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  • 1
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders characterized by onset with gait ataxia, dysarthria, dysmetria and dysdiadochokinesia. We have demonstrated previously genetic heterogeneity within these disorders by excluding the disease locus from the ...
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2022-01-31
    Description: Magmas from continental arcs built on thick crust have elevated incompatible element abundances and “enriched” radiogenic isotope ratios compared to magmas erupted in island and continental arcs overlying thinner crust. The relative influence of the slab, mantle, and upper plate on this variability is heavily debated. The Andean Southern Volcanic Zone (SVZ; 33-46° S) is an ideal setting to investigate the production of enriched continental arc compositions, because both crustal thickness and magma chemistry vary coherently along strike. However, the scarcity of primitive magmas in the thick-crusted northern SVZ has hindered previous regional studies. To better address the origin of enriched continental compositions, we investigate the geochemistry (major and trace element abundances, 87Sr/86Sr and 143Nd/144Nd ratios) of new mafic samples from Don Casimiro and Maipo volcanoes in Diamante-Maipo Caldera Complex of the northern SVZ. While evolved Diamante-Maipo samples show evidence for crustal assimilation, the trace element and isotopic enrichment of the most mafic samples cannot result from crustal processing, as no known regional or global basement lithologies are enriched in all of the necessary incompatible trace elements. Subduction erosion models similarly fail to account for the enriched isotopic and trace element signature of these samples. Instead, we suggest that the enrichment of northern SVZ magmas is derived from an enriched ambient mantle component (similar to EM1-type ocean island basalts), superimposed on a northward decline in melt extent. A substantial, but nearly uniform contribution of melts from subducting sediment and altered oceanic crust are required at all latitudes. The EM1-like enrichment may arise from recycling of metasomatized subcontinental lithospheric mantle (M-SCLM), as the isotopic trajectory of primitive rear-arc monogenetic cones trend towards the compositions of SCLM melts sampled across South America. Isotopic data from spatially distributed rear-arc centres demonstrate that the arc-parallel variations in the degree of EM1-type enrichment observed in arc-front samples are also present up to 600 km behind the trench in the rear-arc. Rear-arc trace element systematics require significant but variable quantities of slab melts to be transported to the mantle wedge at these large trench distances. Overall, we show that a unified model incorporating variable mantle enrichment, slab additions, and melt extents can account for along and acrossarc trends within the SVZ. The recognition that mantle enrichment plays a key role in the production of enriched continental compositions in the SVZ has important implications for our understanding of the chemical evolution of the Earth. If ambient mantle enrichment is not taken into account, petrogenetic models of evolved lavas may overestimate the role of crustal assimilation, which, in turn, may lead models of continental crust growth to overestimate the amount of continental material that has been recycled back into the mantle.
    Type: Article , PeerReviewed
    Format: text
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  • 3
    Publication Date: 2012-10-09
    Description: Background Genetic differences between men and women may contribute to sex differences in prevalence and progression of many common complex diseases. Using the WTCCC GWAS, we analysed whether there are sex-specific differences in effect size estimates at 142 established loci for seven complex diseases: rheumatoid arthritis, type 1 diabetes (T1D), Crohn’s disease, type 2 diabetes (T2D), hypertension, coronary artery disease and bipolar disorder. Methods For each Single nucleotide polymorphism (SNP), we calculated the per-allele odds ratio for each sex and the relative odds ratios (RORs; the effect size is higher in men with ROR greater than one). RORs were then meta-analysed across loci within each disease and across diseases. Results For each disease, summary RORs were not different from one, but there was between-SNP heterogeneity in the RORs for T1D and T2D. Four loci in T1D, three in Crohn’s disease and three in T2D showed differences in the genetic effect between men and women ( P 〈 0.05). We probed these differences in additional independent replication samples for T1D and T2D. The differences remained for the T1D loci CTSH , 17q21 and 20p13 and the T2D locus BCL11A, when WTCCC data and replication data were meta-analysed . Only CTSH showed different genetic effect between men and women in the replication data alone. Conclusion Our results exclude the presence of large and frequent differences in the effect size estimates between men and women for the established loci in the seven common diseases explored. Documenting small differences in genetic effects between men and women requires large studies and systematic evaluation.
    Print ISSN: 0300-5771
    Electronic ISSN: 1464-3685
    Topics: Medicine
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