Description: The paleoceanographic development of the eastern Fram Strait during the transition from the cold Late Glacial and into the warm Early Holocene was elucidated via a multiproxy study of a marine sediment record retrieved at the western Svalbard slope. The multiproxy study includes analyses of planktic foraminiferal fauna, bulk sediment grain size and CaCO3 content in addition to Mg/Ca ratios and stable isotopes (delta C-13 and delta O-18) measured on the planktic foraminifer Neogloboquadrina pachyderma. Furthermore paleosubsurface water temperatures were reconstructed via Mg/Ca ratios (sSST(Mg/Ca)) and transfer functions (sSST(Transfer)) enabling comparison between the two proxies within a single record. The age model was constrained by four accelerator mass spectrometry (AMS) C-14 dates. From 14,000 to 10,300 cal yr B.P. N. pachyderma dominated the planktic fauna and cold polar sea surface conditions existed. The period was characterized by extensive sea ice cover, iceberg transport and low subsea surface temperatures (sSST(Transfer) similar to 2.1 degrees C; sSST(Mg/Ca) similar to 3.5 degrees C) resulting in restricted primary production. Atlantic Water inflow was reduced compared to the present-day and likely existed as a subsurface current. At ca. 10,300 cal yr B.P. Atlantic Water inflow increased and the Arctic Front retreated north-westward resulting in increased primary productivity, higher foraminiferal fluxes and a reduction in sea ice cover and iceberg transport. The fauna rapidly became dominated by the subpolar planktic foraminifer Turborotalita quinqueloba and summer sSST(Transfer) increased by similar to 3.5 degrees C. Concurrently, the sSST(Mg/Ca) recorded by N. pachyderma rose only similar to 0.5 degrees C. From ca. 10,300 to 8600 cal yr B.F. the average sSST(Mg/Ca) and sSST(Transfer) were similar to 4.0 degrees C and similar to 55 degrees C, respectively. The relatively modest change in sSST(Mg/Ca) compared to sSST(Transfer) can probably be tied to a change of the main habitat depth and/or shift in the calcification season for N. pachyderma during this period.

Description: In osteosarcoma, a primary mesenchymal bone cancer occurring predominantly in younger patients, invasive tumor growth leads to extensive bone destruction. This process is insufficiently understood, cannot be efficiently counteracted and calls for novel means of treatment. The endocytic collagen receptor, uPARAP/Endo180, is expressed on various mesenchymal cell types and is involved in bone matrix turnover during normal bone growth. Human osteosarcoma specimens showed strong expression of this receptor on tumor cells, along with the collagenolytic metalloprotease, MT1-MMP. In advanced tumors with ongoing bone degeneration, sarcoma cells positive for these proteins formed a contiguous layer aligned with the degradation zones. Remarkably, osteoclasts were scarce or absent from these regions and quantitative analysis revealed that this scarcity marked a strong contrast between osteosarcoma and bone metastases of carcinoma origin. This opened the possibility that sarcoma cells might directly mediate bone degeneration. To examine this question, we utilized a syngeneic, osteolytic bone tumor model with transplanted NCTC-2472 sarcoma cells. When analyzed in vitro , these cells were capable of degrading the protein component of surface-labeled bone slices in a process dependent on MMP activity and uPARAP/Endo180. Systemic treatment of the sarcoma-inoculated mice with a mouse monoclonal antibody that blocks murine uPARAP/Endo180 led to a strong reduction of bone destruction. Our findings identify sarcoma cell-resident uPARAP/Endo180 as a central player in the bone degeneration of advanced tumors, possibly following an osteoclast-mediated attack on bone in the early tumor stage. This points to uPARAP/Endo180 as a promising therapeutic target in osteosarcoma with particular prospects for improved neoadjuvant therapy.