Precessional cyclicity of seawater Pb isotopes in the late Miocene Mediterranean

Astronomical tuning in the Mediterranean region is primarily based on organically‐mediated proxies, such as cyclicity of organic rich layers or changes in foraminiferal assemblages. Both during and post deposition, organic proxies can be affected by complex processes not immediately related to the changes in precession (insolation) they are assumed to reflect. Here we present an isotopic proxy which exhibits precessional cyclicity yet is inorganic. Seawater lead (Pb) isotope records over four precessional cycles between 6.6 and 6.5 Ma, from bulk sediment leachates of three Messinian, circum‐Mediterranean marginal locations, show variations consistent with precessional cyclicity. During insolation minima, the Pb isotope signatures from all three sites converge to similar values, suggesting a regional process is affecting all three locations at that time. Data from the marginal sites are compared with new data from ODP Site 978 and published data from a variety of geological archives from the Mediterranean region to determine the mechanism(s) causing the observed variability. While the comparisons are not fully conclusive, the timing of events suggest that increased dust production from North Africa during insolation minima is the most likely control. This hypothesis implies that authigenic marine Pb isotope records have the potential to provide a reliable inorganic tie point for Mediterranean cyclostratigraphy where sub‐precessional resolution is required. An inorganic tie point could also provide the means to resolve long‐standing problems in Mediterranean stratigraphy on precessional and sub‐precessional timescales which have been obscured due to post‐depositional changes (e.g., sapropel burn‐down) or suboptimal ecological conditions (e.g., the Messinian Salinity Crisis)

Profiles of Global Gene Expression in Ionizing-Radiation–Damaged Human Diploid Fibroblasts Reveal Synchronization behind the G(1) Checkpoint in a G(0)-like State of Quiescence

Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40–45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G(2) to M at 2 hr post-IR and a similarly severe arrest of progression from G(1) to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G(1) checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G(1) checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G(0) growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G(1) checkpoint but with prominent induction of additional markers of G(0) quiescence such as GAS1

Speleothem evidence for Late Miocene extreme Arctic amplification – an analogue for near-future anthropogenic climate change?

The Miocene provides an excellent climatic analogue for near-future runaway anthropogenic warming, with atmospheric CO2 concentrations and global average temperatures similar to those projected for the coming century under extreme-emissions scenarios. However, the magnitude of Miocene Arctic warming remains unclear due to the scarcity of reliable proxy data. Here we use stable oxygen isotope and trace element analyses, alongside clumped isotope and fluid inclusion palaeothermometry of speleothems to reconstruct palaeo-environmental conditions near the Siberian Arctic coast during the Tortonian (8.68 ± 0.09 Ma). Stable oxygen isotope records suggest warmer-than-present temperatures. This is supported by temperature estimates based on clumped isotopes and fluid inclusions giving mean annual air temperatures between +6.6 and +11.1 °C, compared with −12.3 °C today. Trace elements records reveal a highly seasonal hydrological environment. Our estimate of &gt; 18 °C of Arctic warming supports the wider consensus of a warmer-than-present Miocene and provides a rare palaeo-analogue for future Arctic amplification under high-emissions scenarios. The reconstructed increase in mean surface temperature far exceeds temperatures projected in fully coupled global climate models, even under extreme-emissions scenarios. Given that climate models have consistently underestimated the extent of recent Arctic amplification, our proxy data suggest Arctic warming may exceed current projections.</p

Expedition 395 summary

The intersection between the Mid-Atlantic Ridge and Iceland hotspot provides a natural laboratory where the composition and dynamics of Earth's upper mantle can be observed. Plume-ridge interaction drives variations in the melting regime, which result in a range of crustal types, including a series of V-shaped ridges (VSRs) and V-shaped troughs (VSTs) located south of Iceland. Mantle upwelling beneath Iceland dynamically supports regional bathymetry, and its variations may lead to changes in the height of oceanic gateways, which in turn control the flow of deep water on geologic timescales. Expeditions 384, 395C, and 395 recovered extensive successions of basaltic crust and thick (up to 1.3 km) overlying sediment cover, including successions through a number of contourite drifts of regional significance. Major, trace, and isotope geochemistry of basalts recovered during these expeditions will provide insight into spatial and temporal variations in mantle melting processes. Such analyses will provide data for testing the hypothesis that the Iceland plume thermally pulses on two timescales (5–10 and ~30 Ma), leading to fundamental changes in crustal architecture. This idea will be tested against alternative hypotheses involving propagating rifts and buoyant mantle upwelling. The rapidly accumulated sediments of contourite drifts have the potential to yield exceptional millennial-scale paleoceanographic records, including proxies for current strength, which is thought to be modulated by the dynamic support of the Greenland-Scotland Ridge, an oceanic gateway of global import. The recovered sediments also provide a record of subarctic climate change stretching back to the latest Eocene, including the long-term evolution of the Greenland ice sheet, critical intervals of Miocene and Pliocene warmth, the intensification of Northern Hemisphere glaciation, and Pleistocene millennial-scale variability.The objectives of Expeditions 395, 395C, and 384 are to explore the relationships between deep Earth processes, ocean circulation, and climate. These objectives were addressed by recovering sediment and basement cores from six sites, completed across three expeditions. Sites U1555 and U1563 are located at a VST/VSR pair nearest to the Reykjanes Ridge, on ~2.8 and 5.2 My old crust, respectively. Sites U1554 and U1562 are located in Björn drift above a VST/VSR pair, on ~12.4 and 14.2 My old crust, respectively. Site U1564 is located in Gardar drift above 32.4 My old oceanic crust that is devoid of V-shaped features. Finally, Site U1602 is located on the eastern Greenland margin above crust that is estimated to be Eocene in age and thus formed during the initial separation of Greenland from Scandinavia. Considered together, the sediments, basalts, and vast array of measurements collected during Expeditions 395, 395C, and 384 will provide a major advance in our understanding of mantle dynamics and the linked nature of Earth's interior, oceans, and climate.<p/

ARF-BP1 as a potential therapeutic target

In this review, we discuss the recent identification of ARF-BP1 (also known as Mule, UREB1, E3histone, LASU1, and HectH9). ARF-BP1, a HECT domain-containing E3 ubiquitin ligase, interacts with ARF and p53. Its ubiquitin ligase activity is inhibited by ARF. Inactivation of ARF-BP1 stabilised p53 and induced apoptosis. Notably, inactivation of ARF-BP1 also caused cell growth repression in p53-null cells and breast cancer cells with mutant p53. Thus, ARF-BP1 emerges as a novel therapeutic target against cancer regardless of p53 status