Écrire pour la Postérité : entre justification et glorification de soi. Le cas du Testament politique et des mémoires du cardinal de Richelieu

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Knockout of Vdac1 activates hypoxia-inducible factor through reactive oxygen species generation and induces tumor growth by promoting metabolic reprogramming and inflammation

BACKGROUND: Mitochondria are more than just the powerhouse of cells; they dictate if a cell dies or survives. Mitochondria are dynamic organelles that constantly undergo fusion and fission in response to environmental conditions. We showed previously that mitochondria of cells in a low oxygen environment (hypoxia) hyperfuse to form enlarged or highly interconnected networks with enhanced metabolic efficacy and resistance to apoptosis. Modifications to the appearance and metabolic capacity of mitochondria have been reported in cancer. However, the precise mechanisms regulating mitochondrial dynamics and metabolism in cancer are unknown. Since hypoxia plays a role in the generation of these abnormal mitochondria, we questioned if it modulates mitochondrial function. The mitochondrial outer-membrane voltage-dependent anion channel 1 (VDAC1) is at center stage in regulating metabolism and apoptosis. We demonstrated previously that VDAC1 was post-translationally C-terminal cleaved not only in various hypoxic cancer cells but also in tumor tissues of patients with lung adenocarcinomas. Cells with enlarged mitochondria and cleaved VDAC1 were also more resistant to chemotherapy-stimulated cell death than normoxic cancer cells. RESULTS: Transcriptome analysis of mouse embryonic fibroblasts (MEF) knocked out for Vdac1 highlighted alterations in not only cancer and inflammatory pathways but also in the activation of the hypoxia-inducible factor-1 (HIF-1) signaling pathway in normoxia. HIF-1α was stable in normoxia due to accumulation of reactive oxygen species (ROS), which decreased respiration and glycolysis and maintained basal apoptosis. However, in hypoxia, activation of extracellular signal-regulated kinase (ERK) in combination with maintenance of respiration and increased glycolysis counterbalanced the deleterious effects of enhanced ROS, thereby allowing Vdac1 (-/-) MEF to proliferate better than wild-type MEF in hypoxia. Allografts of RAS-transformed Vdac1 (-/-) MEF exhibited stabilization of both HIF-1α and HIF-2α, blood vessel destabilization, and a strong inflammatory response. Moreover, expression of Cdkn2a, a HIF-1-target and tumor suppressor gene, was markedly decreased. Consequently, RAS-transformed Vdac1 (-/-) MEF tumors grew faster than wild-type MEF tumors. CONCLUSIONS: Metabolic reprogramming in cancer cells may be regulated by VDAC1 through vascular destabilization and inflammation. These findings provide new perspectives into the understanding of VDAC1 in the function of mitochondria not only in cancer but also in inflammatory diseases

Young children's understanding of disabilities: the influence of development, context and cognition

Throughout Europe, educational support for children with disabilities has moved towards a model of inclusive education. Such policy changes mean that for all children there will be an increased likelihood of working with and encountering children with differing disabilities and difficulties. Previous research had indicated that children had poorly differentiated views of developmental differences. The present study investigated children?s representations of different disabilities. Seventy-nine 8-9 and 10-11 year old Greek children from an urban school and a rural school completed an attitudes toward school inclusion rating scale and a semi-structured interview. Responses to the attitude scale provided generally positive views of educational inclusion. However, children were less positive about activities that might directly reflect upon themselves. Children?s responses in the interviews indicated that they were developing rich representations of differences and diversities. Children had the greatest understanding of sensory and physical disabilities, followed by learning disabilities. There was limited knowledge of dyslexia and hyperactivity and no child was familiar with the term autism. Both groups of children identified a range of developmental difficulties, with older children being more aware of specific learning disabilities, their origin and impact. Results are discussed in terms of children?s developing knowledge systems and the implications for educational practices

Panta Rhei benchmark dataset: socio-hydrological data of paired events of floods and droughts

As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions and feedbacks in complex human-water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e., two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed, and in the quantity of socio-hydrological data. The benchmark dataset comprises: 1) detailed review style reports about the events and key processes between the two events of a pair; 2) the key data table containing variables that assess the indicators which characterise management shortcomings, hazard, exposure, vulnerability and impacts of all events; 3) a table of the indicators-of-change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators-of-change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses e.g. focused on causal links between risk management, changes in hazard, exposure and vulnerability and flood or drought impacts. The data can also be used for the development, calibration and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al. 2023, link for review: https://dataservices.gfz-potsdam.de/panmetaworks/review/923c14519deb04f83815ce108b48dd2581d57b90ce069bec9c948361028b8c85/).</p

No detection of methane on Mars from early ExoMars Trace Gas Orbiter observations

The detection of methane on Mars has been interpreted as indicating that geochemical or biotic activities could persist on Mars today. A number of different measurements of methane show evidence of transient, locally elevated methane concentrations and seasonal variations in background methane concentrations. These measurements, however, are difficult to reconcile with our current understanding of the chemistry and physics of the Martian atmosphere, which-given methane's lifetime of several centuries-predicts an even, well mixed distribution of methane. Here we report highly sensitive measurements of the atmosphere of Mars in an attempt to detect methane, using the ACS and NOMAD instruments onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter from April to August 2018. We did not detect any methane over a range of latitudes in both hemispheres, obtaining an upper limit for methane of about 0.05 parts per billion by volume, which is 10 to 100 times lower than previously reported positive detections. We suggest that reconciliation between the present findings and the background methane concentrations found in the Gale crater would require an unknown process that can rapidly remove or sequester methane from the lower atmosphere before it spreads globally

Martian dust storm impact on atmospheric H₂O and D/H observed by ExoMars Trace Gas Orbiter

Global dust storms on Mars are rare but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere, primarily owing to solar heating of the dust. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars. Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes, as well as a decrease in the water column at low latitudes. Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H2O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals. The observed changes in H2O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere

Constraints on the structure and seasonal variations of Triton's atmosphere from the 5 October 2017 stellar occultation and previous observations

Context. A stellar occultation by Neptune's main satellite, Triton, was observed on 5 October 2017 from Europe, North Africa, and the USA. We derived 90 light curves from this event, 42 of which yielded a central flash detection. Aims. We aimed at constraining Triton's atmospheric structure and the seasonal variations of its atmospheric pressure since the Voyager 2 epoch (1989). We also derived the shape of the lower atmosphere from central flash analysis. Methods. We used Abel inversions and direct ray-tracing code to provide the density, pressure, and temperature profiles in the altitude range similar to 8 km to similar to 190 km, corresponding to pressure levels from 9 mu bar down to a few nanobars. Results. (i) A pressure of 1.18 +/- 0.03 mu bar is found at a reference radius of 1400 km (47 km altitude). (ii) A new analysis of the Voyager 2 radio science occultation shows that this is consistent with an extrapolation of pressure down to the surface pressure obtained in 1989. (iii) A survey of occultations obtained between 1989 and 2017 suggests that an enhancement in surface pressure as reported during the 1990s might be real, but debatable, due to very few high S/N light curves and data accessible for reanalysis. The volatile transport model analysed supports a moderate increase in surface pressure, with a maximum value around 2005-2015 no higher than 23 mu bar. The pressures observed in 1995-1997 and 2017 appear mutually inconsistent with the volatile transport model presented here. (iv) The central flash structure does not show evidence of an atmospheric distortion. We find an upper limit of 0.0011 for the apparent oblateness of the atmosphere near the 8 km altitude.J.M.O. acknowledges financial support from the Portuguese Foundation for Science and Technology (FCT) and the European Social Fund (ESF) through the PhD grant SFRH/BD/131700/2017. The work leading to these results has received funding from the European Research Council under the European Community's H2020 2014-2021 ERC grant Agreement nffi 669416 "Lucky Star". We thank S. Para who supported some travels to observe the 5 October 2017 occultation. T.B. was supported for this research by an appointment to the National Aeronautics and Space Administration (NASA) Post-Doctoral Program at the Ames Research Center administered by Universities Space Research Association (USRA) through a contract with NASA. We acknowledge useful exchanges with Mark Gurwell on the ALMA CO observations. This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium).Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. J.L.O., P.S.-S., N.M. and R.D. acknowledge financial support from the State Agency for Research of the Spanish MCIU through the "Center of Excellence Severo Ochoa" award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709), they also acknowledge the financial support by the Spanish grant AYA-2017-84637-R and the Proyecto de Excelencia de la Junta de Andalucia J.A. 2012-FQM1776. The research leading to these results has received funding from the European Union's Horizon 2020 Research and Innovation Programme, under Grant Agreement no. 687378, as part of the project "Small Bodies Near and Far" (SBNAF). P.S.-S. acknowledges financial support by the Spanish grant AYA-RTI2018-098657-J-I00 "LEO-SBNAF". The work was partially based on observations made at the Laboratorio Nacional de Astrofisica (LNA), Itajuba-MG, Brazil. The following authors acknowledge the respective CNPq grants: F.B.-R. 309578/2017-5; R.V.-M. 304544/2017-5, 401903/2016-8; J.I.B.C. 308150/2016-3 and 305917/2019-6; M.A. 427700/20183, 310683/2017-3, 473002/2013-2. This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) -Finance Code 001 and the National Institute of Science and Technology of the e-Universe project (INCT do e-Universo, CNPq grant 465376/2014-2). G.B.R. acknowledges CAPES-FAPERJ/PAPDRJ grant E26/203.173/2016 and CAPES-PRINT/UNESP grant 88887.571156/2020-00, M.A. FAPERJ grant E26/111.488/2013 and A.R.G.Jr. FAPESP grant 2018/11239-8. B.E.M. thanks CNPq 150612/2020-6 and CAPES/Cofecub-394/2016-05 grants. Part of the photometric data used in this study were collected in the frame of the photometric observations with the robotic and remotely controlled telescope at the University of Athens Observatory (UOAO; Gazeas 2016). The 2.3 m Aristarchos telescope is operated on Helmos Observatory by the Institute for Astronomy, Astrophysics, Space Applications and Remote Sensing of the National Observatory of Athens. Observations with the 2.3 m Aristarchos telescope were carried out under OPTICON programme. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 730890. This material reflects only the authors views and the Commission is not liable for any use that may be made of the information contained therein. The 1. 2m Kryoneri telescope is operated by the Institute for Astronomy, Astrophysics, Space Applications and Remote Sensing of the National Observatory of Athens. The Astronomical Observatory of the Autonomous Region of the Aosta Valley (OAVdA) is managed by the Fondazione Clement Fillietroz-ONLUS, which is supported by the Regional Government of the Aosta Valley, the Town Municipality of Nus and the "Unite des Communes valdotaines Mont-Emilius". The 0.81 m Main Telescope at the OAVdA was upgraded thanks to a Shoemaker NEO Grant 2013 from The Planetary Society. D.C. and J.M.C. acknowledge funds from a 2017 'Research and Education' grant from Fondazione CRT-Cassa di Risparmio di Torino. P.M. acknowledges support from the Portuguese Fundacao para a Ciencia e a Tecnologia ref. PTDC/FISAST/29942/2017 through national funds and by FEDER through COMPETE 2020 (ref. POCI010145 FEDER007672). F.J. acknowledges Jean Luc Plouvier for his help. S.J.F. and C.A. would like to thank the UCL student support observers: Helen Dai, Elise Darragh-Ford, Ross Dobson, Max Hipperson, Edward Kerr-Dineen, Isaac Langley, Emese Meder, Roman Gerasimov, Javier Sanjuan, and Manasvee Saraf. We are grateful to the CAHA, OSN and La Hita Observatory staffs. This research is partially based on observations collected at Centro Astronomico HispanoAleman (CAHA) at Calar Alto, operated jointly by Junta de Andalucia and Consejo Superior de Investigaciones Cientificas (IAA-CSIC). This research was also partially based on observation carried out at the Observatorio de Sierra Nevada (OSN) operated by Instituto de Astrofisica de Andalucia (CSIC). This article is also based on observations made with the Liverpool Telescope operated on the island of La Palma by Liverpool John Moores University in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias with financial support from the UK Science and Technology Facilities Council. Partially based on observations made with the Tx40 and Excalibur telescopes at the Observatorio Astrofisico de Javalambre in Teruel, a Spanish Infraestructura Cientifico-Tecnica Singular (ICTS) owned, managed and operated by the Centro de Estudios de Fisica del Cosmos de Aragon (CEFCA). Tx40 and Excalibur are funded with the Fondos de Inversiones de Teruel (FITE). A.R.R. would like to thank Gustavo Roman for the mechanical adaptation of the camera to the telescope to allow for the observation to be recorded. R.H., J.F.R., S.P.H. and A.S.L. have been supported by the Spanish projects AYA2015-65041P and PID2019-109467GB-100 (MINECO/FEDER, UE) and Grupos Gobierno Vasco IT1366-19. Our great thanks to Omar Hila and their collaborators in Atlas Golf Marrakech Observatory for providing access to the T60cm telescope. TRAPPIST is a project funded by the Belgian Fonds (National) de la Recherche Scientifique (F.R.S.-FNRS) under grant PDR T.0120.21. TRAPPIST-North is a project funded by the University of Liege, and performed in collaboration with Cadi Ayyad University of Marrakesh. E.J. is a FNRS Senior Research Associate

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field