106 research outputs found

    Síntesis de xerogeles y preparación de recubrimientos nanoparticulados de TiO2-anatasa dopada con Er3+ o Eu3+ para aplicaciones fotoluminiscentes

    Full text link
    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Inorgánica. Fecha de lectura: 15-07-201

    An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species

    Get PDF
    12 p.-7 fig.The C-terminal ends of small GTPases contain hypervariable sequences which may be posttranslationally modified by defined lipid moieties. The diverse structural motifs generated direct proteins towards specific cellular membranes or organelles. However, knowledge on the factors that determine these selective associations is limited. Here we show, using advanced microscopy, that the isoprenylation and palmitoylation motif of human RhoB (–CINCCKVL) targets chimeric proteins to intraluminal vesicles of endolysosomes in human cells, displaying preferential co-localization with components of the late endocytic pathway. Moreover, this distribution is conserved in distant species, including cells from amphibians, insects and fungi. Blocking lipidic modifications results in accumulation of CINCCKVL chimeras in the cytosol, from where they can reach endolysosomes upon release of this block. Remarkably, CINCCKVL constructs are sorted to intraluminal vesicles in a cholesterol-dependent process. In the lower species, neither the C-terminal sequence of RhoB, nor the endosomal distribution of its homologs are conserved; in spite of this, CINCCKVL constructs also reach endolysosomes in Xenopus laevis and insect cells. Strikingly, this behavior is prominent in the filamentous ascomycete fungus Aspergillus nidulans, in which GFP-CINCCKVL is sorted into endosomes and vacuoles in a lipidation-dependent manner and allows monitoring endosomal movement in live fungi. In summary, the isoprenylated and palmitoylated CINCCKVL sequence constitutes a specific structure which delineates an endolysosomal sorting strategy operative in phylogenetically diverse organisms.This work was supported by grants SAF2009-11642 and SAF2012-36519 from MINECO and RETIC RD12/0013/0008 to DPS, grants BIO2012-30695 fromcMINECO and S2010/BMD-2414 from Comunidad de Madrid to MAP, and grants from the Norwegian Cancer Society and the South-Eastern Norway Regional Health Authority to HS. CLO is supported by the FPI program from MINECO (BES-2010-033718). The stay of CLO at HS laboratory was supported by the short stay grant EEBB-I-12-04482 from MINECO.Peer reviewe

    Critical warm ischemia time point for cardiac donation after circulatory death.

    Get PDF
    Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.Fundación Mutua Madrileña.S

    Innovative Approaches for Organizing an Inclusive Optics and Photonics Conference in Virtual Format

    Get PDF
    The COVID pandemic is forcing the renewal of scientific conferences, offering opportunities to introduce technological and inclusive developments. Our analysis focuses on the implementation of inclusive practices for female and early-career researchers in a virtual scientific conference. This organization approach was applied in the XIII Spanish Optical Meeting (RNO2021), which was also characterized by avatars interacting in an online metaverse. The effectiveness of inclusive policies and novel technological tools was evaluated using the participation data and a post-conference survey. Our study reveals the high impact of inclusive actions and a strong interest in the scientific community to explore conference advances

    Effect of exogenous surfactants on viability and DNA synthesis in A549, immortalized mouse type II and isolated rat alveolar type II cells

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>In mechanically ventilated preterm infants with respiratory distress syndrome (RDS), exogenous surfactant application has been demonstrated both to decrease DNA-synthesis but also and paradoxically to increase epithelial cell proliferation. However, the effect of exogenous surfactant has not been studied directly on alveolar type II cells (ATII cells), a key cell type responsible for alveolar function and repair.</p> <p>Objective</p> <p>The aim of this study was to investigate the effects of two commercially available surfactant preparations on ATII cell viability and DNA synthesis.</p> <p>Methods</p> <p>Curosurf<sup>® </sup>and Alveofact<sup>® </sup>were applied to two ATII cell lines (human A549 and mouse iMATII cells) and to primary rat ATII cells for periods of up to 24 h. Cell viability was measured using the redox indicator resazurin and DNA synthesis was measured using BrdU incorporation.</p> <p>Results</p> <p>Curosurf<sup>® </sup>resulted in slightly decreased cell viability in all cell culture models. However, DNA synthesis was increased in A549 and rat ATII cells but decreased in iMATII cells. Alveofact<sup>® </sup>exhibited the opposite effects on A549 cells and had very mild effects on the other two cell models.</p> <p>Conclusion</p> <p>This study showed that commercially available exogenous surfactants used to treat preterm infants with RDS can have profound effects on cell viability and DNA synthesis.</p

    An umbrella review of systematic reviews with meta-analyses evaluating positive and negative outcomes of hydroxychloroquine and chloroquine therapy

    Get PDF
    Background & aims: Hydroxychloroquine (HCQ) and chloroquine (CQ) are anti-malarial drugs frequently used in the rheumatologic field. Recently they were identified as possible therapeutic options against Coronavirus Disease (COVID-19). Therefore, the present study aimed to map and grade the diverse health outcomes associated with HCQ/CQ using an umbrella review approach. Methods: Umbrella review of systematic reviews of observational and intervention studies. For observational studies, random-effects summary effect size, 95% confidence interval, and 95% prediction interval were estimated. We also assessed heterogeneity, evidence for small-study effect and evidence for excess significance bias. The quality of evidence was then graded using validated criteria from highly convincing to weak. The evidence from randomized-controlled trials (RCTs) was graded using the GRADE tool. Results: From 313 articles returned, 6 meta-analyses were included (n = 25 outcomes). Among meta-analyses of observational studies, HCQ/CQ is weakly associated with a reduced risk for cardiovascular events and diabetes when used for autoimmune diseases; it is also associated with higher risk of death when used for COVID-19 and with spontaneous abortion. Among meta-analyses of RCTs, HCQ/CQ is associated with an improvement of articular manifestations of the rheumatic diseases. Conclusions: There is high evidence of the efficacy of HCQ/CQ in the rheumatologic field. The lack of evidence for efficacy and risk of death associated with the use of HCQ/CQ for COVID-19, indicate the inappropriateness of its inclusion in recent COVID-19 therapy guidelines and urgent need for Randomised Controlled Trials to determine their eventual appropriateness as a therapy in that circumstance

    Physical activity and exercise for the prevention and management of mild cognitive impairment and dementia:A collaborative international guideline

    Get PDF
    Background: Physical activity and exercise have been suggested as effective interventions for the prevention and management of mild cognitive impairment (MCI) and dementia, but there are no international guidelines. Objectives: To create a set of evidence- and expert consensus-based prevention and management recommendations regarding physical activity (any bodily movement produced by skeletal muscles that results in energy expenditure) and exercise (a subset of physical activity that is planned, structured, repetitive), applicable to a range of individuals from healthy older adults to those with MCI/dementia. Methods: Guideline content was developed with input from several scientific and lay representatives' societies. A systematic search across multidisciplinary databases was carried out until October 2021. Recommendations for prevention and management were developed according to the GRADE and complemented by consensus statements from the expert panels. Recommendations: Physical activity may be considered for the primary prevention of dementia. In people with MCI there is continued uncertainty about the role of physical activity in slowing the conversion to dementia. Mind-body interventions have the greatest supporting evidence. In people with moderate dementia, exercise may be used for maintaining disability and cognition. All these recommendations were based on a very low/low certainty of evidence. Conclusions: Although the scientific evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia is inconclusive, this panel, composed of scientific societies and other stakeholders, recommends their implementation based on their beneficial effects on almost all facets of health
    corecore