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Acquired drug resistance and metastasis in breast cancer (BC) are coupled with epigenetic deregulation of gene expression. Epigenetic drugs, aiming to reverse these aberrant transcriptional patterns and sensitize cancer cells to other therapies, provide a new treatment strategy for drug-resistant tumors. Here we investigated the ability of DNA methyltransferase (DNMT) inhibitor decitabine (DAC) to increase the sensitivity of BC cells to anthracycline antibiotic doxorubicin (DOX). Three cell lines representing different molecular BC subtypes, JIMT-1, MDA-MB-231 and T-47D, were used to evaluate the synergy of sequential DAC + DOX treatment in vitro. The cytotoxicity, genotoxicity, apoptosis, and migration capacity were tested in 2D and 3D cultures. Moreover, genome-wide DNA methylation and transcriptomic analyses were employed to understand the differences underlying DAC responsiveness. The ability of DAC to sensitize trastuzumab-resistant HER2-positive JIMT-1 cells to DOX was examined in vivo in an orthotopic xenograft mouse model. DAC and DOX synergistic effect was identified in all tested cell lines, with JIMT-1 cells being most sensitive to DAC. Based on the whole-genome data, we assume that the aggressive behavior of JIMT-1 cells can be related to the enrichment of epithelial-to-mesenchymal transition and stemness-associated pathways in this cell line. The four-week DAC + DOX sequential administration significantly reduced the tumor growth, DNMT1 expression, and global DNA methylation in xenograft tissues. The efficacy of combination therapy was comparable to effect of pegylated liposomal DOX, used exclusively for the treatment of metastatic BC. This work demonstrates the potential of epigenetic drugs to modulate cancer cells' sensitivity to other forms of anticancer therapy.
2022
The modified Target Diagram (MTD) was developed to evaluate the performance of low-cost sensors (LCS) for air quality monitoring in comparison with reference methods by reporting relative expanded uncertainty and its contributors. An MTD provides several pieces of information, including compliance with regulation, sources of error and how to diminish them, completeness and validity of LCS calibration etc. It allows the user to examine the effect of selecting different regression types and residual fitting on the LCS measurement uncertainty. The ordinary least squared regression with fitted residuals and dynamic between reference analyser uncertainty rather than constant ones yielded more realistic LCS measurement uncertainty compared to other options. The MTD is a fast visual tool to extract several pieces of information on evaluation of any candidate method against reference method.
2022
Northern Fulmars (Fulmarus glacialis) are a pelagic seabird species distributed at northern and polar latitudes. They are often used as an indicator of plastic pollution in the North Sea region, but data are lacking from higher latitudes, especially when it comes to chicks. Here, we investigated amounts of ingested plastic and their characteristics in fulmar chicks from the Faroe Islands. Plastic particles (≥1 mm) in chicks of two age classes were searched using a digestion method with KOH. In addition, to evaluate if additive tissue burden reflects plastic ingestion, we measured liver tissue concentrations of two pollutant classes associated with plastic materials: polybrominated diphenyl ethers (PBDEs) and several dechloranes, using gas chromatography with high-resolution mass spectrometry. The most common shape was hard fragment (81%) and the most common polymer was polyethylene (73%). Plastic contamination did not differ between either age class, and we found no correlation between neither the amount and mass of plastic particles and the concentration of additives. After comparison with previous studies on adult fulmars, we do not recommend using chicks for biomonitoring adults because chicks seem to ingest more plastics than adults.
2022
Plastic burdens in northern fulmars from Svalbard: looking back 25 years
The northern fulmar Fulmarus glacialis ingests a larger number of (micro)plastics than many other seabirds due to its feeding habits and gut morphology. Since 2002, they are bioindicators of marine plastics in the North Sea region, and data are needed to extend the programme to other parts of their distribution areas, such as the Arctic. In this study, we provide data on ingested plastics by fulmars collected in 1997 in Kongsfjorden, Svalbard. An extraction protocol with KOH was used and for half of the birds, the gizzard and the proventricular contents were analysed separately. Ninety-one percent of the birds had ingested at least one piece of plastic with an average of 10.3 (±11.9 SD) pieces. The gizzards contained significantly more plastics than the proventriculus. Hard fragments and polyethylene were the most common characteristics. Twelve percent of the birds exceeded the EcoQO value of 0.1 g.
2022
2022
2022
Based on the hourly output from the 2000–2014 simulations of the National Center for Atmospheric Research's vertically extended version of the Whole Atmosphere Community Climate Model in specified dynamics configuration, we examine the roles of planetary waves (PWs), gravity waves, and atmospheric tides in driving the mean meridional circulation (MMC) in the lower thermosphere (LT) and its response to the sudden stratospheric warming phenomenon with an elevated stratopause in the northern hemisphere. Sandwiched between the two summer-to-winter overturning circulations in the mesosphere and the upper thermosphere, the climatological LT MMC is a narrow gyre that is characterized by upwelling in the middle winter latitudes, equatorward flow near 120 km, and downwelling in the middle and high summer latitudes. Following the onset of the sudden stratospheric warmings, this gyre reverses its climatological direction, resulting in a “chimney-like” feature of un-interrupted polar descent from the altitude of 150 km down to the upper mesosphere. This reversal is driven by the westward-propagating PWs, which exert a brief but significant westward forcing between 70 and 125 km, exceeding gravity wave and tidal forcings in that altitude range. The attendant polar descent potentially leads to a short-lived enhanced transport of nitric oxide into the mesosphere (with excess in the order of 1 parts per million), while carbon dioxide is decreased.
2022
2022
2022
High-Resolution Emissions from Wood Burning in Norway—The Effect of Cabin Emissions
Emissions from wood burning for heating in secondary homes or cabins is an important part in the development of high-resolution emissions in specific areas. Norway is used as case study as 20% of the national wood consumption for heating occurs in cabins. Our study first shows a method to estimate emissions from cabins based on traffic data to derive cabin occupancy, which combined with heating need allows for the spatial and temporal distribution of emissions. The combination of residential (RWC) and cabin wood combustion (CWC) emissions shows large spatial and temporal differences, and a temporally “cabin population” can in areas be orders of magnitude larger than the registered population. While RWC emissions have been steadily reduced, CWC have kept relatively constant or even increased, which results in an increase in the cabin share to total heating emissions up to 25–35%. When comparing with regional emission inventories, our study shows that the gradient between rural and urban areas is not well-represented in regional inventories, which resembles a population-based distribution and does not allocate emissions in cabin municipalities. CWC emissions may become an increasing environmental concern as higher densification trends in mountain areas are observed.
2022
To assess how climate-sensitive factors may affect the exposure to organochlorines (OCs) and perfluoroalkyl substances (PFASs), we monitored concentrations in eggs of the common goldeneye (Bucephala clangula) over two decades (1999–2019) in central Norway. The goldeneye alternates between marine and freshwater habitats and is sensitive to climate variation, especially due to alterations in ice conditions which may affect feeding conditions. We assessed how biological factors such as diet (stable isotopes δ13C and δ15N), the onset of egg laying, and physical characteristics such as winter climate (North Atlantic Oscillation: NAOw) influenced exposure. We predicted compounds to show different temporal trends depending on whether they were still in production (i.e. some PFASs) or have been banned (i.e. legacy OCs and some PFASs). Therefore, we controlled for potential temporal trends in all analyses. There were declining trends for α- and γ-hexachlorocyclohexane (HCH), oxychlordane, cis-chlordane, cis-nonachlor, p,p′-dichlorodiphenyltrichloroethane (p.p′-DDT) and less persistent polychlorinated biphenyl (PCB) congeners (e.g. PCB101). In contrast, the dominant compounds, such as p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and persistent PCB congeners, were stable, whereas hexachlorobenzene (HCB) increased over time. Most OCs were positively related to δ15N, suggesting higher exposure in birds feeding at upper trophic levels. Chlordanes and HCB were positively associated with δ13C, indicating traces of marine input for these compounds, whereas the relationships to most PCBs were negative. Among PFASs, perfluorooctanesulfonamide (PFOSA) and perfluorohexane sulfonic acid (PFHxS) declined. Most PFASs were positively associated with δ13C, whereas there were no associations with δ15N. Egg laying date was positively associated to perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), suggesting that some of the PFAS load originated from the wintering locations. Although NAOw had little impact on the exposure to organohalogenated contaminants, factors sensitive to climate change, especially diet, were associated with the exposure to OHCs in goldeneyes.
2022
2022
Anthropogenic activities are introducing multiple chemical contaminants into ecosystems that act as stressors for wildlife. Perfluoroalkyl substances (PFAS) and mercury (Hg) are two relevant contaminants that may cause detrimental effects on the fitness of many aquatic organisms. However, there is a lack of information on their impact on the expression of secondary sexual signals that animals use for mate choice. We have explored the correlations between integument carotenoid-based colourations, blood levels of carotenoids, and blood levels of seven PFAS and of total Hg (THg) in 50 adult male black-legged kittiwakes (Rissa tridactyla) from the Norwegian Arctic during the pre-laying period, while controlling for other colouration influencing variables such as testosterone and body condition. Kittiwakes with elevated blood concentrations of PFAS (PFOSlin, PFNA, PFDcA, PFUnA, or PFDoA) had less chromatic but brighter bills, and brighter gape and tongue; PFOSlin was the pollutant with the strongest association with bill colourations. Conversely, plasma testosterone was the only significant correlate of hue and chroma of both gape and tongue, and of hue of the bill. Kittiwakes with higher concentrations of any PFAS, but not of THg, tended to have significantly higher plasma concentrations of the carotenoids astaxanthin, zeaxanthin, lutein, and cryptoxanthin. Our work provides the first correlative evidence that PFAS exposure might interfere with the carotenoid metabolism and the expression of integument carotenoid-based colourations in a free-living bird species. This outcome may be a direct effect of PFAS exposure or be indirectly caused by components of diet that also correlate with elevated PFAS concentrations (e.g., proteins). It also suggests that there might be no additive effect of THg co-exposure with PFAS on the expression of colourations. These results call for further work on the possible interference of PFAS with the expression of colourations used in mate choice.
2022
2022
Common Considerations for Genotoxicity Assessment of Nanomaterials
Genotoxicity testing is performed to determine potential hazard of a chemical or agent for direct or indirect DNA interaction. Testing may be a surrogate for assessment of heritable genetic risk or carcinogenic risk. Testing of nanomaterials (NM) for hazard identification is generally understood to require a departure from normal testing procedures found in international standards and guidelines. A critique of the genotoxicity literature in Elespuru et al., 2018, reinforced evidence of problems with genotoxicity assessment of nanomaterials (NM) noted by many previously. A follow-up to the critique of problems (what is wrong) is a series of methods papers in this journal designed to provide practical information on what is appropriate (right) in the performance of genotoxicity assays altered for NM assessment. In this “Common Considerations” paper, general considerations are addressed, including NM characterization, sample preparation, dosing choice, exposure assessment (uptake) and data analysis that are applicable to any NM genotoxicity assessment. Recommended methods for specific assays are presented in a series of additional papers in this special issue of the journal devoted to toxicology methods for assessment of nanomaterials: the In vitro Micronucleus Assay, TK Mutagenicity assays, and the In vivo Comet Assay. In this context, NM are considered generally as insoluble particles or test articles in the nanometer size range that present difficulties in assessment using techniques described in standards such as OECD guidelines.
2022
Here we provide an overview of the newly commenced project ‘ReGAME - Reliable Global Methane Emissions estimates in a changing world’, funded by Research Council of Norway from 2021-2025, where we combine new developments in atmospheric methane observations: isotopic ratios (deuterium and 13C in methane), and the Integrated Carbon Observation System (ICOS) ground-based station network with atmospheric models (the chemistry transport model OsloCTM, and inversion model FLEXINVERT) to understand how and why atmospheric methane levels are increasing. The project has a particular focus on understanding the state of Arctic methane reservoirs such as ocean seeps and high latitude wetlands. This includes plans for a new observing system aboard the ice breaking vessel RV Kronprins Haakon and ocean observations, e.g., dynamics of Seep fluxes assessed during 1 year of continuous measurements at a seep site the NorEMSO project, updated information on spatial seep distribution via echo sounding, as well as high resolution high-latitude inversion modeling of atmospheric methane with FLEXINVERT. Furthermore, we investigate the utility of including of satellite data (TROPOMI aboard the Sentinel 5P mission) together with ground-based data, in inversion modeling. The inclusion of satellite data into inversion models is quite novel and offers rewards by increasing spatial coverage compared to ground based networks alone, potentially reducing uncertainties in the model outputs, and challenges due to satellite data uncertainties, spatial/ temporal coverage, and handling large data fields
2022
2022
Monitoring of long-range transported air pollutants in Norway. Annual Report 2021.
This report presents results from the monitoring of atmospheric composition and deposition of air pollution in 2021, and focuses on main components in air and precipitation, particulate and gaseous phase of inorganic constituents, particulate carbonaceous matter, ground level ozone and particulate matter. The level of pollution in 2021 was generally low with few high episodes.
NILU
2022
Advanced in vitro models are needed to support next-generation risk assessment (NGRA), moving from hazard assessment based mainly on animal studies to the application of new alternative methods (NAMs). Advanced models must be tested for hazard assessment of nanomaterials (NMs). The aim of this study was to perform an interlaboratory trial across two laboratories to test the robustness of and optimize a 3D lung model of human epithelial A549 cells cultivated at the air–liquid interface (ALI). Potential change in sensitivity in hazard identification when adding complexity, going from monocultures to co- and tricultures, was tested by including human endothelial cells EA.hy926 and differentiated monocytes dTHP-1. All models were exposed to NM-300K in an aerosol exposure system (VITROCELL® cloud-chamber). Cyto- and genotoxicity were measured by AlamarBlue and comet assay. Cellular uptake was investigated with transmission electron microscopy. The models were characterized by confocal microscopy and barrier function tested. We demonstrated that this advanced lung model is applicable for hazard assessment of NMs. The results point to a change in sensitivity of the model by adding complexity and to the importance of detailed protocols for robustness and reproducibility of advanced in vitro models
2022