Upregulated flotillins and sphingosine kinase 2 derail AXL vesicular traffic to promote epithelial-mesenchymal transition

Altered endocytosis and vesicular trafficking are major players during tumorigenesis. Flotillin overexpression, a feature observed in many invasive tumors and identified as a marker of poor prognosis, induces a deregulated endocytic and trafficking pathway called upregulated flotillin-induced trafficking (UFIT). Here, we found that in non-tumoral mammary epithelial cells, induction of the UFIT pathway promotes epithelial-to-mesenchymal transition (EMT) and accelerates the endocytosis of several transmembrane receptors, including AXL, in flotillin-positive late endosomes. AXL overexpression, frequently observed in cancer cells, is linked to EMT and metastasis formation. In flotillin-overexpressing non-tumoral mammary epithelial cells and in invasive breast carcinoma cells, we found that the UFIT pathway-mediated AXL endocytosis allows its stabilization and depends on sphingosine kinase 2, a lipid kinase recruited in flotillin-rich plasma membrane domains and endosomes. Thus, the deregulation of vesicular trafficking following flotillin upregulation, and through sphingosine kinase 2, emerges as a new mechanism of AXL overexpression and EMT-inducing signaling pathway activation.This work was supported by the Fondation pour la Recherche Médicale (DEQ20161136700) and the Fondation ARC pour la recherche sur le cancer (ARCPJA32020060002078). Collection of breast tumor samples was supported by the Russian Science Foundation (19-75-30016). C.G.-R. was supported by the Institut National de la Santé et de la Recherche Médicale.Peer reviewe

The GEOTRACES Intermediate Data Product 2014

The GEOTRACES Intermediate Data Product 2014 (IDP2014) is the first publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2013. It consists of two parts: (1) a compilation of digital data for more than 200 trace elements and isotopes (TEIs) as well as classical hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing a strongly inter-linked on-line atlas including more than 300 section plots and 90 animated 3D scenes. The IDP2014 covers the Atlantic, Arctic, and Indian oceans, exhibiting highest data density in the Atlantic. The TEI data in the IDP2014 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at cross-over stations. The digital data are provided in several formats, including ASCII spreadsheet, Excel spreadsheet, netCDF, and Ocean Data View collection. In addition to the actual data values the IDP2014 also contains data quality flags and 1-? data error values where available. Quality flags and error values are useful for data filtering. Metadata about data originators, analytical methods and original publications related to the data are linked to the data in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2014 data providing section plots and a new kind of animated 3D scenes. The basin-wide 3D scenes allow for viewing of data from many cruises at the same time, thereby providing quick overviews of large-scale tracer distributions. In addition, the 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of observed tracer plumes, as well as for making inferences about controlling processes

Involvement of flotillin over-expression in cell invasion

L’invasion cellulaire est un phénomène pendant lequel les cellules présentent des changements importants dans leur forme et acquièrent la capacité à dégrader les structures qui les entourent afin de migrer au sein d’un organisme. L’invasion est cruciale pour la stabilité physiologique d’un organisme car elle intervient à différentes étapes de notre vie notamment lors du développement embryonnaire ou pendant une réaction immunitaire. Cependant ce mécanisme est également majeur lors de la progression tumorale. Dans nos organismes, les cellules sont entourées par la matrice extracellulaire (MEC) qui doit être remodelée ou dégradée lors du processus d’invasion. Cette dégradation est réalisée par des structures cellulaires spécialisées, les invadopodes, qui sont des sites où sont libérés les protéines spécialisées dans la dégradation de la MEC, parmi lesquelles MT1-MMP joue un rôle prépondérant. Les capacités à envahir et à dégrader la MEC d’une cellule dépendent donc fortement de la libération de MT1-MMP aux sites de dégradation. Les mécanismes qui permettent le transport de MT1-MMP aux zones d’intérêts sont encore mal compris. Dans ce contexte, nous avons mis en évidence que les Flotillines sont d’importants régulateurs de l’adressage et la libération de MT1-MMP à ces sites de dégradations. Les Flotillines 1 et 2 sont des protéines ubiquitaires très conservées. La quantité de Flotillines est augmentée dans de nombreux cancers invasifs et ceci est considéré comme un marqueur de mauvais pronostic. Lors de mon projet, nous avons mis en évidence que l’augmentation de la quantité de Flotillines dans des cellules normales de différentes origines, est suffisante pour induire une forte invasion cellulaire in vivo et in vitro (respectivement dans des modèles de xénogreffes chez le poisson zèbre dans modèles de sphéroïdes 3D dans des matrices de collagènes). De même, la suppression des Flotillines dans des cellules cancéreuses est associée à une diminution de leurs capacités invasives in vivo et in vitro. Ces résultats s’expliquent par le fait que les Flotillines régulent le trafic intracellulaire de MT1-MMP et augmentent sa libération aux sites de dégradation favorisant ainsi l’invasion cellulaire.Tumor cell invasion and consecutive metastasis formation are the main cause of death in cancer patients. Invading tumor cells are surrounded by stroma and extracellular matrix (ECM) that is remodeled or degraded during the metastatic process. ECM degradation is mediated by specialized organelles called invadosomes. Their function strongly depends on matrix metalloproteinases (MMPs) that degrade ECM. Among all the MMPs, MT1-MMP plays a major role the invasive behavior of metastatic cells.Flotillin 1 and 2 are two ubiquitous and highly conserved membrane proteins that can assemble in large oligomers, known to participate in membrane proteins clustering and endocytosis. Flotillins are overexpressed in many invasive cancers and considered as markers of poor prognosis, results we confirmed using several sarcoma and carcinoma models. During my project we identified Flotillins as regulators of MT1-MMP trafficking and cell invasion.We used a dual reciprocal approach consisting of the overexpression of Flotillins in non tumoral cells and of down-regulation of Flotillins in metastatic cells. We showed that flotillins downregulation in invasive cancer cells dramatically inhibit their invasive properties as monitored in vitro using a 3D-collagen invasion assay and in vivo using zebrafish xenografts. Reciprocally, ectopic overexpression of Flotillins in non-tumoral cells is sufficient to induce their invasive behavior in vitro and in vivo. This increase of invasion is mainly due to a higher ability to degrade the matrix in a MT1-MMP-dependent manner. Finally, we showed that Flotillins are critical regulators of the trafficking and the release of MT1-MMP at the degradation site

Late summer particulate organic carbon export and twilight zone remineralisation in the Atlantic sector of the Southern Ocean

As part of the GEOTRACES Bonus-GoodHope (BGH) expedition (January-March 2008) in the Atlantic sector of the Southern Ocean, particulate organic carbon (POC) export was examined from the surface to the mesopelagic twilight zone using water column distributions of total Th-234 and biogenic particulate Ba (Ba-xs). Surface POC export production was estimated from steady state and non steady state modelling of Th-234 fluxes, which were converted into POC fluxes, using the POC/Th-234 ratio of large, potentially sinking particles (>53 mu m) collected via in situ pumps. Deficits in Th-234 activities were observed at all stations from the surface to the bottom of the mixed layer, yielding Th-234 export fluxes from the upper 100 m of 496 +/- 214 dpm m(-2) d(-1) to 1195 +/- 158 dpm m(-2) d(-1) for the steady state model and of 149 +/- 517 dpm m(-2) d(-1) to 1217 +/- 231 dpm m(-2) d(-1) for the non steady state model. Using the POC/(234)Thp ratio of sinking particles (ratios varied from 1.7 +/- 0.2 mu mol dpm(-1) to 4.8 +/- 1.9 mu mol dpm(-1)) POC export production at 100 m was calculated to range between 0.9 +/- 0.4 and 5.1 +/- 2.1 mmol C m(-2) d(-1), assuming steady state and between 0.3 +/- 0.9 m(-2) d(-1) and 4.9 +/- 3.3 mmol C m(-2) d(-1), assuming non steady state. From the comparison of both approaches, it appears that during late summer export decreased by 56 to 16% for the area between the sub-Antarctic zone and the southern Antarctic Circumpolar Current Front (SACCF), whereas it remained rather constant over time in the HNLC area south of the SACCF. POC export represented only 6 to 54% of new production, indicating that export efficiency was, in general, low, except in the vicinity of the SACCF, where export represented 56% of new production. Attenuation of the POC sinking flux in the upper mesopelagic waters (100-600 m depth interval) was evidenced both, from excess Th-234 activities and from particulate biogenic Ba (Baxs) accumulation. Excess Th-234 activities, reflected by Th-234/U-238 ratios as large as 1.21 +/- 0.05, are attributed to remineralisation/disaggregation of Th-234-bearing particles. The accumulation of excess Th-234 in the 100-600 m depth interval ranged from 458 +/- 633 dpm m(-2) d(-1) to 3068 +/- 897 dpm m(-2) d(-1), assuming steady state. Using the POC/(234)Thp ratio of sinking particles (>53 mu m), this Th-234 accumulation flux was converted into a POC remineralisation flux which ranged between 0.9 +/- 1.2 mmol C m(-2) d(-1) and 9.2 +/- 2.9 mmol C m(-2) d(-1). Mesopelagic particulate biogenic Ba has been reported to reflect bacterial degradation of organic matter and to be related to oxygen consumption and bacterial carbon respiration. We observed that the highest Baxs contents (reaching up to > 1000 pM), in general, occurred between 200 and 400 m. Depth-weighted average mesopelagic Baxs (meso-Baxs) values were converted into respired C fluxes, which ranged between 0.23 and 6.4 mmol C m(-2) d(-1), in good agreement with Th-234-based remineralisation fluxes. A major outcome from this study is the observed significant positive correlation between POC remineralisation as estimated from meso-Ba-xs contents and from Th-234 excess (R-2 = 0.73; excluding 2 outliers). Remineralisation of POC in the twilight zone was particularly efficient relative to POC export resulting in negligible bathy-pelagic (>600 m) POC export fluxes in the sub-Antarctic zone, the Polar Front zone and the northern Weddell Gyre, while the subtropical zone as well as the vicinity of the SACCF had significant deep POC fluxes

Mg isotopes fractionation processes in marine calcareous skeletons: methodology developments and preliminary results on echinoderms (sea urchin and starfish)

info:eu-repo/semantics/nonPublishe

A proxy tool-box for assessing southern ocean biological pump efficiency

info:eu-repo/semantics/nonPublishe

Combining field monitoring and aerial imagery to evaluate the role of gully erosion in a Mediterranean catchment (Tunisia)

International audienceThe objective of this study was to address the role of gully erosion on sediment delivery at the catchment scale by assessing the contribution of gullies to the total sediment yield at the outlet of the Kamech (Cape Bon, Tunisia), which is a small cultivated catchment in the Mediterranean environment. The methodology was based on the long-term analysis of the evolution of gully volume, and the total volume of sediment that reached the catchment outlet. The evolution of gully volume was assessed by field surveys and image analysis. The total volume of sediment was calculated using intensive field monitoring of the runoff and erosion in the reservoir at the catchment outlet. The contribution of gullies to the total flux of sediment that reached the catchment outlet was estimated to be less than 30%. This means that siltation of the reservoir was mainly due to erosion processes other than gully erosion, i.e., topsoil erosion processes such as rill and interrill erosion in cropland areas. This result was consistent with a previous independent estimation of the apportionment of gully and topsoil erosion sources conducted at the same site using the fingerprinting approach. Therefore, the study confirms that, even in a heavily eroded agricultural catchment area with a dense network of gullies, gully erosion nevertheless accounted for less than 30% of the total erosion balance. The results also showed that the cumulated gully length has decreased in the last fifty years, thus revealing the declining role of gullies. However, the decrease in gully activity could not be linked to an isolated factor. Complementary observations, such as the appearance of vegetation in the permanent gullies and the decrease in the percentage of active gullies, showed that the degree of hydro-sedimentary connectivity in the Kamech catchment has probably entered a decreasing phase. We also analysed the potential use of historical aerial images for studying gully erosion. We found that these images were useful for calculating accurate ortho-photography but failed to provide a DEM with the precision required to measure the historical volume of gullies

Impact de la topographie et de la circulation atmosphérique sur l’îlot de chaleur urbain en situation de canicule (Dijon, France).

National audienceHeatwaves and hot days lead to increased thermal stress, and the latter is potentially exacerbated in urban areas. We examine here the combination of these phenomena using a dense network of air temperature observations in Dijon (northeastern France) over the 2014-2021 period. To that end, we analyze (i) local-scale to synoptic-scale atmospheric circulation and (ii) local factors (landuse and topography) influencing the temperature. The five heatwaves that occurred during the period last 4 to 5 days and are associated with large-scale atmospheric blocking, that also favor thermal inversions. Out of the 24 nights under study, 60% are characterized by an urban heat island (UHI) above +3°C and a thermal inversion often exceeding 0.5°C/100 m under calm wind conditions (2 m/s); and 10% by a weak UHI, a weak thermal inversion and variable wind conditions. Similar statistics are obtained for the 105 hot days of the period. Heatwaves and hot days are conducive to two contrasted spatial patterns depending on wind conditions. Windy conditions (>2 m/s) act to ventilate urban heat excess and limit topographic influence. This results in homogeneous air temperature across the study area. In contrast, calm conditions (wind 2 m/s); 10% par un faible ICU, une faible inversion thermique et des conditions de vent variables. Des statistiques comparables sont obtenues par jours de fortes chaleurs (105 jours). Canicules et fortes chaleurs sont associées à deux structures contrastées en fonction des conditions de vent. Un vent non négligeable (>2 m/s) contribue à ventiler l’excès de chaleur de la ville et à limiter le contrôle de la topographie. En résultent des températures très homogènes sur l’ensemble de l’aire d’étude. Au contraire, un vent faible (<2 m/s) maximise le contrôle de l’occupation du sol et de la topographie sur la température de l’air. En résulte un excès de chaleur en ville. La plaine, à l’est, est relativement plus fraîche que le plateau à l’ouest, de même qu’un axe traversant l’agglomération le long du talweg et du cours d’eau (vallée de l’Ouche). Cet axe frais naturel limite l’ICU ou, a minima, favorise de relatifs Îlots de Fraîcheur Urbains nocturnes. Cette étude montre la pertinence de l’analyse combinée d’un réseau de mesures de la température de l’air, de la circulation atmosphérique et des descripteurs géophysiques pour mettre à jour les déterminants de la température de l’air et la spatialiser

MT1-MMP targeting to endolysosomes is mediated by upregulation of flotillins

International audienc

PRISMA and EnMAP comparison in the context of wheat nitrogen status assessment

Over the past few decades, spaceborne hyperspectral imagery has evolved significantly, opening up new possibilities in the realm of agricultural research and monitoring. This technology has witnessed remarkable advancements in agricultural applications, such as crop type mapping and vegetation classification. In addition, hyperspectral data has proven invaluable in detecting biotic and abiotic stresses in agricultural systems. Furthermore, the retrieval of biophysical traits such as leaf area index, chlorophyll content and nitrogen concentration through hyperspectral data analysis has contributed to a deeper understanding of crop health and growth dynamics. Through the use of spaceborne hyperspectral imagery, agricultural stakeholders can make data-driven decisions, optimize agricultural practices, and ensure the sustainable production of food. The following experiment was carried out as part of the SPAGHYTI project, a collaboration led by CONSTELLR, a leading provider of space-based water, carbon, and temperature insights. CONSTELLR's mission is to advance understanding of the planet's ecosystems, enabling a more equitable and sustainable future governance of global resources. The SPAGHYTI project, conducted under the aegis of the SKYWIN competitiveness cluster, aims to develop field-level applications that deliver pertinent and actionable information to farmers. Specifically, the two applications are dedicated to the nitrogen status assessment and the monitoring abiotic and biotic stress levels of winter wheat in the Walloon region of Belgium. These applications leverage hyperspectral satellite imagery and aim to provide affordable access to high-quality information. The SPAGHYTI project encompasses a comprehensive value chain, covering sensor technology to end-user implementation. This paper reports a methodology built on the analysis of EnMAP and PRISMA data with the aim of assessing the added value of hyperspectral data for estimating the nitrogen content of wheat crops. An intensive field campaign was carried out from March to July 2023, i.e., during the nitrogen amendment period. Samples were taken from trial plots and several farmers' plots. These plots have been selected to match with the extent of the EnMAP and PRISMA images acquired. For each of these plots, dry matter and nitrogen content measurements were carried out in the laboratory. In addition, spectral data were acquired for each sampling unit using field portable spectroradiometer (ASD FieldSec 4). The first step of the study focuses on quantifying signal to noise ratio and its impacts on vegetated surfaces. Pure pixels of vegetation and invariants were selected in order to perform statistical analysis in both cases. Different wavelengths, wavelength combinations and spectral indices were then selected as the most relevant for estimating the nitrogen status of wheat by computing their correlation with the ground truth measurements of canopy nitrogen content (CNC). Different methods for estimating the nitrogen status of wheat were assessed according to their performances. Eventually, two different methods have been designed and implemented. The two methods rely on the estimation of dry matter (DM) and canopy nitrogen content (CNC) in order to produce a Nitrogen Nutrition Index (NNI). The first method relies on the use of hyperspectral vegetation indices (HVI) to estimate CNC and DM with simple linear regression. The second method relies on biophysical variables retrieved from physically-based model that have a direct correlation with the variables of interest. These performance results obtained from EnMAP and PRISMA are then compared to operational nitrogen status products derived from Sentinel-2 MSI data and the potential complementarity based on frequent Sentinel-2 data and precise hyperspectral retrieval is investigated