ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment

Mechanisms underlying the resistance of acute lymphoblastic leukemia (ALL) blasts to L-asparaginase are still incompletely known. Here we demonstrate that human primary bone marrow mesenchymal stromal cells (MSCs) successfully adapt to L-asparaginase and markedly protect leukemic blasts from the enzyme-dependent cytotoxicity through an amino acid tradeoff. ALL blasts synthesize and secrete glutamine, thus increasing extracellular glutamine availability for stromal cells. In turn, MSCs use glutamine, either synthesized through glutamine synthetase (GS) or imported, to produce asparagine, which is then extruded to sustain asparagine-auxotroph leukemic cells. GS inhibition prevents mesenchymal cells adaptation to L-asparaginase, lowers glutamine secretion by ALL blasts, and markedly hinders the protection exerted by MSCs on leukemic cells. The pro-survival amino acid exchange is hindered by the inhibition or silencing of the asparagine efflux transporter SNAT5, which is induced in mesenchymal cells by ALL blasts. Consistently, primary MSCs from ALL patients express higher levels of SNAT5 (P <.05), secrete more asparagine (P <.05), and protect leukemic blasts (P <.05) better than MSCs isolated from healthy donors. In conclusion, ALL blasts arrange a pro-leukemic amino acid trade-off with bone marrow mesenchymal cells, which depends on GS and SNAT5 and promotes leukemic cell survival during L-asparaginase treatment

Virtual geosite communication through a webgis platform: A case study from santorini island (Greece)

We document and show a state-of-the-art methodology that could allow geoheritage sites (geosites) to become accessible to scientific and non-scientific audiences through immersive and non-immersive virtual reality applications. This is achieved through a dedicated WebGIS platform, particularly handy in communicating geoscience during the COVID-19 era. For this application, we selected nine volcanic outcrops in Santorini, Greece. The latter are mainly associated with several geological processes (e.g., dyking, explosive, and effusive eruptions). In particular, they have been associated with the famous Late Bronze Age (LBA) eruption, which made them ideal for geoher-itage popularization objectives since they combine scientific and educational purposes with ge-otourism applications. Initially, we transformed these stunning volcanological outcrops into geo-spatial models\u2014the so called virtual outcrops (VOs) here defined as virtual geosites (VGs)\u2014through UAV-based photogrammetry and 3D modeling. In the next step, we uploaded them on an online platform that is fully accessible for Earth science teaching and communication. The nine VGs are currently accessible on a PC, a smartphone, or a tablet. Each one includes a detailed description and plenty of annotations available for the viewers during 3D exploration. We hope this work will be regarded as a forward model application for Earth sciences' popularization and make geoheritage open to the scientific community and the lay public

Commercial-UAV-based structure from motion for geological and geohazard studies

In the present work we applied the use of the UAV-based Structure from Motion technique (SfM) to geological and geohazard studies, with emphasis placed on active tectonics and volcano-tectonics cases. Our aim is to obtain high-resolution orthomosaics and Digital Surface Models (DSMs) in two study areas: the Theistareykir Fissure Swarm within the Northern Volcanic Zone (NVZ) of Iceland and the active Khoko landslide, Enguri reservoir, in the Greater Caucasus, Georgia. The first is affected by seismic and volcanic hazard, the second by landslide and hydrogeological hazard. Regarding the NVZ, by analysing the resulting Orthomosaics and DSMs we collected a total of 453 quantitative measurements of the amount of opening and opening direction of Holocene extension fractures and 36 measurements of the height of fault scarps. These data allowed us to assess an overall spreading direction of N106.4° during Holocene times within the studied rift zone, which has been compared with geodetic motion vectors, and a stretching ratio of 1.013–1.017 for 8–10 ka old lava units. We conclude that deformation in the area is related to both dyke intrusions and extensional tectonics. In the Greater Caucasus, we applied the method to identify the main geomorphological features related to the Khoko landslide and to measure the scarp height of the principal slip surfaces, in order to improve geomorphological knowledge of the landslide, and contribute to the assessment of the hydrogeological hazard of the area. At a general level, our results suggest that the use of UAV-based SfM is a convenient and efficient way to collect plenty of data aimed at better assessing geohazards in areas prone to catastrophic natural phenomena like earthquakes, volcanic eruptions and landslides

Virtual Outcrops Building in Extreme Logistic Conditions for Data Collection, Geological Mapping, and Teaching: The Santorini's Caldera Case Study, Greece

In the present work, we test the application of boat-camera-based photogrammetry as a tool for Virtual Outcrops (VOs) building on geological mapping and data collection. We used a 20 MPX camera run by an operator who collected pictures almost continuously, keeping the camera parallel to the ground and opposite to the target during a boat survey. Our selected target was the northern part of Santorini's caldera wall, a structure of great geological interest. A total of 887 pictures were collected along a 5.5-km-long section along an almost vertical caldera outcrop. The survey was performed at a constant boat speed of about 4 m/s and a coastal approaching range of 35.8 to 296.5m. Using the Structure from Motion technique we: i) produced a successful and high-resolution 3D model of the studied area, ii) designed high-resolution VOs for two selected caldera sections, iii) investigated the regional geology, iv) collected qualitative and quantitative structural data along the vertical caldera cliff, and v) provided a new VO building approach in extreme logistic conditions

Virtual geosite communication through a webgis platform: A case study from santorini island (Greece)

We document and show a state-of-the-art methodology that could allow geoheritage sites (geosites) to become accessible to scientific and non-scientific audiences through immersive and non-immersive virtual reality applications. This is achieved through a dedicated WebGIS platform, particularly handy in communicating geoscience during the COVID-19 era. For this application, we selected nine volcanic outcrops in Santorini, Greece. The latter are mainly associated with several geological processes (e.g., dyking, explosive, and effusive eruptions). In particular, they have been associated with the famous Late Bronze Age (LBA) eruption, which made them ideal for geoher-itage popularization objectives since they combine scientific and educational purposes with ge-otourism applications. Initially, we transformed these stunning volcanological outcrops into geo-spatial models—the so called virtual outcrops (VOs) here defined as virtual geosites (VGs)—through UAV-based photogrammetry and 3D modeling. In the next step, we uploaded them on an online platform that is fully accessible for Earth science teaching and communication. The nine VGs are currently accessible on a PC, a smartphone, or a tablet. Each one includes a detailed description and plenty of annotations available for the viewers during 3D exploration. We hope this work will be regarded as a forward model application for Earth sciences' popularization and make geoheritage open to the scientific community and the lay public. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A New Way to Explore Volcanic Areas: QR-Code-Based Virtual Geotrail at Mt. Etna Volcano, Italy

In this body of work, we showcase a historic virtual geotrail on the eastern flank of the iconic Mt. Etna volcano (Italy), along a series of outstanding geological sites and features subsequent to an important eruption that took place in 1928. A geohistoric account of such a major eruption, is of great interest, since it is the only event since 1669 to have caused the destruction of a town (Mascali) in the Etna region. Volcanologists, educators, the lay public, tourists and volcano explorers can now access a series of \u201cvirtual geostops\u201d belonging to this virtual geotrail, such that \u201cvisitors\u201d can virtually fly above these sites by scanning a QR code on the printed or electronic version of the present manuscript, as well as on the poster provided as additional material for this manuscript. The virtual geostops that comprise the virtual geotrail were developed using the structure-from-motion (SfM) photogrammetry technique from images captured by using unmanned aerial vehicles (UAVs). The main result of our work is the virtual geotrail, subdivided in two parts and composed of eight geostops, each showing outstanding examples of geological features resulting from volcanic phenomena that took place also during 1979. Our approach is designed to support classical field trips, and it can undoubtedly become complementary to traditional field teaching in earth sciences, both now and in the future

How academics and the public experienced immersive virtual reality for geo-education

Immersive virtual reality can potentially open up interesting geological sites to students, academics and others who may not have had the opportunity to visit such sites previously. We study how users perceive the usefulness of an immersive virtual reality approach applied to Earth Sciences teaching and communication. During nine immersive virtual reality-based events held in 2018 and 2019 in various locations (Vienna in Austria, Milan and Catania in Italy, Santorini in Greece), a large number of visitors had the opportunity to navigate, in immersive mode, across geological landscapes reconstructed by cutting-edge, unmanned aerial system-based photogrammetry techniques. The reconstructed virtual geological environments are specifically chosen virtual geosites, from Santorini (Greece), the North Volcanic Zone (Iceland), and Mt. Etna (Italy). Following the user experiences, we collected 459 questionnaires, with a large spread in participant age and cultural background. We find that the majority of respondents would be willing to repeat the immersive virtual reality experience, and importantly, most of the students and Earth Science academics who took part in the navigation confirmed the usefulness of this approach for geo-education purposes

Monocyte–macrophage polarization and recruitment pathways in the tumour microenvironment of B-cell acute lymphoblastic leukaemia

B-cell acute lymphoblastic leukaemia (B-ALL) reprograms the surrounding bone marrow (BM) stroma to create a leukaemia-supportive niche. To elucidate the contribution of immune cells to the leukaemic microenvironment, we investigated the involvement of monocyte/macrophage compartments, as well as several recruitment pathways in B-ALL development. Immunohistochemistry analyses showed that CD68-expressing macrophages were increased in leukaemic BM biopsies, compared to controls and predominantly expressed the M2-like markers CD163 and CD206. Furthermore, the "non-classical" CD14+CD16++ monocyte subset, expressing high CX3CR1 levels, was significantly increased in B-ALL patients' peripheral blood. CX3CL1 was shown to be significantly upregulated in leukaemic BM plasma, thus providing an altered migratory pathway possibly guiding NC monocyte recruitment into the BM. Additionally, the monocyte/macrophage chemoattractant chemokine ligand 2 (CCL2) strongly increased in leukaemic BM plasma, possibly because of the interaction of leukaemic cells with mesenchymal stromal cells and vascular cells and due to a stimulatory effect of leukaemia-related inflammatory mediators. C5a, a macrophage chemoattractant and M2-polarizing factor, further appeared to be upregulated in the leukaemic BM, possibly as an effect of PTX3 decrease, that could unleash complement cascade activation. Overall, deregulated monocyte/macrophage compartments are part of the extensive BM microenvironment remodelling at B-ALL diagnosis and could represent valuable targets for novel treatments to be coupled with classical chemotherapy