16 research outputs found

    Calpain-mediated cleavage generates a ZBTB18 N-terminal product that regulates HIF1A signaling and glioblastoma metabolism

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    Proteolytic cleavage is an important post-translational mechanism to increase protein variability and functionality. In cancer, this process can be deregulated to shut off tumor-suppressive functions. Here, we report that in glioblastoma (GBM), the tumor suppressor ZBTB18 is targeted for protein cleavage by the intracellular protease calpain. The N-terminal (Nte) ZBTB18 cleaved fragment localizes to the cytoplasm and thus, is unable to exert the gene expression repressive function of the uncleaved protein. Mass spectrometry (MS) analysis indicates that the Nte ZBTB18 short form (SF) interacts with C-terminal (Cte) binding proteins 1 and 2 (CTBP1/2), which appear to be involved in HIF1A signaling activation. In fact, we show that the new ZBTB18 product activates HIF1A-regulated genes, which in turn lead to increased lipid uptake, lipid droplets (LD) accumulation, and enhanced metabolic activity. We propose that calpain-mediated ZBTB18 cleavage represents a new mechanism to counteract ZBTB18 tumor suppression and increase tumor-promoting functions in GBM cells

    Regional to Interhemispheric Connectivity of the Atlantic Ocean Circulation

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    This thesis investigates the connectivity and interaction of remote regions in the Atlantic Ocean based on high-resolution model experiments. Connectivity between remote regions has important implications on a range of spatial and temporal scales. It can affect global climate variability, the coherence of circulation changes on regional scales and the spreading of marine organisms. Based on several advancements in modelling, it is demonstrated how interhemispheric connectivity contributes to changes of the Atlantic Meridional Overturning Circulation (AMOC) on climate timescales. At the same time, the effect of wind-forcing and the interaction of individual AMOC pathways with eddies on regional scales are shown to be highly important to understand AMOC variability on sub-decadal timescales, with further implications on interdisciplinary research questions

    Simulated see surface temperature combined with ice cover with an overlay of total cloud cover and windspeed from FOCI simulation

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    Visualisation of daily sea surface temperature projected on surface elevation combined with sea ice cover with an overlay of total cloud cover and windspeed from FOCI simulation for one year displaying the Southern Ocean/Atlantic region. This simulation was generated with the open-source software Paraview (www.paraview.org)

    Animation of pathways of the upper limb of the overturning circulation in the South Atlantic, realized by tracking virtual fluid particles in an eddy-rich ocean model

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    The animation visualizes pathways of the upper limb of the overturning circulation in the South Atlantic by means of virtual fluid particle trajectories. The animation has been created with ParaView. The trajectories present a subset of the trajectories evaluated in Rühs et al. (2019). They have been calculated by using the ARIANE tool (version 2.2.6; Blanke and Raynauld, 1997; Blanke et al., 1999) in qualitative mode and 5-day mean 3D velocity output from the eddy-rich ocean-sea-ice model configuration INALT20 (experiment KFS044; Schwarzkopf et al., 2019). Specifically, particles were released over the full depth and width of the northward flowing North Brazil current at 6S and were then advected backwards in time until they reach the Pacific Ocean through Drake Passage or the Indian Ocean through the Agulhas Current system. Along-track temperatures were recorded and are visualized by the color of the trajectories (red=warm, blue=cold). The animation shows that water particles flowing from the Indian Ocean to the tropical Atlantic are relative warm, while particles entering from the Pacific Ocean tend to colder – the reason for the frequently used terminology “warm water route” and “cold water route”

    Atlantic meridional overturning response to increased Southern Ocean wind stress in a climate model with an eddy-rich ocean

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    The Southern Hemisphere westerly winds experienced significant changes over recent decades and are projected to further strengthen, altering ocean hydrography and dynamics. While anomalies of Southern Hemisphere origin are hypothesised to impact the Atlantic Meridional Overturning Circulation (AMOC), many details of this relationship remain unknown as previous modelling studies are limited by the application of forced, coarse resolution ocean models, or a short integration length. Here a coupled, nested climate model configuration, covering the Atlantic Ocean at an eddy-rich 1/10° resolution is applied to study the adjustment of the large-scale circulation to a 30% increase of the Southern Ocean wind stress. The AMOC responds to the stronger wind stress with a strengthening of 0.6 to 1.4 Sv across the entire Atlantic after approximately 80 years. At that time, anomalous watermass transformation mainly occurs at the entry into the Nordic Seas. A density anomaly in the overflow water then induces anomalous sinking in the eastern subpolar gyre, providing a link between AMOC changes in density and depth coordinates. Our study suggests that these watermass changes are caused by northward propagating anomalies and provides a detailed hypothesis for the link between the Indian Ocean inflow via Agulhas leakage and the AMOC. Nevertheless, due to coupled ocean-atmosphere adjustments, anomalies do not simply follow the main volume transport pathways along the western boundary. Mixing between advectively transported and locally forced anomalies leads to an increasingly complex evolution of watermass anomalies and less certainty in the relative contributions of involved mechanisms towards subpolar latitudes

    Mesoscale ocean eddies determine dispersal and connectivity of corals at the RMS Titanic wreck site

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    Highlights: • Mesoscale ocean eddies strongly impact the dispersal of larvae from RMS Titanic • The Titanic could act as a stepping stone connecting remote ecosystems • Interactions between eddies and currents shape ecosystem connectivity Abstract The sinking of the RMS Titanic on 15 April 1912 remains one of most iconic maritime disasters in history. Today, the wreck site lies in waters 3,800 m deep approximately 690 km south southeast of Newfoundland, Atlantic Canada. The wreck and debris field have been colonized by many marine organisms including the octocoral Chrysogorgia agassizii. Because of the rapid deterioration of the Titanic and the vulnerability of natural deep-sea coral populations to environmental changes, it is vital to understand the role the Titanic as well as other such structures could play in connecting ecosystems along the North American slope. Based on Lagrangian experiments with more than one million virtual particles and different scenarios for larval behavior, given the uncertainties around the biology of chrysogorgiids, the dispersal of larvae spawned at the Titanic wreck is studied in a high-resolution numerical ocean model. While the large-scale bathymetry shields the Titanic from a strong mean flow, mesoscale ocean eddies can considerably affect the deep circulation and cause a significant speed up, or also a reversal, of the circulation. As a consequence, the position of upper and mid-ocean eddies in the model largely controls the direction and distance of larval dispersal, with the impact of eddies outweighing the importance of active larval swimming in our experiments. Although dependent on larval buoyancy and longevity, we find that the Titanic could be reached by larvae spawned on the upper slope east of the Grand Banks. Therefore, the Titanic could act as a stepping stone connecting the upper to the deep continental slope off Newfoundland. From the Titanic, larvae then spread into deep Canadian waters and areas beyond national jurisdiction

    Robust estimates for the decadal evolution of Agulhas leakage from the 1960s to the 2010s

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    Agulhas leakage, the transport of warm and salty waters from the Indian Ocean into the South Atlantic, has been suggested to increase under anthropogenic climate change, due to strengthening Southern Hemisphere westerly winds. The resulting enhanced salt transport into the South Atlantic may counteract the projected weakening of the Atlantic overturning circulation through warming and ice melting. Here we combine existing and new observation- and model-based Agulhas leakage estimates to robustly quantify its decadal evolution since the 1960s. We find that Agulhas leakage very likely increased between the mid-1960s and mid-1980s, in agreement with strengthening winds. Our models further suggest that increased leakage was related to enhanced transport outside eddies and coincided with strengthened Atlantic overturning circulation. Yet, it appears unlikely that Agulhas leakage substantially increased since the 1990s, despite continuously strengthening winds. Our results stress the need to better understand decadal leakage variability to detect and predict anthropogenic trends

    Gas chromatographic analysis of volatile hydrocarbons to detect irradiated chicken, pork and beef - an intercomparison study A report in English and German

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    This report provides a detailed description of an inter-laboratory study to detect irradiation treatment of chicken carcasses, pork and beef using a method suitable for routine application. The 17 participating laboratories determined the quantity of four different radiation-induced hydrocarbons (1-tetradecene, pentadecane, 1,7-hexadecadiene, 8-heptadecene) in coded samples approx. 3 and 6 months after irradiation. The quantities detected were used to identify the samples as irradiated or non-irradiated. The samples of each type of meat to be examined had been supplied by two different producers. The dose range that was tested (approx. 0.6 to 7.5 kGy) included commercially used doses (approx. 1 to 5 kGy). The method employed enable 98.3% of a total of 864 samples to be correctly identified as irradiated or non-irradiated. This result is remarkable: Although the marker concentrations in the various samples showed a clear dose dependency, the variation was quite marked. The high rate of correct identifications could be achieved by defining a sample only as irradiated if certain quantities of at least 3 of the radiolytic products to be determined had been found. A similar identification rate was achieved if quantification of markers was omitted to identify a sample only as irradiated when all the expected radiolysis products could be clearly detected. For all three types of meat, no significant differences in marker yields could be shown for the products of the respective two producers. Also, in none of the types of meat, any significant difference could be revealed for the quantiatitive results achieved three and six months after irradiation. These results show that irradiation of chicken carcasses, pork and beef in the commerically used dose range can be clearly detected throughout the entire period in which products are normally stored and that the method described is suitable for routine analyses in food control laboratories. (orig.)Available from TIB Hannover: RR 1068(1993,1) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman
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