85 research outputs found
Selective modulation of estrogen receptor alpha in metabolic and vascular protection : medical implication for a new hormonal treatment of menopause
No full textLa diminution de la production de 17&dièse946;-estradiol (E2) à la ménopause s’accompagne de nombreux troubles affectant la qualité de vie des femmes et augmente la survenue de pathologies telles que l’ostéoporose, l’obésité et les maladies cardiovasculaires. Cependant, en raison de préoccupations vis-à-vis du risque de maladies veineuses thromboemboliques et de cancer du sein, moins de 10% des femmes ont recours au traitement de la ménopause actuellement. Il est donc nécessaire de développer de nouvelles options thérapeutiques pour améliorer la santé des femmes. L’estétrol (E4), un œstrogène naturel de la grossesse, est actuellement en essai clinique de phase 3 comme nouveau traitement de la ménopause. Contrairement aux œstrogènes utilisés classiquement, l’E4 n’augmente pas les facteurs de la coagulation et pourrait limiter le risque de thrombose. Les travaux de mon équipe d’accueil ont mis en évidence que l’E4 confère plusieurs effets protecteurs sur le plan artériel dans des modèles précliniques de souris. Cette action bénéfique implique l’activation du récepteur aux œstrogènes (ER)&dièse945;. Toutefois, l’impact de cet œstrogène dans un contexte de perturbations métaboliques en réponse à un régime gras restait inconnu. L’objectif de mon travail de thèse a été double : déterminer l’impact de l’E4 dans un contexte de désordres métaboliques et progresser dans les mécanismes d’action de cet œstrogène dans la protection artérielle. Ainsi, j’ai pu montrer que : L’E4 offre une protection face aux effets délétères d’un régime gras sur différents paramètres métaboliques (prévention de l’obésité et de la stéatose hépatique, normalisation de la glycémie et de l’hyperlipidémie) et sur la paroi artérielle (prévention de l’athérosclérose). L’E4, comme l’E2, accélère la cicatrisation endothéliale après agression de la carotide. Cependant alors que l’E2 active directement ER&dièse945; dans la cellule endothéliale, l’action de l’E4 est relayée par ER&dièse945; dans les cellules musculaires lisses. Cette spécificité d’action de l’E4 est associée à une signature transcriptionnelle qui lui est propre, différente de l’E2 dans la carotide. Ce travail contribue à améliorer notre compréhension du mode d’action de l’E4 sur le plan métabolique et artériel et repositionne cet œstrogène naturel non pas comme un « œstrogène faible » mais comme un véritable modulateur sélectif de ER&dièse945;The decrease in 17&dièse946;-estradiol (E2) production occurring at the time of menopause is associated to a variety of disorders, which can affect greatly the quality of life of women. They also cause an increase in the occurrence of different pathologies such as osteoporosis and metabolic and cardiovascular diseases. However, due to concerns regarding the risk of thromboembolism and of breast cancer, less than 10% of women are currently taking a menopausal hormone treatment. Thus, developing new therapeutic strategies is of great necessity in order to improve women’s health. Estetrol (E4) is a natural estrogen produced by the fetal liver during pregnancy and is currently developed in phase III clinical trial as new hormone treatment. E4 does not increase the production of coagulation factors and thus could lessen the risk of thrombosis. My team’s research work demonstrated that E4 mediates several arterial protective effects in pre-clinical mouse models. These beneficial actions rely on the activation of estrogen receptor (ER)&dièse945;. However, the effect of E4 under metabolic stress, i.e. in response to a high fat diet, was unknown. My PhD project aimed at defining the impact of E4 on metabolic disorders and at exploring the mechanisms of action of this estrogen on the arterial wall. In this context, I shown that: E4 prevents the development of atheroma induced by a high fat diet and the associated metabolic disorders including obesity, liver steatosis, glucose intolerance and hyperlipidemia. As E2, E4 accelerates endothelial healing after injury of the carotid artery. In response to E2, this action depends on the activation of ER&dièse945; directly in endothelial cells, whereas the effect of E4 relies on ER&dièse945; in smooth muscle cells. This differential cellular targeting in response to E4 is associated to a unique transcriptional profile in the carotid, different from E2. Globally, this work refines our understanding of E4 action in metabolic and vascular tissues. Rather than a “weak estrogen”, E4 could be redefined as a selective estrogen receptor modulato
A Brief History of Human Time - Cross-verified Dataset
No full text
This cross-verified dataset contains 2.2 million individuals, it can be used for research purposes. This dataset is linked to the following paper that should be cited directly instead of the data itself:
Morgane Laouenan, Palaash Bhargava, Jean-Benoît Eyméoud, Olivier Gergaud, Guillaume Plique, Etienne Wasmer (2022) A cross-verified database of notable people, 3500BC-2018AD, Scientific Data, June 2022.
Bibtex:
@article{bhht3,
author = {Laouenan, Morgane and Bhargava, Palaash and Eyméoud, Jean-Benoît and Gergaud, Olivier and Plique, Guillaume and Wasmer, Etienne},
title = {A cross-verified database of notable people, 3500BC-2018AD},
journal = {Scientific Data},
publisher = {Nature Publishing Group},
year = {2022},
month = {Jun},
day = {09},
volume = {9},
number = {1},
pages = {290},
issn = {2052-4463},
doi = {10.1038/s41597-022-01369-4},
url = {https://doi.org/10.1038/s41597-022-01369-4}
}
This dataset is subject to CC-BY-SA licensing.
</p
A Brief History of Human Time - Codes & Datasets
No full text
This compressed folder includes the code used for scraping and building the dataset, the intermediate datasets and the (not cross-verified) exhaustive dataset. This dataset is linked to the following paper that should be cited directly instead of the data itself:
Morgane Laouenan, Palaash Bhargava, Jean-Benoît Eyméoud, Olivier Gergaud, Guillaume Plique, Etienne Wasmer (2022) A cross-verified database of notable people, 3500BC-2018AD, Scientific Data, June 2022.
Bibtex:
@article{bhht3,
author = {Laouenan, Morgane and Bhargava, Palaash and Eyméoud, Jean-Benoît and Gergaud, Olivier and Plique, Guillaume and Wasmer, Etienne},
title = {A cross-verified database of notable people, 3500BC-2018AD},
journal = {Scientific Data},
publisher = {Nature Publishing Group},
year = {2022},
month = {Jun},
day = {09},
volume = {9},
number = {1},
pages = {290},
issn = {2052-4463},
doi = {10.1038/s41597-022-01369-4},
url = {https://doi.org/10.1038/s41597-022-01369-4}
}
The intermediate files as well as the exhaustive database are not cross-verified and should not be used directly or under the full responsibility of users.
All datasets included in this folder are subject to CC-BY-SA licensing.
</p
Author response
No full textThe adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability
Role of saturated covers as oxygen buffers in cold climates
No full text[T]his report explores a hybrid-applied solution: the use of saturated covers, which involve lifting an elevated water table into a tailing impoundment that maintains saturation within the tailing profile without allowing excess water directly along the surface of the embankment. The objective of this project is to evaluate the efficacy of saturated covers in Northern regions by testing oxygen diffusion in a series of experiments with two levels of saturation using an instrumented column. While there has been some research detailing the beneficial use of saturated covers, such as in the Oxygen diffusion in saturated covers methodology and literature review (Gagne Turcotte et al., 2020) completed prior to this lab scale study, the methodology used within this study relied heavily on prediction variables/models: De and Kr, but
these proved to be more complicated than expected (Gagne Turcotte et al., 2020). Additionally, mine tailings by nature are rather unique and each sample of tailings has its own unique characteristics that need to be accounted for. Thus, the creation of this methodology occurred, with a specific emphasis on applied methods.--from IntroductionPublication is a an outcome of the oxygen diffusion in saturated covers project
Leslie Kaplan: Renverser la norme. A Round Table
No full textWith Leslie Kaplan (author), Julien Lefort-Favreau (Queens University), Jennifer Pap (University of Denver), Éric Trudel (Bard College), Nathalie Dupont (Bucknell University), Morgane Kieffer (Université Jean Monnet). Recorded on March 12, 2021
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