| 1. |
- Fromell, Karin, et al.
(författare)
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The effect of airborne Palladium nanoparticles on human lung cells, endothelium and blood-A combinatory approach using three in vitro models
- 2023
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Ingår i: Toxicology in Vitro. - : Elsevier. - 0887-2333 .- 1879-3177. ; 89
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Tidskriftsartikel (refereegranskat)abstract
- A better understanding of the mechanisms behind adverse health effects caused by airborne fine particles and nanoparticles (NP) is essential to improve risk assessment and identification the most critical particle exposures. While the use of automobile catalytic converters is decreasing the exhausts of harmful gases, concentrations of fine airborne particles and nanoparticles (NPs) from catalytic metals such as Palladium (Pd) are reaching their upper safe level. Here we used a combinatory approach with three in vitro model systems to study the toxicity of Pd particles, to infer their potential effects on human health upon inhalation. The three model systems are 1) a lung system with human lung cells (ALI), 2) an endothelial cell system and 3) a human whole blood loop system. All three model systems were exposed to the exact same type of Pd NPs. The ALI lung cell exposure system showed a clear reduction in cell growth from 24 h onwards and the effect persisted over a longer period of time. In the endothelial cell model, Pd NPs induced apoptosis, but not to the same extent as the most aggressive types of NPs such as TiO2. Similarly, Pd triggered clear coagulation and contact system activation but not as forcefully as the highly thrombogenic TiO2 NPs. In summary, we show that our 3-step in vitro model of the human lung and surrounding vessels can be a useful tool for studying pathological events triggered by airborne fine particles and NPs.
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| 2. |
- Kern, Wolfgang, et al.
(författare)
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Multicenter prospective evaluation of diagnostic potential of flow cytometric aberrancies in myelodysplastic syndromes by the ELN iMDS flow working group
- 2023
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Ingår i: Cytometry Part B - Clinical Cytometry. - : Wiley. - 1552-4949 .- 1552-4957. ; 104:1, s. 51-65
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myelodysplastic syndromes (MDS) represent a diagnostic challenge. This prospective multicenter study was conducted to evaluate pre-defined flow cytometric markers in the diagnostic work-up of MDS and chronic myelomonocytic leukemia (CMML). Methods: Thousand six hundred and eighty-two patients with suspected MDS/CMML were analyzed by both cytomorphology according to WHO 2016 criteria and flow cytometry according to ELN recommendations. Flow cytometric readout was categorized ‘non-MDS’ (i.e. no signs of MDS/CMML and limited signs of MDS/CMML) and ‘in agreement with MDS’ (i.e., in agreement with MDS/CMML). Results: Flow cytometric readout categorized 60% of patients in agreement with MDS, 28% showed limited signs of MDS and 12% had no signs of MDS. In 81% of cases flow cytometric readouts and cytomorphologic diagnosis correlated. For high-risk MDS, the level of concordance was 92%. A total of 17 immunophenotypic aberrancies were found independently related to MDS/CMML in ≥1 of the subgroups of low-risk MDS, high-risk MDS, CMML. A cut-off of ≥3 of these aberrancies resulted in 80% agreement with cytomorphology (20% cases concordantly negative, 60% positive). Moreover, >3% myeloid progenitor cells were significantly associated with MDS (286/293 such cases, 98%). Conclusion: Data from this prospective multicenter study led to recognition of 17 immunophenotypic markers allowing to identify cases ‘in agreement with MDS’. Moreover, data emphasizes the clinical utility of immunophenotyping in MDS diagnostics, given the high concordance between cytomorphology and the flow cytometric readout. Results from the current study challenge the application of the cytomorphologically defined cut-off of 5% blasts for flow cytometry and rather suggest a 3% cut-off for the latter.
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| 3. |
- Porwit, Anna, et al.
(författare)
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Multiparameter flow cytometry in the evaluation of myelodysplasia : Analytical issues: Recommendations from the European LeukemiaNet/International Myelodysplastic Syndrome Flow Cytometry Working Group
- 2023
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Ingår i: Cytometry Part B - Clinical Cytometry. - : Wiley. - 1552-4949 .- 1552-4957. ; 104:1, s. 27-50
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Forskningsöversikt (refereegranskat)abstract
- Multiparameter flow cytometry (MFC) is one of the essential ancillary methods in bone marrow (BM) investigation of patients with cytopenia and suspected myelodysplastic syndrome (MDS). MFC can also be applied in the follow-up of MDS patients undergoing treatment. This document summarizes recommendations from the International/European Leukemia Net Working Group for Flow Cytometry in Myelodysplastic Syndromes (ELN iMDS Flow) on the analytical issues in MFC for the diagnostic work-up of MDS. Recommendations for the analysis of several BM cell subsets such as myeloid precursors, maturing granulocytic and monocytic components and erythropoiesis are given. A core set of 17 markers identified as independently related to a cytomorphologic diagnosis of myelodysplasia is suggested as mandatory for MFC evaluation of BM in a patient with cytopenia. A myeloid precursor cell (CD34+CD19−) count >3% should be considered immunophenotypically indicative of myelodysplasia. However, MFC results should always be evaluated as part of an integrated hematopathology work-up. Looking forward, several machine-learning-based analytical tools of interest should be applied in parallel to conventional analytical methods to investigate their usefulness in integrated diagnostics, risk stratification, and potentially even in the evaluation of response to therapy, based on MFC data. In addition, compiling large uniform datasets is desirable, as most of the machine-learning-based methods tend to perform better with larger numbers of investigated samples, especially in such a heterogeneous disease as MDS.
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| 4. |
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| 5. |
- van der Velden, Vincent H.J., et al.
(författare)
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Flow cytometric analysis of myelodysplasia : Pre-analytical and technical issues—Recommendations from the European LeukemiaNet
- 2023
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Ingår i: Cytometry Part B - Clinical Cytometry. - : Wiley. - 1552-4949 .- 1552-4957. ; 104:1, s. 15-26
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Tidskriftsartikel (refereegranskat)abstract
- Background: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures. Methods: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group. Results: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies. Conclusions: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice.
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| 6. |
- Hylander, Kristoffer, et al.
(författare)
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Rapid post-fire re-assembly of species-rich bryophyte communities in Afroalpine heathlands
- 2021
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Ingår i: Journal of Vegetation Science. - : Wiley. - 1100-9233 .- 1654-1103. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- Questions In some fire-prone ecosystems, bryophytes play a crucial role by providing the surface fuel that controls the fire return interval. Afroalpine heathlands are such an ecosystem, yet almost nothing is known about the bryophytes in this system. We do not know the level of species richness, or if there is a successive accumulation of species over time, or if some species are adapted to specific phases along the successional gradient, for example early-successional species sensitive to competition. Location Afroalpine heathlands in Ethiopia. Methods We made an inventory of all bryophytes in 48 plots of 5 m x 5 m, distributed along a chronosequence from 1 to 25 years post fire. The heathlands are located between 3500 m and 3800 m a.s.l. and are managed by traditional pasture burning with fire intervals of 8-20 years. Results We found in total 111 taxa of bryophytes. Post-fire mortality was almost 100%. The youngest plots had only a few cosmopolitan species often found after fire. Initially, species richness increased monotonically while starting to level off around 15 years after fire, when many plots had around 30 species and a high cover of Breutelia diffracta, which is a key ground-living species, important as surface fuel. Most species were found with sporophytes, a pattern even stronger for the most frequent species. Conclusions Interestingly, bryophyte diversity is already remarkably high by only 15 years after total eradication. The relatively slow accumulation of species in the first years after fire suggests that dispersal in space, and not time, is the major mechanism by which sites regain their diversity (i.e. spore banks play a smaller role than colonization of wind-borne spores). This indicates that the high species richness is built up through colonization from surrounding heathlands, and perhaps also from higher-altitude alpine grasslands and lower-altitude forests, and that the bryophyte diversity in this system is maintained by the traditional fire and grazing management.
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| 7. |
- Bamberg, Krister, et al.
(författare)
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Electrolyte handling in the isolated perfused rat kidney : demonstration of vasopressin V2-receptor-dependent calcium reabsorption
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 125:4, s. 274-280
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Tidskriftsartikel (refereegranskat)abstract
- Background The most profound effect of vasopressin on the kidney is to increase water reabsorption through V-2-receptor (V2R) stimulation, but there are also data suggesting effects on calcium transport. To address this issue, we have established an isolated perfused kidney model with accurate pressure control, to directly study the effects of V2R stimulation on kidney function, isolated from systemic effects. Methods The role of V2R in renal calcium handling was studied in isolated rat kidneys using a new pressure control system that uses a calibration curve to compensate for the internal pressure drop up to the tip of the perfusion cannula. Results Kidneys subjected to V2R stimulation using desmopressin (DDAVP) displayed stable osmolality and calcium reabsorption throughout the experiment, whereas kidneys not administered DDAVP exhibited a simultaneous fall in urine osmolality and calcium reabsorption. Epithelial sodium channel (ENaC) inhibition using amiloride resulted in a marked increase in potassium reabsorption along with decreased sodium reabsorption. Conclusions A stable isolated perfused kidney model with computer-controlled pressure regulation was developed, which retained key physiological functions. The preparation responds to pharmacological inhibition of ENaC channels and activation of V2R. Using the model, the dynamic effects of V2R stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of V2R in renal calcium reabsorption.
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| 8. |
- Johansson, Maria Ulrika, et al.
(författare)
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Ecosystem restoration in fire-managed savanna woodlands : Effects on biodiversity, local livelihoods and fire intensity
- 2020
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 50, s. 190-202
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Tidskriftsartikel (refereegranskat)abstract
- Ethiopia aims to restore 15 million ha degraded forests and woodlands, but effects on the potentially contrasting goals of long-term carbon storage, biodiversity and sustainable livelihoods are unknown. To quantify the effects of grazing exclusion on vegetation and fire behaviour, we established six 30 x 30 m fenced exclosures with grazed controls, in a mesic wooded savanna. Experimental burns were done after 1.5 years. Tree seedlings were few but more common inside fences. Field layer cover and biomass increased inside fences, and grass species increased in numbers and cover. Fire intensity was higher inside fences, killing shrubs and saplings but not mature trees. Interviews confirmed that overgrazing has resulted in cool fires, causing shrub encroachment. High-intensity fires occurred in the 1980s after a zoonotic disease killed most livestock. Short-term increase in carbon storage through fire and grazing exclusion may lead to loss of pasture, and in the long-term increased wildfire risk.
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| 9. |
- Johansson, Maria Ulrika, et al.
(författare)
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Fire and grazing controlling a tropical tree line : Effects of long-term grazing exclusion in Bale Mountains, Ethiopia
- 2020
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Ingår i: Journal of Vegetation Science. - : Wiley. - 1100-9233 .- 1654-1103. ; 31:5, s. 841-853
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Tropical tree lines are often associated with abrupt shifts in vegetation, soils and disturbance regimes, but the underlying mechanisms are poorly understood. We analysed the role of grazing, fuels and fire in maintaining a sharp tree line with flammable heathland above non-flammable forest.Location: Bale Mountains, Ethiopia.Methods: The study used grazing exclosures, repeated vegetation sampling, soil analyses and burning and sowing experiments along an altitudinal gradient with Hagenia abyssinica forest, Erica trimera forest and Erica heathland; all were heavily grazed, the Erica heathland also burnt on short rotation.Results: Contrary to expectation, livestock exclusion did not increase flammability in the forest, but instead resulted in a dense carpet of non-flammable herbs. In the heathland, livestock exclusion led to somewhat faster post-fire fuel recovery, but no major change in vegetation. Seeding of tree species resulted in some seedling establishment, but notably Hagenia grew poorly in the heathland, even when protected from livestock. A bioassay, as well as observations of outpost trees on atypical soil above the tree line, suggests that this poor growth is caused by the acidic soils, rather than harsh climate. Despite frequent fires, heathland soils had lower pH and higher organic matter content than forest soils. Below the tree line, tree seedling establishment was successful only in forest gaps, and if livestock was excluded. In both forest and heathland rapid vegetative regeneration in the ground flora after disturbance restricted major species shifts.Conclusions: These results suggest that the contrasting fire potential between heathland and forest, and thus the sharp tree line would be maintained, or possibly even accentuated, in the absence of livestock grazing, and that Hagenia colonization upwards into the heathland is restricted not only by fire and grazing, but also the acidic soils, which is a legacy of centuries of dominance by Erica.
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| 10. |
- Johansson, Ulrika, 1974-, et al.
(författare)
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Integration of Primary Endocrine Cells and Supportive Cells Using Functionalized Silk Promotes the Formation of Prevascularized Islet-like Clusters
- 2020
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Ingår i: ACS Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 6:2, s. 1186-1195
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic islet transplantation has not yet succeeded as an overall treatment for type 1 diabetes because of limited access to donor islets, as well as low efficacy and poor reproducibility of the current procedure. Herein, a method to create islets-like composite clusters (coclusters) from dispersed endocrine cells and supportive cells is described, attempting to improve compatibility with the recipient and more efficiently make use of the donor-derived material. To mimic the extracellular matrix environment, recombinant,spider silk functionalized with cell binding motifs are used as 3D support for the coclusters. A cell binding motif derived from fibronectin (FN) was found superior in promoting cell adherence, while a plain RGD-motif incorporated in the repetitive part of the silk protein (2R) increased the mobility and cluster formation of endocrine cells. Self-assembly of a mixture of FN/2R silk is utilized to integrate endocrine cells together with endothelial and mesenchymal cells into islet-like coclusters. Both xenogenic and allogenic versions of these coclusters were found to be viable and were able to respond to dynamic glucose stimulation with insulin release. Moreover, the endothelial cells were found to be colocalized with the endocrine cells, showing that the silk combined with supportive cells may promote vascularization. This method to engineer combined islet-like coclusters allows donor-derived endocrine cells to be surrounded by supportive cells from the recipient, which have the potential to further promote engraftment in the host and considerably reduce risk of rejection.
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