Benthic oxygen fluxes in a coastal upwelling system (Ria de Vigo, NW Iberia) measured by aquatic eddy covariance

Organic carbon mineralization and nutrient cycling in benthic environments are critically important for their biogeochemical functioning, but are poorly understood in coastal up - welling systems. The main objective of this study was to determine benthic oxygen fluxes in a muddy sediment in the Ria de Vigo (NW Iberian coastal upwelling), by applying the aquatic eddy covariance (AEC) technique during 2 campaigns in different seasons (June and October 2017). The main drivers of benthic fluxes were studied and compared among days in each season and between seasons. The 2 campaigns were characterized by an upwelling-relaxation period followed by a downwelling event, the last of which was due to the extratropical cyclone Ophelia in October. The mean (±SD) seasonal benthic oxygen fluxes were not significantly different for the 2 campaigns despite differences in hydrodynamic and biogeochemical conditions (June: -20.9 ± 7.1 mmol m-2d-1vs. October: -26.5 ± 3.1 mmol m-2d-1). Benthic fluxes were controlled by different drivers depending on the season. June was characterized by sinking labile organic material, which enhanced benthic fluxes in the downwelling event, whereas October had a significantly higher bottom velocity that stimulated the benthic fluxes. Finally, a comparison with a large benthic chamber (0.50 m2) was made during October. Despite methodological differences between AEC and chamber measurements, concurrent fluxes agreed within an acceptable margin (AEC:benthic chamber ratio = 0.78 ± 0.13; mean ± SD). Bottle incubations of water sampled from the chamber interior indicated that mineralization could explain this difference. These results show the importance of using non-invasive techniques such as AEC to resolve benthic flux dynamicsPostprin

Tide and wind coupling in a semienclosed bay driven by coastal upwelling

The Ría de Vigo is a semi-enclosed bay in which tidal residual currents are associated with coastal upwelling events. Both upwelling and downwelling favourable winds generate a bidirectional exchange flow with the shelf – a two-layer circulation with surface waters leaving (entering) the ria and a compensating inflow (outflow) through the bottom layer under upwelling (downwelling) conditions. This vertical circulation changes the vertical density structure inside the ria. In the ria, the tide is mainly semidiurnal (M2, S2 and K2), with some energy in the diurnal band (K1). Our velocity observations show that the vertical structure of the tidal currents in the ria do not exhibit a classic barotropic profile with a bottom boundary layer beneath uniform “free-stream” flow as the tidal bottom boundary layer is affected by stratification. This links tidal circulation to the wind-driven residual circulation, since the latter also greatly helps to control the stratification. We quantify this effect by fitting tidal ellipses to observed velocities through the water column. In addition to this indirect coupling through stratification, there is a direct interaction in which velocities in the upper and bottom layers are best correlated with winds while the mid-water velocities are best correlated with tides. These wind-tide interactions are expected to play a key role in the resuspension and transport of nutrients and phytoplankton in the Ria.CTM2012-3515

Cambios diarios en la composición y abundancia de copépodos planctónicos al sur de Bahía de La Paz (Octubre 2002)

The goal of this work to analyze the changes in the copepods community, and its relationships with the sea temperature, chl-a concentration and tidal level south of Bahía de La Paz during October 2002. The statistical analysis split the study period with different communities. During the first phase, the oceanic and neritic-oceanic species were dominant (e.g. Labidocera acutifrons, L. acuta, L. diandra, and L. trispinosa), whereas during the second period an increase of the abundance and species richness of coastal and estuarine species was measured (e.g. Acartia lilljeborgii, A. clausi, Nannocalanus minor, and Canthocalanus pauper). These changes were mainly associated with changes in the tide level with respect to de mean sea level as well as with the chlorophyll-a concentration.El objetivo de este trabajo fue analizar los cambios de la comunidad de copépodos y su relación con la temperatura del mar, concentración de Cl a y la altura de la marea al sur de Bahía de La Paz durante octubre del 2002. El análisis estadístico dividió el periodo de estudio en dos etapas con distintas comunidades. En la primera etapa dominaron especies oceánicas y neríticooceánicas (Ej. Labidocera acutifrons, L. acuta, L. diandra, L. trispinosa), y en la segunda se incrementó la abundancia y número de especies costeras y lagunares (Ej. Acartia lilljeborgii, A. clausi, Nannocalanus minor y Canthocalanus pauper). Estos cambios, se asociaron principalmente a cambios en la altura de la marea con respecto al nivel medio del mar y a incrementos en la concentración de Cl a

Monocyte Activation and Ageing Biomarkers in the Development of Cardiovascular Ischaemic Events or Diabetes in People with HIV

We investigated whether blood telomere length (TL), epigenetic age acceleration (EAA), and soluble inflammatory monocyte cytokines are associated with cardiovascular events or diabetes (DM) in people living with HIV (PLHIV). This was a case-control study nested in the Spanish HIV/AIDS Cohort (CoRIS). Cases with myocardial infarction, stroke, sudden death, or diabetes after starting antiretroviral therapy were included with the available samples and controls matched for sex, age, tobacco use, pre-ART CD4 cell count, viral load, and sample time-point. TL (T/S ratio) was analysed by quantitative PCR and EAA with DNA methylation changes by next-generation sequencing using the Weidner formula. Conditional logistic regression was used to explore the association with cardiometabolic events. In total, 180 participants (94 cases (22 myocardial infarction/sudden death, 12 strokes, and 60 DM) and 94 controls) were included. Of these, 84% were male, median (IQR) age 46 years (40-56), 53% were current smokers, and 22% had CD4 count ≤ 200 cells/mm3 and a median (IQR) log viral load of 4.52 (3.77-5.09). TL and EAA were similar in the cases and controls. There were no significant associations between TL, EAA, and monocyte cytokines with cardiometabolic events. TL and EAA were mildly negatively correlated with sCD14 (rho = -0.23; p = 0.01) and CCL2/MCP-1 (rho = -0.17; p = 0.02). We found no associations between TL, EAA, and monocyte cytokines with cardiovascular events or diabetes. Further studies are needed to elucidate the clinical value of epigenetic biomarkers and TL in PLHIV.This study was funded by an unrestricted and competitive grant from “The Fellowship Program” of Gilead Sciences (Exp. GLD16/00133). CoRIS is supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I + D + i and co-financed by Instituto de Salud Carlos III-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). The integrated HIV BioBank is supported by the Instituto de Salud Carlos III RD12/0017/0037.S

Causes of hOCT1-dependent cholangiocarcinoma resistance to sorafenib and sensitization by tumor-selective gene therapy

Although the multi-tyrosine kinase inhibitor sorafenib is useful in the treatment of several cancers, cholangiocarcinoma (CCA) is refractory to this drug. Among other mechanisms of chemoresistance, impaired uptake through human organic cation transporter type 1 (hOCT1) (gene SLC22A1) has been suggested. Here we have investigated the events accounting for this phenotypic characteristic and have evaluated the interest of selective gene therapy strategies to overcome this limitation. Gene expression and DNA methylation of SLC22A1 were analyzed using intrahepatic (iCCA) and extrahepatic (eCCA) biopsies (Copenhagen and Salamanca cohorts; n = 132) and The Cancer Genome Atlas (TCGA)-CHOL (n = 36). Decreased hOCT1 mRNA correlated with hypermethylation status of the SLC22A1 promoter. Treatment of CCA cells with decitabine (demethylating agent) or butyrate (histone deacetylase inhibitor) restored hOCT1 expression and increased sorafenib uptake. MicroRNAs able to induce hOCT1 mRNA decay were analyzed in paired samples of TCGA-CHOL (n = 9) and Copenhagen (n = 57) cohorts. Consistent up-regulation in tumor tissue was found for miR-141 and miR-330. High proportion of aberrant hOCT1 mRNA splicing in CCA was also seen. Lentiviral-mediated transduction of eCCA (EGI-1 and TFK-1) and iCCA (HuCCT1) cells with hOCT1 enhanced sorafenib uptake and cytotoxic effects. In chemically induced CCA in rats, reduced rOct1 expression was accompanied by impaired sorafenib uptake. In xenograft models of eCCA cells implanted in mouse liver, poor response to sorafenib was observed. However, tumor growth was markedly reduced by cotreatment with sorafenib and adenoviral vectors encoding hOCT1 under the control of the BIRC5 promoter, a gene highly up-regulated in CCA. Conclusion: The reason for impaired hOCT1-mediated sorafenib uptake by CCA is multifactorial. Gene therapy capable of selectively inducing hOCT1 in tumor cells can be considered a potentially useful chemosensitization strategy to improve the response of CCA to sorafenib

The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma

[Background] Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. The aim of this study was to develop non-invasive surveillance method for NAFLD-HCC.[Methods] Using comprehensive ultra-high-performance liquid chromatography mass-spectrometry, we investigated 1,295 metabolites in serum from 249 patients. Area under the receiver operating characteristic curve was calculated for all detected metabolites and used to establish their diagnostic potential. Logistic regression analysis was used to establish the diagnostic score.[Findings] We show that NAFLD-HCC is characterised by a complete rearrangement of the serum lipidome, which distinguishes NAFLD-HCC from non-cancerous individuals and other HCC patients. We used machine learning to build a diagnostic model for NAFLD-HCC. We quantified predictive metabolites and developed the NAFLD-HCC Diagnostic Score (NHDS), presenting superior diagnostic potential compared to alpha-fetoprotein (AFP). Patients’ metabolic landscapes show a progressive depletion in unsaturated fatty acids and acylcarnitines during transformation. Upregulation of fatty acid transporters in NAFLD-HCC tumours contribute to fatty acid depletion in the serum.[Interpretation] NAFLD-HCC patients can be efficiently distinguished by serum metabolic alterations from the healthy population and from HCC patients related to other aetiologies (alcohol and viral hepatitis). Our model can be used for non-invasive surveillance of individuals with metabolic syndrome(s), allowing for early detection of NAFLD-HCC. Therefore, serum metabolomics may provide valuable insight to monitor patients at risk, including morbidly obese, diabetics, and NAFLD patients.We thank all funding sources: The laboratory of JBA is supported by the Novo Nordisk Foundation (14040, 0058419), Danish Cancer Society (R98-A6446, R167-A10784, R278-A16638), and the Danish Medical Research Council (4183-00118A, 1030-00070B). Data used for validation in this study provided by JMB was funded by the Spanish Ministry of Economy and Competitiveness and ’Instituto de Salud Carlos III’ grants (PI18/01075, Miguel Servet Programme CON14/00129 and CPII19/00008) co-financed by ’Fondo Europeo de Desarrollo Regional’ (FEDER); CIBERehd, Spain; IKERBASQUE, Basque foundation for Science, Spain; BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD); Department of Health of the Basque Country (2017111010), Euskadi RIS3 (2019222054, 2020333010); Department of Industry of the Basque Country (Elkartek: KK-2020/00008), AECC Scientific Foundation and European Commission Horizon 2020 program (ESCALON project no.: 825510). Similarly, MAJ was funded by grants from the Fondo Nacional De Ciencia y Tecnología de Chile (FONDECYT #1191145 to M.A.) and the Comisión Nacional de Investigación, Ciencia y Tecnología (CONICYT, AFB170005, CARE Chile UC).Peer reviewe

Towards a life cycle sustainability assessment method for the quantification and reduction of impacts of buildings life cycle

The construction and building sectorsare one of the highestconsumersof resourcesand energy. Literature evidences the potentialities of the design phase towardsthe improvement of environmental, economic and social performance of buildings. Thus, the Life Cycle Sustainability Assessment (LCSA) approach is recognized as suitable method. It isbased on the “triple bottom line”principle, to calculate environmental, economic, social impacts produced by buildings during itslife cycle. The present paper aims to present a methodological framework based on anLCSA, used during design stages of buildings and integrated into a building’s design technology such as Building Information Modeling (BIM). A conceptual approach to conduct the data integration and a possible workflow to integrate the LCSA into BIMis proposed. The value of the present approach is the possibility to conductquantitative environmental, economic and social assessment of buildings to guide designers to measure and predict the building’s performanc

Azokh caves excavations 2002-2006: Middle-Upper palaeolithic transition in Nagorno-Karabagh

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu