Barium uptake into the shells of the common mussel (<i>Mytilus edulis</i>) and the potential for estuarine paleo-chemistry reconstruction

In this study we test if calcite shells of the common mussel, Mytilus edulis, contain barium in proportion to the water in which they grew. Similar to all bivalves analyzed to date, the [Ba/Ca]shell profiles are characterized by a relatively flat background [Ba/Ca]shell, interrupted by sharp [Ba/Ca]shell peaks. Previous studies have focused on these [Ba/Ca]shell peaks, but not on the background [Ba/Ca]shell. We show that in both laboratory and field experiments, there is a direct relationship between the background [Ba/Ca]shell and [Ba/Ca]water in M. edulis shells. The laboratory and field data provided background Ba/Ca partition coefficients (DBa) of 0.10 ± 0.02 and 0.071 ± 0.001, respectively. This range is slightly higher than the DBa previously determined for inorganic calcite, and slightly lower than foraminiferal calcite. These data suggest that M. edulis shells can be used as an indicator of [Ba/Ca]water, and therefore, fossil or archaeological M. edulis shells could be used to extend knowledge of estuarine dissolved Ba throughputs back in time. Moreover, considering the inverse relationship between [Ba/Ca]water and salinity, background [Ba/Ca]shell data could be used as an estuary specific indicator of salinity. The cause of the [Ba/Ca]shell peaks is more confusing, both the laboratory and field experiments indicate that they cannot be used as a direct proxy of [Ba/Ca]water or phytoplankton production, but may possibly be caused by barite ingestion

Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34+ progenitor cell-derived NK cells

Summary: Umbilical cord blood (UCB) CD34+ progenitor cell-derived natural killer (NK) cells exert efficient cytotoxicity against various melanoma cell lines. Of interest, the relative cytotoxic performance of individual UCB donors was consistent throughout the melanoma panel and correlated with IFNγ, TNF, perforin and granzyme B levels. Importantly, intrinsic perforin and Granzyme B load predicts NK cell cytotoxic capacity. Exploring the mode of action revealed involvement of the activating receptors NKG2D, DNAM-1, NKp30, NKp44, NKp46 and most importantly of TRAIL. Strikingly, combinatorial receptor blocking led to more pronounced inhibition of cytotoxicity (up to 95%) than individual receptor blocking, especially in combination with TRAIL-blocking, suggesting synergistic cytotoxic NK cell activity via engagement of multiple receptors which was also confirmed in a spheroid model. Importantly, lack of NK cell-related gene signature in metastatic melanomas correlates with poor survival highlighting the clinical significance of NK cell therapies as a promising treatment for high-risk melanoma patients