| 41. |
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| 42. |
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| 43. |
- Rahman, Mizanur, et al.
(author)
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Comparable response following exposure to biodiesel and diesel exhaust particles in advanced multicellular human lung models
- 2023
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In: Toxics. - : MDPI. - 2305-6304. ; 11:6
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Journal article (peer-reviewed)abstract
- Biodiesel is considered to be a sustainable alternative for fossil fuels such as petroleum-based diesel. However, we still lack knowledge about the impact of biodiesel emissions on humans, as airways and lungs are the primary target organs of inhaled toxicants. This study investigated the effect of exhaust particles from well-characterized rapeseed methyl ester (RME) biodiesel exhaust particles (BDEP) and petro-diesel exhaust particles (DEP) on primary bronchial epithelial cells (PBEC) and macrophages (MQ). The advanced multicellular physiologically relevant bronchial mucosa models were developed using human primary bronchial epithelial cells (PBEC) cultured at air–liquid interface (ALI) in the presence or absence of THP-1 cell-derived macrophages (MQ). The experimental set-up used for BDEP and DEP exposures (18 µg/cm2 and 36 µg/cm2) as well as the corresponding control exposures were PBEC-ALI, MQ-ALI, and PBEC co-cultured with MQ (PBEC-ALI/MQ). Following exposure to both BDEP and DEP, reactive oxygen species as well as the stress protein heat shock protein 60 were upregulated in PBEC-ALI and MQ-ALI. Expression of both pro-inflammatory (M1: CD86) and repair (M2: CD206) macrophage polarization markers was increased in MQ-ALI after both BDEP and DEP exposures. Phagocytosis activity of MQ and the phagocytosis receptors CD35 and CD64 were downregulated, whereas CD36 was upregulated in MQ-ALI. Increased transcript and secreted protein levels of CXCL8, as well as IL-6 and TNF-α, were detected following both BDEP and DEP exposure at both doses in PBEC-ALI. Furthermore, the cyclooxygenase-2 (COX-2) pathway, COX-2-mediated histone phosphorylation and DNA damage were all increased in PBEC-ALI following exposure to both doses of BDEP and DEP. Valdecoxib, a COX-2 inhibitor, reduced the level of prostaglandin E2, histone phosphorylation, and DNA damage in PBEC-ALI following exposure to both concentrations of BDEP and DEP. Using physiologically relevant multicellular human lung mucosa models with human primary bronchial epithelial cells and macrophages, we found BDEP and DEP to induce comparable levels of oxidative stress, inflammatory response, and impairment of phagocytosis. The use of a renewable carbon-neutral biodiesel fuel does not appear to be more favorable than conventional petroleum-based alternative, as regards of its potential for adverse health effects.
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| 44. |
- Rankin, Gregory D., et al.
(author)
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Acute Exposure to Diesel Exhaust Increases Muscle Sympathetic Nerve Activity in Humans
- 2021
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In: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 10:10
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Journal article (peer-reviewed)abstract
- Background: Diesel exhaust (DE) emissions are a major contributor to ambient air pollution and are strongly associated with cardiovascular morbidity and mortality. Exposure to traffic-related particulate matter is linked with acute adverse cardiovascular events; however, the mechanisms are not fully understood. We examined the role of the autonomic nervous system during exposure to DE that has previously only been indirectly investigated.Methods and Results: Using microneurography, we measured muscle sympathetic nerve activity (MSNA) directly in the peroneal nerve of 16 healthy individuals. MSNA, heart rate, and respiration were recorded while subjects rested breathing filtered air, filtered air with an exposure mask, and standardized diluted DE (300 µg/m3) through the exposure mask. Heart rate variability was assessed from an ECG. DE inhalation rapidly causes an increase in number of MSNA bursts as well as the size of bursts within 10 minutes, peaking by 30 minutes (P<0.001), compared with baseline filtered air with an exposure mask. No significant changes occurred in heart rate variability indices during DE exposure; however, MSNA frequency correlated negatively with total power (r2=0.294, P=0.03) and low frequency (r2=0.258, P=0.045). Heart rate correlated positively with MSNA frequency (r2=0.268, P=0.04) and the change in percentage of larger bursts (burst amplitude, height >50% of the maximum burst) from filtered air with an exposure mask (r2=0.368, P=0.013).Conclusions: Our study provides direct evidence for the rapid modulation of the autonomic nervous system after exposure to DE, with an increase in MSNA. The quick increase in sympathetic outflow may explain the strong epidemiological data associating traffic-related particulate matter to acute adverse cardiovascular events such as myocardial infarction.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02892279.
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| 45. |
- Sandström, Alfred, et al.
(author)
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Collaborative research enhances selectivity in a lake fishery
- 2024
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In: Fisheries Management and Ecology. - : John Wiley & Sons. - 0969-997X .- 1365-2400.
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Journal article (peer-reviewed)abstract
- Size and species selectivity are crucial for developing sustainable fisheries. Our objective was to estimate the selectivity of whitefish fisheries in a large European lake through a collaboration of fishers, regional managers, and scientists. Fishers were given special permits to test, within a common framework and together with scientists, selectivity enhancement strategies adapted to their own experiences. Fishers and scientists jointly tested gillnets and pontoon traps and how fishing depth, soak time, fishing season, and mesh size were affected by bycatches of undersized fish of sensitive species. Results indicated that the selectivity of the fishery could be increased, particularly by targeting whitefish adjacent to spawning sites where spatiotemporal overlap with bycatch species was lower. Proposed changes to the fishery, such as new gear, would be costly initially but could become profitable over time due to a lower cost of handling bycatch. Our findings demonstrated that co-constructed knowledge can contribute to the governance of aquatic resources.
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| 46. |
- Sandström, Alfred, et al.
(author)
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Getting Choosy About Whitefish in Lake Vättern : Using Participatory Approaches to Improve Fisheries Selectivity
- 2020
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In: Collaborative Research in Fisheries. - Cham : Springer. - 9783030267834 - 9783030267841 ; , s. 43-59
-
Book chapter (peer-reviewed)abstract
- Our case study was channeled through a comanagement group and initiated by fishermen. The aim was to develop the selectivity of the fisheries in Lake Vättern through a collaboration of fishermen, regional managers, and scientists. The case study was planned collectively within the fisheries co-management group and through workshops with participating fishermen. Fishermen were given special permits to test various strategies adapted to their own experiences and the properties of their local fishing grounds. First, the population structure of the focal species, whitefish, was investigated in a joint study utilizing fishermen’s experiential knowledge and genetic analyses of whitefish. The results showed that the population is divided into at least two unique stocks that ideally should be managed separately. Second, the results from studies on by-catch in different areas, seasons, and gears indicated a substantial potential to increase the selectivity in this fishery, particularly by targeting whitefish aggregations adjacent to spawning areas. Our study highlights the potential of the participatory approach when facilitating solutions to problems related to small-scale fisheries management. Nevertheless, we also identify some factors that might jeopardize the long-term success and dissemination of results from this case study. The recent discovery of high levels of dioxins and dioxin-like PCBs in muscle tissue of whitefish might make it harder for fishermen to sell their catch. Moreover, since the comanagement group only has an advisory function, the Swedish national authority needs to take the initiative and first implement the suggested changes in management.
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| 47. |
- Sandström, Niklas, 1981-, et al.
(author)
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Miniaturized and multiplexed high-content screening of drug and immune sensitivity in a multichambered microwell chip
- 2022
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In: CELL REPORTS METHODS. - : Elsevier BV. - 2667-2375. ; 2:7
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Journal article (peer-reviewed)abstract
- Here, we present a methodology based on multiplexed fluorescence screening of two-or three-dimensional cell cultures in a newly designed multichambered microwell chip, allowing direct assessment of drug or im-mune cell cytotoxic efficacy. We establish a framework for cell culture, formation of tumor spheroids, fluores-cence labeling, and imaging of fixed or live cells at various magnifications directly in the chip together with data analysis and interpretation. The methodology is demonstrated by drug cytotoxicity screening using ovarian and non-small cell lung cancer cells and by cellular cytotoxicity screening targeting tumor spheroids of renal carcinoma and ovarian carcinoma with natural killer cells from healthy donors. The miniaturized format allowing long-term cell culture, efficient screening, and high-quality imaging of small sample volumes makes this methodology promising for individualized cytotoxicity tests for precision medicine.
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| 48. |
- Sandström, Robin, et al.
(author)
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Microwave-Induced Structural Ordering of Resilient Nanostructured L10-FePt Catalysts for Oxygen Reduction Reaction
- 2020
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In: ACS Applied Energy Materials. - : American Chemical Society (ACS). - 2574-0962. ; 3:10, s. 9785-9791
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Journal article (peer-reviewed)abstract
- We show how structurally ordered L10 face-centered tetragonal (fct) FePt nanoparticles are produced by a solid-state microwave-assisted synthesis method. The structural phase as well as the incorporated Fe into the nanoparticles is confirmed by X-ray diffraction and high resolution high-angle annular dark field scanning transmission electron microscopy experiments. The prepared particles exhibit a remarkable resilience toward crystallite growth at high temperatures. Directly correlated to the L10 phase, the best oxygen reduction reaction (ORR) characteristics are achieved for particles with a 1:1 Fe:Pt atomic ratio and an average size of ~2.9 nm where Pt-specific evaluation provided a high mass and specific activity of ~570 A/gPt and ~600 μA/cm2Pt respectively. Our results demonstrate that well-structured catalysts possessing activities vastly exceeding Pt/C (~210 A/gPt & ~250 μA/cm2Pt), can be synthesized through a fast and highly eco-friendly method. We note that the achieved mass activity represent a significant leap toward the theoretical maximum for fully ordered FePt nanoparticles.
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| 49. |
- Schepke, Elizabeth, et al.
(author)
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DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study
- 2022
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In: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 48:6
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Journal article (peer-reviewed)abstract
- Aims: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. Methods: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. Results: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients. Conclusions: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
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| 50. |
- Selley, Liza, et al.
(author)
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Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages
- 2020
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In: Metallomics. - : Royal Society of Chemistry. - 1756-5901 .- 1756-591X. ; 12:3, s. 371-386
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Journal article (peer-reviewed)abstract
- Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4–25 μg ml−1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.
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