Blood flow diverts extracellular vesicles from endothelial degradative compartments to promote angiogenesis.

Extracellular vesicles released by tumors (tEVs) disseminate via circulatory networks and promote microenvironmental changes in distant organs favoring metastatic seeding. Despite their abundance in the bloodstream, how hemodynamics affect the function of circulating tEVs remains unsolved. We demonstrated that efficient uptake of tEVs occurs in venous endothelial cells that are subjected to hemodynamics. Low flow regimes observed in veins partially reroute internalized tEVs toward non-acidic and non-degradative Rab14-positive endosomes, at the expense of lysosomes, suggesting that endothelial mechanosensing diverts tEVs from degradation. Subsequently, tEVs promote the expression of pro-angiogenic transcription factors in low flow-stimulated endothelial cells and favor vessel sprouting in zebrafish. Altogether, we demonstrate that low flow regimes potentiate the pro-tumoral function of circulating tEVs by promoting their uptake and rerouting their trafficking. We propose that tEVs contribute to pre-metastatic niche formation by exploiting endothelial mechanosensing in specific vascular regions with permissive hemodynamics.

Non-invasive investigations of closed landfills: An example in a karstic area.

The monitoring of existing landfills is a pending environmental issue for the years to come. This monitoring is particularly challenging in the more and more common case of closed landfills, where direct investigation is difficult or impossible, calling for non-invasive methods, which in turn are stretched to maximizing their imaging capabilities in front of difficult logistical constraints, requiring novel and well-conceived scientific approaches. In this study we present a non-invasive approach designed and calibrated to identify the state of the subsoil underlying a closed urban waste landfill. In the presented case, two main questions had to be addressed: (a) whether large karstic cavities are present under the landfill, and (b) if any leachate leakage is present. A 3D Electrical Resistivity Tomography (ERT) configuration was used to solve the problem. The survey design has made use of forward model simulations, in order to verify whether the proposed approach was capable of imaging the possible large karstic cavities. This preliminary study showed the importance of choosing a suitable measurement protocol to recover the true position of the cavities. The analysis of the real field data did not show any anomaly compatible with the presence of large cavities, and thus, in comparison with the previous simulations, led to the conclusion that such cavities are not present. However, the results showed the presence of an electrically conductive anomaly, potentially be linked to leachate release. Direct investigations (drilling and sampling) confirmed the presence of fresh water in a silty sediment environment, both contributing towards the observed larger electrical conductivity, larger than the surrounding drier limestone bedrock. The presented general approach proved to be a valuable, generalizable, tool towards for the characterization and monitoring of closed landfills.

The geophysical toolbox applied to forest ecosystems - A review.

Studying the forest subsurface is a challenge because of its heterogeneous nature and difficult access. Traditional approaches used by ecologists to characterize the subsurface have a low spatial representativity. This review article illustrates how geophysical techniques can and have been used to get new insights into forest ecology. Near-surface geophysics offers a wide range of methods to characterize the spatial and temporal variability of subsurface properties in a non-destructive and integrative way, each with its own advantages and disadvantages. These techniques can be used alone or combined to take advantage of their complementarity. Our review led us to define three topics how near-surface geophysics can support forest ecology studies: 1) detection of root systems, 2) monitoring of water quantity and dynamics, and 3) characterisation of spatial heterogeneity in subsurface properties at the stand level. The number of forest ecology studies using near-surface geophysics is increasing and this multidisciplinary approach opens new opportunities and perspectives for improving quantitative assessment of biophysical properties and exploring forest response to the environment and adaptation to climate change.

A Review on Applications of Time-Lapse Electrical Resistivity Tomography Over the Last 30 Years : Perspectives for Mining Waste Monitoring.

Mining operations generate large amounts of wastes which are usually stored into large-scale storage facilities which pose major environmental concerns and must be properly monitored to manage the risk of catastrophic failures and also to control the generation of contaminated mine drainage. In this context, non-invasive monitoring techniques such as time-lapse electrical resistivity tomography (TL-ERT) are promising since they provide large-scale subsurface information that complements surface observations (walkover, aerial photogrammetry or remote sensing) and traditional monitoring tools, which often sample a tiny proportion of the mining waste storage facilities. The purposes of this review are as follows: (i) to understand the current state of research on TL-ERT for various applications; (ii) to create a reference library for future research on TL-ERT and geoelectrical monitoring mining waste; and (iii) to identify promising areas of development and future research needs on this issue according to our experience. This review describes the theoretical basis of geoelectrical monitoring and provides an overview of TL-ERT applications and developments over the last 30 years from a database of over 650 case studies, not limited to mining operations (e.g., landslide, permafrost). In particular, the review focuses on the applications of ERT for mining waste characterization and monitoring and a database of 150 case studies is used to identify promising applications for long-term autonomous geoelectrical monitoring of the geotechnical and geochemical stability of mining wastes. Potential challenges that could emerge from a broader adoption of TL-ERT monitoring for mining wastes are discussed. The review also considers recent advances in instrumentation, data acquisition, processing and interpretation for long-term monitoring and draws future research perspectives and promising avenues which could help improve the design and accuracy of future geoelectric monitoring programs in mining wastes.

Tumor extracellular vesicles drive metastasis (it's a long way from home).

Among a plethora of functions, extracellular vesicles released by primary tumors spread in the organism and reach distant organs where they can induce the formation of a premetastatic niche. This constitutes a favorable microenvironment for circulating tumor cells which facilitates their seeding and colonization. In this review, we describe the journey of extracellular vesicles (EVs) from the primary tumor to the future metastatic organ, with a focus on the mechanisms used by EVs to target organs with a specific tropism (i.e., organotropism). We then highlight important tumor EV cargos in the context of premetastatic niche formation and summarize their known effects on extracellular matrix remodeling, angiogenesis, vessel permeabilization, resident cell activation, recruitment of foreign cells, and ultimately the formation of a pro-inflammatory and immuno-tolerant microenvironment. Finally, we discuss current experimental limitations and remaining opened questions in light of metastatic diagnosis and potential therapies targeting PMN formation.

Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes.

Cancer extracellular vesicles (EVs) shuttle at distance and fertilize pre-metastatic niches facilitating subsequent seeding by tumor cells. However, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Using mouse models, we show that GTPases of the Ral family control, through the phospholipase D1, multi-vesicular bodies homeostasis and tune the biogenesis and secretion of pro-metastatic EVs. Importantly, EVs from RalA or RalB depleted cells have limited organotropic capacities in vivoand are less efficient in promoting metastasis. RalA and RalB reduce the EV levels of the adhesion molecule MCAM/CD146, which favors EV-mediated metastasis by allowing EVs targeting to the lungs. Finally, RalA, RalB, and MCAM/CD146, are factors of poor prognosis in breast cancer patients. Altogether, our study identifies RalGTPases as central molecules linking the mechanisms of EVs secretion and cargo loading to their capacity to disseminate and induce pre-metastatic niches in a CD146-dependent manner.

[Influence of fluid mechanics on metastasis formation]. / Influence de la mécanique des fluides sur la formation des métastases.

Metastases are the main cause of cancer-related deaths. The chain of events leading to their development is called "the metastatic cascade". The biological and biochemical aspects of this process have been well studied but the importance of biomechanical parameters only recently became a focus in the field. Studies have shown the biological fluids (blood, lymph and interstitial fluid) to play a key role in the metastatic cascade. These fluids participate in the transport of circulating tumor cells (CTCs) as well as the factors that they secrete, while at the same time influencing the events of the metastatic cascade through the forces that they generate. The hemodynamic properties and topological constraints of the vascular architecture control the formation of metastatic niches and the metastatic potential of tumor cells. In this review, we discuss the importance of these mechanical forces and highlight the novel questions and research avenues that they open.

TITLE: Influence de la mécanique des fluides sur la formation des métastases. ABSTRACT: La suite d'évènements menant à l'apparition de métastases est appelée « cascade métastatique ¼. L'étude récente de la composante biomécanique de cette cascade a révélé le rôle central des liquides biologiques dans la dissémination métastatique. Tout en participant au transport des cellules tumorales circulantes et des facteurs qu'elles sécrètent, ces liquides circulants influencent cette cascade par les forces mécaniques qu'ils génèrent. Les propriétés hémodynamiques et les contraintes topologiques de l'architecture vasculaire contrôlent la formation de niches métastatiques et le potentiel métastatique des cellules tumorales.

Live tracking of extracellular vesicles in larval zebrafish.

Formerly considered as insignificant cell debris, extracellular vesicles (EVs) have emerged as potent mediators of cell-cell communication, both in proximity and at distance from the producing cell. EVs are transported in body fluids and can be internalized by specific distant cells to ultimately deliver a functional message. Despite their striking importance in many physiological and pathological contexts, the exact mechanisms by which EVs impose local and distant modifications of the microenvironment in vivo remain to be fully understood. We realized that some conceptual gaps are direct consequences of the difficulty to visualize the shuttling and targeting of EVs in real time in vivo. The zebrafish larvae offered attractive features for live tracking of EVs, within circulating fluids. Here, we describe the experimental procedures that we have built for dissecting the dissemination of EVs at high spatio-temporal resolution in vivo.

Assessing the extent of citrus trees root apparatus under deficit irrigation via multi-method geo-electrical imaging.

Tree rooting strategies are driven by external and internal factors such as climate conditions (rain frequency, wind direction), soil structure and crop type. In order to ensure water efficiency for irrigated crops, it is essential to know how each crop adapts its rooting strategy. We couple Mise-a-la-masse (MALM) with Electrical Resistivity Tomography (ERT) for investigating orange tree roots undergoing different irrigation strategies (Partial Root-zone Drying - or PRD - versus Full Irrigation). This is a totally novel approach giving an overall picture of roots structure and functioning in the subsoil. Our results show clear differences of rooting extent between different irrigation strategies, and identify privileged direction of root development due to distinct RWU patterns. These results are corroborated also by seasonal monitoring of evapotranspiration (ET) and soil water content (SWC), which exhibit very large differences in the soil water distribution in space and time for the trees undergoing different irrigation schedules.

Studying the Fate of Tumor Extracellular Vesicles at High Spatiotemporal Resolution Using the Zebrafish Embryo.

Tumor extracellular vesicles (EVs) mediate the communication between tumor and stromal cells mostly to the benefit of tumor progression. Notably, tumor EVs travel in the bloodstream, reach distant organs, and locally modify the microenvironment. However, visualizing these events in vivo still faces major hurdles. Here, we describe an approach for tracking circulating tumor EVs in a living organism: we combine chemical and genetically encoded probes with the zebrafish embryo as an animal model. We provide a first description of tumor EVs' hemodynamic behavior and document their intravascular arrest. We show that circulating tumor EVs are rapidly taken up by endothelial cells and blood patrolling macrophages and subsequently stored in degradative compartments. Finally, we demonstrate that tumor EVs activate macrophages and promote metastatic outgrowth. Overall, our study proves the usefulness and prospects of zebrafish embryo to track tumor EVs and dissect their role in metastatic niches formation in vivo.