Los Pirineos en el contexto de las montañas del mundo: rasgos generales y peculiaridades

29 páginas.Este trabajo introductorio intenta presentar la cordillera de los Pirineos, y especialmente sus características naturales dominantes, señalando en particular aquellas que comparte con otras cordilleras del globo, y aquellas que son peculiares de esta cadena, o compartidas con pocos sistemas montañosos similares. Veamos pues, en primer lugar, algunos rasgos generales de la mayor parte de las cordilleras.Peer reviewe

Metabolomics Profile in Depression:A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls

Background: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. Methods: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. Results: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q <.05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. Conclusions: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity

IL-1α Mediated Chorioamnionitis Induces Depletion of FoxP3+ Cells and Ileal Inflammation in the Ovine Fetal Gut

Endotoxin induced chorioamnionitis increases IL-1 and provokes an inflammatory response in the fetal ileum that interferes with intestinal maturation. In the present study, we tested in an ovine chorioamnionitis model whether IL-1 is a major cytokine driving the inflammatory response in the fetal ileum.Sheep bearing singleton fetuses received a single intraamniotic injection of recombinant ovine IL-1α at 7, 3 or 1 d before caesarian delivery at 125 days gestational age (term = 150 days).3 and 7 d after IL-1α administration, intestinal mRNA levels for IL-4, IL-10, IFN-γ and TNF-α were strongly elevated. Numbers of CD3+ and CD4+ T-lymphocytes and myeloidperoxidase+ cells were increased whereas FoxP3+ T-cells were detected at low frequency. This increased proinflammatory state was associated with ileal mucosal barrier loss as demonstrated by decreased levels of the intestinal fatty acid binding protein and disruption of the tight junctional protein ZO-1.Intraamniotic IL-1α causes an acute detrimental inflammatory response in the ileum, suggesting that induction of IL-1 is a critical element in the pathophysiological effects of endotoxin induced chorioamnionitis. A disturbed balance between T-effector and FoxP3+ cells may contribute to this process

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

Blood coagulation and beyond: Position paper from the Fourth Maastricht Consensus Conference on Thrombosis

The 4th Maastricht Consensus Conference on Thrombosis (MCCT), included the following themes: Theme 1: The coagulome as a critical driver of cardiovascular disease Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infections associated-coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies This theme included state of the art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: how to utilize ex vivo models? Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularised organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation (ECMO) associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management Plenary presentations addressed controversial areas, ie thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies and clinically tested factor XI(a) inhibitors,both possibly with reduced bleeding risk. Finally, Covid-19 associated coagulopathy is revisited

Dissociation of transforming growth factors beta 1 and beta 2 from surfactant protein A (SP-A) by deglycosylation or deoxycholate treatment

We were able to demonstrate the presence of transforming growth factor beta 1 and transforming growth factor beta 2 (TGF-beta 1,2) in human as well as porcine pulmonary surfactants and SP-A purified from these surfactants. Human SP-A contained 480 +/- 74 pg TGF-beta 1 and 61 +/- 16 pg TGF-beta 2 per mg SP-A and human pulmonary surfactant contained 140 +/- 28 pg TGF-beta 1 and 67 +/- 13 TGF-beta 2 per mg protein. Porcine SP-A contained 306 +/- 46 pg TGF-beta 1 and 43 +/- 12 pg TGF-beta 2 per mg SP-A and porcine pulmonary surfactant contained 75 +/- 18 pg TGF-beta 1 and 22 +/- 13 TGF-beta 2 per mg protein. Size-exclusion chromatography indicated binding of TGF-beta 1,2 to SP-A Deglycosylation of SP-A released TGF-beta 1,2 from SP-A indicating a role for the carbohydrate moieties of SP-A in binding of TGF-beta 1,2. TGF-beta-free SP-A was obtained by incubating SP-A with 5 mM deoxycholate at pH 9.2 followed by size-exclusion chromatography, a protocol which can be used to study the biological activities of SP-A and TGF-beta 1,2 separately. In addition, we demonstrated that after incubation of SP-A with TGF-beta 1,2, only a part of the added TGF-beta 1,2 can be measured, whereas after acid treatment almost all added TGF-beta 1,2 was determined, suggesting that complex formation between SP-A and TGF-beta 1,2 influences the measurements of TGF-beta 1,2 in biological samples

Dissociation of transforming growth factors beta 1 and beta 2 from surfactant protein A (SP-A) by deglycosylation or deoxycholate treatment

We were able to demonstrate the presence of transforming growth factor beta 1 and transforming growth factor beta 2 (TGF-beta 1,2) in human as well as porcine pulmonary surfactants and SP-A purified from these surfactants. Human SP-A contained 480 +/- 74 pg TGF-beta 1 and 61 +/- 16 pg TGF-beta 2 per mg SP-A and human pulmonary surfactant contained 140 +/- 28 pg TGF-beta 1 and 67 +/- 13 TGF-beta 2 per mg protein. Porcine SP-A contained 306 +/- 46 pg TGF-beta 1 and 43 +/- 12 pg TGF-beta 2 per mg SP-A and porcine pulmonary surfactant contained 75 +/- 18 pg TGF-beta 1 and 22 +/- 13 TGF-beta 2 per mg protein. Size-exclusion chromatography indicated binding of TGF-beta 1,2 to SP-A Deglycosylation of SP-A released TGF-beta 1,2 from SP-A indicating a role for the carbohydrate moieties of SP-A in binding of TGF-beta 1,2. TGF-beta-free SP-A was obtained by incubating SP-A with 5 mM deoxycholate at pH 9.2 followed by size-exclusion chromatography, a protocol which can be used to study the biological activities of SP-A and TGF-beta 1,2 separately. In addition, we demonstrated that after incubation of SP-A with TGF-beta 1,2, only a part of the added TGF-beta 1,2 can be measured, whereas after acid treatment almost all added TGF-beta 1,2 was determined, suggesting that complex formation between SP-A and TGF-beta 1,2 influences the measurements of TGF-beta 1,2 in biological samples