Senescence in the development and response to cancer with immunotherapy : A double-edged sword

Altres ajuts: This research was funded by the "la Caixa" Foundation, grant number P-CP042702.Cellular senescence was first described as a physiological tumor cell suppressor mechanism that leads to cell growth arrest with production of the senescence-associated secretory phenotype known as SASP. The main role of SASP in physiological conditions is to attract immune cells to clear senescent cells avoiding tumor development. However, senescence can be damage-associated and, depending on the nature of these stimuli, additional types of senescence have been described. In the context of cancer, damage-associated senescence has been described as a consequence of chemotherapy treatments that were initially thought of as a tumor suppressor mechanism. However, in certain contexts, senescence after chemotherapy can promote cancer progression, especially when immune cells become senescent and cannot clear senescent tumor cells. Moreover, aging itself leads to continuous inflammaging and immunosenescence which are responsible for rewiring immune cells to become defective in their functionality. Here, we define different types of senescence, pathways that activate them, and functions of SASP in these events. Additionally, we describe the role of senescence in cancer and its treatments, including how aging and chemotherapy contribute to senescence in tumor cells, before focusing on immune cell senescence and its role in cancer. Finally, we discuss potential therapeutic interventions to reverse cell senescence

One-Dimensional Modeling of Mechanical and Friction Losses Distribution in a Four-Stroke Internal Combustion Engine

[EN] As the road transport accounts between 15%-18% of worldwide CO2 emissions, the automotive sector has a deep commitment to mitigate global warming. Consequently, stricter regulations have been adopted by the European Union and worldwide to reduce that big impact. Approximately, 10% of the energy generated by fuel combustion in the engine is destined to the auxiliaries components activation and the movement of mechanical elements with relative motion between themselves. A reduction on that figure or alternatively a mechanical efficiency improvement can be directly translated on target alignment. The aim of this work is developing a model to predict the mechanical and friction losses and its distribution in a four-stroke direct injection-diesel engine and simulating different strategies, which increment the engine efficiency. A 1D model has been developed and fitted in GT-SUITE based on the experimental results of a 1.6-L diesel engine. Additionally, a description of the tribological performance has been realized in different parts of the engine where friction is present. Finally, the engine friction maps have been broken down in order to quantify the friction losses produced in the piston ring assembly, crankshaft bearings, and valvetrainTormos, B.; Martín, J.; Blanco-Cavero, D.; Jiménez-Reyes, AJ. (2020). One-Dimensional Modeling of Mechanical and Friction Losses Distribution in a Four-Stroke Internal Combustion Engine. Journal of Tribology. 142(1). https://doi.org/10.1115/1.4044856S142

Magneto-optical effects in interacting localized and propagating surface plasmon modes

We report that the effect of an external magnetic field on the propagation of surface plasmons can be effectively modified through the coupling between localized (LSP) and propagating (SPP) surface plasmons. When these plasmon modes do not interact, the main effect of the magnetic field is a modification of the wavevector of the SPP mode, leaving the LSP virtually unaffected. Once both modes start to interact, there is a strong variation of the magnetic field induced modification of the SPP dispersion curve and, simultaneously, the LSP mode becomes sensitive to the magnetic field.This work was supported by the EU (NMP3-SL- 2008-214107-Nanomagma), the Spanish MICINN (“MAGPLAS” MAT2008-06765-C02-01/NAN and “FUNCOAT” CONSOLIDER INGENIO 2010 CSD2008-00023), the Comunidad de Madrid (“NANOBIOMAGNET” S2009/MAT-1726 and “MICROSERES-CM” S2009/TIC-1476), and CSIC (“CRIMAFOT” PIF08-016-4). We thank A. Cebollada and J. M. García-Martín for growing and characterizing the Au/Co/Au trilayers and reading this manuscript, and R. Quidant and G.Badenes for fruitful discussions.Peer reviewe

Plasmon-enhanced magneto-optical activity in ferromagnetic membranes

Experimental and theoretical evidence of plasmon-enhanced Kerr rotation in purely ferromagnetic membranes with sufficiently small dimensions to be out of extraordinary optical transmission conditions (45 nm pore diameter, 90nm lattice constant), is reported in this work. It is shown that the spectral location of the enhanced Kerr rotation region varies as the refractive index of the material inside the pore is modified. A similar behavior is obtained if the pore radius changes while keeping the pore concentration unchanged. Those are clear signatures indicating that localized surface plasmon resonances propagating along the pores govern the magneto-optical response of the membraneWe acknowledge Spanish MICINN (Grant Nos. MAT2008-06765-C02-01/NAN, CSD2008-00023, and MAT2007-65420-C02-01), CSIC (Grant No. PIF 200560F0121 BIOPTOMAG), CM(Grant No. S-0505/MAT/0194 NANOMAGNET), and European Commission (Grant No. NMP3-SL-2008-214107-Nanomagma) for financial support.Peer reviewe

Magnetoplasmonic Interferometers and Applications

Comunicación presentada en el 2nd Early Stage Researchers Workshop in Nanoscience, celebrado en Madrid el 28 y 29 de junio de 2012.Surface plasmons polaritons (SPP) are evanescent waves that propagate along a dielectric-metal interface. They can be confined in subwavelength metal structures, i.e. below the diffraction limit, which leads to many possible applications, including miniaturized optical devices. Within that context, the development of active plasmonics is important to achieve nanophotonic devices with advanced functionalities. This requires a system where the plasmon properties can be manipulated using an external agent. Among the different control agents considered so far, the magnetic field seems a promising candidate, since it is able to modify the dispersion relation of SPP at reasonable magnetic field strengths, and with a high switching speed. This modulation comes from the non-diagonal elements of the dielectric tensor, εij, appearing when the magnetic field is turned on. For noble metals, the ones typically used in plasmonics, these elements are proportional to the applied magnetic field but, unfortunately, very small at field values reasonable for developing applications. On the other hand, ferromagnetic metals have sizeable εij values at small magnetic fields (proportional to their magnetization), but are optically too absorbent. A smart system to develop magnetic field tunable plasmonic devices is the use of multilayers of noble and ferromagnetic metals. That is the framework of the present work, where we analyze the magnetic field induced SPP wavevector modulation (Ak) in Au/Co/Au films as a function of the wavelength and its possible application as a sensor.N

Il-15 enhances the persistence and function of bcma-targeting car-t cells compared to il-2 or il-15/il-7 by limiting car-t cell dysfunction and differentiation

Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the treatment of B-lymphoid malignancies. For multiple myeloma (MM), B-cell maturation antigen (BCMA)-targeted CAR-T cells have achieved outstanding complete response rates, but unfortunately, patients often relapse within a year of receiving the therapy. Increased persistence and reduced dysfunction are crucial features that enhance the durability of CAR-T cell responses. One of the factors that influence CAR-T cell in vivo longevity and loss of function, but which has not yet been extensively studied for BCMA-directed CAR-T cells, are the cytokines used during their production. We here compared the impact of IL-2, IL-15 and a combination of IL-15/IL-7 on the phenotype and function of ARI2h, an academic BCMA-directed CAR-T cell that is currently being administered to MM patients. For this study, flow cytometry, in vitro cytotoxicity assays and analysis of cytokine release were performed. In addition, ARI2h cells expanded with IL-2, IL-15, or IL-15/IL-7 were injected into MM tumor-bearing mice to assess their in vivo efficacy. We demonstrated that each of the cytokine conditions was suitable for the expansion of ARI2h cells, with clear in vitro activity. Strikingly, however, IL-15-produced ARI2h cells had improved in vivo efficacy and persistence. When explored further, it was found that IL-15 drove a less-differentiated ARI2h phenotype, ameliorated parameters related to CAR-T cell dysfunction, and lowered the release of cytokines potentially involved in cytokine release syndrome and MM progression. Moreover, we observed that IL-15 was less potent in inducing T cell senescence and DNA damage accumulation, both of which may contribute to an unfavorable CAR-T cell phenotype. These findings show the superiority of IL-15 to IL-2 and IL-15/IL-7 in the quality of anti-BCMA CAR-T cells, particularly their efficacy and persistence, and as such, could improve the duration of responses if applied to the clinical production of CAR-T cells for patients

Factors involved in soil organic matter stabilization in Peruvian Amazonian soils (Ucayali region) and the molecular composition of extractable lipids

Poster E1012b presentado en el 27th International Meeting on Organic Geochemistry September 13–18, 2015, Prague, Czech RepublicAmazonian ecosystems are considered important sinks for atmospheric CO2 on Earth. It is therefore desirable to preserve their biodiversity and productivity. In this communication an assessment of the influence of different agro-forestry practices on soil C storage in representative ecosystems from the Peruvian Ucayali region is approached by analyzing the soil lipid fraction. In fact, this organic matter fraction is an important source of analytical surrogates of soil C stabilization and accumulation processes (Naafs at al., 2004; Poulenard et al., 2004; Rumpel et al., 2004). Top (0–20 cm) and subsoil (20–40 cm) samples were taken from the Amazonian Ucayali region (Pucallpa, Perú), ranging from recent alluvial soils in muddy zones of riverside areas (wetlands referred to as ‘mud’, ‘beach’ and low ‘restinga’ soils) to more developed soils located in medium and higher riverine terraces, as well as in hills. The lipid fraction was Soxhlet extracted with a mixture of ichloromethane:methanol (2:1 by vol.), saponified and divided into neutral and acid subfractions. The acid fractions were then sequentially methylated and silylated prior to the chromatographic analysis (González-Vila et al., 2003). Neutral and acid sub-fractions were separated and the major compounds were identified by gas chromatography-mass spectrometry using an HP G1800A GCD System (electron impact detector at 70 eV) equipped with a DB-5 fused silica capillary column (30 m × 0.32 mm i.d., film thickness 0.25 µm) and using He as carrier gas at a flow rate of 1.5 mL min-1. The chromatographic oven temperature was programmed to increase from 40 to 100 ºC at 30 ºC min-1 and then to 300 ºC at 6 ºC min -1. The values of soil organic matter and lipids ranged from 25.8 to 5.8 g kg-1, and from 5.2 to 0.2 g kg-1, respectively. This variability as well as the differences in lipid molecular composition could suggest differences in the soils’ use and management practices (Van Bergen et al.,1996). The main families of signature lipids detected in the soil extracts were n-alkanes, linear isoprenoids, cyclic alkanes, n-fatty acids, branched fatty acids, unsaturated fatty acids, hydroxyacids, n-alcohols, ketones, polycyclic hydrocarbons and sterols. Very significant differences in qualitative and quantitative lipid composition were found in terms of soil depth. This effect was more pronounced in the soils from the riverine high terraces devoted to agro-forestry practices (Figs. 1 and 2). In addition, lipidic compounds of high molecular weight (i.e., di- and triterpenes) were detected as regular components of the free lipid fractions from the different ecosystems (wetlands, terraces and hills) reflecting specific vegetation and soil-use influences. Xenobiotic compounds (naphthenic acids) detected within the unresolved chromatographic ‘hump’ (highly unresolved mixture of cyclic or branched hydrocarbons) were also observed, indicating anthropogenic contamination by mineral oils. Likewise, dialkyl phthalates (Phth) from plasticizers were also detected.Projects CGL2012-38655-C04-01 and CGL2008-04296 and fellowship BES-2013-062573 given to N.T.J.M by the Spanish Ministry of Economy and Competitiveness. Dr. J.M.R. is the recipient of a fellowship from the JAE-Doc subprogram financed by the CSIC and the European Social Fund.Peer Reviewe

Estudio de suelos de parques y jardines de Sevilla: relación entre diversos parámetros generales de los suelos y los contenidos de Cu y Zn, y efecto de la profundidad en la toma de muestras.

The urban soils of Seville have been studied within a European project (URBSOIL) during recent years. Relatively high levels of some metals (Cu, Pb and Zn) have been found in the nearest sites to the historical city centre suggesting a definite human influence. In general, a high metal availability has been found, which is a cause of concern. The object of this work was to study the relations between some general parameters in soils (pH, texture, electrical conductivity, calcium carbonate equivalent, organic carbon, N, C/N ratio) and the Cu and Zn contents, as well as to study the effect of depth on and the relations between them.Los suelos urbanos de Sevilla han sido estudiados en los últimos años dentro del proyecto URBSOIL. Previamente se habían encontrado niveles relativamente elevados de algunos metales (Cu, Pb y Zn) en las zonas más cercanas al centro histórico de la ciudad, con lo que parece evidente la influencia humana en el origen de estos metales. En general se había encontrado una alta disponibilidad de los metales, lo que incrementa la preocupación por este tipo de contaminación. El objetivo de este trabajo es estudiar las relaciones entre los parámetros generales de los suelos (pH, granulometría, conductividad eléctrica, carbonato, carbono orgánico, nitrógeno y relación C/N) y los contenidos de Cu y Zn, así como estudiar la variación con la profundidad. Para ello, se han tomado muestras en un total de 32 puntos, a dos profundidades (0 a 10 cm y 10 a 20 cm) en varios parques y jardines de Sevilla, desde diciembre de 2003 a marzo de 2004. Las muestras se caracterizaron midiendo sus propiedades más importantes y sus contenidos pseudototales de Cu y Zn por digestión con agua regia.

Active deformation and shallow structure of the Wagner, Consag, and Delfín Basins, northern Gulf of California, Mexico

Oblique rifting began synchronously along the length of the Gulf of California at 6 Ma, yet there is no evidence for the existence of oceanic crust or a spreading transform fault system in the northern Gulf. Instead, multichannel seismic data show a broad shallow depression, ∼70 × 200 km, marked by active distributed deformation and six ∼10-km-wide segmented basins lacking well-defined transform faults. We present detailed images of faulting and magmatism based on the high resolution and quality of these data. The northern Gulf crust contains a dense (up to 18 faults in 5 km) complex network of mainly oblique-normal faults, with small offsets, dips of 60–80° and strikes of N-N30°E. Faults with seafloor offsets of tens of meters bound the Lower and two Upper Delfín Basins. These subparallel basins developed along splays from a transtensional zone at the NW end of the Ballenas Transform Fault. Twelve volcanic knolls were identified and are associated with the strands or horsetails from this zone. A structural connection between the two Upper Delfín Basins is evident in the switching of the center of extension along axis. Sonobuoy refraction data suggest that the basement consists of mixed igneous sedimentary material, atypical of mid-ocean ridges. On the basis of the near-surface manifestations of active faulting and magmatism, seafloor spreading will likely first occur in the Lower Delfín Basin. We suggest the transition to seafloor spreading is delayed by the lack of strain-partitioned and focused deformation as a consequence of shear in a broad zone beneath a thick sediment cover