ALBERT

Beschreibung: Background Thrombosis is a well-described complication of L-asparaginase (asp) treatment in patients with acute lymphoblastic leukemia (ALL), with an incidence of 5-10%. Although asp-associated thrombi can occur anywhere, most are venous and 50% of venous thromboses occur in the central nervous system (CNS); 18% of these are associated with cerebral infarction or stroke. Ninety percent of thrombotic events occur early in the treatment of ALL, during induction and consolidation, consistent with the predominant use of asp during these phases of therapy. Morbidity and mortality have been reported in as many as 50% of patients. Although the mechanism by which asp causes thromboses is thought to be inhibition of protein synthesis resulting in decreased levels of plasma coagulation factors, specific patterns of plasma coagulation factors (including decreases in antithrombotic proteins such as ATIII, protein S, C, and components of the fibrinolytic pathway) have not been good predictors of thrombosis. Risk factors for CNS thrombosis include older age at diagnosis and high risk (HR) disease. Although quantification of proteins in the cerebrospinal fluid (CSF) has been used to identify markers of other diseases, CSF proteomics has not been studied in ALL. We hypothesize that changes in some proteins in the CSF will occur after asp, will be more prominent in patients on HR ALL protocols than in those on standard risk (SR) protocols, and will anticipate CNS thrombosis. In this study, we pilot feasibility and describe serial proteomic analysis of CSF in newly diagnosed patients with ALL or lymphoblastic lymphoma (LL). Methods Sequential patients, ages 0-30 years, with B-cell ALL, T-cell ALL, or LL diagnosed August 2012-August 2013 at the University of North Carolina and treated according to risk stratified Children’s Oncology Group protocols and the US Intergroup C10403 protocol for adolescents and young adults were offered participation. All patients were on a treatment protocol which utilized PEG-asp on Day 4 of therapy. Following consent approved by our Institutional Review Board, 1 mL of CSF was collected at the time of scheduled lumbar punctures (LP) on Days 0, 8, and 29 of induction. Samples were centrifuged at 1500rpm for 10 minutes within an hour of LP, stored in 50mcL aliquots at -800C. and transported on dry ice to the Duke Proteomics Core Facility. Because of cost ($1000/sample), 5 patients (15 samples) were selected for initial study, including the one patient who had a CNS thrombosis on day 22 of consolidation. Thawed batched duplicate samples were immunodepleted using a MARS-14 LC column (Agilent) and Agilent 1000 HPLC to remove high abundance plasma proteins, and quantitative MS analysis was performed in a label-free fashion using one-dimensional liquid-chromatography tandem mass spectrometry on a Synapt G2 HDMS system (Waters Corporation). Data Analysis was performed in Rosetta Elucidator v3.3 (Rosetta Biosoftware). Results Samples were obtained on each of 22 patients (11 male, 11 female). Characteristics of the 5 patient samples set chosen for analysis are shown in Table 1. 636 proteins were identifiable in each sample including several that have potential roles in coagulation. Thirteen proteins met a cut-off of ±1.5-fold change and p

Beschreibung: Abstract Radiocarbon and uranium-thorium dating results are presented from a genus of calcitic Antarctic cold-water octocorals (family Coralliidae), which were collected from the Marie Byrd Seamounts in the Amundsen Sea (Pacific sector of the Southern Ocean) and which to date have not been investigated geochemically. The geochronological results are set in context with solution and laser ablation-based element/Ca ratios (Li, B, Mg, Mn, Sr, Ba, U, Th). Octocoral radiocarbon ages on living corals are in excellent agreement with modern ambient deep-water �14C, while multiple samples of individual fossil coral specimens yielded reproducible radiocarbon ages. Provided that local radiocarbon reservoir ages can be derived for a given time, fossil Amundsen Sea octocorals should be reliably dateable by means of radiocarbon. In contrast to the encouraging radiocarbon findings, the uranium-series data are more difficult to interpret. The uranium concentration of these calcitic octocorals is an order of magnitude lower than in the aragonitic hexacorals that are conventionally used for geochronological investigations. While modern and Late Holocene octocorals yield initial δ234U in good agreement with modern seawater, our results reveal preferential inward diffusion of dissolved alpha-recoiled 234U and its impact on fossil coral δ234U. Besides alpha-recoil related 234U diffusion, high-resolution sampling of two fossil octocorals further demonstrates that diagenetic uranium mobility has offset apparent coral U-series ages. Combined with the preferential alpha-recoil 234U diffusion, this process has prevented fossil octocorals from preserving a closed system U-series calendar age for longer than a few thousand years. Moreover, several corals investigated contain significant initial thorium, which cannot be adequately corrected for because of an apparently variable initial 232Th/230Th. Our results demonstrate that calcitic cold-water corals are unsuitable for reliable U-series dating. Mg/Ca ratios within single octocoral specimens are internally strikingly homogeneous, and appear promising in terms of their response to ambient temperature. Magnesium/lithium ratios are significantly higher than usually observed in other deep marine calcifiers and for many of our studied corals are remarkably close to seawater compositions. Although this family of octocorals is unsuitable for glacial deep-water �14C reconstructions, our findings highlight some important differences between hexacoral (aragonitic) and octocoral (calcitic) biomineralisation. Calcitic octocorals could still be useful for trace element and some isotopic studies, such as reconstruction of ambient deep water neodymium isotope composition or pH, via boron isotopic measurements.

Beschreibung: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biogeosciences 10 (2013): 2001-2010, doi:10.5194/bg-10-2001-2013.

Beschreibung: Atmospheric CO2 concentration is hypothesized to influence vegetation distribution via tree–grass competition, with higher CO2 concentrations favouring trees. The stable carbon isotope (δ13C) signature of vegetation is influenced by the relative importance of C4 plants (including most tropical grasses) and C3 plants (including nearly all trees), and the degree of stomatal closure – a response to aridity – in C3 plants. Compound-specific δ13C analyses of leaf-wax biomarkers in sediment cores of an offshore South Atlantic transect are used here as a record of vegetation changes in subequatorial Africa. These data suggest a large increase in C3 relative to C4 plant dominance after the Last Glacial Maximum. Using a process-based biogeography model that explicitly simulates 13C discrimination, it is shown that precipitation and temperature changes cannot explain the observed shift in δ13C values. The physiological effect of increasing CO2 concentration is decisive, altering the C3/C4 balance and bringing the simulated and observed δ13C values into line. It is concluded that CO2 concentration itself was a key agent of vegetation change in tropical southern Africa during the last glacial–interglacial transition. Two additional inferences follow. First, long-term variations in terrestrial δ13Cvalues are not simply a proxy for regional rainfall, as has sometimes been assumed. Although precipitation and temperature changes have had major effects on vegetation in many regions of the world during the period between the Last Glacial Maximum and recent times, CO2 effects must also be taken into account, especially when reconstructing changes in climate between glacial and interglacial states. Second, rising CO2 concentration today is likely to be influencing tree–grass competition in a similar way, and thus contributing to the "woody thickening" observed in savannas worldwide. This second inference points to the importance of experiments to determine how vegetation composition in savannas is likely to be influenced by the continuing rise of CO2 concentration.

Beschreibung: The PMIP2/MOTIF Data Archive has been supported by CEA, CNRS, the EU project MOTIF (EVK2-CT-2002-00153) and the Programme National d’Etude de la Dynamique du Climat (PNEDC).

Beschreibung: The Late Permian mass extinction event about 252 million years ago was the most severe biotic crisis of the past 500 million years and occurred during an episode of global warming. The loss of around two-thirds of marine genera is thought to have had substantial ecological effects, but the overall impacts on the functioning of marine ecosystems and the pattern of marine recovery are uncertain. Here we analyse the fossil occurrences of all known benthic marine invertebrate genera from the Permian and Triassic periods, and assign each to a functional group based on their inferred lifestyle. We show that despite the selective extinction of 62–74% of these genera, all but one functional group persisted through the crisis, indicating that there was no significant loss of functional diversity at the global scale. In addition, only one new mode of life originated in the extinction aftermath. We suggest that Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed. Functional diversity was, however, reduced in particular regions and habitats, such as tropical reefs; at these smaller scales, recovery varied spatially and temporally, probably driven by migration of surviving groups. We find that marine ecosystems did not return to their pre-extinction state, and by the Middle Triassic greater functional evenness is recorded, resulting from the radiation of previously subordinate groups such as motile, epifaunal grazers.