Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-26, pub-electronic 2021-07-30Publication status: PublishedFunder: European Commission; Grant(s): 667787Funder: European Research Council; Grant(s): ERC-ADG-2014 671262Funder: Cancer Research UK; Grant(s): A27412 and A22902Funder: Institut Curie; Grant(s): #Funder: Ligue Contre le Cancer; Grant(s): #Funder: Institut National de la Santé et de la Recherche Médicale; Grant(s): #Conjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma, originating from partially sunlight-exposed mucosa. We explored the mutational landscape of ConjMel and studied the correlation with etiological factors. We collected 47 primary ConjMel samples and performed next-generation sequencing of 400 genes. Hotspot mutations in BRAF, NRAS, HRAS, and KIT were observed in 16 (34%), 5 (11%), 2, and 2 cases, respectively. Patients with BRAF and CDKN2A-mutated ConjMel tended to be younger while the NF1-mutated one tended to be older. The eight tumors arising from nevi were enriched in CTNNB1 mutations (63% vs. 8%; Fisher’s exact p-test = 0.001) compared to non-nevi ConjMel and five were devoid of BRAF, RAS, NF1, or KIT mutations, suggesting a specific oncogenic process in these tumors. The two KIT-mutated cases carried SF3B1 mutations and were located on sun-protected mucosa, a genotype shared with genital and anorectal mucosal melanomas. Targetable mutations were observed in ERBB2, IDH1, MET, and MAP2K1 (one occurrence each). Mutational landscape of ConjMel characterizes distinct molecular subtypes with oncogenic drivers common with mucosal and skin melanomas. CTNNB1 mutations were associated with nevus-derived ConjMel. Concomitant KIT/SF3B1 mutations in sun-protected cases suggest a common tumorigenic process with genital and anorectal mucosal melanomas

Targeted long-read sequencing of the Ewing sarcoma 6p25.1 susceptibility locus identifies germline-somatic interactions with EWSR1-FLI1 binding

Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Dépôts conformes par voie liquide sur toplogie 3D

International audienc

The toxicity of trace metal elements in Downy Oak in Gardanne Mining Basin

International audienceThe Gardanne mining basin is undoubtedly one of the peri‐urban territories of the Bouches‐du‐Rhône where air pollution is a major issue both in terms of public health and the preservation of natural environments. The various industrial activities, including the aluminum smelter, have contributed to exacerbating pollution with metallic trace elements [1;2]. Indeed, Bauxite manufacturing by the Bayer process in alumina production is associated with a by‐product, bauxite residue (BR), also termed “red mud”, a complex mixture of elemental constituents. Throughout the world, BR storage sites have been sources of adverse effects on the environment and the Mange Gary site is not an exception. The purpose of this work falls within the context of the environmental transition policy undertaken by the aluminum plant.We investigated the impact of the BR from Mange Garri on some populations of Quercus pubescens

Conflits environnementaux, milieux naturels et décisions publiques : Étude de deux cas industriels

International audienceAu travers d’études de cas, on explore ici la dynamique de deux conflits environnementaux portant sur des projets industriels affectant de manière significative des milieux naturels et on considère l’interaction des décisions publiques et privées. Le premier cas met en scène l’usine d’alumine ALTEO à Gardanne qui a rejeté des boues rouges dans la Méditerranée de 1967 à 2015 et qui a été autorisée ensuite à poursuivre un rejet d’eau sans éléments solides mais en dérogation à certaines normes. Le second cas concerne le projet d’une unité « biomasse » par le groupe E.ON pour alimenter une centrale électrique dans la même ville. Cette très grosse unité représente un enjeu pour les milieux terrestres car la ressource sera prélevée en partie dans un environnement subissant de multiples pressions. On décrit la dynamique des conflits, en identifiant les parties-prenantes et en mettant en exergue l’enchaînement de leurs décisions et en s’attachant particulièrement à celles des décisionnaires publics. On constate l’imbrication de niveaux décisionnels publics face à des enjeux liés aux milieux naturels car ceux-ci transcendent les découpages politiques et administratifs. On observe aussi que les attitudes des parties-prenantes, au-delà des intérêts avérés, expriment des « valeurs » accordées à la nature, dont les divergences sont amplifiées par la dispersion et la fragmentation des savoirs relatifs au fonctionnement des milieux naturels. Le recueil de 1 184 prises de position permet d’associer les attitudes envers les projets aux catégories de parties-prenantes. On examine aussi le rôle de la distance aux sites dans ces attitudes, en montrant que les déterminants des attitudes ne sont pas nécessairement liés à l’impact direct que peut ressentir chacune des parties-prenantes. On conclut en insistant sur la nécessité d’arènes de débat organisées par l’autorité publique pour favoriser la convergence des savoirs et de l’information.Through case studies we explore the dynamics of two environmental conflicts about industrial projects that affect significantly the natural milieus, and we consider the interactions between public and private decisions. The first case stages an alumina plant run by a French company ALTEO in Gardanne (France), which has dumped wastes called “red muds” in the Mediterranean sea as of 1967 until 2015 and which has be authorized to continue rejecting water, without solid particles, but in derogation to legal norms. The second case bears on the project of “biomass” unit by the German group E.ON to provide energy for power plant, in the same city. This very big unit is a challenge because the raw material will be collected for a part in a nearby environment of forests affected by anthropogenic pressures. One describes first the dynamics of the two projects by identifying all the stakeholders and stressing the chain of their decisions, especially focusing on the public ones. One infers the intricate imbrication of several levels of public decision reflecting the discordance between administrative divisions and real natural milieus. One also infers that beyond vested interests the attitudes of the stakeholders reflect different “values” assigned to Nature and divergent because of the fragmentation of knowledge relative to natural milieus. The collection of 1184 public positions allows matching the attitudes with the stakeholder categories. The attitudes toward the projects are also considered as a function of the distance to the plant location, and it comes out that are not necessarily linked to the direct impact for the stakeholder. The conclusion stresses the need for arenas of debate to improve the circulation of information and the convergence of knowledge for an attenuation of the conflicts

The toxicity of trace metal elements in Downy Oak in Gardanne Mining Basin

International audienceThe Gardanne mining basin is undoubtedly one of the peri‐urban territories of the Bouches‐du‐Rhône where air pollution is a major issue both in terms of public health and the preservation of natural environments. The various industrial activities, including the aluminum smelter, have contributed to exacerbating pollution with metallic trace elements [1;2]. Indeed, Bauxite manufacturing by the Bayer process in alumina production is associated with a by‐product, bauxite residue (BR), also termed “red mud”, a complex mixture of elemental constituents. Throughout the world, BR storage sites have been sources of adverse effects on the environment and the Mange Gary site is not an exception. The purpose of this work falls within the context of the environmental transition policy undertaken by the aluminum plant.We investigated the impact of the BR from Mange Garri on some populations of Quercus pubescens

Histo-pathological evaluation of the action on the wall of the great saphenous vein with 2% polidocanol foam, based on various air-liquid volumes ratio. Pilot study on ten in situ saphenous vein great segments. Counting and measuring of bubbles in light microscopy according to for each ratio and time exposure

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