Publications

2024

• Épisode 8 : Etienne & les statistiques
  
  • Elouin Amélie
  • Donier-Meroz Etienne
  , 2024. Cette semaine Amélie reçoit le docteur Etienne Donier-Meroz, ancien thésard du Centre de Recherche en Économie et Statistique (CREST) à l’ENSAE ! Dans cet épisode Etienne nous parle de statistiques… Comme il le dit: les statistiques sont présentes partout et permettent de prédire certains phénomènes qui nous entourent. Il nous explique tout !
• Correction of non-random mutational biases along a linear bacterial chromosome by the mismatch repair endonuclease NucS
  
  • Dagva Oyut
  • Thibessard Annabelle
  • Lorenzi Jean-Noël
  • Labat Victor
  • Piotrowski Emilie
  • Rouhier Nicolas
  • Myllykallio Hannu
  • Leblond Pierre
  • Bertrand Claire
  Nucleic Acids Research, Oxford University Press, 2024, 52 (9), pp.5033-5047. The linear chromosome of Streptomyces exhibits a highly compartmentalized structure with a conserved central region flanked by variable arms. As double strand break (DSB) repair mechanisms play a crucial role in shaping the genome plasticity of Streptomyces, we investigated the role of EndoMS/NucS, a recently characterized endonuclease involved in a non-canonical mismatch repair (MMR) mechanism in archaea and actinobacteria, that singularly corrects mismatches by creating a DSB. We showed that Streptomyces mutants lacking NucS display a marked colonial phenotype and a drastic increase in spontaneous mutation rate. In vitro biochemical assays revealed that NucS cooperates with the replication clamp to efficiently cleave G/T, G/G and T/T mismatched DNA by producing DSBs. These findings are consistent with the transition-shifted mutational spectrum observed in the mutant strains and reveal that NucS-dependent MMR specific task is to eliminate G/T mismatches generated by the DNA polymerase during replication. Interestingly, our data unveil a crescent-shaped distribution of the transition frequency from the replication origin towards the chromosomal ends, shedding light on a possible link between NucS-mediated DSBs and Streptomyces genome evolution. (10.1093/nar/gkae132)
  DOI : 10.1093/nar/gkae132
• G-quadruplex ligands in cancer therapy: Progress, challenges, and clinical perspectives
  
  • Figueiredo Joana
  • Mergny Jean-Louis
  • Cruz Carla
  Life Sciences, Elsevier, 2024, 340, pp.122481. Guanine-rich sequences can form G-quadruplexes (G4) in living cells, making these structures promising anti- cancer targets. Compounds able to recognize these structures have been investigated as potential anticancer drugs; however, no G4 binder has yet been approved in the clinic. Here, we describe G4 ligands structure-activity relationships, in vivo effects as well as clinical trials. Addressing G4 ligand characteristics, targeting challenges, and structure-activity relationships, this review provides insights into the development of potent and selective G4-targeting molecules for therapeutic applications. (10.1016/j.lfs.2024.122481)
  DOI : 10.1016/j.lfs.2024.122481
• Épisode 7 : Carla & la lutte contre l'antibiorésistance
  
  • Noury Dorian
  • Faivre Carla
  , 2024. Cette semaine Dorian reçoit la doctorante Carla Faivre ! Dans cet épisode Carla nous parlera de son sujet de thèse : la lutte contre l'antibiorésistance... Comme elle le dit: les antibiotiques ce n'est pas automatique! Certaines bactéries ont appris à contourner l'effet des antibiotiques, et le but de Carla est de modifier ces antibiotiques afin qu'ils retrouvent de l'efficacité. Elle va tout nous expliquer ! - enregistrement et montage des interviews par les doctorants du Laboratoire d'Optique et Biosciences. - dépôt sur MediHal par Elsa BALDUZZI
• Episode 3: Manuel & drugs for cancer and parasite treatment
  
  • Galante Giulia
  • Pérez Soto Manuel
  , 2024. This week Giulia receives the PhD-student Manuel Pérez Soto! In this episode Manuel will tell us about his PhD-thesis : designing drugs for cancer and parasite treatment... In this episode Manuel will tell us about his PhD trip and for once, it's a real trip : research exchange in a French laboratory and towards patent application. - Recording and editing of the interviews by the PhD students of the Laboratory of Optics and Biosciences. - Upload to MediHal by Elsa BALDUZZI.
• Chirped pulse upconversion for femtosecond mid-infrared spectroscopy at 100 kHz
  
  • Jonušas Mindaugas
  • Bournet Quentin
  • Bonvalet Adeline
  • Natile Michele
  • Guichard Florent
  • Zaouter Yoann
  • Georges Patrick
  • Druon Frédéric
  • Hanna Marc
  • Joffre Manuel
  Optics Express, Optical Society of America - OSA Publishing, 2024, 32 (5), pp.8020. We demonstrate that chirped pulse up-conversion (CPU), a method routinely used with systems based on 1-kHz Titanium:Sapphire lasers, can be extended to a repetition rate of 100 kHz with an Ytterbium diode-pumped femtosecond amplifier. Individual mid-infrared spectra can thus be measured directly in the near infrared using a fast CMOS linescan camera. After an appropriate Fourier processing, a spectral resolution of 1.1 cm-1 is reported, currently limited by our spectrometer. Additionally, we demonstrate the application of CPU to a pump-probe measurement of the vibrational relaxation in carboxy-hemoglobin, and we show that the combination of fast scanning and fast acquisition enables a straightforward removal of pump scattering interference. (10.1364/oe.515291)
  DOI : 10.1364/oe.515291
• Spatial modeling of telomere intra-nuclear distribution reveals non-random organization that varies during cell cycle and depends on LAP2 and BAF
  
  • Keller Debora
  • Stinus Sonia
  • Umlauf David
  • Gourbeyre Edith
  • Biot Eric
  • Olivier Nicolas
  • Mahou Pierre
  • Beaurepaire Emmanuel
  • Andrey Philippe
  • Crabbe Laure
  , 2022. Abstract Genome organization within the 3D nuclear volume influences major biological processes but is completely lost during mitosis, which represents a major challenge to maintain cellular identity and cell fate. To restore a functional G1 nucleus for the next cell cycle, it is imperative to reestablish genome organization during post-mitotic nuclear assembly. Importantly, the configuration of linear chromosomes has been shown to directly impact spatial genome architecture. Both centromeres and telomeres are known to associate with nuclear structures, such as the nuclear envelope, and support chromatin distribution. Here, using high-resolution 3D imaging combined with 3D spatial statistics and modeling, we showed that telomeres generally followed a regular distribution compared to what is expected under a random organization. While the preferential localization of telomeres at nuclear periphery was restricted to early G1, we found a strong clustering of centromeres in addition to their predominant peripheral localization at all cell cycle stages. We then conducted a targeted screen using MadID to identify the molecular pathways driving or maintaining telomere anchoring to the nuclear envelope. Among these factors, we could show that LAP2α transiently localizes to telomeres in anaphase, at a stage where LAP2α initiates the reformation of the nuclear envelope. Moreover, co-depletion of LAP proteins and their partner BAF impacted telomere redistribution in the next interphase. There results suggest that in addition to their crucial role in genome protection, telomeres also participate in reshaping functional G1 nuclei after mitosis. (10.1101/2022.12.22.521599)
  DOI : 10.1101/2022.12.22.521599
• Preferential formation of Z-RNA over intercalated motifs in long noncoding RNA
  
  • Bhatt Uditi
  • Cucchiarini Anne
  • Luo Yu
  • Evans Cameron
  • Mergny Jean-Louis
  • Iyer K. Swaminathan
  • Smith Nicole
  Genome Research, Cold Spring Harbor Laboratory Press, 2024, pp.gr.278236.123. Secondary structure is a principal determinant of lncRNA function, predominantly regarding scaffold formation and interfaces with target molecules. Noncanonical secondary structures that form in nucleic acids have known roles in regulating gene expression and include G-quadruplexes (G4s), intercalated-motifs (iMs), and R-loops (RLs). In this paper, we utilized computational tools G4-iM Grinder and QmRLFS-finder to predict the formation of each of these structures throughout the lncRNA transcriptome in comparison to protein-coding transcripts. The importance of the predicted structures in lncRNA in biological contexts was assessed by combining our results with publicly available lncRNA tissue expression data followed by pathway analysis. The formation of predicted G4 (pG4) and iM (piM) structures in select lncRNA sequences was determined in vitro using biophysical experiments under near-physiological conditions. We found that the majority of the tested pG4s form highly stable G4 structures and identify many previously unreported G4s in biologically important lncRNAs. In contrast, none of the piM sequences were able to form iM structures, consistent with the idea that RNA is unable to form iMs. These C-rich sequences instead formed Z-RNA structures, which have not been previously observed in regions containing cytosine repeats and represent an interesting and under-explored target for protein-RNA interactions. Our results highlight the prevalence and potential structure-associated functions of noncanonical secondary structures in lncRNA and observe G4 and Z-RNA structure formation in many lncRNA sequences for the first time, furthering understanding of the structure-function relationship in lncRNAs. (10.1101/gr.278236.123)
  DOI : 10.1101/gr.278236.123
• Épisode 6 : Maxime & un modèle de rein sur puce
  
  • Lordon de Bonniol Du Tremont Blandine
  • Mauviel Maxime
  , 2024. Cette semaine Blandine reçoit le docteur Maxime Mauviel ! Dans cet épisode Maxime nous parlera de son sujet de thèse : la construction d'un modèle de rein sur puce... Pas de panique, Maxime va tout expliquer ! - enregistrement et montage des interviews par les doctorants du Laboratoire d'Optique et Biosciences. - dépôt sur MediHal par Elsa BALDUZZI
• Maximizing the efficiency of intrapulse difference frequency generation by pulse shaping and recycling
  
  • Bournet Quentin
  • Jonusas Mindaugas
  • Guichard Florent
  • Natile Michele
  • Zaouter Yoann
  • Joffre Manuel
  • Bonvalet Adeline
  • Druon Fréderic
  • Hanna Marc
  • Georges Patrick
  Applied Physics B - Laser and Optics, Springer Verlag, 2024, 130 (2), pp.33. <div><p>Intrapulse Difference Frequency Generation (iDFG) is an interesting technique for generating femtosecond pulses in the Mid-Infrared (MIR) range with unique properties such as robust Carrier-Envelope Phase (CEP) stability. However, its efficiency is low compared to other techniques. In this paper, we describe an iDFG system operating within the 4 to 10 µm range that features an original architecture to enhance efficiency. First, we introduce an interesting technique on the generation process. This approach involves polarization and spectral phase shaping techniques on the driving pulse to maximize the number of photons enrolled in the process. Second, we demonstrate that the polarization shaping allows further enhancement of efficiency by recycling the iDFG signal to pump a subsequent optical parametric amplification (OPA) stage. These two concepts and the associated parameters optimization are described into details, and supported by experimental results. Combined with a high-power Yb-fiber-based pump laser, these techniques allow to achieve record efficiencies, and generate µJ-level, fewcycle, tunable, CEP-stable pulses in the MIR at repetition rates above 100 kHz.</p></div> (10.1007/s00340-023-08162-0)
  DOI : 10.1007/s00340-023-08162-0
• Episode 2 : Laurianne &amp; RNA modification enzymes
  
  • Imezar Maria
  • Tay Laurianne
  , 2024. This week Maria receives the PhD-student Laurianne Tay ! In this episode Laurianne will tell us about her PhD-thesis : RNA modificiation enzymes... 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.
• G-quadruplexes in Haloferax volcanii
  
  • Aktary Zackie
  • Cucchiarini Anne
  • Vesco Guglielmo
  • Noury Dorian
  • Jourdain Thomas
  • Verga Daniela
  • Mahou Pierre
  • Olivier Nicolas
  • Valková Natália
  • Porubiaková Otilia
  • Brázda Václav
  • Bouvier Marie
  • Kwapisz Marta
  • Clouet-D’orval Béatrice
  • Allers Thorsten
  • Lestini Roxane
  • Mergny Jean‐louis
  • Guittat Lionel
  BioRxiv, BioRxiv, 2024. The archaeal domain is a taxonomically rich component of microbial communities that inhabit a wide range of habitats on Earth, including the human body. Phylogenomic analyses have indicated that archaea represent the closest known relatives of eukaryotes, thus suggesting that eukaryotes may have evolved from an archaeal ancestor. G-quadruplex structures (G4), formed by guanine rich sequences, are among the most intensively studied local DNA/RNA structures and regulate key biological processes such as replication and gene expression. A bioinformatics analysis of the genome of the salt-loving archaea H. volcanii revealed a large number of potential G4 sequences (PQS). Biophysical analyses showed that a representative panel of these sequences form stable G4 structures under physiological conditions in vitro . In addition, immunofluorescence experiments using the G4-specific antibody, BG4, detected G4s in vivo at the single-cell level with super-resolution microscopy. Moreover, we directly visualized G4 in exponentially growing or stationary cells both at the DNA and RNA levels. G4s were also observed in the RNA and DNA of the hyperthermophile archaeon T. barophilus . Finally, we identified helicases potentially involved in G4 unfolding. Together, with H. volcanii as a new model, our work helps to fill the gap between bacteria and eukaryotic organisms for G4 studies and will aid in uncovering the evolutionary history of G4 structures in the tree of life. (10.1101/2024.01.16.575881)
  DOI : 10.1101/2024.01.16.575881
• Épisode spécial: "C'est quoi la thèse?" - discussion entre collégiens &amp; thésards
  
  • Elouin Amélie
  • Kuhner Robin
  • Imezar Maria
  • Poelman Teo
  • Balaazi Aniss
  • Maguer William
  • Bouchenak Adam
  , 2024. Toute l'équipe des Voix'yageurs vous souhaitent une excellente année 2024! Pour bien commencer celle-ci, voici notre petit cadeau : un épisode spécial ! Nous avons le plaisir de recevoir quatre collégiens autour d'une table ronde sur le sujet énigmatique "Mais au fait, c'est quoi la thèse ?". Vous retrouvez Maria Imezar et Robin Kuhner , doctorants au Laboratoire d'Optique et Bioscience qui répondront ensembles aux questions de Teo Poelman, Aniss Balaazi, William Maguer et Adam Bouchenak, élèves de 3ème, animé par Amélie Elouin. - enregistrement et montage des interviews par les doctorants du Laboratoire d'Optique et Biosciences. - dépôt sur MediHal par Elsa BALDUZZI
• Abundance of G-Quadruplex Forming Sequences in the Hepatitis Delta Virus Genomes
  
  • Brázda Václav
  • Valková Natália
  • Dobrovolná Michaela
  • Mergny Jean-Louis
  ACS Omega, ACS Publications, 2024, 9, pp.4096-4101. Hepatitis Delta virus (HDV) is a unique and highly unusual RNA satellite virus that depends on the presence of the hepatitis B virus (HBV) to be infectious. Its single-stranded RNA genome is very compact and variable, consisting of eight major genotypes distributed unequally on various continents. The significance of noncanonical secondary structures in DNA or RNA, such as G-quadruplexes (G4s), is becoming more evident especially for transcription, replication, and translation. G4s are formed from guanine-rich sequences and have been found in most eukaryotic and prokaryotic genomes, as well as viruses. In this study, we analyzed the G-quadruplex propensity of HDV genomes using G4Hunter. In contrast to the HBV virus, which has a G4 density similar to that of the human genome, the HDV virus possesses a significantly higher number of potential quadruplex-forming sequences (PQS) with a density more than four times higher than that of the human genome. This observation suggests a crucial role for G-quadruplexes in HDV, particularly because the tracks with the potential to form G-quadruplexes are well conserved. Furthermore, the high prevalence of the G-quadruplex-forming sequence could represent a promising therapeutic target to control HDV replication. (10.1021/acsomega.3c09288)
  DOI : 10.1021/acsomega.3c09288
• Multiplexed Orthogonal Polarizations Harmonic Imaging for Probing Dynamic Biological Processes
  
  • Gleeson Matthew
  • Escot Sophie
  • Solinas Xavier
  • Asadipour Bahar
  • Supatto Willy
  • Mahou Pierre
  • Stringari Chiara
  • Beaurepaire Emmanuel
  ACS photonics, American Chemical Society, 2024, 11 (8), pp.3259-3266. Polarization-resolved nonlinear optical microscopy can provide label-free images of anisotropic biomaterials. Existing techniques are often limited by their complexity, chromaticity, or slowness. In this article, we propose a simple implementation based on the passive splitting of the excitation beam into slightly delayed orthogonally polarized pulse trains. Label-free second- and third-harmonic signals corresponding to each polarization state are separated by time-resolved photon counting, resulting in the acquisition of image pairs that are automatically registered with submicron spatial precision and nanosecond simultaneity. We demonstrate the utility of this small-footprint approach for live studies by presenting structural imaging of tubulin, myelinated axons, and blood vessels in zebrafish larvae, dynamic imaging of flowing microcrystals in the zebrafish larval otolith cavity, and mitotic spindles in dividing embryonic cells. (10.1021/acsphotonics.4c00660)
  DOI : 10.1021/acsphotonics.4c00660
• Inactivating negative regulators of cortical branched actin enhances persistence of single cell migration
  
  • Fokin Artem I
  • Boutillon Arthur
  • James John
  • Courtois Laura
  • Vacher Sophie
  • Simanov Gleb
  • Wang Yanan
  • Polesskaya Anna
  • Bièche Ivan
  • David Nicolas B
  • Gautreau Alexis M
  Journal of Cell Science, Company of Biologists, 2024, 137 (1), pp.jcs261332. The Rac1-WAVE-Arp2/3 pathway pushes the plasma membrane by polymerizing branched actin, thereby powering membrane protrusions that mediate cell migration. Here, using knock-down (KD) or knock-out (KO), we combine the inactivation of the Arp2/3 inhibitory protein Arpin, the Arp2/3 subunit ARPC1A and the WAVE complex subunit, CYFIP2, that all enhance the polymerization of cortical branched actin (CBA). Inactivation of the 3 CBA negative regulators increases migration persistence of human breast MCF10A cells, and of endodermal cells in the zebrafish embryo, significantly more than any single or double inactivation. In the triple KO, but not triple KD cells, the “super-migrator” phenotype was associated with a heterogenous down-regulation of vimentin expression and a lack of coordination in collective behaviors, such as wound healing and acinus morphogenesis. Re-expression of vimentin in triple KO cells restored to a large extent normal persistence of single cell migration, suggesting that vimentin down-regulation contributes to the maintenance of the super-migrator phenotype in triple KO cells. Constant excessive production of branched actin at the cell cortex thus commits cells into a motile state through changes in gene expression. (10.1242/jcs.261332)
  DOI : 10.1242/jcs.261332
• Emerging Functional Connections Between Metabolism and Epigenetic Remodeling in Neural Differentiation
  
  • Sánchez-Ramírez Edgar
  • Ung Thi Phuong Lien
  • Stringari Chiara
  • Aguilar-Arnal Lorena
  Molecular Neurobiology, Springer, 2024. Stem cells possess extraordinary capacities for self-renewal and differentiation, making them highly valuable in regenerative medicine. Among these, neural stem cells (NSCs) play a fundamental role in neural development and repair processes. NSC characteristics and fate are intricately regulated by the microenvironment and intracellular signaling. Interestingly, metabolism plays a pivotal role in orchestrating the epigenome dynamics during neural differentiation, facilitating the transition from undifferentiated NSC to specialized neuronal and glial cell types. This intricate interplay between metabolism and the epigenome is essential for precisely regulating gene expression patterns and ensuring proper neural development. This review highlights the mechanisms behind metabolic regulation of NSC fate and their connections with epigenetic regulation to shape transcriptional programs of stemness and neural differentiation. A comprehensive understanding of these molecular gears appears fundamental for translational applications in regenerative medicine and personalized therapies for neurological conditions. (10.1007/s12035-024-04006-w)
  DOI : 10.1007/s12035-024-04006-w
• Additive CHARMM Force Field for Pterins and Folates
  
  • Balduzzi Elsa
  • Yin Wenlu
  • Lambry Jean‐christophe
  • Myllykallio Hannu
  • Aleksandrov Alexey
  Journal of Computational Chemistry, Wiley, 2024, 46 (1). Folates comprise a crucial class of biologically active compounds related to folic acid, playing a vital role in numerous enzymatic reactions. One-carbon metabolism, facilitated by the folate cofactor, supports numerous physiological processes, including biosynthesis, amino acid homeostasis, epigenetic maintenance, and redox defense. Folates share a common pterin heterocyclic ring structure capable of undergoing redox reactions and existing in various protonation states. This study aimed to derive molecular mechanics parameters compatible with the CHARMM36 all-atom additive force field for pterins and biologically important folates, including pterin, biopterin, and folic acid. Three redox forms were considered: oxidized, dihydrofolate, and tetrahydrofolate states. Across all protonation states, a total of 18 folates were parameterized. Partial charges were derived using the CHARMM force field parametrization protocol, based on targeting reference quantum mechanics monohydrate interactions, electrostatic potential, and dipole moment. Bonded terms were parameterized using one-dimensional adiabatic potential energy surface scans, and two-dimensional scans to parametrize in-ring torsions associated with the puckering states of dihydropterin and tetrahydropterin. The quality of the model was demonstrated through simulations of three protein complexes using optimized and initial parameters. These simulations underscored the significantly enhanced performance of the folate model developed in this study compared to the initial model without optimization in reproducing structural properties of folate-protein complexes. Overall, the presented molecular mechanics model will be valuable for modeling folates in various redox states and serve as a staring point for parameterizing other folate derivatives. (10.1002/jcc.27548)
  DOI : 10.1002/jcc.27548
• Synergistic effect of Gemcitabin-loaded metal organic frameworks nanoparticles with particle therapy
  
  • Maury Pauline
  • Hirayama Ryoichi
  • Li Xue
  • Mahou Pierre
  • Porcel Erika
  • Schanne-Klein Marie-Claire
  • Lacombe Sandrine
  • Gref Ruxandra
  • Porcel Erika
  International Journal of Pharmaceutics, Elsevier, 2024, 665, pp.124721. Combination of nanoagents with radiations has opened up new perspectives in cancer treatment, improving both tumor diagnosis and therapeutic index. This work presents the first investigation of an innovative strategy that combines porous metal-organic frameworks (nanoMOFs) loaded with the anti-cancer drug Gemcitabine monophosphate (GemMP) and particle therapy-a globally emerging technique that offers more precise radiation targeting and enhanced biological efficacy compared to conventional radiotherapy. This radiochemotherapy has been confronted with two major obstacles limiting the efficacy of therapeutics when tested in vivo: (i) the presence of hypoxia, one of the most important causes for radiotherapy failure and (ii) the presence of a microenvironment, main biological barrier to the direct penetration of nanoparticles into cancer cells. On the one hand, this study explore the effects of hypoxia on drug delivery systems in combination with radiation, demonstrating that GemMP-loaded nanoMOFs significantly enhance the anticancer efficacy of particle therapy under both normoxic (pO₂ = 20 %) and hypoxic (pO₂ = 0.5 %) conditions. Notably, the presence of GemMP-loaded nanoMOFs allows the irradiation dose to be reduced by 1.4-fold in normoxia and at least 1.6-fold in hypoxia, achieving the same cytotoxic effect (SF=10 %) as carbon or helium ions alone. Synergistic effects between GemMP-loaded nanoMOFs and radiations have been observed and quantified. On the other hand, we also highlighted the ability of the nanoMOFs to diffuse through an extracellular matrix and accumulate in cells. An higher effect of the encapsulated GemMP than the free drug was observed, confirming the key role of the nanoMOFs in transporting the active substance to the cancer cells as a Trojan horse. This paves the way to the design of "all-in-one" nanodrugs where each component plays a role in the optimization of cancer therapy to maximize cytotoxic effects on hypoxic tumor cells while minimizing toxicity on healthy tissue. (10.1016/j.ijpharm.2024.124721)
  DOI : 10.1016/j.ijpharm.2024.124721
• New 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline derivatives: synthesis and biological evaluation as novel anticancer agents by targeting G-quadruplex
  
  • Guillon Jean
  • Le Borgne Marc
  • Milano Vittoria
  • Guédin-Beaurepaire Aurore
  • Moreau Stéphane
  • Pinaud Noël
  • Ronga Luisa
  • Savrimoutou Solène
  • Albenque-Rubio Sandra
  • Marchivie Mathieu
  • Kalout Haouraa
  • Walker Charley
  • Chevallier Louise
  • Buré Corinne
  • Largy Eric
  • Gabelica Valérie
  • Mergny Jean-Louis
  • Baylot Virginie
  • Ferrer Jacky
  • Idrissi Yamina
  • Chevret Edith
  • Desplat Vanessa
  • Schelz Zsuzsanna
  • Zupkó István
  Pharmaceuticals, MDPI, 2024, 17 (1), pp.30. The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines 12 and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines 13 are reported here in six steps starting from various halogeno-quinazoline-2,4-(1H,3H)-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines 12b, 12f, and 12i displayed the most interesting antiproliferative activities against six human cancer cell lines. In the series of quinoline derivatives, 6-phenyl-bis(3-dimethylaminopropyl)aminomethylphenylquinoline 13a proved to be the most active. G-quadruplexes (G4) stacked non-canonical nucleic acid structures found in specific G-rich DNA, or RNA sequences in the human genome are considered as potential targets for the development of anticancer agents. Then, as small aza-organic heterocyclic derivatives are well known to target and stabilize G4 structures, their ability to bind G4 structures have been determined through FRET melting, circular dichroism, and native mass spectrometry assays. Finally, telomerase inhibition ability has been also assessed using the MCF-7 cell line. (10.3390/ph17010030)
  DOI : 10.3390/ph17010030
• Daily life in the Open Biologist’s second job, as a Data Curator
  
  • Scorza Livia C.T.
  • Zieliński Tomasz
  • Kalita Irina
  • Lepore Alessia
  • El Karoui Meriem
  • Millar Andrew J
  Wellcome Open Research, F1000Research, 2024, 9, pp.523. Background: Data reusability is the driving force of the research data life cycle. However, implementing strategies to generate reusable data from the data creation to the sharing stages is still a significant challenge. Even when datasets supporting a study are publicly shared, the outputs are often incomplete and/or not reusable. The FAIR (Findable, Accessible, Interoperable, Reusable) principles were published as a general guidance to promote data reusability in research, but the practical implementation of FAIR principles in research groups is still falling behind. In biology, the lack of standard practices for a large diversity of data types, data storage and preservation issues, and the lack of familiarity among researchers are some of the main impeding factors to achieve FAIR data. Past literature describes biological curation from the perspective of data resources that aggregate data, often from publications. Methods: Our team works alongside data-generating, experimental researchers so our perspective aligns with publication authors rather than aggregators. We detail the processes for organizing datasets for publication, showcasing practical examples from data curation to data sharing. We also recommend strategies, tools and web resources to maximize data reusability, while maintaining research productivity. Conclusion: We propose a simple approach to address research data management challenges for experimentalists, designed to promote FAIR data sharing. This strategy not only simplifies data management, but also enhances data visibility, recognition and impact, ultimately benefiting the entire scientific community (10.12688/wellcomeopenres.22899.1)
  DOI : 10.12688/wellcomeopenres.22899.1
• Understanding the cell fate and behavior of progenitors at the origin of the mouse cardiac mitral valve
  
  • Farhat Batoul
  • Bordeu Ignacio
  • Jagla Bernd
  • Ibrahim Stéphanie
  • Stefanovic Sonia
  • Blanc Hugo
  • Loulier Karine
  • Simons Benjamin
  • Beaurepaire Emmanuel
  • Livet Jean
  • Pucéat Michel
  Developmental Cell, Elsevier, 2024, 59 (3). Congenital heart malformations include mitral valve defects, which remain largely unexplained. During embryogenesis, a restricted population of endocardial cells within the atrioventricular canal undergoes an endothelial-to-mesenchymal transition to give rise to mitral valvular cells. However, the identity and fate decisions of these progenitors as well as the behavior and distribution of their derivatives in valve leaflets remain unknown. We used single-cell RNA sequencing (scRNA-seq) of genetically labeled endocardial cells and microdissected mouse embryonic and postnatal mitral valves to characterize the developmental road. We defined the metabolic processes underlying the specification of the progenitors and their contributions to subtypes of valvular cells. Using retrospective multicolor clonal analysis, we describe specific modes of growth and behavior of endocardial cell-derived clones, which build up, in a proper manner, functional valve leaflets. Our data identify how both genetic and metabolic mechanisms specifically drive the fate of a subset of endocardial cells toward their distinct clonal contribution to the formation of the valve. (10.1016/j.devcel.2023.12.006)
  DOI : 10.1016/j.devcel.2023.12.006
• The circularly permuted globin domain of Androglobin exhibits atypical heme stabilization and nitric oxide interaction
  
  • Reeder Brandon J
  • Deganutti Giuseppe
  • Ukeri John
  • Atanasio Silvia
  • Svistunenko Dimitri A
  • Ronchetti Christopher
  • Mobarec Juan Carlos
  • Welbourn Elizabeth
  • Asaju Jeffrey
  • Vos Marten H
  • Wilson Michael T
  • Reynolds Christopher A
  Chemical Science, The Royal Society of Chemistry, 2024, 15 (18), pp.6738-6751. In the decade since the discovery of androglobin, a multi-domain hemoglobin of metazoans associated with ciliogenesis and spermatogenesis, there has been little advance in the knowledge of the biochemical and structural properties of this unusual member of the hemoglobin superfamily. Using a method for aligning remote homologues, coupled with molecular modelling and molecular dynamics, we have identified a novel structural alignment to other hemoglobins. This has led to the first stable recombinant expression and characterization of the circularly permuted globin domain. Exceptional for eukaryotic globins is that a tyrosine takes the place of the highly conserved phenylalanine in the CD1 position, a critical point in stabilizing the heme. A disulfide bond, similar to that found in neuroglobin, forms a closed loop around the heme pocket, taking the place of androglobin’s missing CD loop and further supporting the heme pocket structure. Highly unusual in the globin superfamily is that the heme iron binds nitric oxide as a five-coordinate complex similar to other heme proteins that have nitric oxide storage functions. With rapid autoxidation and high nitrite reductase activity, the globin appears to be more tailored toward nitric oxide homeostasis or buffering. The use of our multi-template profile alignment method to yield the first biochemical characterisation of the circularly permuted globin domain of androglobin expands our knowledge of the fundamental functioning of this elusive protein and provides a pathway to better define the link between the biochemical traits of androglobin with proposed physiological functions. (10.1039/D4SC00953C)
  DOI : 10.1039/D4SC00953C
• Mesure de la transparence cornéenne par l’analyse d’images oct
  
  • Plamann Karsten
  • Vilbert Maëlle
  • Bocheux Romain
  • Georgeon Cristina
  • Borderie Vincent
  • Pernot Pascal
  • Irsch Kristina
  Photoniques, EDP Sciences, 2024 (127), pp.46-51. La cornée est la première des deux lentilles de l’oeil. La transparence de la cornée saine est due à sa structure très régulière qui peut être perturbée en présence de pathologies. Pour diagnostiquer la transparence cornéenne, nous avons développé des méthodes basées sur l’analyse d’images obtenues par tomographie par cohérence optique (OCT) qui permettent d’obtenir des valeurs physiques comme le libre parcours moyen des photons et le pourcentage de transmission cohérente de la lumière, qui impactent la vision. (10.1051/photon/202412746)
  DOI : 10.1051/photon/202412746
• Structure of a DNA G-quadruplex that Modulates SP1 Binding Sites Architecture in HIV-1 Promoter
  
  • de Rache Aurore
  • Marquevielle Julien
  • Bouaziz Serge
  • Vialet Brune
  • Andreola Marie-Line
  • Mergny Jean-Louis
  • Amrane Samir
  Journal of Molecular Biology, Elsevier, 2024, 436 (2), pp.168359. Nucleic acid sequences containing guanine tracts are able to form non-canonical DNA or RNA structures known as G-quadruplexes (or G4s). These structures, based on the stacking of G-tetrads, are involved in various biological processes such as gene expression regulation. Here, we investigated a G4 forming sequence, HIVpro2, derived from the HIV-1 promoter. This motif is located 60 nucleotides upstream of the proviral Transcription Starting Site (TSS) and overlaps with two SP1 transcription factor binding sites. Using NMR spectroscopy, we determined that HIVpro2 forms a hybrid type G4 structure with a core that is interrupted by a single nucleotide bulge. An additional reverse-Hoogsteen AT base pair is stacked on top of the tetrad. SP1 transcription factor is known to regulate transcription activity of many genes through the recognition of Guanine-rich duplex motifs. Here, the formation of HIVpro2 G4 may modulate SP1 binding sites architecture by competing with the formation of the canonical duplex structure. Such DNA structural switch potentially participates to the regulation of viral transcription and may also interfere with HIV-1 reac- tivation or viral latency. (10.1016/j.jmb.2023.168359)
  DOI : 10.1016/j.jmb.2023.168359