Spatio-Temporal Variability of Suspended Particulate Matter in a High-Arctic Estuary (Adventfjorden, Svalbard) Using Sentinel-2 Time-Series

Arctic coasts, which feature land-ocean transport of freshwater, sediments, and other terrestrial material, are impacted by climate change, including increased temperatures, melting glaciers, changes in precipitation and runoff. These trends are assumed to affect productivity in fjordic estuaries. However, the spatial extent and temporal variation of the freshwater-driven darkening of fjords remain unresolved. The present study illustrates the spatio-temporal variability of suspended particulate matter (SPM) in the Adventfjorden estuary, Svalbard, using in-situ field campaigns and ocean colour remote sensing (OCRS) via high-resolution Sentinel-2 imagery. To compute SPM concentration (CSPMsat), a semi-analytical algorithm was regionally calibrated using local in-situ data, which improved the accuracy of satellite-derived SPM concentration by ~20% (MRD). Analysis of SPM concentration for two consecutive years (2019, 2020) revealed strong seasonality of SPM in Adventfjorden. Highest estimated SPM concentrations and river plume extent (% of fjord with CSPMsat > 30 mg L−1) occurred during June, July, and August. Concurrently, we observed a strong relationship between river plume extent and average air temperature over the 24 h prior to the observation (R2 = 0.69). Considering predicted changes to environmental conditions in the Arctic region, this study highlights the importance of the rapidly changing environmental parameters and the significance of remote sensing in analysing fluxes in light attenuating particles, especially in the coastal Arctic Ocean.publishedVersio

Seasonal riverine inputs may affect diet and mercury bioaccumulation in Arctic coastal zooplankton

Climate change driven increases in permafrost thaw and terrestrial runoff are expected to facilitate the mobilization and transport of mercury (Hg) from catchment soils to coastal areas in the Arctic, potentially increasing Hg exposure of marine food webs. The main aim of this study was to determine the impacts of seasonal riverine inputs on land-ocean Hg transport, zooplankton diet and Hg bioaccumulation in an Arctic estuary (Adventfjorden, Svalbard). The Adventelva River was a source of dissolved and particulate Hg to Adventfjorden, especially in June and July during the river's main discharge period. Stable isotope and fatty acid analyses suggest that zooplankton diet varied seasonally with diatoms dominating during the spring phytoplankton bloom in May and with increasing contributions of dinoflagellates in the summer months. In addition, there was evidence of increased terrestrial carbon utilization by zooplankton in June and July, when terrestrial particles contributed substantially to the particulate organic matter pool. Total (TotHg) and methyl Hg (MeHg) concentrations in zooplankton increased from April to August related to increased exposure to riverine inputs, and to shifts in zooplankton diet and community structure. Longer and warmer summer seasons will probably increase riverine runoff and thus Hg exposure to Arctic zooplankton.Seasonal riverine inputs may affect diet and mercury bioaccumulation in Arctic coastal zooplanktonpublishedVersio

TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model

TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed. We have previously shown that TNF autovaccination successfully generates high anti-TNF antibody titres, blocks TNF and ameliorates collagen-induced arthritis in DBA/1 mice. In this study, we examined the ability of TNF autovaccination to generate anti-TNF antibody titres and block metastasis in the murine B16F10 melanoma model. We found that immunisation of C57BL/6 mice with TNF autovaccine produces a 100-fold antibody response to TNF compared to immunisation with phosphate-buffered saline vehicle control and significantly reduces both the number (P<0.01) and size of metastases (P<0.01) of B16F10 melanoma cells. This effect is also observed when an anti-TNF neutralising monoclonal antibody is administered, confirming the essential role TNF plays in metastasis in this model. This study suggests that TNF autovaccination is a cheaper and highly efficient alternative that can block TNF and reduce metastasis in vivo and trials with TNF autovaccination are already underway in patients with metastatic cancer

Is less more? Lessons from aptamer selection strategies

Aptamers have many inherent advantages originating from their in vitro selection and tailored chemical synthesis that makes them appealing alternatives of antibodies in bioaffinity assays. However, what ultimately matters, and that is the prerequisite to give way to all these advantages, is how well, and how selectively the aptamers bind to their targets. With the aptamer selection largely in the hand of life scientists, analytical chemists focused mostly on methodological development of aptamer-based assays using a fairly restricted number of aptamers to prove their concepts. However, ideally the development of an aptamer-based assay should start from the selection of aptamers to ensure their proper functionality in real samples. For instance information on the sample matrix can be implemented within counter-selection steps to discard aptamer candidates that show cross-reactivity to matrix components or critical interferents. In general, a larger consideration of the analytical use during selection and characterization of aptamers have been shown to increase the applicability of aptamers. Therefore, this review is a short, subjective view on trends in aptamer development highlighting factors to consider during their selection for a successful analytical application

Improved environmental status : 50 years of declining fish mercury levels in boreal and subarctic Fennoscandia

Temporally (1965–2015) and spatially (55°–70°N) extensive records of total mercury (Hg) in freshwater fish showed consistent declines in boreal and subarctic Fennoscandia. The database contains 54 560 fish entries (n: pike > perch ≫ brown trout > roach ≈ Arctic charr) from 3132 lakes across Sweden, Finland, Norway, and Russian Murmansk area. 74% of the lakes did not meet the 0.5 ppm limit to protect human health. However, after 2000 only 25% of the lakes exceeded this level, indicating improved environmental status. In lakes where local pollution sources were identified, pike and perch Hg concentrations were significantly higher between 1965 and 1990 compared to values after 1995, likely an effect of implemented reduction measures. In lakes where Hg originated from long-range transboundary air pollution (LRTAP), consistent Hg declines (3–7‰ per year) were found for perch and pike in both boreal and subarctic Fennoscandia, suggesting common environmental controls. Hg in perch and pike in LRTAP lakes showed minimal declines with latitude, suggesting that drivers affected by temperature, such as growth dilution, counteracted Hg loading and food web exposure. We recommend that future fish Hg monitoring sampling design should include repeated sampling and collection of pollution history, water chemistry, fish age, and stable isotopes to enable evaluation of emission reduction policies

Systems analysis of apoptosis protein expression allows the case-specific prediction of cell death responsiveness of melanoma cells.

Many cancer entities and their associated cell line models are highly heterogeneous in their responsiveness to apoptosis inducers and, despite a detailed understanding of the underlying signaling networks, cell death susceptibility currently cannot be predicted reliably from protein expression profiles. Here, we demonstrate that an integration of quantitative apoptosis protein expression data with pathway knowledge can predict the cell death responsiveness of melanoma cell lines. By a total of 612 measurements, we determined the absolute expression (nM) of 17 core apoptosis regulators in a panel of 11 melanoma cell lines, and enriched these data with systems-level information on apoptosis pathway topology. By applying multivariate statistical analysis and multi-dimensional pattern recognition algorithms, the responsiveness of individual cell lines to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or dacarbazine (DTIC) could be predicted with very high accuracy (91 and 82% correct predictions), and the most effective treatment option for individual cell lines could be pre-determined in silico. In contrast, cell death responsiveness was poorly predicted when not taking knowledge on protein-protein interactions into account (55 and 36% correct predictions). We also generated mathematical predictions on whether anti-apoptotic Bcl-2 family members or x-linked inhibitor of apoptosis protein (XIAP) can be targeted to enhance TRAIL responsiveness in individual cell lines. Subsequent experiments, making use of pharmacological Bcl-2/Bcl-xL inhibition or siRNA-based XIAP depletion, confirmed the accuracy of these predictions. We therefore demonstrate that cell death responsiveness to TRAIL or DTIC can be predicted reliably in a large number of melanoma cell lines when investigating expression patterns of apoptosis regulators in the context of their network-level interplay. The capacity to predict responsiveness at the cellular level may contribute to personalizing anti-cancer treatments in the future

NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer

The most lethal aspects of gastric adenocarcinoma (GA) are its invasive and metastatic properties. This aggressive phenotype remains poorly understood. We have recently identified neuroepithelial cell transforming gene 1 (NET1), a guanine exchange factor (GEF), as a novel GA-associated gene. Neuroepithelial cell transforming gene 1 expression is enhanced in GA and it is of functional importance in cell invasion. In this study, we demonstrate the activity of NET1 in driving cytoskeletal rearrangement, a key pathological mechanism in gastric tumour cell migration and invasion. Neuroepithelial cell transforming gene 1 expression was increased 10-fold in response to treatment with lysophosphatidic acid (LPA), resulting in an increase in active levels of RhoA and a 2-fold increase in cell invasion. Lysophosphatidic acid-induced cell invasion and migration were significantly inhibited using either NET1 siRNA or a RhoA inhibitor (C3 exoenzyme), thus indicating the activity of both NET1 and RhoA in gastric cancer progression. Furthermore, LPA-induced invasion and migration were also significantly reduced in the presence of cytochalasin D, an inhibitor of cytoskeletal rearrangements. Neuroepithelial cell transforming gene 1 knockdown resulted in AGS cell rounding and a loss of actin filament organisation, demonstrating the function of NET1 in actin organisation. These data highlight the importance of NET1 as a driver of tumour cell invasion, an activity mediated by RhoA activation and cytoskeletal reorganisation