Étude de la matière organique dissoute provenant de la décharge d'eau souterraine d'une flèche de sable en milieu côtier

RÉSUMÉ: L'est du Canada est sujet à une augmentation du niveau de la mer depuis la fin de l'Holocène. Cette augmentation est principalement associée à un ajustement isostatique et a provoqué des transgressions marines, lesquelles ont généré une submersion de la végétation terrigène établie le long de la côte nord-est de l'Amérique du Nord. Au fil du temps, la matière organique (MO) terrigène associée à cette végétation côtière est susceptible de former des horizons composés d'anciens sols organiques appelés paléosols. Ces paléosols sont souvent enfouis sous des sédiments côtiers tels que le sable et les galets, lesquels ont une perméabilité élevée qui permet l'advection d'eau dans les sédiments et les paléosols. Par conséquent, les paléosols peuvent constituer une source de vieille MO terrigène pour l'océan côtier et sont donc susceptibles d'influencer sa biogéochimie à une échelle locale, voir régionale, en affectant non seulement les bilans carbone, mais également les processus biogéochimiques en cours dans le système. La présente étude se concentre sur la dynamique tidale des flux de matière organique dissoute (DOM) mobilisée à partir d'un paléosol localisé sous les sédiments d'une flèche de sable située dans la Baie-des-Chaleurs (QC, Canada). Les trois principaux objectifs consistent à : 1) déterminer les débits de décharge d'eau souterraine provenant de la flèche en utilisant la loi de Darcy ainsi que la mesure de l'activité en 222Rn dans la zone de décharge ; 2) estimer les flux de C organique dissous (COD) du système en utilisant les concentrations en DOC mesurées dans la zone de décharge et les débits de décharge calculés ; et 3) caractériser la MOD de la zone de décharge et des sources environnantes potentielles à partir de leur signature optique (absorbance et fluorescence) afin de déterminer les sources possibles de MOD pour le système. Les résultats de l'analyse hydrologique obtenus en appliquant la loi de Darcy montrent une forte variation des flux de décharge d'eau souterraine, avec des valeurs passant de 0 cm·j-1 à marée haute à 106 cm·j-1 à marée descendante. Le suivi de l'activité en 222Rn dans la zone de décharge a permis d'établir que la contribution des eaux riches en 222Rn aux débits de décharge d'eau souterraine obtenus selon la loi de Darcy varie de 13 à 31 %. Les résultats de l'analyse du 222Rn suggèrent également la présence de deux cellules distinctes d'eau souterraine qui proviennent toutes deux de la recirculation d'eau de mer dans la flèche de sable et illustrent la complexité de la relation entre la variation du niveau de marée et la décharge des eaux souterraines. Les flux de COD provenant de la décharge d'eau souterraine sont estimés à 391,3 (± 100,2) et 360,0 (± 423,5) mmol C·j-1·m-1 en 2018 et 2019, respectivement. Bien qu'il demeure encore difficile d'établir le lien en les flux de MOD et la présence du paléosol sous la flèche de sable, les résultats démontrent une nette différence entre les propriétés optiques de la MOD de la zone de décharge et celles des sources environnantes potentielles. En effet, l'analyse optique de la MOD de la zone de décharge révèle un fort caractère terrigène, une haute aromaticité et un important degré d'humification, suggérant ainsi que la présence du paléosol influence les caractéristiques optiques de la MOD dans la zone de décharge. Les résultats soulignent le rôle complexe des paléosols localisés en zone intertidale sur les flux de MOD et les caractéristiques optiques de l'océan côtier, et ils soulignent la nécessité de mieux quantifier l'impact des systèmes côtiers transgressifs sur les bilans de carbone régionaux et locaux. -- Mot(s) clé(s) en français : Décharge d'eau souterraine, Matière organique dissoute, Transgression marine, Paléosol, Océan côtier. -- ABSTRACT: Since the Late Holocene, eastern Canada has been subjected to a sea-level rise that is mainly associated with post-glacial rebound. This rise has caused marine transgressions and thus submersion of terrigenous vegetation along the northeastern coast of North America. Over time, terrigenous organic matter (OM) from coastal vegetation is likely to form horizons of old organic soils, which are commonly known as paleosols. These paleosols are often buried under coastal sediments such as sands that have a high permeability and allow water in the sediments to advect through the paleosols. Therefore, paleosols can be a source of terrigenous OM to subterranean estuaries (STE). Here, we focused on the tidal dynamics of dissolved organic matter (DOM) fluxes mobilized from the paleosol of a sand spit located in Chaleur Bay (Québec, Canada). We estimated volumetric submarine groundwater discharge (SGD) fluxes using Darcy's law and radon-222 (222Rn), and we determined associated dissolved organic carbon (DOC) fluxes exported to receiving water. We also focused on the characterization of SGD-derived DOM based on the absorbance and fluorescence of the colored dissolved organic matter (CDOM). A multivariate data analysis was realized to better understand DOM sources. Results from Darcy's law show a wide range of SGD fluxes, reaching 106 cm·d-1 during the ebb tide. The contribution of 222Rn-rich groundwaters to total discharge rates determined using Darcy's law ranged between 13 and 31%. Furthermore, analysis of 222Rn activity in the discharge zone suggested the presence of two different cells of recirculated saline groundwater in the sand spit and illustrates the complex relationship between tidal oscillation and SGD. Results indicated mean potential SGD-derived DOC fluxes of 60.7 (± 15.5) and 55.8 (± 36.5) mol C·yr-1 in 2018 and 2019, respectively. The optical analysis of DOM from the discharge zone revealed an important old terrigenous component to the DOM pool. Our findings revealed a clear difference between the optical properties of DOM from the discharge zone and the endmembers. Furthermore, these findings demonstrate the complex role of the paleosol as a source of organic carbon to the coastal ocean and highlight the need to better quantify the impact of transgressive coastal systems on regional and local carbon budgets. -- Mot(s) clé(s) en anglais : Submarine Groundwater Discharge, Dissolved Organic Matter, Marine Transgression, Paleosol, Coastal Ocean

Characterization of three new serous epithelial ovarian cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Cell lines constitute a powerful model to study cancer, and here we describe three new epithelial ovarian cancer (EOC) cell lines derived from poorly differentiated serous solid tumors (TOV-1946, and TOV-2223G), as well as the matched ascites for one case (OV-1946).</p> <p>Methods</p> <p>In addition to growth parameters, the cell lines were characterized for anchorage independent growth, migration and invasion potential, ability to form spheroids and xenografts in SCID mice.</p> <p>Results</p> <p>While all cell lines were capable of anchorage independent growth, only the TOV-1946 and OV-1946 cell lines were able to form spheroid and produce tumors. Profiling of keratins, p53 and Her2 protein expression was assessed by immunohistochemistry and western blot analyses. Somatic <it>TP53 </it>mutations were found in all cell lines, with TOV-1946 and OV-1946 harboring the same mutation, and none harbored the commonly observed somatic mutations in <it>BRAF</it>, <it>KRAS </it>or germline BRCA1/2 mutations found to recur in the French Canadian population. Conventional cytogenetics and spectral karyotype (SKY) analyses revealed complex karyotypes often observed in ovarian disease.</p> <p>Conclusion</p> <p>This is the first report of the establishment of matched EOC cell lines derived from both solid tumor and ascites of the same patient.</p

The 20S proteasome core, active within apoptotic exosome-like vesicles, induces autoantibody production and accelerates rejection

Autoantibodies to components of apoptotic cells, such as anti-perlecan antibodies, contribute to rejection in organ transplant recipients. However, mechanisms of immunization to apoptotic components remain largely uncharacterized. We used large-scale proteomics, with validation by electron microscopy and biochemical methods, to compare the protein profiles of apoptotic bodies and apoptotic exosome-like vesicles, smaller extracellular vesicles released by endothelial cells downstream of caspase-3 activation. We identified apoptotic exosome-like vesicles as a central trigger for production of anti-perlecan antibodies and acceleration of rejection. Unlike apoptotic bodies, apoptotic exosome-like vesicles triggered the production of anti-perlecan antibodies in naïve mice and enhanced anti-perlecan antibody production and allograft inflammation in mice transplanted with an MHC (major histocompatibility complex)–incompatible aortic graft. The 20S proteasome core was active within apoptotic exosome-like vesicles and controlled their immunogenic activity. Finally, we showed that proteasome activity in circulating exosome-like vesicles increased after vascular injury in mice. These findings open new avenues for predicting and controlling maladaptive humoral responses to apoptotic cell components that enhance the risk of rejection after transplantation

The uracil-DNA glycosylase UNG protects the fitness of normal and cancer B cells expressing AID

Abstract In B lymphocytes, the uracil N-glycosylase (UNG) excises genomic uracils made by activation-induced deaminase (AID), thus underpinning antibody gene diversification and oncogenic chromosomal translocations, but also initiating faithful DNA repair. Ung−/− mice develop B-cell lymphoma (BCL). However, since UNG has anti- and pro-oncogenic activities, its tumor suppressor relevance is unclear. Moreover, how the constant DNA damage and repair caused by the AID and UNG interplay affects B-cell fitness and thereby the dynamics of cell populations in vivo is unknown. Here, we show that UNG specifically protects the fitness of germinal center B cells, which express AID, and not of any other B-cell subset, coincident with AID-induced telomere damage activating p53-dependent checkpoints. Consistent with AID expression being detrimental in UNG-deficient B cells, Ung−/− mice develop BCL originating from activated B cells but lose AID expression in the established tumor. Accordingly, we find that UNG is rarely lost in human BCL. The fitness preservation activity of UNG contingent to AID expression was confirmed in a B-cell leukemia model. Hence, UNG, typically considered a tumor suppressor, acquires tumor-enabling activity in cancer cell populations that express AID by protecting cell fitness

Platelet EVs contain an active proteasome involved in protein processing for antigen presentation via MHC-I molecules

In addition to their hemostatic role, platelets play a significant role in immunity. Once activated, platelets release extracellular vesicles (EVs) formed by the budding of their cytoplasmic membranes. Because of their heterogeneity, platelet EVs (PEVs) are thought to perform diverse functions. It is unknown, however, whether the proteasome is transferred from platelets to PEVs or whether its function is retained. We hypothesized that functional protein processing and antigen presentation machinery are transferred to PEVs by activated platelets. Using molecular and functional assays, we found that the active 20S proteasome was enriched in PEVs, along with major histocompatibility complex class I (MHC-I) and lymphocyte costimulatory molecules (CD40L and OX40L). Proteasome-containing PEVs were identified in healthy donor blood, but did not increase in platelet concentrates that caused adverse transfusion reactions. They were augmented, however, after immune complex injections in mice. The complete biodistribution of murine PEVs after injection into mice revealed that they principally reached lymphoid organs, such as spleen and lymph nodes, in addition to the bone marrow, and to a lesser extent, liver and lungs. The PEV proteasome processed exogenous ovalbumin (OVA) and loaded its antigenic peptide onto MHC-I molecules, which promoted OVA-specific CD8+ T-lymphocyte proliferation. These results suggest that PEVs contribute to adaptive immunity through cross-presentation of antigens and have privileged access to immune cells through the lymphatic system, a tissue location that is inaccessible to platelets