Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition

Altres ajuts: This work was supported by research funding from the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias cofinanced by the European Regional Development Fund (ERDF); Fundación Asociación Española Contra el Cáncer (M.C. and P.A.) and Gilead Fellowships (GLD16/00144, GLD18/00047, F.B). M.C. holds a contract from Ministerio de Ciencia, Innovación y Universidades. S.B. is the recipient of a postdoctoral fellowship from Fundación Alfonso Martin Escudero.Patients diagnosed with primary central nervous system lymphoma (PCNSL) often face dismal outcomes due to the limited availability of therapeutic options. PCNSL cells frequently have deregulated B-cell receptor (BCR) signaling, but clinical responses to its inhibition using ibrutinib have been brief. In this regard, blocking nuclear export by using selinexor, which covalently binds to XPO1, can also inhibit BCR signaling. Selinexor crosses the blood-brain barrier and was recently shown to have clinical activity in a patient with refractory diffuse large B-cell lymphoma in the CNS. We studied selinexor alone or in combination with ibrutinib in pre-clinical mouse models of PCNSL. Orthotopic xenograft models were established by injecting lymphoma cells into the brain parenchyma of athymic mice. Tumor growth was monitored by bioluminescence. Malignant cells and macrophages were studied by immunohistochemistry and flow cytometry. Selinexor blocked tumor growth and prolonged survival in a bioluminescent mouse model, while its combination with ibrutinib further increased survival. CNS lymphoma in mice was infiltrated by tumor-promoting M2-like macrophages expressing PD-1 and SIRPα. Interestingly, treatment with selinexor and ibrutinib favored an anti-tumoral immune response by shifting polarization toward inflammatory M1-like and diminishing PD-1 and SIRPα expression in the remaining tumor-promoting M2-like macrophages. These data highlight the pathogenic role of the innate immune microenvironment in PCNSL and provide pre-clinical evidence for the development of selinexor and ibrutinib as a new promising therapeutic option with cytotoxic and immunomodulatory potential. The online version of this article (10.1007/s11060-020-03580-y) contains supplementary material, which is available to authorized users

Barcelona Coastal Monitoring with the “Patí a Vela”, a Traditional Sailboat Turned into an Oceanographic Platform

Special issue Technological Oceanography.-- 16 pages, 12 figures, 3 tables.-- Data supporting reported results can be found at https://paticientific.org/index.php/dades/ (accessed on 13 April 2022) and through https://zenodo.org/search (accessed on 13 April 2022) by searching “pati cientific”.Shelf waters near large cities, such as Barcelona, are affected not only by meteorological episodes but also by anthropogenic influence. Scientists usually use data from on-site coastal platforms to analyze and understand these complex water ecosystems because remote sensing satellites have low spatiotemporal resolution and do not provide reliable data so close to the coast. However, platforms with conventional oceanographic instrumentation are expensive to install and maintain. This study presents the scientific adaptation and initial measurements from a “patí a vela”, which is a very popular unipersonal catamaran in Barcelona. This versatile sailing vessel has been adapted to contain several low-cost sensors and instruments to measure water properties. Here, we describe the setup of a multi-parameter prototype, and then focus on results obtained using a low-cost temperature profiler. First, the temperature data are compared and validated with another conventional oceanographic instrument used in monthly oceanographic cruises. Then, field measurements between July and November 2021 are used to explore the relationship between air and water temperature in the Barcelona coastal area, showing the seasonal evolution of the temperature profile. We conclude that citizen sampling from fully sustainable sailing boats may turn into an effective strategy to monitor the urban coastal watersThis work has been carried out within the framework of the 2019 Barcelona Pla de Ciència, with funding from the Barcelona City Council through the project “Development of a citizen monitoring program for the Barcelona coastal waters: the Scientific Patí Vela” (PATI CIENTIFIC; references 19SO1645-006, 19SO1649-006, 19SO1651-006). [...] The ICM authors also recognize the institutional support of the Spanish Government through the Severo Ochoa Center of Excellence accreditation (CEX2019-000928-S)Peer reviewe

RETRO-BMC - 2017 : La gran retroflexió de l'Atlàntic sud

Diario de la campaña oceanográfica RETRO-BMC, a bordo del buque oceanográfico Hespérides del 8 al 28 de abril del 2017, publicado en la página web de ICM Divulga.-- 29 pages, figures[ES] La campaña Retro-BMC está enmarcada en el proyecto VA-DE-RETRO, centrado en el estudio de la retroflexión del Atlántico sur. El objetivo del proyecto es comprender los mecanismos y características de las retroflexiones: seguir la trayectoria, observar las transformaciones y destino final de las aguas que la forman e identificar las teleconexiones que permiten que ambas regiones de retroflexión operen de manera unificada. El proyecto VA-DE-RETRO incluye el programa divulgativo “Pequeños Oceanógrafos”. La campaña incluye la sección “Oceanografía en tiempo real” destinada a estudiantes universitarios. Al sur del océano Atlántico se encuentran dos corrientes de aguas marinas muy diferentes: la corriente de Brasil, descendente del giro subtropical; y la corriente de las Malvinas, aguas frías que suben desde la región antártica trayendo aguas del océano Pacífico. Al chocar, ambas corrientes se desvían de su trayectoria hacia el océano interior. Este brusco cambio de dirección de las corrientes se conoce como retroflexión. ¿Cómo se generan las retroflexiones? ¿Qué importancia tienen en la circulación de los océanos? ¿Afectarán a la distribución de nutrientes? El equipo VA-DE-RETRO trabajará durante 20 días a bordo del Hespérides para dar respuesta a estas preguntas y comprender el funcionamiento de las válvulas que mantienen la circulación oceánica. ¡Cónoce cómo trabajan los oceanógrafos siguiendo el diario de campaña! - Objetivos Científicos: · Objetivos Científicos · Divulgación científica - Participantes - Diario de Campaña: · 28 de marzo 2017. 10 días para embarcar · 7 de abril 2017. Ushuaia y el Hespérides · 8 y 9 de abril 2017. El Canal de Beagle · 9 y 10 de abril 2017. El inmenso gigante · 9 y 10 de abril 2017. Observadores del mar · 11 de abril 2017. Transito Beagle-Confluencia · 12 de abril 2017. Salida de Ushuaia y navegación por el Canal Beagle · 12 de abril 2017 · 13 de abril 2017. Sección Sur · 14 de abril 2017. El tránsito · 15 de abril 2017. En la Confluencia · 16 de abril 2017. CTDs y SeaSoar · 19 de abril 2017. El alma del BIO Hespérides: su tripulación · 20 de abril 2017. L’oceanografia és ciència d’observació · 21 de abril 2017. Un océano caprichoso · 22 de abril 2017. Hespérides · 23 de abril 2017. Oceanógrafos · 24 de abril 2017. Resumen de campaña (I): el filamento de agua del Río de la Plata · 26 de abril 2017. El tiempo · 27 de abril 2017. Las tertulias de Álvaro · 27 de abril 2017. Resumen de campaña (II): las masas de agua de la Corriente de Malvinas · 27 de abril 2017. Batiscafo Katiuska y Confluencia · 28 de abril 2017. Resumen de campaña (III): la termoclina del giro subtropical y la Corriente de Brasil - Peque científicos. Preguntas y respuestas: · En alta mar · Hacia el puerto - Oceanografía en tiempo real: · Datos obtenidos a bordo día a día. Canal de Beagle. Región de Confluencia · Predicciones de modelos operacionales · Datos satélite y Argo · Climatologías y secciones históricas[CAT] Tornem a pujar a bord de l’Hespérides cap a l’Atlàntic sud, a la regió de confluència de Brasil-Malvines, per estudiar les retroflexions que es produeixen en una de les zones més enèrgiques de l’oceà globalPeer reviewe

Diapycnal mixing in the Brazil-Malvinas confluence front

20 pages, 24 figures, 4 tables.-- Data availability: Data will be made available on requestDiapycnal mixing in the Brazil-Malvinas Confluence Zone (BMC) is assessed on the basis of microstructure measurements done as part of an April 2017 cruise, which explored the mesoscalar and regional frontal dynamics. Sampling was done down to 400 m in 11 locations on both sides of the BMC, over the slope and in the abyssal waters. Turbulent scales, non-dimensional numbers, energy dissipation rates and diapycnal eddy diffusivities are calculated, which allow us to assess the state of the small-scale turbulence in the frontal region. Active turbulence was present at all depths and stations, with high-dissipation patches ranging from several metres to a few tens of metres. The frontal zone is characterized by high energy dissipation and eddy diffusivity. The geometric mean eddy diffusivity for all stations and the entire water column is 7.0 × 10-4 m2 s−1. The mean values halve when only considering the more stratified seasonal thermocline, 3.8 × 10-4 m2 s−1, and are twice larger south than north of the BMC. High dissipation rates coincide with high vertical shear, possibly related to the convergence of the two intense currents and/or the generation of internal waves by the associated mesoscalar and submesoscalar features. The layered structures related to intruding filaments favor double diffusive convection and salt fingering. Near-bottom mixing at the stations on the continental slope is possible related to shear-driven Kelvin-Helmoltz instabilitiesThis study has been supported by the Spanish Government through projects VA-DE-RETRO (CTM2014-56987-P) and SAGA (RTI2018-100844-B-C33)With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

Informe de Campaña RETRO-BMC

Pelegrí, Josep Lluís ... et al.-- Informe de Campaña RETRO-BMC, BIO Hespérides, Ushuaia‐Santos, 8‐28 abril 2017.-- 73 pages, 9 figures, 5 tables, annexesLa campaña RETRO‐MC se realizó a bordo del BIO Hespérides con salida de Ushuaia el 8 de abril y llegada a Santos el 28 de abril de 2017. La campaña se hizo en dos fases, una primera fase de 24 horas de trabajo (8 y 9 de abril) en el Canal de Beagle y una segunda fase de 12 días de trabajo (13 a 24 de abril) en la Confluencia de Brasil‐MalvinasProyecto VA‐DE‐RETRO (CTM2014‐56987‐P) Ministerio de Economía y CompetitividadPeer Reviewe

Data from Pati Cientific 2022-04-19 TD-5

Sea temperature vs depth measured by the Pati Cientific at Somorrostro, Barcelona, on 2022-04-19.Peer reviewe

Data from Pati Cientific 2022-04-19 TD-2

Sea temperature vs depth measured by the Pati Cientific at Somorrostro, Barcelona, on 2022-04-19. Project: AULAMARPeer reviewe

Data from Pati Cientific 2022-01-11 TD-5

Sea temperature vs depth measured by the Pati Cientific at Somorrostro, Barcelona, on 2022-01-11. Project: Patí CientíficPeer reviewe

Data from Pati Cientific 2022-01-18 TD-2

Sea temperature vs depth measured by the Pati Cientific at Somorrostro, Barcelona, on 2022-01-18. Project: Patí CientíficPeer reviewe

Data from Pati Cientific 2022-04-19 TD-3

Sea temperature vs depth measured by the Pati Cientific at Somorrostro, Barcelona, on 2022-04-19. Project: AULAMARPeer reviewe