela
  • Mourad Raphael
  • Radulescu Ovidiu
  • Mergny Jean-Louis
  • Bertrand Edouard
  • Andrau Jean-Christophe
  Nature Genetics, Nature Publishing Group, 2025, 57 (8), pp.1981-1993. Despite their central role in transcription, it has been difficult to define universal sequences associated to eukaryotic promoters. Within chromatin context, recruitment of the transcriptional machinery requires promoter opening but how DNA elements could contribute to this process is unclear. Here, we show that G-quadruplex (G4) secondary DNA structures are highly enriched at mammalian promoters. G4s are located at the deepest point of nucleosome exclusion at promoters and correlate with maximum promoter activity. We found that experimental G4s exclude nucleosomes in vivo and in vitro while favouring strong positioning. At model promoters, impairing G4s affected both transcriptional activity and chromatin opening. G4 destabilization also resulted in an inactive promoter state and affected transition to effective RNA production. Finally, G4 stabilization resulted in global reduction of proximal promoter pausing. Altogether, our data introduce G4s as bona fide promoter elements allowing nucleosome exclusion and facilitating pause release by the RNA Polymerase II. (10.1038/s41588-025-02263-6)
  DOI : 10.1038/s41588-025-02263-6
• Synthesis of new 1,3-bis[(4-(substituted-aminomethyl)phenyl)methyl]benzene and 1,3-bis[(4-(substituted-aminomethyl)phenoxy)methyl]benzene derivatives, designed as novel potential G-quadruplex antimalarial ligands
  
  • Albenque-Rubio Sandra
  • Guillon Jean
  • Agnamey Patrice
  • Damiani Céline
  • Savrimoutou Solène
  • Ronga Luisa
  • Hanot Marie
  • Zangmo Tshering
  • Pinaud Noël
  • Moreau Stéphane
  • Mergny Jean-Louis
  • Marchivie Mathieu
  • Moukha Serge
  • Estela Fabienne
  • Dozolme Pascale
  • Cohen Anita
  • Sonnet Pascal
  Drugs and Drug Candidates, MDPI, 2025, 4 (3), pp.39. Background: Based on our previously reported series of novel 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene and 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene derivatives, we have now designed, synthesized, and tested a new series of novel restricted and simplified structural analogues of these compounds against Plasmodium falciparum in vitro; i.e., the 1,3-bis[(4-(substituted-aminomethyl)phenyl)methyl]benzene and 1,3-bis[(4-(substituted-aminomethyl)phenoxy)methyl]benzene compounds. Methods &amp; results: The pharmacological results revealed significant antimalarial activity, with IC50 values in the submicromolar to micromolar range. Additionally, the in vitro cytotoxicity of these new nitrogen-containing polyphenyl- or -phenoxymethylbenzene compounds was evaluated on human HepG2 cells. The compound 1f, the 1,3-bis[(4-(3-(morpholin-1-yl)propyl)aminomethyl)phenoxy)methyl]benzene derivative, emerged as one of the most potent and promising antimalarial candidates, demonstrating a cytotoxicity/antiprotozoal activity ratio of 594 against the chloroquine-sensitive Plasmodium falciparum 3D7 strain. Additionally, the 1,3-bis[((substituted aminomethyl)phenyl)methyl]benzene compound 1j and the 1,3-bis[((substituted aminomethyl)phenoxy)methyl]benzenes 2p and 2q also showed strong antimalarial potential, with selectivity indexes (SI) of over 303, 280, and 217, respectively, against the 3D7 strain, which has mefloquine-reduced sensitivity. Furthermore, the 1,3-bis[(4-(pyridin-2-ylethylaminomethyl)phenyl)methyl]benzene 2k was identified as the most noteworthy antimalarial compound, exhibiting a selectivity index (SI) that was superior to 178 against the chloroquine-resistant Plasmodium falciparum W2 strain. It has previously been suggested that the telomeres of P. falciparum may serve as potential targets for these polyaromatic compounds; thus, we assessed the ability of our novel derivatives to stabilize parasitic telomeric G-quadruplexes using a FRET melting assay. Conclusions: However, regarding the stabilization of the protozoan G-quadruplex, it was noted that the few substituted derivatives, which showed interesting stabilization profiles, were not necessarily the most effective antimalarial compounds against both Plasmodium strains. Moreover, these new compounds did not show promising stabilizing effects on the different G4 sequences. Therefore, no correlation arises between their antimalarial activity and the selectivity of their binding to G-quadruplexes. (10.3390/ddc4030039)
  DOI : 10.3390/ddc4030039
• Spatial distribution and stability of Gd_0.6Eu_0.4VO₄ nanoparticles injected in mouse ear pinnae
  
  • Proiou Eleni
  • Pinakidou Fani
  • Paloura Eleni C
  • Pétri Nicolas
  • Gacoin Thierry
  • Laplace-Builhé Corinne
  • Schuck Götz
  • Alexandrou Antigoni
  • Katsikini Maria
  Trends in Analytical Chemistry, Elsevier, 2025, 182, pp.118049. X-Ray Fluorescence (XRF) mapping is employed for the study of the spatial distribution of GdVO₄:Eu nanoparticles (NPs) after their injection into mouse ear pinnae. The injected NP colloids were detectable in a concentration range from 5 to 30 mM in vanadate ions (90-530 nM in NP concentrations). The distribution maps were recorded separately for Gd, Eu, and V and reveal that the three elements are collocalized, indicating the NP stability after the injection. The distribution pattern of the NPs is not homogeneous; they follow bifurcated paths of easy flow demonstrating the complexity of the tissue-colloid interactions. The V-K, Gd-L 3 and Eu-L 3 -edge Xray Absorption Fine Structure (XAFS) spectra of the NPs recorded prior to and after their injection confirm that the integrity of the nanoparticles is preserved after injection. This combined XRF/XAFS analysis paves the way for studies on the long-term fate of injected Gd-containing NPs in tissues. (10.1016/j.trac.2024.118049)
  DOI : 10.1016/j.trac.2024.118049
• Intrinsic variation of the polarization-resolved SHG from collagen: Multiscale analysis and application to parchments
  
  • Galante Giulia
  • Robinet Laurianne
  • Heu-Thao Sylvie
  • Caporal Clément
  • Latour Gaël
  • Schanne-Klein Marie-Claire
  APL Photonics, AIP Publishing LLC, 2025, 10 (5), pp.056106. Second harmonic generation (SHG) microscopy is nowadays the gold standard technique for collagen structural imaging in intact tissues with sub-micrometer resolution. This multiphoton modality can be combined with polarimetry to provide key information about the 3D hierarchical organization of collagen. Notably, the so-called anisotropy parameter processed from polarization-resolved SHG (P-SHG) has been shown to vary with the orientational disorder of the fibrils within the focal volume and with their out-of-plane orientation. However, analytical equations describing both effects within the same formalism are still lacking. In this work, we present a unified multiscale theoretical approach of the intrinsic variations of the anisotropy parameter. We then measure these variations in the very same collagen samples to ensure reliable comparisons. To that end, we use parchments, which are materials made from animal skins and which contain almost exclusively collagen. These parchments are manufactured in different ways to obtain different collagen distributions. Our series of measurements exhibit a good agreement with our theoretical approach, which shows the relevance of P-SHG measurements to probe collagen multiscale organization in tissues. (10.1063/5.0250484)
  DOI : 10.1063/5.0250484
• The Mappa mundi of Albi: Insight into the manufacturing, life and conservation state of an 8th century world map
  
  • Robinet Laurianne
  • Heu-Thao Sylvie
  • Galante Giulia
  • Latour Gaël
  • Tournié Aurélie
  • Daher Céline
  • Dan Anca
  • Schanne-Klein Marie-Claire
  • Michelin Anne
  • Deschaux Jocelyne
  Journal of Cultural Heritage, Elsevier, 2025, 74, pp.341-352. The Mappa mundi of Albi is one of the oldest examples of spatial representation of the Western world. The small map conserved on the verso of folio 57 in manuscript 29 of the Médiathèque Pierre Amalric in Albi (France) was drawn on parchment, probably made in the second half of the 8th century, somewhere between south-western France and northern Spain, maybe in Albi itself. Because of its exceptional importance for the history of space representation, the map, together with the Index of seas and winds facing it, on the recto of folio 58, was recorded in the UNESCO Memory of the World Register in 2015. The detailed study published here has examined the manuscript’s structure and characterised the different constitutive materials. Observations and physicochemical analyses were performed on the map and the index, from the micro to the macroscale, combining optical microscopy, XRF, FORS, FTIR, and micro-Raman spectroscopy, hyperspectral imaging, proteomic analysis, and non-linear optical microscopy. Three manuscripts conserved at the same library or suspected to have been produced in the scriptorium of Albi have also been examined for comparisons. This material investigation complements the historical studies of the map by shedding new light on the manufacturing, life, and conservation state of this exceptional document. (10.1016/j.culher.2025.05.013)
  DOI : 10.1016/j.culher.2025.05.013
• A Chimeric Photo-Controllable CRISPR/Cas12a System for Universal and Fast Diagnostics
  
  • Yan Xinrong
  • Liu Bin
  • Zhou Shuguang
  • Fan Yanjun
  • Wei Shijiong
  • Qiu Dehui
  • Xiang Henglong
  • Zhou Jiahang
  • Mergny Jean-Louis
  • Monchaud David
  • Ju Huangxian
  • Zhou Jun
  Analytical Chemistry, American Chemical Society, 2025, 97 (44), pp.24634 - 24642. The potential of clustered regularly interspaced short palindromic repeats (CRISPR) and corresponding CRISPR-associated (Cas) protein systems (CRISPR/Cas) systems for biomedical applications is tremendous; however, precise control of their activity is essential to better harness this potential and, beyond this, to develop reliable diagnostic reagents. Herein, we report on such a strategy by controlling the CRISPR/Cas12a activity using a photo-controllable CRISPR RNA (crRNA). To this end, the 3′ end of crRNA was conjugated to a G-quadruplex (G4) block through a photocleavable linker: upon photo irradiation, the G4 trigger is removed, thus allowing for the DNA target to access and hybridize with the crRNA, and thus be processed by the CRISPR/Cas12a system. The efficiency of this approach was demonstrated by the detection of human papillomavirus 16 DNA in 50 clinical samples: our one-pot strategy was found to be as efficient as the routinely implemented method (qPCR), with 95.7% sensitivity and 100% specificity, in addition to be faster (25 versus 60 min) and both simpler and less expensive (being implementable as lateral flow test strips). Collectively, this new and fully controllable CRISPR/Cas system holds great potential for next-generation clinical diagnostics. (10.1021/acs.analchem.5c04782)
  DOI : 10.1021/acs.analchem.5c04782
• Mechanism of Ultrafast Flavin Photoreduction in the Active Site of Flavoenzyme LSD1 Histone Demethylase
  
  • Zhuang Bo
  • Ramodiharilafy Rivo
  • Aleksandrov Alexey
  • Liebl Ursula
  • Vos Marten H
  Chemical Science, The Royal Society of Chemistry, 2025, 16, pp.338 - 344. Photoreduction of oxidized flavins has a functional role in photocatalytic and photoreceptor flavoproteins. In flavoproteins without light-dependent physiological functions, ultrafast, reversible flavin photoreduction is supposedly photoprotective by nature, and holds potential for nonnatural photocatalytic applications. In this work, we combine protein mutagenesis, ultrafast spectroscopy, molecular dynamics simulations and quantum mechanics calculations to investigate the nonfunctional flavin photoreduction in a flavoenzyme, lysine-specific demethylase 1 (LSD1) which is pivotal in DNA transcription. LSD1 harbors an oxidized flavin adenine dinucleotide (FAD) cofactor and multiple electron-donating residues in the active site. Upon photoexcitation, the FAD cofactor is photoreduced in &lt; 200 fs by electron transfer (ET) from nearby residue(s), and the charge pairs recombine in ca. 2 ps. Site-directed mutagenesis pinpoints a specific tryptophan residue, W751, as the primary electron donor, whereas a tyrosine residue, Y761, despite being located closer to the flavin ring, does not effectively contribute to the process. Based on a hybrid quantum–classical computational approach, we characterize the W751–FAD and Y761–FAD charge-transfer states (CTW751 and CTY761, respectively), as well as the FAD locally excited state (LEFAD), and demonstrate that the coupling between LEFAD and CTW751 is larger than those involving CTY761 by an order of magnitude, rationalizing the experimental observations. More generally, this work highlights the role of the intrinsic protein environment and details of donor–acceptor molecular configurations on the dynamics of short-range ET involving a flavin cofactor and amino acid residue(s). (10.1039/D4SC06857B)
  DOI : 10.1039/D4SC06857B
• Ultrafast dynamics of the UV-induced electronic relaxation in DNA guanine-thymine dinucleotides: from the Franck-Condon states to the minima of the potential energy surfaces
  
  • Petropoulos Vasilis
  • Martinez-Fernandez Lara
  • Uboldi Lorenzo
  • Maiuri Margherita
  • Cerullo Giulio
  • Balanikas Evangelos
  • Markovitsi Dimitra
  Physical Chemistry Chemical Physics, Royal Society of Chemistry, 2025. We study the DNA dinucleotide 5’-dGpdT-3’ (abbreviated as GT) as a model system for the relaxation of the electronic excited states in stacked nucleobases. Quantum chemistry calculations determine the Franck-Condon... (10.1039/D5CP00788G)
  DOI : 10.1039/D5CP00788G