SURFER v2.0: a flexible and simple model linking anthropogenic CO2 emissions and solar radiation modification to ocean acidification and sea level rise

We present SURFER, a novel reduced model for estimating the impact of CO2 emissions and solar radiation modification options on sea level rise and ocean acidification over timescales of several thousands of years. SURFER has been designed for the analysis of CO2 emission and solar radiation modification policies, for supporting the computation of optimal (CO2 emission and solar radiation modification) policies and for the study of commitment and responsibility under uncertainty. The model is based on a combination of conservation laws for the masses of atmospheric and oceanic carbon and for the oceanic temperature anomalies, and of adhoc parameterisations for the different sea level rise contributors: ice sheets, glaciers and ocean thermal expansion. It consists of 9 loosely coupled ordinary differential equations, is understandable, fast and easy to modify and calibrate. It reproduces the results of more sophisticated, high-dimensional earth system models on timescales up to millennia

Lost options commitment: how short-term policies affect long-term scope of action

We propose to explore the sustainability of climate policies based on a novel commitment metric. This metric allows to quantify how future generations' scope of action is affected by short-term climate policy. In an example application, we show that following a moderate emission scenario like SSP2-4.5 could commit future generations to heavily rely on carbon dioxide removal or/and solar radiation modification to avoid unmanageable sea level rise.Comment: 9 pages, 19 figure

Lost options commitment: how short-term policies affect long-term scope of action

We propose to explore the sustainability of climate policies based on a novel commitment metric. This metric allows to quantify how future generations’ scope of action is affected by short-term climate policy. In an example application, we show that following a moderate emission scenario like SSP2-4.5 could commit future generations to heavily rely on carbon dioxide removal or/and solar radiation modification to avoid unmanageable sea level rise

Association among salivary alpha-amylase activity and executive functioning in healthy children

Salivary alpha-amylase (sAA) is employed in basic research as a surrogate and non-invasive marker of the activity of Autonomous Nervous System (ANS) and Adrenomedullar System (AMS). In particular, sAA has showed a statistically sig- nificant association with levels of peripheral noradrenaline under acute psychoso- cial stress conditions in young and healthy participants. In this study, our aim was directed to describe the relation among sAA and cognitive performance in differ- ent executive tasks in a sample composed by 69 healthy children (45 boys). The tasks employed to assess executive functioning belong to the ENFEN battery (which measures different aspects of executive functions through four subtests: Phonologic and Semantic Fluency, Trail Making Test, Towers, and Interference). Saliva samples were obtained at baseline (10 minutes before the start of neuro- psychological assessment), just one minute before and just one minute after the end of the last subtest of ENFEN. Our statistical analyses showed a direct and sig- nificant association among sAA and scores in Phonologic Fluency, Trail Making, Towers and Interference subtests of ENFEN after controlling the effect of BMI. These results show a positive lineal association among sAA and executive behav- ior in healthy children. We discuss these findings in relation with those studies what have suggested a main role of the noradrenergic central action mediated via Locus Coeruleus-Noradrenaline System (LC-NA System) in the regulation of executive behavior.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Association among salivary alpha-amylase activity and working memory functioning in healthy children

Salivary Alpha-Amylase (sAA) shows a statistically significant association with levels of peripheral noradrenaline under acute psychosocial stress conditions in young and healthy participants. In this study, our aim was directed to examine the relation among sAA and cognitive performance in various executive tasks in an experimental sample composed by 69 healthy children although we only could obtain the complete set of data for 44 boys and girls for this battery. The cogni- tive tasks employed were: Digits, Letters & Numbers, Arithmetic and Visual Span subtests of WISC-V (this full set of subtests is employed to the assessment of verbal and visual working memory). Saliva samples were obtained at baseline (10 minutes before the start of neuropsychological assessment), one minute before the start, after the end of the verbal tasks, and one minute after the end of the visual span task. Our statistical analyses showed a significant association among sAA levels and some of the parameters employed to describe the perfor- mance of each participant in the subscales of Digits and Letters & Numbers after controlling the effect of BMI. Scores in Letters & Numbers and visual span were associated with levels of salivary flow rate. These results are coherent with the findings of a previous pilot study conducted in our laboratory and are interpreted in relation with those results which have suggested a main role of the Locus Coeruleus-Noradrenaline System (LC-NA System) in the regulation of the level of arousal and executive behaviors.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Evolutionary and phenotypic characterization of two spike mutations in European lineage 20E of SARS-CoV-2.

We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutrali- zation by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multi- ple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investi- gated was consistent with the lack of advantage observed in the clinical and ex- perimental data

Rab18 Dynamics in Adipocytes in Relation to Lipogenesis, Lipolysis and Obesity

Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection