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Comprehensive mapping of transcription terminator Rho utilization (Rut) sites across the Mycobacterium tuberculosis genome
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The Reticular formation: An integrative network for postural control
No full textInternational audienceThe reticular formation (RF), a complex network within the brainstem, plays a pivotal role in postural control, by integrating multisensory information and coordinating motor responses, to maintain balance and stability. This theoretical review synthesizes current knowledge on the anatomical and functional organization of the RF, highlighting its contributions to muscle tone regulation, anticipatory postural adjustments (APA), and gaze stability. Anatomically divided into median, paramedian, and lateral columns, the RF operates through both ascending and descending pathways. The ascending reticular activating system (ARAS) regulates arousal andalertness, while the descending reticulospinal tracts modulate postural muscle tone and motor coordination. Functionally, the RF maintains baseline muscle tone via excitatory and inhibitory pathways and supports APA by preparing the body for movement-induced perturbations. Moreover, the RF is integral to the coordination of eye and head movements, ensuring visual stability during motion. Collectively, these mechanisms position the RF as a central integrator of posture and movement, with implications for understanding motor control and informinginterventions in neurorehabilitation and movement optimization.La formation réticulée (FR), un réseau complexe situé dans le tronc cérébral, joue un rôle central dans le contrôle postural en intégrant des informations multisensorielles et en coordonnant les réponses motrices afin de maintenir l’équilibre et la stabilité. Cette revue théorique synthétise les connaissances actuelles sur l’organisation anatomique et fonctionnelle de la FR, en soulignant ses contributions à la régulation du tonus musculaire, aux ajustements posturaux anticipés (APA) et à la stabilité du regard. Anatomiquement, la FR est divisée en colonnes médiane, paramédiane et latérale, et fonctionne à travers des voies ascendantes et descendantes. Le système réticulaire activateur ascendant (SRAA) régule l’éveil et la vigilance, tandis que les faisceaux réticulospinaux descendants modulent le tonus musculaire postural et la coordination motrice. Sur le plan fonctionnel, la FR maintient le tonus musculaire de base par l’intermédiaire de voies excitatrices et inhibitrices, et soutient les APA en préparant le corps aux perturbations induites par le mouvement. De plus, la FR est essentielle à la coordination des mouvements des yeux et de la tête, garantissant la stabilité visuelle lors des déplacements. Dans leur ensemble, ces mécanismes placent la FR comme intégrateur central de la posture et du mouvement, avec des implications majeures pour la compréhension du contrôle moteur et l’élaboration d’interventions en neuro-rééducation et en optimisation du mouvement
Comparative Evaluation of Nozzle Designs for Enhanced Oxaliplatin Delivery in Pressurized IntraPeritoneal Aerosol Chemotherapy: An In Vivo Study of a Porcine Model
No full textInternational audienceVarious nozzle designs are used in pressurized intraperitoneal aerosol chemotherapy (PIPAC), but comparative in vivo data on their pharmacologic effects are limited.Three groups of four pigs each received PIPAC with oxaliplatin (92 mg) using nebulizers with different designs: group 1 (full-spray-cone single directional), group 2 (hollow-spray-cone single directional), and group 3 (full-spray-cone multidirectional). Oxaliplatin concentrations (mu g/g) were measured in blood, peritoneal tissue, and intra-abdominal fluid using inductively coupled plasma mass spectrometry.No significant differences in mean oxaliplatin concentrations in peritoneal tissue were observed: group 1 (12.37 +/- 10.81 mu g/g), group 2 (5.83 +/- 6.18 mu g/g), group 3 (9.46 +/- 6.10 mu g/g) ( p = 0.1002). However, group 3 had a significantly higher mean total oxaliplatin concentration in visceral peritoneal tissue (3.97 +/- 0.63 mu g/g) than group 1 (2.6 +/- 0.56 mu g/g) or group 2 (2.15 +/- 0.37 mu g/g ( p = 0.028). The mean total tissue uptake was also higher in group 3 (41.98 mg) than in group 1 (28.14 mg) or group 2 (36.65 mg) (p = 0.05). Pairwise comparisons showed no significant differences (group 1 vs group 2 [p = 0.1000], group 2 vs group 3 [p = 0.700]). No significant differences in blood absorption were noted (p = 0.106).The full-spray-cone multidirectional nebulizer design in group 3 resulted in significantly higher oxaliplatin concentrations in the small bowel peritoneum with greater total oxaliplatin tissue uptake than with the two other designs
Irisin decreases follicle development in cattle and inhibits theca cell steroidogenesis through focal adhesion kinase signaling
No full textInternational audienceIn brief Irisin is a muscle and adipose-derived hormone that is secreted in response to negative energy balance in cattle. We show here that irisin reduced follicle growth and theca cell function. Abstract At the onset of lactation, dairy cattle are anestrous owing mainly to a state of negative energy balance. Adipose tissue is mobilized to meet the energy demands of milk production, and this alters the secretion of adipose-derived hormones, called adipokines. Irisin is a myokine/adipokine that may play a role in fertility; plasma concentrations increase in cattle postpartum, and irisin decreased progesterone and estradiol secretion from bovine granulosa cells in vitro . To our knowledge, the effects of irisin on bovine theca cell function in vitro and on follicle growth in vivo have not been reported. We hypothesized that irisin negatively affects theca cell function in vitro and causes follicle regression in vivo using well-established bovine models. Under physiological concentrations of insulin (0.2 ng/mL), irisin did not affect glucose uptake, but decreased testosterone secretion and stimulated PTK2 and MTOR phosphorylation. Inhibiting PTK2 activity abolished the ability of irisin to decrease testosterone secretion. Injection of irisin directly into a growing follicle in vivo caused follicle regression. We conclude that irisin decreases bovine theca cell steroidogenesis through PTK2 signaling, and combined effects on theca and granulosa cells cause follicle regression
Trump et le canal de Panama
No full textInternational audience[Résumé de l'ouvrage] Un spectre hante le monde : la fragmentation - après des décennies chantant l'ouverture et l'unification sous le signe du progrès technique et de l'accélération des échanges. On passerait ainsi d'un espace mondialisé à un espace haché, émietté en égoïsmes nationaux, intérêts égoïstes insoucieux des autres, effaçant au passage l'espoir d'une gouvernance faisant écho aux intérêts communs d'une humanité unie
La didattica dei segnali discorsivi nell'aula di lingue straniere. Insegnare ad essere partecipanti competenti all'interazione attraverso l'uso di corpora conversazionali
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Molecular recognition of fungal methylated glucosylceramides by ETD151 defensin
No full textInternational audienceThe growing resistance to antifungal drugs and the limited number of antifungals currently available highlight the need for new antifungal strategies. In this context, there is significant potential for plant and insect antifungal defensins, which target fungal glucosylceramides (GlcCer), a growth and virulence determinant. The ETD151 peptide, optimized from the insect defensin Heliomicin, binds to fungal GlcCer as a crucial step in its activity. Nevertheless, further investigation is necessary to elucidate the mechanisms by which ETD151 targets fungal GlcCer at the molecular and atomic scales. The binding affinity was experimentally measured with isothermal titration calorimetry and microscale thermophoresis. The results collectively revealed affinity with a membrane-bound methylated GlcCer in the micromolar range. NMR has been employed to identify the area of ETD151 that would monopolize methylated GlcCer binding, including the two adjacent hydrophobic loops. Furthermore, our findings indicate that ETD151 specifically inserts into and disorders phosphatidylcholine lipid vesicles containing methylated GlcCer. Finally, it is worth noting that the C9-methyl in the sphingoid base plays a pivotal role in the ETD151–GlcCer interaction. Its presence increases the binding affinity between the two partners, resulting in stronger structural changes in ETD151 and deeper insertion into the hydrophobic core of model membranes. This study reveals key biochemical and structural elements of the ETD151–GlcCer interaction, provides a basis for elucidating the structure and dynamics of other GlcCer-targeting defensins in relation to their function, and facilitates the development of defensin-mimetic antifungals
Sedimentation and erosion of fluid-solid systems
No full textThis manuscript synthesizes the main research investigations that I developed since my arrival as associate professor at the University of Tours. These activities are mainly devoted to the physical modeling of extreme events (pyroclastic flows, lahars), involving particulate suspensions, while seeking to understand how sediments transported in these flows settle, and later in their course, over a broader time and space scale, how these sedimentary reservoirs rearrange when exposed to erosion processes during floods. The hazardous nature of these phenomena may often limit their direct observation through video footages, then requiring the implementation of indirect observation methods as well as the description of the physical processes involved through laboratory experiments to overcome the persistent locks of the literature. The first research project presents the description of the fluidization and sedimentation of particles (of variable size, density, and shape) homogeneously suspended into a viscous fluid (of variable density and viscosity). Experiments of gas-solid and liquid-solid suspensions generated in a non-confined reservoir allowed us to propose a general expression of the particle sedimentation velocity from that determined for an isolated particle falling into a pure fluid at rest to which a density and a viscosity correction are required, such as considering the suspension as an equivalent fluid of similar properties. This universal law, determined in the Stokes flow regime, allowed us to describe the effect of the solid concentration as well as that of the particle inertia on the settling velocity. The particle inertia was also observed to control the minimum concentration of the mixture and thus the limit of the bed stability. The investigation of the bed surface fluctuations allowed us to highlight the propagation of concentration waves within the suspension, traveling from the base to the surface, whose wavelengths seem indicating that the bed becomes unstable when the size of heterogeneities may become of the order of that of the reservoir. The second research project presents the transport and sedimentation behavior of the suspensions once released down the dam-break flume. To describe such experimental free-surface flows, made with gas-solid and liquid-solid suspensions taken at different concentrations, we proposed a physical model in which the homogeneous mixture travels and settles independently, at constant speed, while ultimately forming a deposit of constant slope which can be predicted from the two characteristic velocities. Numerical simulations indicate that both the kinematics and deposits geometry are satisfyingly captured by the model, provided that the mixture agitation does not disturb the particle deposition considered similar to that developed in a static suspension of same concentration. Once accumulated down the deltaic plain, the sedimentary reservoir is likely to be confronted to reworking during upcoming events of floods and thus to be affected by erosion through internal seepage flows where a part of the soil, especially the fine matrice, can be ultimately transported towards the surface and gives rise to signatures around the diked river. The third research project presents geophysical observations of the river paleo-environment which provides an overview of the geomorphological situation and allowed us to understand the origin of erosion signatures, while representing the starting point for geomechanical simulations. Numerical predictions of the soil erosion, located beneath the river bed and dikes, developed after repeated episodes of floods, allowed us to explain the distribution of leaks, sand-boils, sinkholes along the protected plain and to characterize situations which may question the safety of the hydraulic facility
Identification and validation of robust hospital-acquired pneumonia subphenotypes associated with all-cause mortality: a multi-cohort derivation and validation
No full textInternational audiencePurpose: Despite optimal antimicrobial therapy, the treatment failure rate of hospital-acquired pneumonia (HAP) routinely reaches 40% in critically ill patients. Subphenotypes have been identified within sepsis and acute respiratory distress syndrome with important predictive and possibly therapeutic implications. We derived prognosis subphenotypes for HAP and explored whether they were associated with biological markers and response to treatment.Methods: We separately analysed data from four cohorts of critically ill patients in France (PNEUMOCARE, n=511, ATLANREA, n=401), Netherlands (MARS, n=1351) and Europe-South America (ENIRRI, n=900) to investigate HAP heterogeneity using unsupervised clustering based on clinical and routine biological variables available at HAP diagnosis. Then, we developed a machine learning-based workflow to create a simplified classification model using discovery datasets. This model was validated by applying it to an independent replication dataset from an international randomized clinical trial comparing linezolid and tedizolid for the treatment of HAP (VITAL, n=726 patients). The primary outcome was the association of subphenotypes with 28-day all-cause mortality. Secondary analyses included subphenotype associations with treatment failure at test-of-cure, respiratory microbiome and cytokine profiles in the ATLANREA subgroup, and treatment response in the VITAL trial.Results: We tested twelve metrics and determined that a two-cluster model best fits all cohorts. HAP subphenotype 2 had greater disease severity, lower body temperature, and worse PaO2/FiO2 ratio than subphenotype 1 patients. Although the prevalence of subphenotype 2 ranged from 26.9% to 66.9% across the four derivation cohorts, the rates of 28-day mortality and treatment failure at test-of-cure were consistently higher to subphenotype 1 (p<0.01 for all comparisons). Subphenotype 2 was associated with greater respiratory microbiome dysbiosis and higher levels of proinflammatory cytokines in the ATLANREA cohort, as well as with statistically significant tedizolid effect modification in the VITAL trial (Relative Risk of treatment failure with tedizolid = 1.52; 95%CI 1.12-2.06 in subphenotype 1 versus = 0.98; 95%CI 0.7-1.38 in subphenotype 2).Conclusion: We identified two robust clinical subphenotypes by extensively analyzing HAP datasets. Their associations with respiratory microbiome composition, systemic inflammation, and treatment efficacy in independent datasets highlight their potential for prognostic value and predictive enrichment in future clinical trials aimed at personalized therapies.Funding: European Union's Horizon 2020 research and innovation program under grant agreement number 847782 (HAP2 project).</p
Identification et caractérisation structurale de molécules bioactives présentes dans un aliment pour poulet de chair, enrichi en larves de mouche soldat noire
No full textLicencePoultry meat is currently the most widely consumed meat in the world, and its consumption is set to increase in the coming years. To feed these animals, the poultry industry depends on vegetable proteins from soya, which has to be imported. However, in view of the negative environmental impact, chicken producers are looking at alternative protein sources, produced more locally. Among these alternatives, insect proteins may be of great potential interest. In this context, one of the scientific projects conducted by the UMR BOA at INRAE Centre Val de Loire was to assess the performance of chickens fed black soldier fly larvae provided in different forms. The analysis of the larvae proteome allowed the identification of potential anti-nutritional factors (protease inhibitors) and antimicrobial peptides, the three-dimensional structure of which was then studied using various molecular modelling tools. A study of the protein profiles and proteolytic activity of the digestive contents of the chickens revealed no significant differences between the diets. Altogether, these results suggest that the larvae incorporated in the diet do not significantly affect the activity of the chicken digestive proteases. However, these larvae added in the diet could also contain original molecules likely to contribute to the animals' intestinal immunity.La viande de volaille est à l’heure actuelle la viande la plus consommée dans le monde et sa consommation devrait augmenter dans les années à venir. Pour nourrir ces animaux, la filière avicole dépend des protéines végétales du soja, importé. Cependant, au regard des impacts écologiques négatifs de la production de soja, les producteurs de poulets s’intéressent à des sources de protéines alternatives produites plus localement. Parmi celles-ci, les protéines d’insecte pourraient répondre à ces besoins. Dans ce contexte, un des projets menés par l’UMR BOA à l’INRAE Centre Val de Loire a consisté à évaluer les performances de poulets nourris avec des larves de mouche soldat noire apportées sous différentes formes. L’analyse du protéome des larves a permis d’identifier des facteurs antinutritionnels potentiels (inhibiteurs de protéases) ainsi que des peptides antimicrobiens, dont la structure tridimensionnelle a ensuite été étudiée par modélisation moléculaire. L’étude des profils protéiques et de l’activité protéolytique des contenus digestifs des poulets n’a pas mis en évidence de différences significatives entre les régimes alimentaires. Ces résultats suggèrent que les larves apportées dans l’aliment n’affectent pas de manière significative l’activité des protéases digestives des poulets. Cependant, ces larves incorporées dans l’aliment pourrait également contenir des molécules originales susceptibles de contribuer à l’immunité intestinale des animaux