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)

Southern Ocean bottom-water cooling and ice sheet expansion during the middle Miocene climate transition

The middle Miocene climate transition (MMCT), around 14 Ma, was associated with a significant climatic shift, but the mechanisms triggering the event remain enigmatic. We present a clumped isotope (Δ47) bottom-water temperature (BWT) record from 16.0 to 12.2 Ma from Ocean Drilling Program (ODP) Site 747 in the Southern Ocean and compare it to existing BWT records from different latitudes. We show that BWTs in the Southern Ocean reached 8–10 ∘C during the Miocene climatic optimum. These high BWT values indicate considerably warmer bottom-water conditions than today. Nonetheless, bottom-water δ18O (calculated from foraminiferal δ18O and Δ47) suggests substantial amounts of land ice throughout the interval of the study. Our dataset further demonstrates that BWTs at Site 747 were variable with an overall cooling trend across the MMCT. Notably, a cooling of around 3–5 ∘C preceded the stepped main increase in benthic δ18O, interpreted as global ice volume expansion, and appears to have been followed by a transient bottom-water warming starting during or slightly after the main ice volume increase. We speculate that a regional freshening of the upper water column at this time may have increased stratification and reduced bottom-water heat loss to the atmosphere, counteracting global cooling in the bottom waters of the Southern Ocean and possibly even at larger scales. Feedbacks required for substantial ice growth and/or tectonic processes may have contributed to the observed decoupling of global ice volume and Southern Ocean BWT.publishedVersio

Precessional variability of 87 Sr/86 Sr in the late Miocene Sorbas Basin: An interdisciplinary study of drivers of interbasin exchange

We present the first subprecessional record of seawater 87Sr/86Sr isotope ratios for a marginal Mediterranean subbasin. The sediments contained in this interval (three precessional cycles between 6.60 and 6.55 Ma) are important because they record conditions during the transition to the Messinian Salinity Crisis (MSC; 5.97 to 5.33 Ma), an event for which many details are still poorly understood. The record, derived from planktic foraminifera of the late Miocene Sorbas Basin (SE Spain), shows brief excursions with precessional cyclicity to 87Sr/86Sr ratios higher than coeval ocean 87Sr/86Sr. The hydrologic conditions required to generate the observed record are investigated using box modeling, constrained using a new paleodepth estimate (150 to 250 m) based on benthic foraminiferal assemblages. The box model results highlight the role of climate‐driven interbasin density contrast as a significant driver of, or impediment to, exchange. The results are particularly significant in the context of the MSC, where 87Sr/86Sr excursions have been interpreted purely as a consequence of physical restriction. To replicate the observed temporal patterns of lithological variations and 87Sr/86Sr isotope excursions, the Sorbas Basin “box” must have a mainly positive hydrologic budget, in contrast with the Mediterranean's negative budget during the late Miocene. This result has implications for the assumption of synchronous deposition of specific sedimentary layers (sapropels) between marginal and open Mediterranean settings at subprecessional resolution. A net positive hydrologic budget in marginal Mediterranean subbasins may reconcile observations of freshwater inclusions in gypsum deposits

Negative Effect of Smoking on the Performance of the QuantiFERON TB Gold in Tube Test.

False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02). Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status

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

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

InterCarb: a community effort to improve interlaboratory standardization of the carbonate clumped isotope thermometer using carbonate standards

Increased use and improved methodology of carbonate clumped isotope thermometry has greatly enhanced our ability to interrogate a suite of Earth-system processes. However, interlaboratory discrepancies in quantifying carbonate clumped isotope (Δ47) measurements persist, and their specific sources remain unclear. To address interlaboratory differences, we first provide consensus values from the clumped isotope community for four carbonate standards relative to heated and equilibrated gases with 1,819 individual analyses from 10 laboratories. Then we analyzed the four carbonate standards along with three additional standards, spanning a broad range of δ47 and Δ47 values, for a total of 5,329 analyses on 25 individual mass spectrometers from 22 different laboratories. Treating three of the materials as known standards and the other four as unknowns, we find that the use of carbonate reference materials is a robust method for standardization that yields interlaboratory discrepancies entirely consistent with intralaboratory analytical uncertainties. Carbonate reference materials, along with measurement and data processing practices described herein, provide the carbonate clumped isotope community with a robust approach to achieve interlaboratory agreement as we continue to use and improve this powerful geochemical tool. We propose that carbonate clumped isotope data normalized to the carbonate reference materials described in this publication should be reported as Δ47 (I-CDES) values for Intercarb-Carbon Dioxide Equilibrium Scale

Salt distribution mapping in natural building and decorative stones

Despite extensive work in the field of salt crystallization throughout the years, there are few reported attempts in the literature to map the distribution of the salt front in porous masonry materials and therefore try to explain the effect pore clogging may have on the damage caused by salt weathering. In the research reported in this paper, relatively new and complimentary test methods (drilling and scratch resistance measurements) for assessing the mechanical properties of materials have been applied to map the distribution of salts within natural building stone. The results show that both methods may be used successfully for salt distribution mapping. Through the application of these techniques, it is confirmed that sodium sulfate salt crystallizes in a thin layer at or just behind the surface of the stone, and that the use of water repellent forces this layer further behind the surface

Salt distribution mapping in natural building and decorative stones

Despite extensive work in the field of salt crystallization throughout the years, there are few reported attempts in the literature to map the distribution of the salt front in porous masonry materials and therefore try to explain the effect pore clogging may have on the damage caused by salt weathering. In the research reported in this paper, relatively new and complimentary test methods (drilling and scratch resistance measurements) for assessing the mechanical properties of materials have been applied to map the distribution of salts within natural building stone. The results show that both methods may be used successfully for salt distribution mapping. Through the application of these techniques, it is confirmed that sodium sulfate salt crystallizes in a thin layer at or just behind the surface of the stone, and that the use of water repellent forces this layer further behind the surface