Description: Background— The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease. Methods and Results— Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each ancestry informative marker, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each ancestry informative marker using these probabilities and CAC, accounting for global ancestry, age, sex, and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, logarithm of odds [LOD]=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0), and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, whereas markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1350 African Americans without diabetes mellitus and 2497 diabetic European Americans from Multi-Ethnic Study of Atherosclerosis and the Diabetes Heart Study. Conclusions— Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical cardiovascular disease.

Description: This paper is an introduction to and an overview of papers presented in the Special Issue of Marine Geology “Methane seeps at the Hikurangi Margin, New Zealand”. In 2006 and 2007, three research cruises to the Hikurangi Margin at the east coast of New Zealand's North Island were dedicated to studying methane seepage and gas hydrates in an area where early reports suggested they were widespread. Two cruises were carried out on RV TANGAROA and one on RV SONNE using the complete spectrum of state-of-the-art equipment for geophysics (seismic, sidescan, controlled source electromagnetics, ocean bottom seismometers and hydrophones, singlebeam and multibeam), seafloor observations (towed camera systems, ROV), sediment and biological sampling (TV-guided multi-corer, gravity-corer, grab, epibenthic sled), deployment of in-situ observatories (landers) as well as water column sampling and oceanographic studies (CTD, moorings). The scientific disciplines involved ranged from geology, geophysics, petrography, geochemistry, to oceanography, biology and microbiology. These cruises confirmed that a significant part of the Hikurangi Margin has been active with locally intense methane seepage at present and in the past, with the widespread occurrence of dead seep faunas and knoll-forming carbonate precipitations offshore and on the adjacent land. A close link to seismically detected fluid systems and the outcropping of the base of the gas hydrate stability zone can be found at some places. Pore fluid and free gas release were found to be linked to tides. Currents as well as density layers modulate the methane distribution in the water column. The paper introduces the six working areas on the Hikurangi Margin, and compiles all seep locations based on newly processed multibeam and multibeam backscatter data, water column hydroacoustic and visual data that are combined with results presented elsewhere in this Special Issue. In total, 32 new seep sites were detected that commonly show chemoherm-type carbonates or carbonate cemented sediment with fissures and cracks in which calyptogenid clams and bathymodiolid mussels together with sibloglinid tube worms live. White bacterial mats of the genus Beggiatoa and dark gray beds of heterotrophic ampharetid polychaetes typically occur at active sites. Bubble release has frequently been observed visually as well as hydroacoustically (flares) and geochemical analyses show that biogenic methane is released. All seep sites, bubbling or not, were inside the gas hydrate stability zone. Gas hydrate itself was recovered at three sites from the seafloor surface or 2.5 m core depth as fist-sized chunks or centimeter thick veins. The strong carbonate cementation that in some cases forms 50 m high knolls as well as some very large areas being paved with clam shells indicates very strong and long lasting seep activity in the past. This activity seems to be less at present but nevertheless makes the Hikurangi Margin an ideal place for methane-related seep studies in the SW-Pacific.

Description: β-thalassemia major causes ineffective erythropoiesis and chronic anemia and is associated with iron overload due to both transfused iron and increased iron absorption, the latter mediated by suppression of the iron-regulatory hormone hepcidin. We sought to determine whether, in β-thalassemia major, transfusion-mediated inhibition of erythropoiesis dynamically affects hepcidin. We recruited 31 chronically transfused patients with β-thalassemia major and collected samples immediately before and 4 to 8 days after transfusion. Pretransfusion hepcidin was positively correlated with hemoglobin and ferritin and inversely with erythropoiesis. The hepcidin-ferritin ratio indicated hepcidin was relatively suppressed given the degree of iron loading. Posttransfusion, hemoglobin and hepcidin increased, and erythropoietin and growth differentiation factor-15 decreased. By multiple regression, pre- and posttransfusion hepcidin concentrations were both associated positively with hemoglobin, inversely with erythropoiesis, and positively with ferritin. Although men and women had similar pretransfusion hemoglobin, men had significantly increased erythropoiesis and lower hepcidin, received a lower transfusion volume per liter blood volume, and experienced a smaller posttransfusion reduction in erythropoiesis and hepcidin rise. Age of blood was not associated with posttransfusion hemoglobin or ferritin change. Hepcidin levels in patients with β-thalassemia major dynamically reflect competing influences from erythropoiesis, anemia, and iron overload. Measurement of these indices could assist clinical monitoring.