Hercynian late-post-tectonic granitic rocks from the Fornos de Algodres area (Northern Central Portugal)

The Fornos de Algodres Complex (FAC) comprises several intrusions of late-post-tectonic Hercynian granitic rocks ranging in composition from hornblende granodiorites and quartz monzodiorites, through coarse porphyritic biotite granites and two-mica granites (coarse-, medium- and fine-grained), to muscovite-rich leucogranites. Field and regional constraints show that the emplacement of this large, composite, batholithic complex post-dates the main Variscan regional deformation phases (D1 + D2 + D3) and associated metamorphic events. Field, petrographic and geochemical data suggest a strong genetic relationship between most of the members of the FAC. However, their Rb-Sr and Sm-Nd isotopic signatures appear to rule out any genetic process involving a single homogeneous source and/or closed-system fractional crystallization of the same parental magma. A model involving hybridization of mantle-derived basaltic liquids with crustal anatectic melts followed by further contamination and fractional crystallization is proposed to explain the isotopic and geochemical variation trends defined by the FAC granitic rocks

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Loss-of-function ABCC8 mutations in pulmonary arterial hypertension

Background: In pulmonary arterial hypertension (PAH), pathological changes in pulmonary arterioles progressively raise pulmonary artery pressure and increase pulmonary vascular resistance, leading to right heart failure and high mortality rates. Recently, the first potassium channelopathy in PAH, because of mutations in KCNK3, was identified as a genetic cause and pharmacological target. Methods: Exome sequencing was performed to identify novel genes in a cohort of 99 pediatric and 134 adult-onset group I PAH patients. Novel rare variants in the gene identified were independently identified in a cohort of 680 adult-onset patients. Variants were expressed in COS cells and function assessed by patch-clamp and rubidium flux analysis. Results: We identified a de novo novel heterozygous predicted deleterious missense variant c.G2873A (p.R958H) in ABCC8 in a child with idiopathic PAH. We then evaluated all individuals in the original and a second cohort for rare or novel variants in ABCC8 and identified 11 additional heterozygous predicted damaging ABCC8 variants. ABCC8 encodes SUR1 (sulfonylurea receptor 1)—a regulatory subunit of the ATP-sensitive potassium channel. We observed loss of ATP-sensitive potassium channel function for all ABCC8 variants evaluated and pharmacological rescue of all channel currents in vitro by the SUR1 activator, diazoxide. Conclusions: Novel and rare missense variants in ABCC8 are associated with PAH. Identified ABCC8 mutations decreased ATP-sensitive potassium channel function, which was pharmacologically recovered

Controls on dryland mountain landscape development along the NW Saharan desert margin: Insights from Quaternary river terrace sequences (Dadès River, south-central High Atlas, Morocco)

This study documents river terraces from upstream reaches of the Dad es River, a major fluvial system draining the south-central High Atlas Mountains. Terraces occur as straths with bedrock bases positioned at 10 m altitudinal intervals up to 40 m (T1-T5) above the valley floor, becoming less common between 50 and 140 m. The rock strength, stratigraphy and structure of the mountain belt influences terrace distribution. Terraces are absent in river gorges of structurally thickened limestone; whilst welldeveloped, laterally continuous terraces (T1-T4) form along wide valleys occupying syncline structures dominated by weaker interbedded limestone-mudstone. Terrace staircases develop in confined canyons associated with weaker lithologies and influence from structural dip and stratigraphic configuration. Terraces comprise a bedrock erosion surface overlain by fluvial conglomerates, rare overbank sands and colluvium. This sequence with some OSL/IRSL age control, suggests terrace formation over a 100 ka climate cycle with valley floor aggradation during full glacials and incision during glacial-interglacial transitions. This integrates with other archives (e.g. lakes, glaciers, dunes), appearing typical of landscape development along the NW Saharan margin south of the High Atlas, and similar to patterns in the western-southern Mediterranean. The 100 ka climate cycle relationship suggests that the terrace sequence documents Late-Middle Pleistocene landscape development. Consistent altitudinal spacing of terraces and their distribution throughout the orogen suggests sustained base-level lowering linked to uplift-exhumation of the High Atlas. Low incision rates (<0.2 mm a 1) and general absence of terrace deformation suggests dominance of isostatically driven base-level lowering with relief generation being Early Pleistocene or older.National Geographic research grant (8609-09

The Nature of the Cold Filaments in the California Current System

Data from the Coastal Transition Zone (CTZ) experiment axe used to describe the velocity fields and water properties associated with cold filaments in the California Current. Combined with previous field surveys and satellite imagery, these show seasonal variability with maximum dynamic height ranges and velocities in summer and minimum values in late winter and early spring. North of Point Arena (between 39 degrees N and 42 degrees N) in spring-summer the flow field on the outer edge of the cold water has the character of a meandering jet, carrying fresh, nutrient-poor water from farther north on its offshore side and cold, salty, nutrient-rich water on its inshore side. At Point Arena in midsummer, the jet often flows offshore and continues south without meandering back onshore as strongly as it does farther north. The flow field south of Point Arena in summer takes on more of the character a field of mesoscale eddies, although the meandering jet from the north continues to be identifiable. The conceptual model for the May-July period between 36 degrees N and 42 degrees N is thus of a surface jet that meanders through and interacts with a field of eddies; the eddies are more dominant south of 39 degrees N, where the jet broadens and where multiple jets and filaments are often present. At the surface, the jet often separates biological communities and may appear as a barrier to cross-jet transport, especially north of Point Arena early in the season (March-May). However, phytoplankton pigment and nutrients are carried on the inshore flank of the jet, and pigment maxima are sometimes found in the core of the jet. The biological effect of the jet is to define a convoluted, 100 to 400-km-wide region next to the coast, within which much of the richer water is contained, and also to carry some of that richer water offshore in meanders along the outer edge of that region.The CTZ program was funded by the Coastal Sciences Program of the Office of Naval Research (Code 1122CS). Support for PTS was provided by ONR grants N00014-87K0009 and N00014-90J1115, with additional support provided by NASA grants NAGW-869 and NAGW-1251