Comparative transcriptomic profile of tolerogenic dendritic cells differentiated with vitamin D3, dexamethasone and rapamycin

Tolerogenic dendritic cell (tolDC)-based therapies have become a promising approach for the treatment of autoimmune diseases by their potential ability to restore immune tolerance in an antigen-specific manner. However, the broad variety of protocols used to generate tolDC in vitro and their functional and phenotypical heterogeneity are evidencing the need to find robust biomarkers as a key point towards their translation into the clinic, as well as better understanding the mechanisms involved in the induction of immune tolerance. With that aim, in this study we have compared the transcriptomic profile of tolDC induced with either vitamin D3 (vitD3-tolDC), dexamethasone (dexa-tolDC) or rapamycin (rapa-tolDC) through a microarray analysis in 5 healthy donors. The results evidenced that common differentially expressed genes could not be found for the three different tolDC protocols. However, individually, CYP24A1, MUCL1 and MAP7 for vitD3-tolDC; CD163, CCL18, C1QB and C1QC for dexa-tolDC; and CNGA1 and CYP7B1 for rapa-tolDC, constituted good candidate biomarkers for each respective cellular product. In addition, a further gene set enrichment analysis of the data revealed that dexa-tolDC and vitD3-tolDC share several immune regulatory and anti-inflammatory pathways, while rapa-tolDC seem to be playing a totally different role towards tolerance induction through a strong immunosuppression of their cellular processes

Caracterización de grandes estructuras sismogénicas y tsunamogénicas del Golfo de Cádiz con tecnologías de muy alta resolución : Cruise Report INSIGHT-Leg 1

Cruise Report INSIGHT-Leg 1 R/V Sarmiento de Gamboa (SDG-68) 29th April - 18th May 2018.-- 139 pages, figures, tables, 2 annexesLarge earthquakes, submarine landslides and the tsunami they might originate are geohazards of great societal concern because they may impact world economies and struck coastal populations. Examples of these events are the 2004 northern Sumatra and 2011 Tohoku earthquakes and respective tsunamis. However, earthquakes of magnitude Mw > 8.0 in areas of relatively slow tectonic deformation and with long recurrence intervals, such as the external part of the Gulf of Cadiz, might also have a significant impact. The most relevant is the 1755 Lisbon earthquake, related submarine landslides and destructive tsunami. The occurrence of faults and landslides able to trigger a catastrophic tsunami reveals that the Gulf of Cadiz is one of the highest geohazard areas in Europe. Migration of sub-seafloor fluids has also been widely documented in the Gulf of Cadiz and such fluids are strongly related to the earthquake cycle and to the occurrence of submarine landslides. Understanding of these active processes can only be developed by using ultra-high-resolution tools able to map with unprecedented detail faults, submarine landslides and fluid escape structures. State-of-the-art techniques are used during INSIGHT-Leg 1, such as microbathymetry obtained from an autonomous underwater vehicle (AUV), sub-bottom profiles, HR multi-channel seismic data (MCS), and groundtruthing using sediment coresWe gratefully acknowledge financial support from Ministerio Economia y Competividad through national project INSIGHT “ImagiNg large SeismogenIc and tsunamiGenic structures of the Gulf of Cadiz with ultra-High resolution Technologies (INSIGHT-Leg1)” (CGL2011-30005-C02-02, PIs: Roger Urgeles and Eulàlia Gràcia) and Ocean Facilities Exchange Group (OFEG) for allowing us to use the AUVs “Abyss” from GEOMAR (Germany

A first appraisal of the seismogenic and tsunamigenic potential of the largest fault systems in the westernmost Mediterranean

15 pages, 10 figures, 3 tables, supplementary material https://doi.org/10.1016/j.margeo.2022.106749.-- Data availability: The data (3D complex mesh of the ARFS and rake values, and the resulting grid files of the tsunami simulations containing the maximum wave amplitude) are archived at PANGAEA repository (https://doi.pangaea.de/10.1594/PANGAEA.941092).-- The EMODnet bathymetry is available at https://www.emodnet-bathymetry.eu/. The stochastic slip distributions have been produced by the code ANTI-FASc (https://github.com/antonioscalaunina/ANTI-FASc) a platform partially based on the code k223d (Herrero and Murphy, 2018 available at https://github.com/s-murfy/k223d), in turn based on the slipk2 (available at https://github.com/andherit/slipk2) and the trilateration codes (available at https://github.com/andherit/trilateration)The westernmost Mediterranean hosts part of the plate boundary between the European and African tectonic plates. Based on the scattered instrumental seismicity, this boundary has been traditionally interpreted as a wide zone of diffuse deformation. However, recent seismic images and seafloor mapping studies support that most of the plate convergence may be accommodated in a few tectonic structures, rather than in a broad region. Historical earthquakes with magnitudes Mw > 6 and historical tsunamis support that the low-to-moderate instrumental seismicity might also have led to underestimation of the seismogenic and tsunamigenic potential of the area. We evaluate the largest active faults of the westernmost Mediterranean: the reverse Alboran Ridge, and the strike-slip Carboneras, Yusuf and Al-Idrissi fault systems. For the first time, we use a dense grid of modern seismic data to characterize the entire dimensions of the main fault systems, accurately describe the geometry of these structures and estimate their seismic source parameters. Tsunami scenarios have been tested based on 3D-surfaces and seismic source parameters, using both uniform and heterogeneous slip distributions. The comparison of our results with previous studies, based on limited information on the fault geometry and kinematics, indicates that accurate fault geometries and heterogeneous slip distributions are needed to properly assess the seismic and tsunamigenic potential in this area. Based on fault scaling relations, the four fault systems have a large seismogenic potential, being able to generate earthquakes with Mw > 7. The reverse Alboran Ridge Fault System has the largest tsunamigenic potential, being able to generate a tsunami wave amplitude greater than 3 m in front of the coasts of Southern Spain and Northern AfricaThis work is supported by the Cluster of Excellence “The Future Ocean”, within the framework of the Excellence Initiative by the Deutsche Forschungsgemeinschaft (DFG) on behalf of the German federal and state governments. This study benefited from an EU Marie Skłodowska-Curie Individual Fellowship to LGP (H2020-MSCA-IF-2017 796013). LGP, CS, FM and RB acknowledge the resources made available by the SISMOLAB-3D at INGV. This work has been carried out in collaboration with the Grup de Recerca Consolidat de la Generalitat de Catalunya “Barcelona Center for Subsurface Imaging” (2017 SGR 1662), and acknowledges the ICM “Severo Ochoa Centre of Excellence” accreditation (CEX2019-000928-S)Peer reviewe

Tectonic evolution of the São Vicente area and tsunamigenic potential of the active structures in the SW Iberian margin: Implications for hazard assessment

Memoria de tesis doctoral presentada por Cristina Sànchez Serra para obtener el título de Doctora en Ciències de la Terra por la Universitat de Barcelona (UB), realizada bajo la dirección de la Dra. Eulàlia Gràcia Mont y del Dr. Roger Urgeles Esclasans del Institut de Ciències del Mar (ICM-CSIC).-- 254 pages, figures, tables, annexesThe southwestern margin of the Iberian Peninsula, which includes the Gulf of Cadiz, is characterized by present-day active deformation mainly driven by the NW-SE trending convergence between the African and Eurasian plates. This area hosts some of the largest earthquakes that have occurred in Western Europe leading to major disasters such as the 1755 Lisbon earthquake and tsunami. In the SW Iberian margin there is not yet a complete understanding of the active tectonics and related contemporary sedimentary processes. Further to that, there is a lack of accurate parameters to properly characterize the main active faults, and produce high-quality models of fault rupture and subsequent tsunami generation and propagation. To fill in, at least partially, these gaps of knowledge, this PhD Thesis develops the following research: 1) An analysis using a multi-scale dataset consisting of multi-beam echo-sounder, 2D multi-channel seismic reflection profiles and high-resolution sidescan sonar (TOBI) data of the Cape São Vicente area to identify the sedimentary and tectonic processes that developed in the region, the interaction between the two and how those gave origin to one of the largest canyons in the Atlantic Ocean. [...]The author of this PhD thesis has been supported by a four-year Pre-Doc FPI “Formación de Personal Investigador” grant (ref. BES-2016-078877) from “Ministerio de Ciencias e Innovación” between 2017 and 2021. The Spanish “Ministerio de Ciencia e Innovación” and the European Regional Development Fund are also acknowledged for funding through grant CTM2015-70155-R (project INSIGHT

Frequency-Magnitude relationships for Underwater Landslides of the Mediterranean Sea

American Geophysical Union Fall Meeting, 11-15 December 2017, New OrleansAn updated version of the submarine landslide database of the Mediterranean Sea contains 955 MTDs and 2608 failure scars showing thatsubmarine landslides are ubiquitous features along Mediterranean continental margins. Their distribution reveals that major deltaic wedgesdisplay the larger submarine landslides, while seismically active margins are characterized by relatively small failures. In all regions,landslide size distributions display power law scaling for landslides > 1 km3. We find consistent differences on the exponent of the powerlaw depending on the geodynamic setting. Active margins present steep slopes of the frequency-magnitude relationship whereas passivemargins tend to display gentler slopes. This pattern likely responds to the common view that tectonically active margins have numerousbut small failures, while passive margins have larger but fewer failures. Available age information suggests that failures exceeding 1000km3 are infrequent and may recur every ~40 kyr. Smaller failures that can still cause significant damage might be relatively frequent, withfailures > 1 km3 likely recurring every 40 years. The database highlights that our knowledge of submarine landslide activity with time islimited to a few tens of thousand years. Available data suggest that submarine landslides may preferentially occur during lowstandperiods, but no firm conclusion can be made on this respect, as only 149 landslides (out of 955 included in the database) have relativelyaccurate age determinations. The timing and regional changes in the frequency-magnitude distribution suggest that sedimentation patternsand pore pressure development have had a major role in triggering slope failures and control the sediment flux from mass wasting to thedeep basinPeer Reviewe

A mixed contour current - turbidity system from the São Vicente Canyon, Gulf of Cadiz: depositional features and significance for submarine slope stability

17 pagesThis project has received funding from the European Union’sHorizon 2020 research and innovation programme under grantagreement No 721403Peer reviewe

Submarine Landslides of the Mediterranean Sea: How large, how often

20th International Sedimentological Congress (ISC), 13-17 August 2018, Quebec City, Canada.-- 1 pageAn updated version of the submarine landslide database of the Mediterranean Sea1 contains 955 MTDs and 2608 failure scars showing that submarine landslides are ubiquitous features along Mediterranean continental margins. Their distribution reveals that major deltaic wedges display the larger submarine landslides, while tectonically active margins are characterized by relatively small failures. In all regions, landslide size distributions display power law scaling for landslides > 1 km3. We find consistent differences on the exponent of the power law depending on the tectonic setting. Active margins present steep slopes of the frequency-magnitude relationship whereas passive margins tend to display gentler slopes. This pattern likely responds to the common view that tectonically active margins have numerous but small failures, while passive margins have larger but fewer failures. Available age information suggests that failures exceeding 1000 km3are infrequent and may recur every ~40 kyr. Smaller failures that can still cause significant damage might be relatively frequent, with failures> 1 km3likely recurring every 40 years. This comprehensive database highlights that our knowledge of submarine landslide dynamics within time is limited to a few tens of thousands of years. Available data suggest that submarine landslides may preferentially occur during lowstand periods, but no firm conclusion can be made on this respect, as only 149 landslides (out of 955 included in the database) have relatively accurate age determinations. The temporal pattern and changes in frequency-magnitude distribution suggest that sedimentation patterns and pore pressure development have had a major role in triggering slope failures and control the mass wasting sediment flux to the deep basinThis work was supported and financed by the SLATE (H2020-MSCA-ITN-2016-721403) “Submarine landslides and their impact on continental margins” European Training Network and the Spanish project “ImagiNg large SeismogenIc and tsunamiGenic structures of the Gulf of Cadiz with ultra-High resolution Technologies” (INSIGHT (CTM2015- 70155-R)Peer Reviewe

Peligrosidad en el Golfo de Cádiz: Revisión de las principales estructuras sismogénicas

Inciativa Ibérica para el Estudio de las Fallas Activas, Tercera Reunión Ibérica sobre Fallas Activas y Paleosismología IBERFAULT 2018 - Third Iberian Meeting on Active Faults and Paleoseismology, 11-13 June 2018, Alicante, Spain.-- 4 pages, 4 figuresThe Gulf of Cadiz is located at the SW Iberian Margin and hosts the African-Eurasian plate boundary. This is one of the most seismogenic areas in Western Europe, where historical and instrumental earthquakes occurred, ranging from Mw 6 to 8.5, and some of them triggered destructive tsunamis. The ICM-CSIC team keeps investigating the Gulf of Cadiz area since more than 15 years, carrying out multiscale bathymetric, high-resolution to deep seismic and sampling surveys. The active structures in the Gulf of Cadiz can be classified in two main families: The WNW-ESE dextral strike-slip faults and the NE-SW thrusts faults. The orientation of these faults is compatible with the current plate convergence in the region. The largest active strike-slip faults are: -the Lineament South and the Lineament North that may generate earthquakes up to Mw 8; while the active NE-SW thrust faults, the Marquês de Pombal, the Horseshoe and the Coral Patch Ridge faults can individually generate earthquakes up to Mw7.8Peer Reviewe

A mixed turbidite - contourite system related to a major submarine canyon: The Marquês de Pombal Drift (south-west Iberian margin)

28 pages, 10 figures, 1 table, supporting information https://doi.org/10.1111/sed.12844.-- Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request.Synchronous interaction between bottom currents and turbidity currents has been reported often in channel–levée systems where the thickness of the turbidity currents exceeds that of the levées. Such interplay between along-slope and down-slope sedimentary processes is one of the mechanisms by which ‘mixed turbidite–contourite systems’ can originate. However, bottom currents flow over large areas of the seafloor, including continental slopes characterized by deeply incised submarine canyons rather than channel levées. In these cases, a direct interaction between along-slope and down-slope currents is, theoretically, unlikely to take place. In this study, oceanographic, swath bathymetry, multichannel seismic data and sediment cores are used to investigate a 25 km long, 10 km wide and up to 0.5 km thick deep-sea late Quaternary deposit that sits adjacent to the north-west flank of one of the major canyons in the North Atlantic, the São Vicente Canyon, in the Alentejo Basin (south-west Iberian margin). The area receives the influence of a strong bottom current, the Mediterranean Outflow Water, which has swept the continental slope at different water depth ranges during glacial and interglacial periods. Architectural patterns and sediment characteristics suggest that this sedimentary body, named Marquês de Pombal Drift, is the result of the interaction between the Mediterranean Outflow Water (particularly during cold periods) and turbidity currents flowing along the São Vicente Canyon. Because the canyon is incised significantly deeper (ca 1.5 km) than the thickness of turbidity currents, an additional process, in comparison to earlier models, is needed to allow the interaction with the Mediterranean Outflow Water and transport sediment out of the canyon. In the São Vicente Canyon, and likely in other canyons worldwide, interaction of turbidity currents with contour currents requires intermediate nepheloid layers that export the finer-grained fraction of turbidity currents out of the canyon at the boundary between major water massesThis research received funding by the European Union’s Horizon 2020 research and innovating programme under the Marie Sklodowska-Curie grant via project ITN-SLATE (grant agreement No 721403). The Spanish “Ministerio de Ciencia e Innovación” and the European Regional Development Fund are also acknowledged for funding through grant CTM2015-70155-R (project INSIGHT)With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

High-resolution imaging of submarine large seismogenic and tsunamigenic structures in the SW Iberian Margin: new insights from insight survey (2018)

Inciativa Ibérica para el Estudio de las Fallas Activas, Tercera Reunión Ibérica sobre Fallas Activas y Paleosismología IBERFAULT 2018 - Third Iberian Meeting on Active Faults and Paleoseismology, 11-13 June 2018, Alicante, Spain.-- 4 pages, 2 figuresLarge earthquakes, submarine landslides and their occasional tsunami originated are geohazards of great societal concern because of the impact on the world economies and coastal populations. Dramatic examples of such events include the 2004 northern Sumatra and 2011 Tohoku earthquakes and tsunamis. However, earthquakes of magnitude > 7.0 in areas of relatively slow tectonic deformation and with long recurrence intervals, such as the external part of the Gulf of Cadiz, might also have a significant impact as the well-known case of the destructive 1755 Lisbon earthquake, related submarine landslides, and resulting tsunami. Although the Gulf of Cadiz is one of the highest geohazard zones in Europe, we currently lack appropriate understanding of both the rupture areas and stress-state of the faults and sediments in which such catastrophic events originated. The relatively great water depths, poor accuracy on the location of moderate-to¬-high magnitude earthquakes, lack of understanding of subsurface hydrology and the few constraints on ages of the sedimentary sequences hinder an appropriate understanding of location and characteristics of earthquake ruptures and associated submarine landslides in the Gulf of Cadiz. Our hypothesis is that such understanding can only be developed by using ultra-high resolution (UHR) tools capable of providing the characterization of faults, submarine landslides, and fluid escape structures while being able to work in deep waters such as those of the external Gulf of Cadiz. INSIGHT tackles this problem by using state-of ¬the-art UHR techniques such as microbathymetry, 2D high-resolution seismic data, and sampling using piston cores. We aim at 1) Map in detail the active faults with largest seismogenic potential, 2) Accurately determine the seismic parameters of these faults, 3) Characterize associated submarine landslides, 4) Assess the likelihood of recent submarine landslides activation, and finally, 5) Evaluate the seismogenic and tsunamigenic potential of the largest tectonic sourcesWe acknowledge financial support from MINECO through Project INSIGHT (CTM2015-70155-R)Peer Reviewe