| 1. |
- Ahrentorp, Fredrik, et al.
(författare)
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Sensitive magnetic biodetection using magnetic multi-core nanoparticles and RCA coils
- 2017
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Ingår i: Journal of Magnetism and Magnetic Materials. - : Elsevier BV. - 0304-8853 .- 1873-4766. ; 427, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- We use functionalized iron oxide magnetic multi-core particles of 100 nm in size (hydrodynamic particle diameter) and AC susceptometry (ACS) methods to measure the binding reactions between the magnetic nanoparticles (MNPs) and bio-analyte products produced from DNA segments using the rolling circle amplification (RCA) method. We use sensitive induction detection techniques in order to measure the ACS response. The DNA is amplified via RCA to generate RCA coils with a specific size that is dependent on the amplification time. After about 75 min of amplification we obtain an average RCA coil diameter of about 1 mu m. We determine a theoretical limit of detection (LOD) in the range of 11 attomole (corresponding to an analyte concentration of 55 fM for a sample volume of 200 mu L) from the ACS dynamic response after the MNPs have bound to the RCA coils and the measured ACS readout noise. We also discuss further possible improvements of the LOD.
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| 2. |
- Berglund, U. W., et al.
(författare)
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Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
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| 3. |
- Bergman, Åke, et al.
(författare)
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Science and policy on endocrine disrupters must not be mixed : a reply to a "common sense" intervention by toxicology journal editors
- 2013
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
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| 4. |
- Bhattacharya, K., et al.
(författare)
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Lactoperoxidase-mediated degradation of single-walled carbon nanotubes in the presence of pulmonary surfactant
- 2015
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Ingår i: Carbon. - : Elsevier BV. - 0008-6223 .- 1873-3891. ; 91, s. 506-517
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Tidskriftsartikel (refereegranskat)abstract
- Carbon nanotubes (CNTs) may elicit inflammatory responses following pulmonary exposure. Conversely, enzymatic biodegradation of CNTs by inflammatory cells has also been reported. The aim of this study was to study the degradation of oxidized single-walled CNTs (ox-SWCNTs) by lactoperoxidase (LPO), a secreted peroxidase present in the airways, and whether pulmonary surfactant affects this biodegradation. To this end, ox-SWCNTs were incubated in vitro with recombinant bovine LPO + H2O2 + NaSCN in the presence and absence of porcine lung surfactant (Curosurf®) and biodegradation was monitored using UV-Vis-NIR spectroscopy, Raman spectroscopy, and scanning electron microscopy. The interaction of recombinant LPO with bundles of ox-SWCNTs was confirmed by atomic force microscopy. Cell-free biodegradation of ox-SWCNTs was also observed ex vivo in murine bronchoalveolar lavage fluid in the presence of H2O2 + NaSCN. Our study provides evidence for biodegradation of ox-SWCNTs with a lung surfactant 'bio-corona' and expands the repertoire of mammalian peroxidases capable of biodegradation of ox-SWCNTs. These findings are relevant to inhalation exposure to these materials, as LPO serves as an important component of the airway defense system.
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| 5. |
- Cavallaro, Sara, et al.
(författare)
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Comparison and optimization of nanoscale extracellular vesicle imaging by scanning electron microscopy for accurate size-based profiling and morphological analysis
- 2021
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Ingår i: Nanoscale Advances. - : Royal Society of Chemistry. - 2516-0230. ; 3:11, s. 3053-3063
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Tidskriftsartikel (refereegranskat)abstract
- Nanosized extracellular vesicles (EVs) have been found to play a key role in intercellular communication, offering opportunities for both disease diagnostics and therapeutics. However, lying below the diffraction limit and also being highly heterogeneous in their size, morphology and abundance, these vesicles pose significant challenges for physical characterization. Here, we present a direct visual approach for their accurate morphological and size-based profiling by using scanning electron microscopy (SEM). To achieve that, we methodically examined various process steps and developed a protocol to improve the throughput, conformity and image quality while preserving the shape of EVs. The study was performed with small EVs (sEVs) isolated from a non-small-cell lung cancer (NSCLC) cell line as well as from human serum, and the results were compared with those obtained from nanoparticle tracking analysis (NTA). While the comparison of the sEV size distributions showed good agreement between the two methods for large sEVs (diameter > 70 nm), the microscopy based approach showed a better capacity for analyses of smaller vesicles, with higher sEV counts compared to NTA. In addition, we demonstrated the possibility of identifying non-EV particles based on size and morphological features. The study also showed process steps that can generate artifacts bearing resemblance with sEVs. The results therefore present a simple way to use a widely available microscopy tool for accurate and high throughput physical characterization of EVs.
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| 6. |
- de Alwis, Pahansen, 1980-, et al.
(författare)
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Exposure aboard high-performance Marine craft increases musculoskeletal pain and lowers contemporary work capacity of the occupants
- 2021
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Ingår i: Journal of Engineering for the Maritime Environment (Part M). - : SAGE Publications. - 1475-0902 .- 2041-3084. ; 235:3, s. 750-762
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Tidskriftsartikel (refereegranskat)abstract
- High-Performance Marine Craft (HPMC) occupants are currently being investigated for various psychophysical impairments degrading work performance postulating that these deteriorations are related to their occupational exposures. However, scientific evidence for this is lacking and the association of exposure conditions aboard HPMC with adverse health and performance effects is unknown. Therefore, the study estimates the prevalence of musculoskeletal pain (MSP) among HPMC occupants and the association of their work exposure with MSP and performance degradation. It also presents a criterion for evaluating the self-reported exposure severity aboard three different types of mono-hull HPMC; displacement, semi-displacement and planing, on a par with the available standard criteria for objectively measurable exposures. Furthermore, another criterion is proposed to assess the performance-degradation of HPMC occupants based on self-reported fatigue symptoms and MSP. Swedish Coast Guard HPMC occupants were surveyed for MSP, fatigue symptoms as well as for work-related and individual risk indicators using a validated web-based questionnaire. Prevalence of MSP and performance-degradation during the past 12 months were assessed and presented as a percentage of the sample. Associations of exposure conditions aboard HPMC with MSP and performance-capacity were systematically evaluated using multiple logistic regression models and expressed as odds ratio (OR). Prevalence of MSP was 72% among which lower back pain was the most prevalent (46%) followed by neck pain (29%) and shoulder pain (23%) while 29% with degraded performance. Exposure to severe conditions aboard semi-displacement craft was associated with lower back (OR = 2.3) and shoulder (OR = 2.6) pain while severe conditions aboard planing craft with neck pain (OR = 2.3) and performance-degradation (OR = 2.6). MSP is common among Swedish coast guards. Severe exposure conditions aboard HPMC are significantly associated with both MSP and performance-degradation. The spine and shoulders are the most susceptible to work-related MSP among HPMC occupants which should be targeted in work-related preventive and corrective measures.
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| 7. |
- Ehrenberg, M., et al.
(författare)
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Systems biology is taking off
- 2003
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 13, s. 2475-2484
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Garg, Neeraj, et al.
(författare)
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Chemoselective Probe Containing a Unique Bioorthogonal Cleavage Site for Investigation of Gut Microbiota Metabolism
- 2018
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Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773. ; 57:42, s. 13805-13809
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Tidskriftsartikel (refereegranskat)abstract
- While metabolites derived from gut microbiota metabolism have been linked to disease development in the human host, the chemical tools required for their detailed analysis and the discovery of biomarkers are limited. A unique and multifunctional chemical probe for mass spectrometric analysis, which contains p-nitrocinnamyloxycarbonyl as a new bioorthogonal cleavage site has been designed and synthesized. Coupled to magnetic beads, this chemical probe allows for straightforward extraction of metabolites from human samples and release under mild conditions. This isolation from the sample matrix results in significantly reduced ion suppression, an increased mass spectrometric sensitivity, and facilitates the detection of metabolites in femtomole quantities. The chemoselective probe was applied to the analysis of human fecal samples, resulting in the discovery of four metabolites previously unreported in this sample type and confirmation of the presence of medically relevant gut microbiota-derived metabolites.
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| 9. |
- Hallström, Elinor, et al.
(författare)
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Climate impact of alcohol consumption in Sweden
- 2018
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Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 201, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about the environmental impact of alcohol is limited and as an effect alcohol is often excluded from environmental studies of diets or included in incomplete ways. This paper describes the climate impact of beer, wine and liquor by using life cycle assessment. The climate impact is quantified per litre of specific alcoholic beverages and per total amount of alcohol consumed based on self-reported data of 50 000 individuals from 2009 within two population-based cohorts in Sweden. The results show that alcoholic beverages generate greenhouse gas (GHG) emissions in the range of 0.73–2.38 kg carbon dioxide equivalents (CO2e) per litre. Alcohol consumption in the population studied generates on average 52 kg CO2e per person and year. Within the 10% of the population with the highest intake of alcohol GHG emissions are up to 202 kg CO2e per person and year. Consumption of wine is responsible for the largest share of GHG emissions from alcoholic beverages (61%) followed by beer (33%), while liquor and strong wine account for a smaller share (6%). Alcohol consumption among men generates 90% higher GHG emissions than among women. Alcohol consumption and in consequence alcohol-related emissions are decreasing with increasing age of men and women. Our results indicate that alcohol consumption in Swedish men and women is responsible for an average of 3% of total diet-related GHG emissions and in sub-populations with the highest consumption up to 6–11%. Limiting alcohol could be an effective option to reduce the climate impact of diets, especially among men.
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| 10. |
- Hallström, Elinor, et al.
(författare)
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Dietary climate impact : Contribution of foods and dietary patterns by gender and age in a Swedish population
- 2021
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Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 306
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Tidskriftsartikel (refereegranskat)abstract
- Dietary climate impact in a Swedish population (56–95 years old) was estimated based on self-reported food intake from 50 000 men and women within two population-based cohorts and on climate data, covering emissions from farm to fork, for 600 foods representative for the Swedish market. Aims were to assess variation in dietary climate impact between population groups and between food categories. Mean dietary climate impact was 2.0 tons of CO2e/person/year, with about a threefold variation between high and low impact individuals. Food loss and waste accounted for 18%. Older individuals and women on average had lower total dietary climate impact per year, while differences between gender were smaller per 1000 kcal. Climate impact was greatly affected by dietary composition and especially by the content of animal-based and discretionary foods, responsible for 71% and 12% of total climate impact, respectively. Results indicate a large potential for reduced climate impact by adopting realistic dietary patterns. Suggested strategies to reach climate goals include reduction of red meat and prioritising lower impact foods within meat, dairy and seafood categories, limited consumption of discretionary foods and decreased over-consumption of total calories, combined with improvements in production including reduction of food loss and waste.
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