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The way Norway is spearheading electrification in the transport sector is of global interest. In this study, we used the Norwegian Emissions from Road Vehicle Exhaust (NERVE) model, a bottom-up high-resolution traffic emission model, to calculate all emissions in Norway (2009–2020) and evaluate potential co-benefit and trade-offs of policies to target climate change mitigation, air quality and socioeconomic factors. Results for municipal data with regard to traffic growth, road network influences, vehicle composition, emissions and energy consumption are presented. Light vehicle CO2 emissions per kilometer have been reduced by 22% since 2009, mainly driven by an increasing bio-fuel mixing and battery electric vehicles (BEV) share. BEVs are mostly located in and around the main cities, areas with young vehicle fleets, and strong local incentives. Beneficiaries of BEVs incentives have been a subset of the population with strong economic indicators. The incentivized growth in the share of diesel-fuelled passenger vehicles has been turned, and together with Euro6 emission standards, light vehicle NOx emissions have been halved since peaking in 2014. BEVs represent an investment in emission reductions in years to come, and current sales set Norway up for an accelerated decline in all exhaust emissions despite the continual growth in traffic.
MDPI
2022
2024
Decitabine (DAC), a DNA methyltransferase (DNMT) inhibitor, is tested in combination with conventional anticancer drugs as a treatment option for various solid tumors. Although epigenome modulation provides a promising avenue in treating resistant cancer types, more studies are required to evaluate its safety and ability to normalize the aberrant transcriptional profiles. As deoxycytidine kinase (DCK)-mediated phosphorylation is a rate-limiting step in DAC metabolic activation, we hypothesized that its intracellular overexpression could potentiate DAC’s effect on cell methylome and thus increase its therapeutic efficacy. Therefore, two breast cancer cell lines, JIMT-1 and T-47D, differing in their molecular characteristics, were transfected with a DCK expression vector and exposed to low-dose DAC (approximately IC20). Although transfection resulted in a significant DCK expression increase, further enhanced by DAC exposure, no transfection-induced changes were found at the global DNA methylation level or in cell viability. In parallel, an integrative approach was applied to decipher DAC-induced, methylation-mediated, transcriptomic reprogramming. Besides large-scale hypomethylation, accompanied by up-regulation of gene expression across the entire genome, DAC also induced hypermethylation and down-regulation of numerous genes in both cell lines. Interestingly, TET1 and TET2 expression halved in JIMT-1 cells after DAC exposure, while DNMTs’ changes were not significant. The protein digestion and absorption pathway, containing numerous collagen and solute carrier genes, ranking second among membrane transport proteins, was the top enriched pathway in both cell lines when hypomethylated and up-regulated genes were considered. Moreover, the calcium signaling pathway, playing a significant role in drug resistance, was among the top enriched in JIMT-1 cells. Although low-dose DAC demonstrated its ability to normalize the expression of tumor suppressors, several oncogenes were also up-regulated, a finding, that supports previously raised concerns regarding its broad reprogramming potential. Importantly, our research provides evidence about the involvement of active demethylation in DAC-mediated transcriptional reprogramming.
Frontiers Media S.A.
2022
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.
Elsevier
2022
Dechloranes and chlorinated paraffins in sediments and biota of two subarctic lakes
Our understanding of the environmental behavior, bioaccumulation and concentrations of chlorinated paraffins (CPs) and Dechloranes (Dec) in the Arctic environment is still limited, particularly in freshwater ecosystems. In this descriptive study, short chain (SCCPs) and medium chain (MCCPs) CPs, Dechlorane Plus (DP) and analogues, and polychlorinated biphenyls (PCBs) were measured in sediments, benthic organisms, three-spined stickleback (Gasterosteus aculeatus), Arctic char (Salvelinus alpinus) and brown trout (Salmo trutta) in two Sub-Arctic lakes in Northern Norway. Takvannet (TA) is a remote lake, with no known local sources for organic contaminants, while Storvannet (ST) is situated in a populated area. SCCPs and MCCPs were detected in all sediment samples from ST with concentration of 42.26–115.29 ng/g dw and 66.18–136.69 ng/g dw for SCCPs and MCCPs, respectively. Only SCCPs were detected in TA sediments (0.4–5.28 ng/g dw). In biota samples, sticklebacks and benthic organisms showed the highest concentrations of CPs, while concentrations were low or below detection limits in both char and trout. The congener group patterns observed in both lakes showed SCCP profiles dominated by higher chlorinated congener groups while the MCCPs showed consistency in their profiles, with C14 being the most prevalent carbon chain length. Anti- and syn-DP isomers were detected in all sediment, benthic and stickleback samples with higher concentrations in ST than in TA. However, they were only present in a few char and trout samples from ST. Dec 601 and 604 were below detection limits in all samples in both lakes. Dec 603 was detected only in ST sediments, sticklebacks and 2 trout samples, while Dec 602 was the only DP analogue found in all samples from both lakes. While there were clear differences in sediment concentrations of DP and Dec 602 between ST and TA, differences between lakes decreased with increasing δ15N. This pattern was similar to the PCB behavior, suggesting the lake characteristics in ST are playing an important role in the lack of biomagnification of pollutants in this lake. Our results suggest that ST receives pollutants from local sources in addition to atmospheric transport.
Frontiers Media S.A.
2024
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Datering av sediment og historisk utvikling av miljøgifter i Ellasjøen, Bjørnøya. Statlig program for forurensningsovervåking, Rapport 904/04.
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