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Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, and especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology and utility of tumor biomarkers in animals such as cats and pigs. In this study, levels of free Hsp70 in the blood of cats with spontaneously occurring tumors were detected using a commercial Hsp70 ELISA (R&D Systems). Sub-analysis of different tumor groups revealed that animals with tumors of epithelial origin presented with significantly elevated circulating Hsp70 concentrations. In addition to free Hsp70 levels measured with the R&D Systems Hsp70 ELISA, levels of exosomal Hsp70 were determined using the compHsp70 ELISA in pigs. Both ELISA systems detected significantly elevated Hsp70 levels (R&D Systems: median 24.9 ng/mL; compHsp70: median 44.2 ng/mL) in the blood of a cohort of APC1311/+ pigs diagnosed with high-grade adenoma polyps, and the R&D Systems Hsp70 ELISA detected also elevated Hsp70 levels in animals with low-grade polyps. In contrast, in flTP53R167H pigs, suffering from malignant osteosarcoma, the compHsp70 ELISA (median 674.32 ng/mL), but not the R&D Systems Hsp70 ELISA (median 4.78 ng/mL), determined significantly elevated Hsp70 concentrations, indicating that in tumor-bearing animals, the dominant form of Hsp70 is of exosomal origin. Our data suggest that both ELISA systems are suitable for detecting free circulating Hsp70 levels in pigs with high-grade adenoma, but only the compHsp70 ELISA can measure elevated, tumor-derived exosomal Hsp70 levels in tumor-bearing animals.

Increased lactate dehydrogenase (LDH) activity, elevated levels of lactate in the tumor microenvironment and overexpression of heat shock proteins can mediate radioresistance of cancer cells. In this study, I aimed to investigate the relationship of LDH and the cellular stress response with respect to radiation resistance. My results showed that the lactate metabolism and heat shock response are co-regulated in two different tumor cell systems and as a functional consequence the radiosensitivity of cancer cells was significantly enhanced by inhibiting lactate metabolism. Strahlenresistenz von Krebszellen kann durch eine erhöhte Laktatdehydrogenase Aktivität, erhöhte Laktat Konzentrationen und eine Überexpression von Hitzeschockproteinen verursacht werden. In meiner Promotion untersuchte ich, inwieweit Strahlenresistenz durch einen Eingriff in den Laktatmetabolismus der Krebszellen überwunden werden kann. Meine Daten zeigten, dass der Laktatstoffwechsel und die Stressantwort in Tumorzellen co-reguliert werden und dass als Konsequenz die Strahlensensitivität von Krebszellen durch Hemmung des Laktatstoffwechsels erhöht wurde.

Permafrost thaw in Arctic watersheds threatens to mobilize hitherto sequestered carbon. We examine the radiocarbon activity (F14C) of dissolved organic carbon (DOC) in the northern Mackenzie River basin. From 2003-2017, DOC-F14C signatures (1.00 ± 0.04; n = 39) tracked atmospheric 14CO2, indicating export of "modern" carbon. This trend was interrupted in June 2018 by the widespread release of aged DOC (0.85 ± 0.16, n = 28) measured across three separate catchment areas. Increased nitrate concentrations in June 2018 lead us to attribute this pulse of 14C-depleted DOC to mobilization of previously frozen soil organic matter. We propose export through lateral perennial thaw zones that occurred at the base of the active layer weakened by preceding warm summer and winter seasons. Although we are not yet able to ascertain the broader significance of this "anomalous" mobilization event, it highlights the potential for rapid and large-scale release of aged carbon from permafrost.

Interactions between organic and detrital mineral phases strongly influence both the dispersal and accumulation of terrestrial organic carbon (OC) in continental margin sediments. Yet the complex interplay among biological, chemical, and physical processes limits our understanding of how organo-mineral interactions evolve during sediment transfer and burial. In particular, diverse OC sources and complex hydrodynamic processes hinder the assessment of how the partnership of organic matter and its mineral host evolves during supply and dispersal over continental margins. In this study, we integrate new and compiled sedimentological (grain size, surface area), organic (%OC, OC-δ13C, OC-F14C), and inorganic isotopic (εNd, 87Sr/86Sr) geochemical data for a broad suite of surface sediments spanning the Western Arctic Ocean from the Bering Sea to the Mackenzie River Delta that capture diverse sources and ages of both terrestrial and marine material deposited in contrasting shelf and slope settings. Spatial gradients in sediment properties were used to delineate regional sources and transport processes influencing the dispersion and persistence of OC-mineral particle associations during export and burial. We found strong relationships between physical parameters, aluminum content, and OC-14C suggesting that terrestrial OC remains tightly associated with its detrital mineral carrier during source-to-sink transport. Notably, carbon and neodymium isotopic data yield consistent information regarding organic matter provenance. Results obtained highlight the potential for coupled organic-inorganic tracer measurements to elucidate sediment sources and to constrain physical and geochemical processes during sediment mobilization and transport in the Western Arctic Ocean. Tandem measurements of carbon and Nd isotopes may provide a new way to identify large-scale biogeochemical and ecological changes in the sources, nature, and fate of OC stemming from predicted increases in sea ice loss and fluvial inputs of dissolved and particulate OC to this complex and dynamic high latitude marginal sea., Geochimica et Cosmochimica Acta, 315, ISSN:0016-7037, ISSN:1872-9533

Terrestrial vegetation and soils hold three times more carbon than the atmosphere. Much debate concerns how anthropogenic activity will perturb these surface reservoirs, potentially exacerbating ongoing changes to the climate system. Uncertainties specifically persist in extrapolating point-source observations to ecosystem-scale budgets and fluxes, which require consideration of vertical and lateral processes on multiple temporal and spatial scales. To explore controls on organic carbon (OC) turnover at the river basin scale, we present radiocarbon (14C) ages on two groups of molecular tracers of plant-derived carbon—leaf-wax lipids and lignin phenols—from a globally distributed suite of rivers. We find significant negative relationships between the 14C age of these biomarkers and mean annual temperature and precipitation. Moreover, riverine biospheric-carbon ages scale proportionally with basin-wide soil carbon turnover times and soil 14C ages, implicating OC cycling within soils as a primary control on exported biomarker ages and revealing a broad distribution of soil OC reactivities. The ubiquitous occurrence of a long-lived soil OC pool suggests soil OC is globally vulnerable to perturbations by future temperature and precipitation increase. Scaling of riverine biospheric-carbon ages with soil OC turnover shows the former can constrain the sensitivity of carbon dynamics to environmental controls on broad spatial scales. Extracting this information from fluvially dominated sedimentary sequences may inform past variations in soil OC turnover in response to anthropogenic and/or climate perturbations. In turn, monitoring riverine OC composition may help detect future climate-change–induced perturbations of soil OC turnover and stocks., Proceedings of the National Academy of Sciences of the United States of America, 118 (8), ISSN:0027-8424, ISSN:1091-6490

Permafrost thaw in Arctic watersheds threatens to mobilize hitherto sequestered carbon. We examine the radiocarbon activity (F14C) of dissolved organic carbon (DOC) in the northern Mackenzie River basin. From 2003-2017, DOC-F14C signatures (1.00 ± 0.04; n=39) tracked atmospheric 14CO2, indicating export of “modern” carbon. This trend was interrupted in June 2018 by the widespread release of aged DOC (0.85 ± 0.16, n = 28) measured across three separate catchment areas. Increased nitrate concentrations in June 2018 lead us to attribute this pulse of 14C-depleted DOC to mobilization of previously frozen soil organic matter. We propose export through lateral perennial thaw zones occurred at the base of the active layer weakened by preceding warm summer and winter seasons. Although we are not yet able to ascertain the broader significance of this “anomalous” mobilization event, it highlights the potential for rapid and large-scale release of aged carbon from permafrost., Geophysical Research Letters, 47 (23), ISSN:0094-8276, ISSN:1944-8007

Permafrost thaw in Arctic watersheds threatens to mobilize hitherto sequestered carbon. We examine the radiocarbon activity (F14C) of dissolved organic carbon (DOC) in the northern Mackenzie River basin. From 2003–2017, DOC‐F14C signatures (1.00 ± 0.04; n = 39) tracked atmospheric 14CO2, indicating export of “modern” carbon. This trend was interrupted in June 2018 by the widespread release of aged DOC (0.85 ± 0.16, n = 28) measured across three separate catchment areas. Increased nitrate concentrations in June 2018 lead us to attribute this pulse of 14C‐depleted DOC to mobilization of previously frozen soil organic matter. We propose export through lateral perennial thaw zones that occurred at the base of the active layer weakened by preceding warm summer and winter seasons. Although we are not yet able to ascertain the broader significance of this “anomalous” mobilization event, it highlights the potential for rapid and large‐scale release of aged carbon from permafrost., Key Points A widespread pulse of aged dissolved organic carbon (DOC) occurred in the Mackenzie River and its tributaries in June 2018Export of aged DOC is consistent with a prolonged warming period and the formation of supra‐permafrost taliksMobilization of aged DOC and nitrate suggests percolation of supra‐permafrost groundwater through previously frozen soil layers