Isotopic provenancing of Pb in Mitrovica, northern Kosovo: source identification of chronic Pb enrichment in soils, house dust and scalp hair

Mitrovica, northern Kosovo, is the site of some of the highest Pb concentrations reported in human populations; exemplified by Pb concentrations in scalp hair of up to 130 μg g-1 and widely-publicized of Pb-related ill-health and mortality amongst internally displaced populations. High human Pb burdens are accompanied by elevated concentrations of potentially harmful elements (PHEs) in soils and house dust within the city, which has a long history of mining and metallurgy. In this study enrichment-levels for PHEs in soils are quantified and compared to environmental quality guidelines and a statistically-derived estimation of background concentration. In addition, Pb isotopes (207Pb/206Pb, 208Pb/206Pb) are used to characterise the isotopic signatures of potential point sources of Pb and a mixing model employed to quantify the contribution of sources to Pb present in soils, house dust, and the scalp hair of children and young people. Pb isotopic evidence suggests that Pb in surface soils and house-dust is predominantly sourced from historical deposition of Pb-containing aerosols from metal smelting, with lower contributions from wind-blown dispersal of metalliferous waste. Pb present in scalp hair is interpreted as the result of non-occupational exposure and the ingestion and/or inhalation of Pb-enriched surface soil and house dust. This study represents one of the very few instances where this type of geochemical tracing technique has been successfully applied to definitively identify the source of Pb present within biological samples. The results of this study are of particular relevance to environmental management and highlight the human health risk posed by the legacy of now inactive mining and metallurgy in addition to the challenge posed in mitigating the risk posed by diffuse soil pollution. © 2015 Elsevier Ltd

Validation of the TOLNet lidars: The Southern California Ozone Observation Project (SCOOP)

The North America-based Tropospheric Ozone Lidar Network (TOLNet) was recently established to provide high spatiotemporal vertical profiles of ozone, to better understand physical processes driving tropospheric ozone variability and to validate the tropospheric ozone measurements of upcoming spaceborne missions such as Tropospheric Emissions: Monitoring Pollution (TEMPO). The network currently comprises six tropospheric ozone lidars, four of which are mobile instruments deploying to the field a few times per year, based on campaign and science needs. In August 2016, all four mobile TOLNet lidars were brought to the fixed TOLNet site of JPL Table Mountain Facility for the 1-week-long Southern California Ozone Observation Project (SCOOP). This intercomparison campaign, which included 400¿h of lidar measurements and 18 ozonesonde launches, allowed for the unprecedented simultaneous validation of five of the six TOLNet lidars. For measurements between 3 and 10¿km¿a.s.l., a mean difference of 0.7¿ppbv (1.7¿%), with a root-mean-square deviation of 1.6¿ppbv or 2.4¿%, was found between the lidars and ozonesondes, which is well within the combined uncertainties of the two measurement techniques. The few minor differences identified were typically associated with the known limitations of the lidars at the profile altitude extremes (i.e., first 1¿km above ground and at the instruments' highest retrievable altitude). As part of a large homogenization and quality control effort within the network, many aspects of the TOLNet in-house data processing algorithms were also standardized and validated. This thorough validation of both the measurements and retrievals builds confidence as to the high quality and reliability of the TOLNet ozone lidar profiles for many years to come, making TOLNet a valuable ground-based reference network for tropospheric ozone profiling.Peer ReviewedPostprint (published version

CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy.

Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called 'don't eat me' signals-including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M)3. Monoclonal antibodies that antagonize the interaction of 'don't eat me' signals with their macrophage-expressed receptors have demonstrated therapeutic potential in several cancers4,5. However, variability in the magnitude and durability of the response to these agents has suggested the presence of additional, as yet unknown 'don't eat me' signals. Here we show that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. We demonstrate a role for tumour-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which is expressed by tumour-associated macrophages. We find that many tumours overexpress CD24 and that tumour-associated macrophages express high levels of Siglec-10. Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24-Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumour growth in vivo and an increase in survival time. These data reveal CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy

River sediment geochemistry and provenance following the Mount Polley mine tailings spill, Canada:The role of hydraulic sorting and sediment dilution processes in contaminant dispersal and remediation

The failure of the Mount Polley tailings storage facility (TSF) in August 2014 was one of the largest magnitude failures on record, and released approximately 25 Mm3 of material, including c. 7.3 Mm3 of tailings into Hazeltine Creek, part of the Quesnel River watershed. This study evaluates the impact of the spill on the geochemistry of river channel and floodplain sediments and utilizes Pb isotope ratios and a multi-variate mixing model to establish sediment provenance. In comparison to sediment quality guidelines and background concentrations, Cu and V were found to be most elevated. Copper in river channel sediments ranged from 88-800 mg kg-1, with concentrations in sand-rich and clay/silt-rich sediments being statistically significantly different. Concentrations in river channel were believed to be influenced by hydraulic sorting during the rising and falling limbs of the flood wave caused by the tailings spill. Results highlight the importance of erosive processes, instigated by the failure, in incorporating soils and sediments into the sediment load transported and deposited within Hazeltine Creek. In this instance, these processes diluted tailings with relatively clean material that reduced metal concentrations away from the TSF failure. This does however, highlight environmental risks in similar catchments downstream of TSFs that contain metal-rich sediment within river channels and floodplain that have been contaminated by historical mining

Origin and Fate of Vanadium in the Hazeltine Creek Catchment following the 2014 Mount Polley Mine Tailings Spill in British Columbia, Canada

This is the final version. Available on open access from American Chemical Society via the DOI in this recordResults are presented from the analysis of aqueous and solid-phase V speciation within samples collected from the Hazeltine Creek catchment affected by the August 2014 Mount Polley mine tailings dam failure, Canada. Electron microprobe and XANES analysis found that V is present as V3+ substituted into magnetite, and V3+ and V4+ substituted into titanite, both of which occur in the spilled Mount Polley tailings. Secondary Fe oxyhydroxides forming in inflow waters and on creek beds have V K-edge XANES spectra exhibiting E½ positions and pre-edge features consistent with the presence of V5+ species, suggesting sorption of this species on these secondary phases. PHREEQC modelling suggests that the stream waters mostly contain V5+, and the inflow and pore waters contain a mixture of V3+ and V5+. These data, and stream, inflow and pore water chemical data, suggest that dissolution of V(III)-bearing magnetite, V(III,IV)-bearing titanite, V(V)-bearing Fe(-Al-Si-Mn) oxhydroxides, V-bearing Al(OH)3 and/or -clay minerals may have occurred. In the circumneutral pH environment of Hazeltine Creek elevated V concentrations are likely naturally attenuated by formation of V(V)-bearing secondary Fe oxyhydroxide, Al(OH)3 or clay mineral colloids, suggesting that the V is not bioavailable. A conceptual model is presented describing the origin and fate of V in Hazeltine Creek that is applicable to other river systems.Natural Environment Research Council (NERC

APPL1 Associates with TrkA and GIPC1 and is Required for Nerve Growth Factor-Mediated Signal Transduction

The neurotrophin receptor TrkA plays critical roles in the nervous system by recruiting signaling molecules that activate pathways required for the growth and survival of neurons. Here, we report APPL1 as a TrkA-associated protein. APPL1 and TrkA coirnmunoprecipitated in sympathetic neurons. We have identified two routes through which this association can occur. APPL1 was isolated as a binding partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass spectrometry. The PDZ domain of GIPC1 directly engaged the C-terminal sequence of APPL1. This interaction provides a means through which APPL1 may be recruited to TrkA. In addition, the APPL1 PTB domain bound to TrkA, indicating that APPL1 may associate with TrkA independently of GIPC1. Isolation of endosomal fractions by high-resolution centrifugation determined that APPL1, GIPC1, and phosphorylated TrkA are enriched in the same fractions. Reduction of APPL1 or GIPC1 protein levels suppressed nerve growth factor (NGF)-dependent MEK, extracellular signal-regulated kinase, and AM activation and neurite outgrowth in PC12 cells. Together, these results indicate that GIPC1 and APPL1 play a role in TrkA function and suggest that a population of endosomes bearing a complex of APPL1, GIPC1, and activated TrkA may transmit NGF signals