Expansion of different subpopulations of CD26 −/low T cells in allergic and non-allergic asthmatics

CD26 displays variable levels between effector (TH ≫ TH > TH > Treg) and naïve/memory (memory > naïve) CD4 T lymphocytes. Besides, IL-6/IL 6R is associated with TH -differentiation and asthma severity. Allergic/atopic asthma (AA) is dominated by TH responses, while TH immunity might either modulate the TH -dependent inflammation in AA or be an important mechanism boosting non-allergic asthma (NAA). Therefore, in this work we have compared the expression of CD26 and CD126 (IL-6Rα) in lymphocytes from different groups of donors: allergic (AA) and non-allergic (NAA) asthma, rhinitis, and healthy subjects. For this purpose, flow cytometry, haematological/biochemical, and in vitro proliferation assays were performed. Our results show a strong CD26-CD126 correlation and an over-representation of CD26 subsets with a highly-differentiated effector phenotype in AA (CD4 CD26 T cells) and NAA (CD4 CD26 γδ-T cells). In addition, we found that circulating levels of CD26 (sCD26) were reduced in both AA and NAA, while loss of CD126 expression on different leukocytes correlated with higher disease severity. Finally, selective inhibition of CD26-mRNA translation led to enhanced T cell proliferation in vitro. These findings support that CD26 down-modulation could play a role in facilitating the expansion of highly-differentiated effector T cell subsets in asthma

U-Pb geochronology of carbonatites from NW Fuerteventura revisited: new data and geological implications

En este trabajo se presentan nuevas edades U-Pb en circones de carbonatitas del sector NW de Fuerteventura. Los circones presentan características tanto texturales como composicionales que indican su origen ígneo y su cristalización a partir de magmas carbonatíticos. La edad obtenida, 24.2 ± 0.3Ma, es algo más joven que la existente para las carbonatitas del sector centro-occidental de la isla, por lo que se propone que habrían existido al menos dos intrusiones alcalino-carbonatíticas con cierta migración temporal en el sentido SW-NE, dentro de una zona de rift. Esta edad, además, restringe el episodio magmático alcalino-carbonatítico de la isla a prácticamente 1 Ma de duración. Sin embargo, este lapso temporal es significativo, en cuanto que representa la consecuencia de los cambios que ha sufrido la placa africana en su movimiento de divergencia con respecto a América del Sur y de convergencia con Eurasia.In this work, new U-Pb zircon ages in carbonatites from the NW sector of Fuerteventura are presented. The zircons show textural and compositional characteristics indicating its igneous origin and its crystallization from carbonatitic magmas. The obtained age, 24.2 ± 0.3 Ma, is slightly younger than the existing age for carbonatites in the central-western sector of the island. Therefore, we propose that at least two alkaline- carbonatitic intrusions would have been emplaced in a rift zone, with a certain degree of time migration from SW to NE. In addition, this age constrains the alkaline-carbonatitic magmatic episode in the island to an almost virtually 1 Ma span. However, this time lapse is meaningful, as it represents the consequence to the changes underwent by the African plate in its divergent movement with respect to South America and its convergence with Eurasia.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEMinisterio de Economía y Competitividad (MINECO)Universidad del País Vascopu

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤ .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice

Classification of current anticancer immunotherapies

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches

Emplazamiento de sills y diques del Pérmico superior en el Macizo de Cinco Villas (Pirineo Navarro)

The emplacement of basaltic sills and dykes outcropping in the Cinco Villas Massif (Western Pyrenees), northwards of the North-pyrenean fault, was controled by the hercynian main-phase cleavage (dykes) and by the orientation of three small half-graben permian basins (sills), unconformably overlain by the Buntsandstein conglomerates. Both types of magmatism are cogenetic and coeval

Geoquímica del magmatismo, Pérmico superior, del Macizo de Cinco Villas (Pirineo Navarro) dc.identifier.citation: Geochemistry of Upper Permian magmatism in Cinco Villas massif (Navarra, Western Pyrenees)

The chemical composition (whole rock) of Upper Permian basaltic sills and dolerite dykes outcropping in the Cinco Villas Massif (Western Pyrenees) allow to recognize: a) their basic, unevolved composition, b) their cogenetism, and c) their subalkaline to alkaline geochemical affinity. These features are similar to those of the Anayet-Ossau basaltic rocks, and suggest their relationship with a common basaltic event, related to post-orogenic extensional tectonics

Geoquímica del magmatismo, Pérmico superior, del Macizo de Cinco Villas (Pirineo Navarro) dc.identifier.citation: Geochemistry of Upper Permian magmatism in Cinco Villas massif (Navarra, Western Pyrenees)

The chemical composition (whole rock) of Upper Permian basaltic sills and dolerite dykes outcropping in the Cinco Villas Massif (Western Pyrenees) allow to recognize: a) their basic, unevolved composition, b) their cogenetism, and c) their subalkaline to alkaline geochemical affinity. These features are similar to those of the Anayet-Ossau basaltic rocks, and suggest their relationship with a common basaltic event, related to post-orogenic extensional tectonics