285 research outputs found

    Future trends of snowfall days in northern Spain from ENSEMBLES regional climate projections

    Get PDF
    In a previous study Pons et al. (Clim Res 54(3):197-207, 2010. doi:10.3354/cr01117g) reported a significant decreasing trend of snowfall occurrence in the Northern Iberian Peninsula since the mid 70s. The study was based on observations of annual snowfall frequency (measured as the annual number of snowfall days NSD) from a network of 33 stations ranging from 60 to 1350 m. In the present work we analyze the skill of Regional Climate Models (RCMs) to reproduce this trend for the period 1961-2000 (using both reanalysis- and historical GCM-driven boundary conditions) and the trend and the associated uncertainty of the regional future projections obtained under the A1B scenario for the first half of the twenty-first century. In particular, we consider the regional simulation dataset from the EU-funded ENSEMBLES project, consisting of thirteen state-of-the-art RCMs run at 25 km resolution over Europe. While ERA40 severely underestimates both the mean NSD and its observed trend (-2.2 days/decade), the corresponding RCM simulations driven by the reanalysis appropriately capture the interannual variability and trends of the observed NSD (trends ranging from -3.4 to -0.7, -2.1 days/decade for the ensemble mean). The results driven by the GCM historical runs are quite variable, with trends ranging from -8.5 to 0.2 days/decade (-1.5 days/decade for the ensemble mean), and the greatest uncertainty by far being associated with the particular GCM used. Finally, the trends for the future 2011-2050 A1B runs are more consistent and significant, ranging in this case from -3.7 to -0.5 days/decade (-2.0 days/decade for the ensemble mean), indicating a future significant decreasing trend. These trends are mainly determined by the increasing temperatures, as indicated by the interannual correlation between temperature and NSD (-0.63 in the observations), which is preserved in both ERA40- and GCM-driven simulations.This research has received funding from the European Union’s Seventh Framework Programme under Grant Agreements 606799 (INTACT Project). The RCM simulations used in this study were obtained from the European Union-funded FP6 Integrated Project ENSEMBLES (Contract No. 505539)

    Overexpression of mitochondrial if1 prevents metastatic disease of colorectal cancer by enhancing anoikis and tumor infiltration of NK cells

    Full text link
    Increasing evidences show that the ATPase Inhibitory Factor 1 (IF1), the physiological inhibitor of the ATP synthase, is overexpressed in a large number of carcinomas contributing to metabolic reprogramming and cancer progression. Herein, we show that in contrast to the findings in other carcinomas, the overexpression of IF1 in a cohort of colorectal carcinomas (CRC) predicts less chances of disease recurrence, IF1 being an independent predictor of survival. Bioinformatic and gene expression analyses of the transcriptome of colon cancer cells with differential expression of IF1 indicate that cells overexpressing IF1 display a less aggressive behavior than IF1 silenced (shIF1) cells. Proteomic and functional in vitro migration and invasion assays confirmed the higher tumorigenic potential of shIF1 cells. Moreover, shIF1 cells have increased in vivo metastatic potential. The higher metastatic potential of shIF1 cells relies on increased cFLIP-mediated resistance to undergo anoikis after cell detachment. Furthermore, tumor spheroids of shIF1 cells have an increased ability to escape from immune surveillance by NK cells. Altogether, the results reveal that the overexpression of IF1 acts as a tumor suppressor in CRC with an important anti-metastatic role, thus supporting IF1 as a potential therapeutic target in CRCThis research was funded by grants from Ministerio de Ciencia, Innovación y Universidades (SAF2013-41945-R, SAF2016-75916-R and SAF2016-75452-R), CIBERER-ISCIII (CB06/07/0017) and Fundación Ramón Areces, Spai

    Size-Controlled Water-Soluble Ag Nanoparticles

    Get PDF
    Ag nanoparticles of two different sizes (1 and 4 nm) were prepared within an apoferritin cavity by using an Ag+-loaded apoferritin as a nanoconfined environment for their construction. The initial amount of Ag' ions injected in the apoferritin cavity dictates the size of the final Ag particles. The protein shell prevents bulk aggregation of the metal particles, which renders them water soluble and extremely stable

    Evaluation of the EURO-CORDEX Regional Climate Models Over the Iberian Peninsula: Observational Uncertainty Analysis

    Get PDF
    ABSTRACT: This work evaluates the daily precipitation and mean temperature of eight CORDEX-EUR11 ERA-Interim-driven simulations of EURO-CORDEX over the Iberian Peninsula (IP) for the period 1989-2008. To this aim, three observational data sets (Iberia01, E-OBS-v19e, and MESAN-0.11) were considered as reference and compared with the models by means of several indices reflecting the mean and extreme regimes over the IP. For precipitation the Lamb weather types were considered to identify synoptic conditions related with higher observational uncertainty. RCMs are able to reproduce the spatial pattern and the variability observed in the IP. However, there is a higher agreement between models and observations for mean temperature than for precipitation, decreasing when extremes are analyzed. For the observational uncertainty analysis, also extreme daily temperatures were considered to obtain a wider picture of this topic. A higher dependence on the observational data set has been found for precipitation than for temperature. This uncertainty is particularly significant when the 50-year return value is considered for which the observational uncertainty doubles the model uncertainty. Only the wet-day frequency presents values lower than 0.5 for all seasons, with most of the rest of values reflecting a similar contribution of both components to the uncertainty. In the case of temperatures, the main contribution of the observations has been found when the lower (MAE01) and upper (MAE99) extremes are considered, with values lower than 0.5. For precipitation the observational uncertainty increases when synoptic patterns affecting the Mediterranean Basin are considered, reflecting the difficulty to properly capture the Mediterranean precipitation regimes.This work was partially funded by the Spanish Government R&D Programme (Exp. CGL2010-21869 and CGL2010-22158-C02) and the European Comission (INDECIS: H2020-690462). Pedro M. M. Soares and Rita M. Cardoso wish to acknowledge the SOLAR (PTDC/GEOMET/7078/2014) Project and the funding by the Instituto Dom Luiz (Project FCT UID/GEO/50019/2019)

    Establishment of a method for determination of arsenic species in seafood by LC-ICP-MS

    Get PDF
    An analytical method for determination of arsenic species (inorganic arsenic (iAs), methylarsonic acid (MA), dimethylarsinic acid (DMA), arsenobetaine (AB), trimethylarsine oxide (TMAO) and arsenocholine (AC)) in Brazilian and Spanish seafood samples is reported. This study was focused on extraction and quantification of inorganic arsenic (iAs), the most toxic form. Arsenic speciation was carried out via LC with both anionic and cationic exchange with ICP-MS detection (LC-ICP-MS). The detection limits (LODs), quantification limits (LOQs), precision and accuracy for arsenic species were established. The proposed method was evaluated using eight reference materials (RMs). Arsenobetaine was the main species found in all samples. The total and iAs concentration in 22 seafood samples and RMs ranged between 0.27-35.2 and 0.02-0.71 mg As kg-1, respectively. Recoveries ranging from 100% to 106% for iAs, based on spikes, were achieved. The proposed method provides reliable iAs data for future risk assessment analysis

    Experience with the use of Rituximab for the treatment of rheumatoid arthritis in a tertiary Hospital in Spain: RITAR study

    Full text link
    There is evidence supporting that there are no relevant clinical differences between dosing rituximab 1000 mg or 2000 mg per cycle in rheumatoid arthritis (RA) patients in clinical trials, and low-dose cycles seem to have a better safety profile. Our objective was to describe the pattern of use of rituximab in real-life practice conditions. Methods: Rituximab for RA in clinical practice (RITAR) study is a retrospective cohort study from 2005 to 2015. Eligibility criteria were RA adults treated with rituximab for active articular disease. Response duration was the main outcome defined as months elapsed from the date of rituximab first infusion to the date of flare. A multivariable analysis was performed to determine the variables associated with response duration. Results: A total of 114 patients and 409 cycles were described, 93.0% seropositive and 80.7% women. Rituximab was mainly used as second-line biological therapy. On demand retreatment was used in 94.6% of cases versus fixed 6 months retreatment in 5.4%. Median response duration to on demand rituximab cycles was 10 months (interquartile range, 7–13). Multivariable analysis showed that age older than 65 years, number of rituximab cycles, seropositivity, and first- or second-line therapy were associated with longer response duration. The dose administered at each cycle was not significantly associated with response duration. Conclusions: Our experience suggests that 1000 mg rituximab single infusion on demand is a reasonable schedule for long-term treatment of those patients with good response after the first cycles, especially in seropositive patients and when it is applied as a first- or second-line biological therap

    The Symbiosis Interactome: a computational approach reveals novel components, functional interactions and modules in Sinorhizobium meliloti

    Get PDF
    <p>Abstract</p> <p>Background</p> <p><it>Rhizobium</it>-Legume symbiosis is an attractive biological process that has been studied for decades because of its importance in agriculture. However, this system has undergone extensive study and although many of the major factors underpinning the process have been discovered using traditional methods, much remains to be discovered.</p> <p>Results</p> <p>Here we present an analysis of the 'Symbiosis Interactome' using novel computational methods in order to address the complex dynamic interactions between proteins involved in the symbiosis of the model bacteria <it>Sinorhizobium meliloti </it>with its plant hosts. Our study constitutes the first large-scale analysis attempting to reconstruct this complex biological process, and to identify novel proteins involved in establishing symbiosis. We identified 263 novel proteins potentially associated with the Symbiosis Interactome. The topology of the Symbiosis Interactome was used to guide experimental techniques attempting to validate novel proteins involved in different stages of symbiosis. The contribution of a set of novel proteins was tested analyzing the symbiotic properties of several <it>S. meliloti </it>mutants. We found mutants with altered symbiotic phenotypes suggesting novel proteins that provide key complementary roles for symbiosis.</p> <p>Conclusion</p> <p>Our 'systems-based model' represents a novel framework for studying host-microbe interactions, provides a theoretical basis for further experimental validations, and can also be applied to the study of other complex processes such as diseases.</p

    Overexpression of the ATPase Inhibitory Factor 1 Favors a Non-metastatic Phenotype in Breast Cancer

    Get PDF
    Partial suppression of mitochondrial oxidative phosphorylation and the concurrent activation of aerobic glycolysis is a hallmark of proliferating cancer cells. Overexpression of the ATPase inhibitory factor 1 (IF1), an in vivo inhibitor of the mitochondrial ATP synthase, is observed in most prevalent human carcinomas favoring metabolic rewiring to an enhanced glycolysis and cancer progression. Consistently, a high expression of IF1 in hepatocarcinomas and in carcinomas of the lung, bladder, and stomach and in gliomas is a biomarker of bad patient prognosis. In contrast to these findings, we have previously reported that a high expression level of IF1 in breast carcinomas is indicative of less chance to develop metastatic disease. This finding is especially relevant in the bad prognosis group of patients bearing triple-negative breast carcinomas. To investigate the molecular mechanisms that underlie the differential behavior of IF1 in breast cancer progression, we have developed the triple-negative BT549 breast cancer cell line that overexpresses IF1 stably. When compared to controls, IF1-cells partially shut down respiration and enhance aerobic glycolysis. Transcriptomic analysis suggested that migration and invasion were specifically inhibited in IF1-overexpressing breast cancer cells. Analysis of gene expression by qPCR and western blotting indicate that IF1 overexpression supports the maintenance of components of the extracellular matrix (ECM) and E-cadherin concurrently with the downregulation of components and signaling pathways involved in epithelial to mesenchymal transition. The overexpression of IF1 in breast cancer cells has no effect in the rates of cellular proliferation and in the cell death response to staurosporine and hydrogen peroxide. However, the overexpression of IF1 significantly diminishes the ability of the cells to grow in soft agar and to migrate and invade when compared to control cells. Overall, the results indicate that IF1 overexpression despite favoring a metabolic phenotype prone to cancer progression in the specific case of breast cancer cells also promotes the maintenance of the ECM impeding metastatic disease. These findings hence provide a mechanistic explanation to the better prognosis of breast cancer patients bearing tumors with high expression level of IF1.CN-T and IM-R were supported by pre-doctoral FPI-MEC and JAE-CSIC fellowships, respectively. This work was supported by grants from the Ministerio de Economía y Competitividad (SAF2013-41945-R; SAF2016-75916-R), Comunidad Madrid (S2011/BMD-2402), and Fundación Ramón Areces 2015, Spain.Peer reviewedPeer Reviewe
    corecore