The leukocyte activation receptor CD69 controls T cell differentiation through its interaction with galectin-1

CD69 is involved in immune cell homeostasis, regulating the T cell-mediated immune response through the control of Th17 cell differentiation. However, natural ligands for CD69 have not yet been described. Using recombinant fusion proteins containing the extracellular domain of CD69, we have detected the presence of a ligand(s) for CD69 on human dendritic cells (DCs). Pulldown followed by mass spectrometry analyses of CD69-binding moieties on DCs identified galectin-1 as a CD69 counterreceptor. Surface plasmon resonance and anti-CD69 blocking analyses demonstrated a direct and specific interaction between CD69 and galectin-1 that was carbohydrate dependent. Functional assays with both human and mouse T cells demonstrated the role of CD69 in the negative effect of galectin-1 on Th17 differentiation. Our findings identify CD69 and galectin-1 to be a novel regulatory receptor-ligand pair that modulates Th17 effector cell differentiation and functionThis work was funded by grants SAF2011-25834 and ERC-2011AdG 294340-GENTRIS to F.S.-M., RECAVA RD06/0014 from the Fondo de Investigaciones Sanitarias to J.V. and F.S.-M., and INDISNET 01592006 from the Comunidad de Madrid to F.S.-M. and P.M. and by grants from the Ministerio de Economia y Competitividad (PI11/01562 to P.N.) and the Generalitat de Catalunya-AGAUR (2009SGR1409 to P.N.). The Ministry of Science and Innovation and the Pro-CNIC Foundation support CNI

A view of the Brazil-Malvinas confluence, March 2015

The encountering of the subtropical Brazil Current (BC) and the subantarctic Malvinas Current (MC) along the western margin of the Argentine Basin forms the Brazil-Malvinas Confluence (BMC), one of the most intense open-ocean fronts in the world ocean and a site for the formation of intermediate water masses. Here, we provide a comprehensive description of the BMC based on physical and biogeochemical data – hydrographic stations, profiling floats and subsurface drifters – gathered in March 2015. We use these data in order to characterize the impinging and outflowing currents and to describe the cross- and along-frontal thermohaline structure. In addition, we compare the in-situ measurements with both climatological data and the Mercator Ocean eddy-resolving reanalysis. The hydrographic sections illustrate the contrasting properties between the two western boundary currents: warm, salty, nutrient- and oxygen-poor oligotrophic subtropical waters carried southward by the BC and the cold, fresh, oxygen- and nutrient-rich subantarctic waters carried northward by the MC. The frontal system is also characterized by the presence of thermohaline intrusions, with the cross-frontal gradients and along-front velocities sharpening as the colliding currents shape the frontal system. We also observe brackish waters spreading on top of the frontal jet as a result of both the confluence dynamics and off-shelf advection favored by north-easterly winds. These low-salinity waters are positively correlated with surface ageostrophic speeds over the frontal jet. The cruise data illustrates the high regional and mesoscale variability as compared with climatological conditions, and further document the submesoscale subsurface complexity, which is not properly captured by available operational models.Fil: Orúe Echevarría, Dorleta. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Pelegrí, Josep L.. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Alonso González, Iván J.. Oceomic, Marine Bio And Technology S.L; EspañaFil: Benítez Barrios, Verónica M.. Oceomic, Marine Bio And Technology S.L; EspañaFil: Emelianov, Mikhail. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: García Olivares, Antonio. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Gasser i Rubinat, Marc. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: De La Fuente, Patricia. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Herrero, Carmen. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Isern Fontanet, Jordi. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Masdeu Navarro, Marta. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Peña Izquierdo, Jesús. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Piola, Alberto Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Ramírez Garrido, Sergio. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Rosell Fieschi, Miquel. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Salvador, Joaquín. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Saraceno, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Barcelona; EspañaFil: Valla, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; ArgentinaFil: Vallès Casanova, Ignasi. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Vidal, Montserrat. Universidad de Barcelona; Españ

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.This work was supported in part by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018), which is included in the Spanish I+D+I Plan and is co-funded by the ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER). The sponsors had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication.S

Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant

Background: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. Methods: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. Results: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. Conclusions: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.This work was funded by grant Ref. no. GLD14-00279 from the GILEAD Fellowship Programme (Spain) and by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018) that is included in the Spanish I+D+I Plan and is co-financed by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER).S

Herramientas de comunicación y divulgación musical orientadas a la transferencia: entornos digitales 2.0

Este proyecto tiene como objeto la formación sobre recursos y herramientas de comunicación y divulgación musical en espacios 2.0, con el fin de utilizarlas en el aula y fomentar la transferencia y el emprendimiento en el ámbito de la musicología

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

ZIF-8 micromembranes for gas separation prepared on laser-perforated brass supports

ZIF-8 is an imidazolate-based metal–organic framework (MOF). ZIF-8 micromembranes of 20–32 μm diameter are prepared by synthesizing the MOF on Nd:YAG laser-perforated 75 μm thick brass sheets (63/37 Cu/Zn). The laser irradiation activates the brass support, promoting ZIF-8 growth. A thick and continuous ZIF-8 membrane is crystallized on the laser irradiation outlet side of the support, while the inlet side and the inner surface of the microperforations are also coated with ZIF-8 intergrowth crystals. Laser perforated brass supports are not only cheap, flexible, strong, and easy to handle and to process as membrane materials; they are also chemically compatible with the ZIF-8 composition because of the shared Zn element. The ZIF-8 membranes obtained are characterized by XRD, SEM, EDX, TGA and N2 sorption analysis. Furthermore, the membranes are applied to the separation of equimolar H2–CH4, He–CH4, CO2–CH4 and O2–N2 mixtures confirming the expected molecular sieving effect due to the MOF microporosity.Financial support (MAT2010-15870 and MAT2010-18519) and FPU Program fellowships (M.N. and B.S.) from the Spanish MINECO, the Aragón Government and the ESF are gratefully acknowledged.Peer Reviewe