| 1. |
- Bergström, Ida, et al.
(author)
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Annexin A1 expression in blood mononuclear cells : a potential marker of glucocorticoid activity in patients with coronary artery disease
- 2014
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Other publication (other academic/artistic)abstract
- An imbalance between pro- and anti-inflammatory actions is believed to drive progression of atherosclerosis. Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of anti-inflammatory effects of glucocorticoids. Here, we investigated whether expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) was altered in patients with coronary artery disease (CAD) and also related findings to glucocorticoid sensitivity ex vivo.We included 57 patients 6-12 months after acute coronary syndrome (ACS), 10 patients with ACS, and healthy controls. AnxA1 mRNA was measured in PBMCs and AnxA1 protein was assessed in monocytes and lymphocyte subsets by flow cytometry. In post-ACS patients and controls, glucocorticoid sensitivity was determined by measuring inhibitory effects of dexamethasone on LPS46 induced cytokine secretion.AnxA1 mRNA levels in PBMCs were higher in patients compared with controls, although most pronounced in ACS patients. AnxA1 protein was most abundant in the monocyte fraction. ACS patients exhibited the highest levels of cell surface-associated AnxA1 protein while levels in post-ACS patients and controls were similar. Ex vivo assays showed that PBMCs from post-ACS patients were more prone to release IL-6. Glucocorticoid sensitivity correlated with cell surface-associated AnxA1 protein in peripheral monocytes. Dexamethasone also induced upregulation of AnxA1 mRNA.AnxA1 expression in PBMCs is closely associated with glucocorticoid actions and cell surface associated AnxA1 appears to be a marker of glucocorticoid sensitivity. Although still speculative, a “normal” expression of cell surface-associated AnxA1 in post-ACS patients may suggest that glucocorticoid actions in vivo are insufficient to provide adequate anti-inflammatory effects in these patients.
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| 2. |
- Bergström, Ida, et al.
(author)
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Annexin A1 in blood mononuclear cells from patients with coronary artery disease : Its association with inflammatory status and glucocorticoid sensitivity
- 2017
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:3
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Journal article (peer-reviewed)abstract
- Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.
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| 3. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
- Ericsson, Olle, et al.
(author)
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Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
- 2019
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In: Prenatal diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 39:11, s. 1011-1015
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Journal article (peer-reviewed)abstract
- To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
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| 5. |
- Feigin, Valery L., et al.
(author)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Journal article (peer-reviewed)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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| 6. |
- Geng, Shiyu, et al.
(author)
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Multifunctional Carbon Aerogels with Hierarchical Anisotropic Structure Derived from Lignin and Cellulose Nanofibers for CO2 Capture and Energy Storage
- 2020
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In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 12:6, s. 7432-7441
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Journal article (peer-reviewed)abstract
- In current times, CO2 capture and light-weight energy storage are receiving significant attention and will be vital functions in next-generation materials. Porous carbonaceous materials have great potential in these areas, whereas most of the developed carbon materials still have significant limitations, such as non-renewable resources, complex and costly processing or the absence of tailorable structure. In this study, a new strategy is developed for using the currently under-utilized lignin and cellulose nanofibers, which can be extracted from renewable resources to produce high-performance multifunctional carbon aerogels with a tailorable, anisotropic pore structure. Both the macro- and microstructure of the carbon aerogels can be simultaneously controlled by discreetly tuning the weight ratio of lignin to cellulose nanofibers in the carbon aerogel precursors, which considerably influences their final porosity and surface area. The designed carbon aerogels demonstrate excellent performance in both CO2 capture and capacitive energy storage, and the best results exhibit a CO2 adsorption capacity of 5.23 mmol g-1 at 273 K and 100 kPa, and a specific electrical double layer capacitance of 124 F g-1 at a current density of 0.2 A g-1, indicating that they have great future potential in the relevant applications.
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| 7. |
- Ingemarsdotter, Emilia, et al.
(author)
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Quantifying the Net Environmental Impact of Using IoT to Support Circular Strategies—The Case of Heavy-Duty Truck Tires in Sweden
- 2021
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In: Circular Economy and Sustainability, 2021. - : Springer Science and Business Media LLC. - 2730-597X .- 2730-5988. ; 1:2, s. 613-650
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Journal article (peer-reviewed)abstract
- The idea of leveraging the Internet of Things (IoT) to support strategies in line with the circular economy (CE) has been gaining traction in literature. However, previous work has predominantly focused on the opportunities that these technologies can bring, and few studies have critically assessed the environmental viability of the proposed strategies. In this study, we assess the net environmental impact of IoT-enabled circular strategies in the specific case of truck tires in the Swedish context, in order to gain insight into when and how it makes environmental sense to embed IoT hardware into products to support circular strategies. We quantify (1) the potential environmental savings in the different life cycle phases made possible through access to sensor data, and (2) the environmental impact from the added technology needed to provide and process the data. Life cycle assessment (LCA) is used to evaluate the difference in impact between the current state and an ‘IoT scenario’. We find that the IoT scenario gives a 4% lower weighted life cycle impact than the current state. Through sensitivity analysis, we show that the conclusions are sensitive to assumptions made about the expected benefits of adding IoT, which depend on the technological context as well as the current and IoT-induced behavior of stakeholders along the product life cycle. The results are also sensitive to assumptions about the environmental impact of the IoT hardware components, implying that design decisions at this level can be important for ensuring a net environmental impact reduction from IoT-enabled circular strategies.
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| 8. |
- Jonasson, Simon, et al.
(author)
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Characteristics of Cellulose Nanofibrils from Transgenic Trees with Reduced Expression of Cellulose Synthase Interacting 1
- 2022
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In: Nanomaterials. - : MDPI. - 2079-4991. ; 12:19
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Journal article (peer-reviewed)abstract
- Cellulose nanofibrils can be derived from the native load-bearing cellulose microfibrils in wood. These microfibrils are synthesized by a cellulose synthase enzyme complex that resides in the plasma membrane of developing wood cells. It was previously shown that transgenic hybrid aspen trees with reduced expression of CSI1 have different wood mechanics and cellulose microfibril properties. We hypothesized that these changes in the native cellulose may affect the quality of the corresponding nanofibrils. To test this hypothesis, wood from wild-type and transgenic trees with reduced expression of CSI1 was subjected to oxidative nanofibril isolation. The transgenic wood-extracted nanofibrils exhibited a significantly lower suspension viscosity and estimated surface area than the wild-type nanofibrils. Furthermore, the nanofibril networks manufactured from the transgenics exhibited high stiffness, as well as reduced water uptake, tensile strength, strain-to-break, and degree of polymerization. Presumably, the difference in wood properties caused by the decreased expression of CSI1 resulted in nanofibrils with distinctive qualities. The observed changes in the physicochemical properties suggest that the differences were caused by changes in the apparent nanofibril aspect ratio and surface accessibility. This study demonstrates the possibility of influencing wood-derived nanofibril quality through the genetic engineering of trees.
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| 9. |
- Jonasson, Simon, et al.
(author)
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Comparison of tension wood and normal wood for oxidative nanofibrillation and network characteristics
- 2021
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In: Cellulose. - : Springer. - 0969-0239 .- 1572-882X. ; 28:2, s. 1085-1104
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Journal article (peer-reviewed)abstract
- Cellulose nanofibrils (CNFs) are top-down nanomaterials obtainable from abundant lignocelluloses. Despite recent advances in processing technologies, the effects of variations in the lignocellulose structure and composition on CNF isolation and properties are poorly understood. In this study, we compared the isolation of CNFs from tension wood (TW) and normal wood (NW) from Populus tremula (aspen). The TW has a higher cellulose content, native cellulose fibrils with a larger crystalline diameter, and less lignin than the NW, making it an interesting material for CNF isolation. The wood powders were oxidized directly by 2,2,6,6-tetramethylpiperidin-1-oxyl, and the morphology and mechanical behaviors of the nanofibril suspensions and networks were characterized. The TW was more difficult to fibrillate by both chemical and mechanical means. Larger nanofibrils (5–10 nm) composed of 1.2 nm structures were present in the TW CNFs, whereas the NW samples contained more of thin (1.6 nm) structures, which also comprised 77% of the solid yield compared to the 33% for TW. This difference was reflected in the TW CNF networks as decreased transmittance (15% vs. 50%), higher degree of crystallinity (85.9% vs. 78.0%), doubled toughness (11 MJ/m3) and higher elongation at break (12%) compared to NW. The difference was ascribed to greater preservation of the hierarchical, more crystalline microfibril structure, combined with a more cellulose-rich network (84% vs. 70%). This knowledge of the processing, structure, and properties of CNFs can facilitate the breeding and design of wood feedstocks to meet the increasing demand for nanoscale renewable materials.
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| 10. |
- Jonasson, Simon, et al.
(author)
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Isolation and characterization of cellulose nanofibers from aspen wood using derivatizing and non-derivatizing pretreatments
- 2020
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In: Cellulose. - : Springer. - 0969-0239 .- 1572-882X. ; 27:1, s. 185-203
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Journal article (peer-reviewed)abstract
- The link between wood and corresponding cellulose nanofiber (CNF) behavior is complex owing the multiple chemical pretreatments required for successful preparation. In this study we apply a few pretreatments on aspen wood and compare the final CNF behavior in order to rationalize quantitative studies of CNFs derived from aspen wood with variable properties. This is relevant for efforts to improve the properties of woody biomass through tree breeding. Three different types of pretreatments were applied prior to disintegration (microfluidizer) after a mild pulping step; derivatizing TEMPO-oxidation, carboxymethylation and non-derivatizing soaking in deep-eutectic solvents. TEMPO-oxidation was also performed directly on the plain wood powder without pulping. Obtained CNFs (44–55% yield) had hemicellulose content between 8 and 26 wt% and were characterized primarily by fine (height ≈ 2 nm) and coarser (2 nm < height < 100 nm) grade CNFs from the derivatizing and non-derivatizing treatments, respectively. Nanopapers from non-derivatized CNFs had higher thermal stability (280 °C) compared to carboxymethylated (260 °C) and TEMPO-oxidized (220 °C). Stiffness of nanopapers made from non-derivatized treatments was higher whilst having less tensile strength and elongation-at-break than those made from derivatized CNFs. The direct TEMPO-oxidized CNFs and nanopapers were furthermore morphologically and mechanically indistinguishable from those that also underwent a pulping step. The results show that utilizing both derivatizing and non-derivatizing pretreatments can facilitate studies of the relationship between wood properties and final CNF behavior. This can be valuable when studying engineered trees for the purpose of decreasing resource consumption when isolation cellulose nanomaterials.
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