Sudden changes in fluvial style across the Permian / Triassic boundary in the eastern Iberian Ranges, Spain: Analysis of possible causes

The sedimentary record of the Late Permian and Early Triassic of the eastern Iberian Ranges shows four major, sudden, or very rapid, vertical changes in fluvial style. The Late Permian sedimentary cycle starts with the Boniches Formation, of alluvial fan-braided fluvial origin, which grades vertically over within a few metres into the Alcotas Formation, deposited by low to high sinuosity, avulsion-prone rivers with extensive floodplains. The Alcotas Formation contains calcimorphic soils, plant remains and pollen and spore assemblages. However, the upper third of the unit is devoid of all organic remains and soils and is characterized by a dominant red colour, the sandstone levels were deposited by high-sinuosity, meandering rivers. This major change took place during the Late Permian and is probably coeval with the emplacement of the Emeishan basaltic Large Igneous Province (LIP) in SE China. Rocks of the Boniches and Alcotas Formations are separated by an angular unconformity from the overlying strata, which consist of the Late Permian conglomeratic Hoz del Gallo Formation, of alluvial fan–gravel braided fluvial origin and the sandy Cañizar Formation, of low-sinuosity sandy river origin. The Permian– Triassic boundary lies, probably between the upper part of the Hoz del Gallo Formation and the first metres of the Cañizar Formation. Late Permian pollen and spore assemblages have been found in the Hoz del Gallo Formation but the Cañizar Formation is barren, with the exception of an Anisian (Middle Triassic) assemblage at the top. Tectonic extensional pulses in the Iberian Basin caused the changes observed between the lower and upper parts of the Boniches Formation, at the base of the Hoz del Gallo Formation and between the lower and upper part of this Formation. The changes observed in the uppermost part of the Alcotas Formation are not easily explained by tectonic causes, nor those in the passage from the Hoz del Gallo Formation to the Cañizar Formation. Similar sedimentary characteristics of the sandy Cañizar Formation such as amalgamated sandstone bodies, erosion and reactivation surfaces, dominant trough cross-stratification, tabular geometry, absence of plant remains and pollen and spores, and absence of silts and clays to those of coeval formations in places as far away as Australia, South Africa and Brazil suggest a global rather than local cause for these abrupt changes in fluvial style. This global cause was probably die-off of plant cover over extensive areas of the catchment, related to the end of the Permian mass extinction and possibly related to the emplacement of the West Siberian basaltic Large Igneous Province (LIP), responsible for drastic atmospheric and marine changes

Genome-Wide Association Studies of the PR Interval in African Americans

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10−8) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta  = 5.1 msec per minor allele, 95% CI  = 4.1–6.1, p = 3×10−23). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8–3.0, p = 3×10−16) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans

52 Genetic Loci Influencing Myocardial Mass.

BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets

Cytotoxic T cell depletion with increasing epithelial abnormality in women with benign breast disease.

PURPOSE: We quantified cytotoxic T cells in nonmalignant breast tissues from women with and without subsequent breast cancer to assess evidence of whether immunosurveillance may be suppressed prior to tumor development. METHODS: We used an age-matched set of breast tissues from women with benign breast disease (BBD) who subsequently developed breast cancer (BBD with later BC), women with BBD who remained cancer free (BBD cancer-free), and normal Komen Tissue Bank (KTB) tissue donors (KTB controls). We evaluated terminal duct lobular units (lobules) for degree of epithelial abnormality and density of dual-positive CD8/CD103 T cells, as CD103+ cells are thought to be a subset of CD8+ cytotoxic T cells located primarily in the intraepithelial compartment. RESULTS: In 10 sets of age-matched women, 256 breast lobules were studied: 85 in BBD women with later BC, 85 in BBD cancer-free women, and 86 in KTB donors. The majority of all lobules were histologically normal (N = 143, 56%), with 65 (25%) nonproliferative fibrocystic change, and 48 (19%) proliferative epithelial change (with or without atypia). In BBD women with later BC, median CD8+/CD103+ cell density was 39.6, 31.7, and 10.5 cells/mm CONCLUSION: In women with BBD, breast lobules with increasing epithelial abnormality show significant decreases in cytotoxic T cells as measured by CD8/CD103 staining, suggesting that impaired immunosurveillance may be a component of the earliest stages of breast cancer development

Genome partitioning of genetic variation for complex traits using common SNPs

We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that similar to 45%, similar to 17%, similar to 25% and similar to 21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further similar to 0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein