HAL Portal ESPCI (Ecole Supérieure de Physique et de Chimie Industrielles)
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Strain phylogroup and environmental constraints shape Escherichia coli dynamics and diversity over a 20-year human gut time series
International audienceEscherichia coli is an increasingly antibiotic-resistant opportunistic pathogen. Few data are available on its ecological and evolutionary dynamics in its primary commensal niche, the vertebrate gut. Using Illumina and/or Nanopore technologies, we sequenced whole genomes of 210 E. coli isolates from 22 stools sampled during a 20-year period from a healthy man (ED) living in Paris, France. All phylogroups, except C, were represented, with a predominance of B2 (34.3%), followed by A and F (19% each) phylogroups. Thirty-five clones were identified based on their haplogroup and pairwise genomic single nucleotide polymorphism distance and classified in three phenotypes according to their abundance and residence time: 25 sub-dominant/transient (52 isolates), five dominant/transient (48 isolates) and five dominant/resident (110 isolates). Four over five dominant/resident clones belonged to B2 and closely related F phylogroups, whereas sub-dominant/transient clones belonged mainly to B1, A and D phylogroups. The long residence times of B2 clones seemed to be counterbalanced by lower colonization abilities. Clones with larger within-host frequency persisted for longer. By comparing ED strain genomes to a collection of commensal E. coli genomes from 359 French individuals, we identified ED-specific genomic properties including an enrichment in genes involved in a metabolic pathway (mhp cluster) and the presence of a very rare antiviral defense island. The E. coli colonization within the gut microbiota was shaped by both the intrinsic properties of the strain lineages, in particular longer residence of phylogroup B2, and the environmental constraints such as diet or phages
C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity
International audienceInfants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders
Inertia-induced power-law scaling in martensites
Martensites subjected to quasistatic deformation are known to exhibit power law distributed acoustic emission in a broad range of scales, however, the origin of the observed scaling behavior and the mechanism of self-organization towards apparent criticality remains obscure. Here we argue that the power law structure of intermittent fluctuations can be at least partially interpreted as an effect of inertia. We build on the insight that inertial dynamics, evidenced by acoustic emission, can become an important factor if the underlying mechanical system is only marginally stable. We first illustrate the possibility of inertia-induced heavy-tailed avalanche size distributions using a prototypical example of a discrete chain with bi-stable springs. We then explore the effects of inertia in fully realistic two-and three-dimensional continuum models of elastic phase transitions. In particular, we demonstrate that a three-dimensional model can produce not only qualitative but also quantitative agreement with experiment.</div
Mouvement collectif de bactéries sans échelle
Microscopic propelling agents in suspension can exhibit collective motion, driving macroscopic flows through exerted forces and torques. These flows feature complex spatiotemporal patterns akin to turbulence. Though observed in various systems, the universalities of "active turbulence" remain unclear. One critical differentiator is the size selection mechanism: self-organization defines the dominant scale in autonomous systems, which varies based on the particular agent interactions. Here, we address the central question of length-scale selection for a dense suspension of swimming bacteria, an archetypal example of wet active matter undergoing active turbulence. In the case of bacteria suspensions, the hydrodynamic interactions cause the collective motion. Thus, the selection mechanism is the outcome of these non-linear interactions. Theoretically, the result of these non-linearities is not precisely established yet, but experimentally, it has been typically reported to be in the order of hundreds of microns.Here, we show that contrary to these seminal observations, motile E.coli suspensions display active turbulence reaching at least up to the millimeter scale. The extent of the turbulent vortices scales proportionally to the externally imposed confinement. Additionally, for large confinements, we find that the size of the collective motion can fluctuate significantly, which is associated with the formation of larger jet structures. To characterize this behavior, we establish an approximative value of the critical density at which the bacteria suspension becomes unstable as a function of confinement. We compute this by characterizing the dependence of T, the correlation time scale of the flow as a function of bacteria density, which theoretically is expected to be maximum at the onset of the active turbulence. We observe that the correlation time scale reaches up to minutes, and the peaks witnessing the transition are higher and better marked for larger confinement heights, consistent with a generic finite-size scaling expected for critical second-order transitions. Based on this, we conclude that bacteria turbulence is scale-free and limited only by confinement. Using a novel three-dimensional flow description relying on an AI-based Lagragian tracking of passive particles, we determine how the flow is organized in three dimensions. We observe a long gradient dependence with respect to z and an anisotropy between the components of the velocity field, where the z component is about half the magnitude of the x-y components. This has implications for the transport properties of the active fluid, which we can characterize since we have long 3D trajectories. We observe that consistent with the scaling of the size of the flow patterns, the diffusion of the passive particle increases with H, indicating new possibilities for enhanced mixing based on this scale-free critical fluid. Complementary to these results, we reveal a long transient state featuring a single large vortex occupying the entire domain. This state can reach up to 1 centimeter in size and appears regardless of the boundary conditions present at the outer perimeter of the sample. It is formed through a coarsening process where smaller turbulent vortex structures are merged. We identify that the ratio between the radius R and the height H is crucial to forming this state, where symmetrical chambers stabilize this type of single vortex structure, in agreement with previous studies of coherent states in smaller geometries. Finally, we use light-controlled bacteria to monitor the development of the instability of the bacteria suspension, discarding this initial instability as the reason for the formation of the large states. The formation of these large states indicates the presence of an inverse energy cascade in bacteria suspensions, allowing bacteria turbulence to reach finite Reynolds numbers.Les agents propulseurs microscopiques en suspension peuvent présenter un mouvement collectif, générant des flux macroscopiques par les forces et couples qu'ils exercent. Ces flux se caractérisent par des mouvement spatio-temporels complexes rappelant la turbulence. Bien qu'observée dans divers systèmes, l'universalité de cette "turbulence active" reste mal comprise. Un facteur déterminant est le mécanisme de sélection de l'échelle: l'auto-organisation dans les systèmes autonomes définit la taille dominante, qui varie selon les interactions des agents. Nous abordons ici la question sur la sélection d'échelle pour une suspension dense de bactéries, un exemple archétypal de matière active humide subissant une turbulence active. Dans ces suspensions, les interactions hydrodynamiques génèrent le mouvement collectif, et le mécanisme de sélection découle de ces interactions non linéaires. Théoriquement, le résultat de ces non-linéarités n'est pas encore bien établi, mais expérimentalement, l'échelle est typiquement de centaines de microns. Nous montrons que, contrairement à ces observations initiales, les suspensions de E. coli présentent une turbulence active atteignant au moins l'échelle millimétrique. L'étendue des vortex turbulents croît proportionnellement au confinement. Pour des confinements élevés, la taille du mouvement collectif fluctue significativement, associée à des structures de jets plus larges. Pour caractériser ce comportement, nous déterminons une densité critique approximative où la suspension devient instable en fonction du confinement, en analysant le temps de corrélation du flux, qui atteint un maximum au formation de la turbulence active. Ce temps de corrélation atteint plusieurs minutes, avec des pics marquant mieux la transition pour des confinements plus grands, en accord avec une mise à l'échelle finie attendue pour des transitions critiques du second ordre. Sur cette base, nous concluons que la turbulence bactérienne est sans échelle et limitée uniquement par le confinement. En utilisant une description tridimensionnelle basée sur un suivi lagrangien par IA de particules passives, nous déterminons comment le flux est organisé en 3D. Une dépendance en z et une anisotropie entre les composantes de vitesse sont observées, la composante z atteignant environ la moitié des composantes x-y. Cela influence les propriétés de transport du fluide actif, étudiées grâce à de longues trajectoires 3D. Conformément à l'échelle des motifs d'écoulement, la diffusion des particules passives croît avec H, ouvrant des perspectives pour un mélange optimisé dans ce fluide critique sans échelle. Nous révélons aussi un état transitoire prolongé avec un grand vortex unique occupant tout le domaine, atteignant 1 centimètre et se formant indépendamment des conditions aux limites. Ce vortex émerge par coalescence de structures turbulentes plus petites. Le rapport entre rayon R et hauteur H est crucial pour stabiliser cet état, en accord avec des études sur des géométries plus petites. Enfin, avec des bactéries contrôlées par la lumière, nous suivons l'instabilité initiale de la suspension, excluant celle-ci comme origine de ces grands états. Leur formation suggère une cascade d'énergie inverse, permettant à la turbulence bactérienne d'atteindre des nombres de Reynolds finis
Electronic interactions of a quatertiophene-based surfactant at the liquid/gas interface
International audienceWe report the synthesis of a new functional molecule, a quater-tiophene based surfactant, which can both adsorb at the water / gas interface (surface active molecule) and aggregates through pi-pi stacking interactions. We assess then the ability of this molecule to create these functionalities at interfaces. This interfacial functional aggregation, characterized here in situ for the first time, is probed thanks to Langmuir trough experiments and spectrometric ellipsometry. These results open some new routes for the design of new water based opto-electronic devices
Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials
International audienceThe objective of this work was to establish prognostic models in stage III colon cancer (CC) on the basis of transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA-France (validation set) trials. 3'RNA sequencing was performed in 1,733 patients from the PETACC-8 trial and 1,248 patients from the IDEA-France trial. Four transcriptomic signatures were analyzed: T-cell and macrophage M2 signatures, the expression of CXCL13, and a score on the basis of the Oncotype DX CC Recurrence Score using the same formula from the stromal score and the cell cycle score. The Immune Proliferative Stromal (IPS) score was defined as the number of dichotomized signatures that fall under the category of a dismal prognosis (from 0 to 4). Time to recurrence (TTR) was defined as the time from the date of random assignment to local and/or metastatic relapse and/or death because of CC, whichever occurs first. High Oncotype-like and M2 scores and low CXCL13 expression and T-cell score were associated with a shorter TTR. A multivariable model including these signatures and all known prognostic factors applied to the IDEA-France cohort by obtaining a value of this model for each patient showed TTR significantly different depending on the quartile of this value and a 3-year rate of patients without recurrence ranging from 56% for the lowest quartile to 89% for the highest quartile (P < .0001). The IPS score was significantly associated with TTR in multivariable analysis. Using transcriptomic data of patients with stage III CC from two large-scale adjuvant trials, a prognostic model on the basis of signatures of the TME and the cell cycle provides important information in addition to known prognostic factors for patient stratification on risk of recurrence
A novel method to study the ecological role of sleep in small mammals
Sleep, is a complex, vital, and universal behavior that strongly differs from mere inactivity. Its ecological role remains, however, largely unknown mostly owing to the lack of methodological tools to record animal sleep states in the wild. By using a small, low power consumption biologger, capable of recording brain activity, body movements, and core physiology, we were able to record and quantify key sleep parameters (circadian distribution, sleep stages and their fragmentation, …), in wild black rats (Rattus rattus) in their natural environment over multiple days. We developed a simple, rapid (<1h), surgical procedure using a custom subdermal flexible electrode that provides signal quality equivalent to the cortical electrodes classically used in lab experiments. We also validated a semi-captive procedure, where the animals could be recorded in their own environment, with ad libitum access to standardized food pellets, and contact with conspecifics without close interactions. Such a protocol allows for the direct investigation of biotic and abiotic factors, like social interactions, food availability or type, light, temperature, and stress, all of which may strongly impact sleep. By evaluating general behavior and sleep patterns in four wild rats over up to ten days after surgery and by tracking feeding behavior for over a month, we show that the animals do not display any obvious signs of pain or stress and stabilized their sleep patterns two days after manipulation. Altogether this novel method and procedure constitute a unique tool for assessing sleep variability and flexibility and provides a proof-of concept for sleep studies in small (<200 g) wild animals
Proceedings of the inaugural Lounsbery Awardee Meeting held in Paris. Fondation Cino et Simone del Duca September 26-27, 2024
International audienceThe prestigious Richard Lounsbery Prize, awarded annually to recognize scientific excellence in biology and medicine among French and American scientists, is administered alternately by the U.S. National Academy of Sciences and the French Académie des sciences. To promote collaboration, the associated French American Scientific Symposium, organized by recent prize recipients, provides a unique forum for dynamic exchanges. The inaugural meeting, held in Paris on September 26-27, 2024, brought together 90 researchers. Featuring 18 oral presentations and nearly 20 posters by leading and emerging scientists, discussions spanned diverse topics, including neuroscience, genetics, developmental biology, and innovative biotechnologies. This spirit of shared discovery has highlighted groundbreaking research, aiming to foster practical applications in medicine and strengthen transatlantic partnerships for future scientific advancements.Le prestigieux prix Richard Lounsbery, décerné chaque année pour récompenser l'excellencescientifique en biologie et en médecine parmi les scientifiques français et américains, estadministré alternativement par l'Académie nationale des sciences des États-Unis etl'Académie des sciences de France. Afin de promouvoir la collaboration, ce symposiumscientifique franco-américain, organisé par les récents lauréats du prix, constitue un forumunique pour des échanges dynamiques. La réunion inaugurale, qui s'est tenue à Paris les 26et 27 septembre 2024, a rassemblé 90 chercheurs, scientifiques de premier plan commejeunes prometteurs autour de sujets variés divers et notamment les neurosciences, lagénétique, la biologie du développement et les biotechnologies innovantes. Ces échanges,qui ont mis en lumière des recherches révolutionnaires, permettront de favoriser lesapplications pratiques en médecine et à renforcer les partenariats transatlantiques pour defutures avancées scientifique
Ion Mobility Mass Spectrometry to Probe Sequences in Supramolecular Copolymers
International audienceThe analysis of the microstructure of supramolecular copolymers is difficult because of their dynamic character. Here, benzene‐1,3,5‐tricarboxamide (BTA) co‐assemblies are analysed by ion mobility ‐ mass spectrometry (IM‐MS) to reveal the presence of various sequences. For example, the IM‐MS mobilogram for hexamers composed of 4 units from a first monomer and 2 units from a second monomer is a broad distribution due to the presence of 9 possible isomeric sequences, which can be sorted out based on calculated collision cross‐sections. This approach gives unprecedented information on supramolecular copolymer sequences
L'oncologie : de l'empirisme à la biologie intégrée
Nouvelle édition avec illustrations en couleursInternational audienceAprès des décennies d’études descriptives, la biologie du cancer vit une véritable révolution : les approches génétiques ont permis d’identifier les dérégulations cellulaires en jeu dans les tumeurs et de développer des traitements ciblés. Des travaux précurseurs ont ainsi élucidé l’action combinée de l’arsenic et de l’acide rétinoïque sur la protéine responsable de la leucémie promyélocytaire. Ce traitement, qui a permis de guérir la quasi-totalité des patients, suscite l’espoir que la compréhension intime des mécanismes de la cancérogénèse puisse bientôt déboucher sur de nouvelles approches thérapeutiques transposables à d’autres cancers