Fant 10001 publikasjoner. Viser side 52 av 401:
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.
2022
2022
Disentangling Aerosol and Cloud effects on Dimming and Brightening in Observations and CMIP6
Periods of dimming and brightening have been recorded in observational datasets of surface solar radiation (SSR) between the mid-20th century and present day. Atmospheric components affect SSR, including aerosols and clouds, though studies disagree somewhat about the relative effect of each component in different regions. Current Earth system models (ESMs) are unable to simulate observed trends in SSR. This study includes an investigation into observed SSR variations between 1961 and 2014 and an evaluation of the effects of cloud cover variations and impacts of aerosol extinction, using timeseries of SSR and cloud cover from in-situ measurements. Historical simulations by 42 ESMs participating in the Coupled Model Intercomparison Project Phase 6 (CMIP6) have also been studied and compared to observations. The observational study indicates that cloud cover has had a dampening effect on the variations of SSR and that emissions of aerosol and aerosol precursors are the main cause of the general trends in observed SSR in four regions—China, Japan, Europe and the United States—during 1961-2014. The study of simulated SSR in CMIP6 yields the conclusion that current ESMs remain unable to simulate the magnitude of observed dimming and brightening in China, Japan and the United States, but that the European SSR trends between 1961 and 2014 are fairly well reproduced in the ESMs. A rough quantification of the regional surface radiation extinction efficiency of aerosol and precursor emissions in the simulations is found to agree with observed values in Europe, but not in the other three regions.
2022
The Screening Programme 2021 was carried out by the Norwegian Institute for Water Research (NIVA) and NILU-Norwegian Institute for Air Research. The spotlight was placed on the occurrence and possible environmental problems of 218 chemicals. The selected substances may be included in numerous products and their usage patterns are not easily defined so an array of different locations and sample-types were investigated. The total number of results exceeds 26 000. Results are can be downloaded from the database Vannmiljø.
Norsk institutt for vannforskning (NIVA)
2022
Human adaptation to climate change is the outcome of long-term decisions continuously made and revised by local communities. Adaptation choices can be represented by economic investment models in which the often large upfront cost of adaptation is offset by the future benefits of avoiding losses due to future natural hazards. In this context, we investigate the role that expectations of future natural hazards have on adaptation in the Colorado River basin of the USA. We apply an innovative approach that quantifies the impacts of changes in concurrent climate extremes, with a focus on flooding events. By including the expectation of future natural hazards in adaptation models, we examine how public policies can focus on this component to support local community adaptation efforts. Findings indicate that considering the concurrent distribution of several variables makes quantification and prediction of extremes easier, more realistic, and consequently improves our capability to model human systems adaptation. Hazard expectation is a leading force in adaptation. Even without assuming increases in exposure, the Colorado River basin is expected to face harsh increases in damage from flooding events unless local communities are able to incorporate climate change and expected increases in extremes in their adaptation planning and decision making.
2022
2022
Background
The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.
Results
The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).
Conclusions
The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
2022
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2022
What caused a record high PM10 episode in northern Europe in October 2020?
In early October 2020, northern Europe experienced an episode with poor air quality due to high concentrations of particulate matter (PM). At several sites in Norway, recorded weekly values exceeded historical maximum PM10 concentrations from the past 4 to 10 years. Daily mean PM10 values at Norwegian sites were up to 97 µg m−3 and had a median value of 59 µg m−3. We analysed this severe pollution episode caused by long-range atmospheric transport based on surface and remote sensing observations and transport model simulations to understand its causes. Samples from three sites in mainland Norway and the Arctic remote station Zeppelin (Svalbard) showed strong contributions from mineral dust to PM10 (23 %–36 % as a minimum and 31 %–45 % as a maximum) and biomass burning (8 %–16 % to 19 %–21 %). Atmospheric transport simulations indicate that Central Asia was the main source region for mineral dust observed in this episode. The biomass burning fraction can be attributed to forest fires in Ukraine and southern Russia, but we cannot exclude other sources contributing, like fires elsewhere, because the model underestimates observed concentrations. The combined use of remote sensing, surface measurements, and transport modelling proved effective in describing the episode and distinguishing its causes.
2022
2022
2022
Multisensory Representation of Air Pollution in Virtual Reality: Lessons from Visual Representation
The world is facing the problem of anthropogenic climate
change and air pollution. Despite many years of development, already
established methods of influencing behaviour remain ineffective. The
effect of such interventions is very often a declaration of behaviour change
that is not followed by actual action. Moreover, despite intensive informa-
tion campaigns, many people still do not have adequate knowledge on the
subject, are not aware of the problem or, worse, deny its existence. Pre-
vious attempts to introduce real change were based on providing infor-
mation, persuasion or visualisation. We propose the use of multi-sensory
virtual reality to investigate the problem more thoroughly and then design
appropriate solutions. In this paper, we introduce a new immersive virtual
environment that combines free exploration with a high level of experi-
mental control, physiological and behavioural measures. It was created on
the basis of transdisciplinary scientific cooperation, participatory design
and research. We used the unique features of virtual environments to
reverse and expand the idea of pollution pods by Pinsky. Instead of closing
participants in small domes filled with chemical substances imitating pol-
lution, we made it possible for them to freely explore an open environment
- admiring the panorama of a small town from the observation deck located
on a nearby hill. Virtual reality technology enables the manipulation of
representations of air pollution, the sensory modalities with which they are
transmitted (visual, auditory, tactile and smell stimuli) and their intensity.
Participants’ reactions from the initial tests of the application showed that
it is a promising solution. We present the possibilities of applying the new
solution in psychological research and its further design and development
opportunities in collaboration with communities and other stakeholders
in the spirit of citizen science.
2022
2022
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2022
This report aims to support the on-going revision of the Ambient Air Quality Directives by providing a series of recommendations on the reciprocal exchange of information and reporting of ambient air quality (e-reporting) following the Commission Implementing Decision (2011/850/EU). It builds on the experience and understanding from the EEA and technical experts at its European Topic Centre for Human Health and the Environment (ETC HE) working with implementing provisions for reporting (IPR) and identifies areas for further efficiency gains in e-reporting, in particular concerning the H-K dataflows.
ETC/HE
2022