CRISPR-Cas : an efficient tool for genome engineering of virulent bacteriophages

Bacteriophages are now widely recognized as major players in a wide variety of ecosystems. Novel genes are often identified in newly isolated phages as well as in environmental metavirome studies. Most of these novel viral genes have unknown functions but appear to be coding for small, non-structural proteins. To understand their biological role, very efficient genetic tools are required to modify them, especially in the genome of virulent phages. We first show that specific point mutations and large deletions can be engineered in the genome of the virulent phage 2972 using the Streptococcus thermophilus CRISPR-Cas Type II-A system as a selective pressure to increase recombination efficiencies. Of significance, all the plaques tested contained recombinant phages with the desired mutation. Furthermore, we show that the CRISPR-Cas engineering system can be used to efficiently introduce a functional methyltransferase gene into a virulent phage genome. Finally, synthetic CRISPR bacteriophage insensitive mutants were constructed by cloning a spacer-repeat unit in a low-copy vector illustrating the possibility to target multiple regions of the phage genome. Taken together, this data shows that the CRISPR-Cas system is an efficient and adaptable tool for editing the otherwise intractable genomes of virulent phages and to better understand phage-host interactions

Experimental Phase Equilibria: Data and Models

Equilibria between silicate melts, crystalline and vapour phases essentially control major and trace element compositions of natural magmas and play an essential role in partial melting as well as in differentiation processes. The development of models of phase equilibria is a prerequisite for assessing the dynamics of magmatic processes, such as magma storage in a reservoir or magma ascent in a conduit. The interest of experimental phase equilibria is essentially twofold. (1) Experimental phase equilibrium results can put precise constraints on the magmatic conditions, either in the magma storage region or in the conduit. Knowledge of pre-eruptive parameters (P, T, H2O in melt, fO2, ...) is necessary for eruption models and consequently for the evaluation of volcanic risk. (2) Experimental phase equilibria constitute our main source of information for the calibration of the mixing properties of multicomponent silicate melts, and for the construction of thermodynamic models which are our tomorrow's tools for the simulation of magmatic processes

CRISPR-Cas : un nouvel outil pour l'étude des génomes de bactériophages

Les bactériophages sont maintenant reconnus pour jouer un rôle majeur dans divers écosystèmes. De nouveaux gènes sont fréquemment identifiés dans les génomes de ces bactériophages issus de différentes études environnementales. La majorité de ces gènes ne peuvent être associés à une fonction connue, d’où la nécessité de développer des outils génétiques performants afin mieux comprendre leur rôle dans la biologie des bactériophages virulents. Dans ce projet de maîtrise, le système CRISPR-Cas de la souche Streptococcus thermophilus DGCC7710 a été utilisé afin de pouvoir étudier des gènes sans fonction connue du bactériophage virulent 2972. Des mutations ponctuelles ainsi que de petites et de grandes délétions ont été réalisées dans le génome de phages virulents en utilisant le système CRISPR-Cas comme pression sélective. Finalement, la méthylation de l’ADN phagique a été démontrée suite à l’insertion d’un gène codant pour une méthyltransférase bactérienne dans le génome du phage 2972.Bacteriophages are now widely recognized as major players in a wide variety of ecosystems. Novel genes are often identified in newly isolated phages as well as in environmental metavirome studies. Most of these novel viral genes have unknown functions but appear to be coding for small, non-structural proteins. To understand their biological role, very efficient genetic tools are required to modify them, especially in the genome of virulent phages. For this MSc project, specific point mutations and large deletions can be engineered in the genome of the virulent phage 2972 using the Streptococcus thermophilus CRISPR-Cas Type II-A. Furthermore, the CRISPR-Cas engineering system can be used to efficiently introduce a functional methyltransferase gene into a virulent phage genome. Finally, synthetic CRISPR bacteriophage insensitive mutants were constructed by cloning a spacer-repeat unit in a low copy vector illustrating the possibility to target multiple regions of the phage genome

Effets de l'entraînement par intervalles à haute intensité sur le profil de risque cardiométabolique de femmes présentant de l'obésité abdominale

L'obésité abdominale est associée à différents problèmes de santé tels qu’une augmentation du risque de diabète de type 2 et de maladies cardiovasculaires. L’activité physique est un élément clé dans la prise en charge de l’obésité. En effet, elle permet de diminuer le risque cardiométabolique. Peu d’études se sont toutefois intéressées à déterminer la meilleure modalité d’entraînement spécifiquement chez les femmes adultes qui présentent une obésité abdominale. Objectifs : Comparer l’impact de deux modalités d’entraînements cardiovasculaires (entraînement continu d’intensité modérée (MICT) et entraînement par intervalles à haute intensité (HIIT)) qui procurent la même dépense énergétique sur le profil de risque cardiométabolique de femmes caractérisées par la présence d’obésité abdominale. Méthodes : Vingt femmes avec obésité abdominale ont été randomisées en deux groupes. Ainsi, 10 femmes (41,8 ± 8,9 ans) ont pris part au groupe MICT et 10 femmes (37,8 ± 5,7 ans), au groupe HIIT. Elles devaient s’entraîner 3 fois par semaine durant 12 semaines et les entraînements n’étaient pas supervisés. Les données physiques et métaboliques ont été recueillies au début et à la fin du programme. Un test-t de Student pour données appariées a été réalisé afin de comparer la moyenne des données au temps 1 et au temps 2 pour chacun des groupes. Les changements entre les deux groupes ont été comparés à l’aide d’un test-t de Student pour données non appariées. Les données recueillies sont des données préliminaires, car l’étude est toujours en cours. Résultats : L’intervention MICT et HIIT n’a entraîné aucune amélioration significative de la VO₂max. Aucune différence significative n’a été constatée suite à l’intervention dans les facteurs de risque cardiométaboliques, et ce, à la fois pour le groupe MICT et le groupe HIIT. Finalement, il n’y a aucune différence significative entre les deux groupes concernant les changements, et ce, pour tous les paramètres étudiés. Conclusions : Nos données préliminaires démontrent que le MICT et le HIIT n’ont provoqué aucun changement significatif, et ce, à la fois au niveau de la condition physique ou du profil de risque cardiométabolique.Abdominal obesity is associated with various health problems such as an increased risk of type 2 diabetes and cardiovascular disease. Physical activity is a key element in the management of obesity as it reduces the cardiometabolic risk. Few studies have, however, been interested in determining the best training modality specifically for adult women having abdominal obesity. Objectives: To compare the impact of two cardiovascular training methods (continuous moderate intensity training(MICT) and high intensity interval training (HIIT)) which provide the same energy expenditure on the cardiometabolic risk profile of women characterized by the presence of abdominal obesity. Methods: A total of 20 women with abdominal obesity were randomized into two groups.Thus, 10 women (41.8 ± 8.9 years) took part in the MICT group and 10 women (37.8 ± 5.7 years) in the HIIT group. They had to train 3 times a week for 12 weeks and the training sessions were not supervised. Physical and metabolic data were collected at the beginning and end of the program. A Student's t-test for paired data was performed in order to compare the mean of the data at time 1 and at time 2 for each group. Changes between the two groups were compared using a Student t-test for unpaired data. The data collected is preliminary data as the study is still ongoing. Results: No significant change in VO₂max were observed following the intervention in the MICT and HIIT groups. Following the intervention, no significant difference was found in the cardiometabolic risk factors for the MICT and HIIT groups. Finally, there is no significant difference between the two groups regarding changes for all parameters studied. Conclusions: Our preliminary data shows that MICT and HIIT interventions were not associated with significant improvements inVO₂max or in cardiometabolic risk profile

Neurogenèse de la respiration chez la lamproie

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Phase equilibrium constraints on the viscosity of silicic magmas with implications for mafic-silicic mixing processes

Isobaric crystallization paths obtained from phase equilibrium experiments show that, whereas in rhyolitic compositions melt fraction trends are distinctly eutectic-like, dacitic and more mafic compositions have their crystallinities linearly correlated with temperature. As a consequence, the viscosities of the latter continuously increase on cooling, whereas for the former they remain constant or even decrease during 80% of the crystallisation interval, which opens new perspectives for the fluid dynamical modeling of felsic magma chambers. Given the typical dike widths observed for basaltic magmas, results of analogue modelling predict that injection of mafic magmas into crystallizing intermediate to silicic plutons under pre-eruption conditions cannot yield homogeneous composition. Homogenization can occur, however, if injection takes place in the early stages of magmatic evolution (i.e. at near liquidus conditions) but only in magmas of dacitic or more mafic composition. More generally, the potential for efficient mixing between silicic and mafic magmas sharing large interfaces at upper crustal levels is greater for dry basalts than for wet ones. At the other extreme, small mafic enclaves found in many granitoids behave essentially as rigid objects during a substantial part of the crystallization interval of the host magmas which implies that finite strain analyses carried out on such markers can give only a minimum estimate of the total amount of strain experienced by the host pluton. Mafic enclaves carried by granitic magmas behave as passive markers only at near solidus conditions, typically when the host granitic magma shows near-solid behavior. Thus they cannot be used as fossil indicators of direction of magmatic flow

FOXO family isoforms

FOXO family of proteins are transcription factors involved in many physiological and pathological processes including cellular homeostasis, stem cell maintenance, cancer, metabolic, and cardiovascular diseases. Genetic evidence has been accumulating to suggest a prominent role of FOXOs in lifespan regulation in animal systems from hydra, C elegans, Drosophila, and mice. Together with the observation that FOXO3 is the second most replicated gene associated with extreme human longevity suggests that pharmacological targeting of FOXO proteins can be a promising approach to treat cancer and other age-related diseases and extend life and health span. However, due to the broad range of cellular functions of the FOXO family members FOXO1, 3, 4, and 6, isoform-specific targeting of FOXOs might lead to greater benefits and cause fewer side effects. Therefore, a deeper understanding of the common and specific features of these proteins as well as their redundant and specific functions in our cells represents the basis of specific targeting strategies. In this review, we provide an overview of the evolution, structure, function, and disease-relevance of each of the FOXO family members.Agencia Estatal de Investigation and the European Regional Development Fund (PID2022-136654OB-I00 financed by MCIN/AEI /10.13039/501100011033 / FEDER, UE).info:eu-repo/semantics/publishedVersio

ОПАЛЬНИЙ ГОЛОВА ОБЛВИКОНКОМУ Г.Г. ДЕМЕНТЬЄВ

У статті висвітлюється життя та діяльність в органах міського самоврядування першого секретаря Дніпропетровського обкому КП(б)У та голови виконкому обласної ради депутатів трудящих, учасника Великої Вітчизняної війни 1941-1945 рр Г.Г.ДементьєваThis article introduces G.G.Dementyevs life and activities in local governmental organs. G.G.Dementyev was the first Secretari of Dniepropetrovsk Regional Executive Committee of the Communist Party ( bolchevyks) of Ukraine, participant in the Great Patriotic War ( from 1941-1945 )