No extreme bipolar glaciation during the main Eocene calcite compensation shift

Major ice sheets were permanently established on Antarctica approximately 34 million years ago, close to the Eocene/Oligocene boundary, at the same time as a permanent deepening of the calcite compensation depth in the world's oceans. Until recently, it was thought that Northern Hemisphere glaciation began much later, between 11 and 5 million years ago. This view has been challenged, however, by records of ice rafting at high northern latitudes during the Eocene epoch and by estimates of global ice volume that exceed the storage capacity of Antarctica at the same time as a temporary deepening of the calcite compensation depth approximately 41.6 million years ago. Here we test the hypothesis that large ice sheets were present in both hemispheres approximately 41.6 million years ago using marine sediment records of oxygen and carbon isotope values and of calcium carbonate content from the equatorial Atlantic Ocean. These records allow, at most, an ice budget that can easily be accommodated on Antarctica, indicating that large ice sheets were not present in the Northern Hemisphere. The records also reveal a brief interval shortly before the temporary deepening of the calcite compensation depth during which the calcite compensation depth shoaled, ocean temperatures increased and carbon isotope values decreased in the equatorial Atlantic. The nature of these changes around 41.6 million years ago implies common links, in terms of carbon cycling, with events at the Eocene/Oligocene boundary and with the 'hyperthermals' of the Early Eocene climate optimum. Our findings help to resolve the apparent discrepancy between the geological records of Northern Hemisphere glaciation and model results that indicate that the threshold for continental glaciation was crossed earlier in the Southern Hemisphere than in the Northern Hemisphere.     

Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers

Chronic viral hepatitis is the most important risk factor for progression to hepatocellular carcinoma (HCC). To identify genetic risk factors for progression to HCC in individuals with chronic hepatitis C virus (HCV), we analyzed 467,538 SNPs in 212 Japanese individuals with chronic HCV with HCC and 765 individuals with chronic HCV without HCC. We identified one intronic SNP in the DEPDC5 locus on chromosome 22 associated with HCC risk and confirmed the association using an independent case-control population (710 cases and 1,625 controls). The association was highly significant when we analyzed the stages separately as well as together (rs1012068, P(combined) = 1.27 × 10(-13), odds ratio = 1.75). The significance level of the association further increased after adjustment for gender, age and platelet count (P = 1.35 × 10(-14), odds ratio = 1.96). Our findings suggest that common variants within the DEPDC5 locus affect susceptibility to HCC in Japanese individuals with chronic HCV infection.     

ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.     

Regulation of primary cilia formation and left-right patterning in zebrafish by a noncanonical Wnt signaling mediator, duboraya

Primary cilia are microtubule-based organelles that project from the surface of nearly every animal cell. Although important functions of primary cilia in morphogenesis and tissue homeostasis have been identified, the mechanisms that control the formation of primary cilia are not understood. Here we characterize a zebrafish gene, termed duboraya (dub), that is essential for ciliogenesis. Knockdown of dub in zebrafish embryos results in both defects in primary cilia formation in Kupffer's vesicle and randomization of left-right organ asymmetries. We show that, at the molecular level, the function of dub in ciliogenesis is regulated by phosphorylation, which in turn depends on Frizzled-2-mediated noncanonical Wnt signaling. We also provide evidence that, at the cellular level, dub function is essential for actin organization in the cells lining Kupffer's vesicle. Taken together, our findings identify a molecular factor that links noncanonical Wnt signaling with the control of left-right axis specification, and provide an entry point for analyzing the mechanisms that regulate primary cilia formation.     

Ice-sheet collapse and sea-level rise at the Bølling warming 14,600 years ago

Past sea-level records provide invaluable information about the response of ice sheets to climate forcing. Some such records suggest that the last deglaciation was punctuated by a dramatic period of sea-level rise, of about 20?metres, in less than 500?years. Controversy about the amplitude and timing of this meltwater pulse (MWP-1A) has, however, led to uncertainty about the source of the melt water and its temporal and causal relationships with the abrupt climate changes of the deglaciation. Here we show that MWP-1A started no earlier than 14,650 years ago and ended before 14,310 years ago, making it coeval with the B?lling warming. Our results, based on corals drilled offshore from Tahiti during Integrated Ocean Drilling Project Expedition 310, reveal that the increase in sea level at Tahiti was between 12 and 22 metres, with a most probable value between 14 and 18 metres, establishing a significant meltwater contribution from the Southern Hemisphere. This implies that the rate of eustatic sea-level rise exceeded 40 millimetres per year during MWP-1A.