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Publications

2026

  • 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
  • Contribution of Paper and Cardboard Waste Valorization to the Energy Transition and Environmental Pollution Reduction
    • Dzokom Alexis
    Sahel Nature Consulting Revue, Sahel Nature Consulting Revue (March 2025), 2026, 01 (12), pp.1-41. <div><p>Sustainable waste management has become a major challenge in the context of increasing urbanization and the transition toward more sustainable energy systems. Among the solid wastes generated in large quantities, paper and cardboard waste represent a valuable resource that can contribute to renewable energy production while reducing the environmental impacts associated with their accumulation. This article examines the role of the energy recovery of paper and cardboard waste, particularly through its conversion into eco-friendly fuel briquettes for domestic and artisanal applications. The study is based on a review of the scientific literature and field experiences related to the collection, processing, and densification of these waste materials. The results indicate that 102.14 tons of briquettes per year, produced from 81.7 tons of paper and cardboard waste annually, provide an estimated energy potential of 1,930,446 MJ per year, with a satisfactory calorific value. This energy output enables the partial or complete substitution of approximately 153.2 tons per year of fuelwood and traditional charcoal commonly used for cooking purposes. Such substitution contributes to a 57.4% reduction in pressure on forest resources, a 67.1% decrease in greenhouse gas emissions, and an improvement in air quality through lower particulate matter emissions (280 mg/MJ PM2.5). Furthermore, the valorization of paper and cardboard waste helps reduce the volume of waste disposed of in landfills or discarded into the environment (64.7% reduction), thereby mitigating the risks of soil, water, and urban environmental pollution. It also promotes the development of local economic activities and employment opportunities in waste collection, recycling, and energy production sectors. The study concludes that the energy valorization of paper and cardboard waste constitutes a relevant strategy for supporting the circular economy, strengthening the energy transition, and promoting sustainable waste management. However, its large-scale development requires a supportive institutional framework, adequate investments, and increased public awareness regarding waste sorting and recycling practices.</p><p>durable des déchets constitue aujourd'hui un enjeu majeur dans le contexte de l'urbanisation croissante et de la transition vers des systèmes énergétiques plus durables. Parmi les déchets solides générés en grande quantité, les papiers et cartons représentent une ressource valorisable pouvant contribuer à la production d'énergie renouvelable tout en réduisant les impacts environnementaux liés à leur accumulation. Cet article analyse le rôle de la valorisation énergétique des déchets de papiers et</p></div>
  • Genre et adoption des pratiques agroécologiques en maraîchage dans la zone soudano-sahelienne : cas de Mandaka et Meskine
    • Dzokom Alexis
    • Mahamat Abaicho
    Sahel Nature Consulting Revue, Sahel Nature Consulting Revue (March 2025), 2026, 01 (15), pp.1- 23. <div><p>L'adoption des pratiques agroécologiques est un facteur clé pour renforcer la résilience des systèmes maraîchers face aux changements climatiques dans les zones soudanosahelienne. Cette étude examine l'influence du genre sur l'adoption de ces pratiques, en comparant la localité de Mandaka (zone montagneuse) et celle de Meskine (zone de plaine). L'analyse se concentre sur trois axes : l'accès différencié aux ressources, le rôle des femmes dans le maraîchage et les contraintes spécifiques liées au genre. Les résultats révèlent que les femmes participent activement aux activités maraîchères mais font face à des contraintes importantes, telles que l'accès limité à la terre et au crédit. Les hommes, quant à eux, adoptent plus facilement certaines pratiques nécessitant des investissements initiaux. Ces différences expliquent partiellement les écarts d'adoption entre sexes et suggèrent la nécessité de stratégies différenciées pour promouvoir l'agroécologie.</p><p>.</p></div>
  • 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
  • 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
  • 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.
  • 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 photochemical processes using multiple-timescale multiple-probing visible transient absorption spectroscopy with two independent femtosecond amplifiers
    • 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
  • Corvis <sup>ST</sup> 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
  • 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. 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. (10.3390/scipharm94020048)
    DOI : 10.3390/scipharm94020048
  • 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