| 1. |
- Baloch, Ramen Munir, et al.
(författare)
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Indoor air pollution, physical and comfort parameters related to schoolchildren's health : Data from the European SINPHONIE study
- 2020
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Ingår i: Science of the Total Environment. - : ELSEVIER. - 0048-9697 .- 1879-1026. ; 739
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Tidskriftsartikel (refereegranskat)abstract
- Substantial knowledge is available on the association of the indoor school environment and its effect among schoolchildren. In the same context, the SINPHONIE (School indoor pollution and health: Observatory network in Europe) conducted a study to collect data and determine the distribution of several indoor air pollutants (IAPs), physical and thermal parameters and their association with eye, skin, upper-, lower respiratory and systemic disorder symptoms during the previous three months. Finally, data from 115 schools in 54 European cities from 23 countries were collected and included 5175 schoolchildren using a harmonized and standardized protocol. The association between exposures and the health outcomes were examined using logistic regression models on the environmental stressors assessed in classroom while adjusting for several confounding factors; a VOC (volatile organic compound) score defined as the sum of the number of pollutants to which the children were highly exposed (concentration > median of the distribution) in classroom was also introduced to evaluate the mul tiexposu re - outcome association. Schoolchildren while adjusting for several confounding factors. Schoolchildren exposed to above or equal median concentration of PM2.5, benzene, limonene, ozone and radon were at significantly higher odds of suffering from upper, lower airways, eye and systemic disorders. Increased odds were also observed for any symptom (sick school syndrome) among schoolchildren exposed to concentrations of limonene and ozone above median values. Furthermore, the risks for upper and lower airways and systemic disorders significantly increased with the VOCs score. Results also showed that increased ventilation rate was significantly associated with decreased odds of suffering from eye and skin disorders whereas similar association was observed between temperature and upper airways symptoms. The present study provides evidence that exposure to IAPs in schools is associated with various health problems in children. Further investigations are needed to confirm our findings. (C) 2020 Elsevier B.V. All rights reserved.
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| 2. |
- Nehme, Ralda, et al.
(författare)
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The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia
- 2022
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear how the 22q11.2 deletion predisposes to psychiatric disease. To study this, we generated induced pluripotent stem cells from deletion carriers and controls and utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Here, we show that upon differentiation into neural progenitor cells, the deletion acted in trans to alter the abundance of transcripts associated with risk for neurodevelopmental disorders including autism. In excitatory neurons, altered transcripts encoded presynaptic factors and were associated with genetic risk for schizophrenia, including common and rare variants. To understand how the deletion contributed to these changes, we defined the minimal protein-protein interaction network that best explains gene expression alterations. We found that many genes in 22q11.2 interact in presynaptic, proteasome, and JUN/FOS transcriptional pathways. Our findings suggest that the 22q11.2 deletion impacts genes that may converge with psychiatric risk loci to influence disease manifestation in each deletion carrier.
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| 3. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 12. |
- Bjärstig, Therese, Docent, 1978-, et al.
(författare)
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Is large-scale wind power a problem, solution, or victim? A frame analysis of the debate in Swedish media
- 2022
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 83
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Tidskriftsartikel (refereegranskat)abstract
- Media content analysis was used with the aim of developing an understanding of how the debate on large-scale wind power has played out over time in Sweden, especially in relation to the enactment of national interest areas for wind power. Covering the period 1999 to 2019 and using NVivo for coding and analysis, we reviewed a total of 788 articles in both national and regional daily newspapers. To identify which actors are present in media and how they frame large-scale wind power, we conducted a frame analysis by applying three theoretical elements developed by previous media studies. The first is a diagnostic element used to pinpoint the cause to a problem, the second a prognostic element used to pinpoint the solution to a problem, and the third a motivating element used to identify the person(s) or object(s) suffering from the problem, that is, victim. Our results emphasize that wind power in recent years has been framed as a solution more often than a cause to a problem. One prevailing framing is the localization of large-scale wind power per se and conflicts with other land-uses and national interests. We also identify a tension between international and national policy objectives and local implementation of large-scale wind power. Governmental agencies are the most common framers over time, together with individuals (e.g. locals and second home owners) and wind entrepreneurs. Importantly, whereas politicians and wind entrepreneurs most often frame wind power as a solution, individuals frame it as a cause to a problem.
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| 16. |
- Esteve-Codina, Anna, et al.
(författare)
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Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.
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| 17. |
- Everitt, Turid, et al.
(författare)
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The Genomic Basis of Adaptation to High Elevations in Africanized Honey Bees
- 2023
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Ingår i: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- A range of different genetic architectures underpin local adaptation in nature. Honey bees (Apis mellifera) in the Eastern African Mountains harbor high frequencies of two chromosomal inversions that likely govern adaptation to this high-elevation habitat. In the Americas, honey bees are hybrids of European and African ancestries and adaptation to latitudinal variation in climate correlates with the proportion of these ancestries across the genome. It is unknown which, if either, of these forms of genetic variation governs adaptation in honey bees living at high elevations in the Americas. Here, we performed whole-genome sequencing of 29 honey bees from both high- and low-elevation populations in Colombia. Analysis of genetic ancestry indicated that both populations were predominantly of African ancestry, but the East African inversions were not detected. However, individuals in the higher elevation population had significantly higher proportions of European ancestry, likely reflecting local adaptation. Several genomic regions exhibited particularly high differentiation between highland and lowland bees, containing candidate loci for local adaptation. Genes that were highly differentiated between highland and lowland populations were enriched for functions related to reproduction and sperm competition. Furthermore, variation in levels of European ancestry across the genome was correlated between populations of honey bees in the highland population and populations at higher latitudes in South America. The results are consistent with the hypothesis that adaptation to both latitude and elevation in these hybrid honey bees are mediated by variation in ancestry at many loci across the genome.
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| 18. |
- Fischer, Benjamin, et al.
(författare)
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A complete workflow for the differentiation and the dissociation of hiPSC-derived cardiospheres
- 2018
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Ingår i: Stem Cell Research. - : Elsevier. - 1873-5061 .- 1876-7753. ; 32, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase. Molecular and functional analyses of the cardiomyocytes reseeded after dissociation confirmed both the identity and the functionality of the cells, which can be used in down-stream applications, either as monolayers or spheroids.
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| 19. |
- Gallagher, Michael D., et al.
(författare)
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TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:3, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
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| 20. |
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| 24. |
- Helldin, Jan Olof, et al.
(författare)
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The impacts of wind power on terrestrial mammals : A synthesis
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We compiled available knowledge and experience of the impact of wind power on terrestrial mammals, both wild and domestic. The literature in the field is very limited, so we also tried to draw lessons from related fields, such as disturbance from noise, construction work, traffic, hunting and outdoor activities, and the effects of habitat change.Although the knowledge is generally sparse, the summary shows that it is possible that terrestrial mammals, especially large carnivores and ungulates including domestic reindeer, are affected by wind power development in various ways.For the larger game species as well as domestic reindeer, the influence from wind power should primarily be due to the network of access roads to the turbines. The main factor is probably the increased access for recreation, hunting and leisure traffic. It is well known that interference from such human activities can impact moose, wild deer, domestic reindeer and large carnivores, and in effect cause a habitat loss.New wind power farms are expected to be situated in more remote, upland, currently roadless areas, at least in the forested landscape. Such areas may serve as refugia for e.g. large predators or as important grazing areas for ungulates. Accordingly, wind power and associated infrastructure in these areas may have an impact on the population level of these species.By contrast, the habitat changes caused by access roads are not necessarily a problem for the larger mammal species. Open land, new edge zones and roadsides could rather benefit many wildlife species. Open land and edges create new browsing areas; roads can facilitate animal movement in the landscape or help animals escaping parasitic insects.The effects of power lines on reindeer tend to differ depending on the geographic scale studied; on a regional scale, an avoidance of large areas around power lines may be observed, while no effects have been shown for reindeer studied near power lines.A few studies available on wild deer, reindeer and large carnivores during construction work suggest that these animals may temporarily avoid wind farms during this period. However, the data is not conclusive.Noise emissions from wind turbines can theoretically disturb animal communication, and also visual stimuli (including reflections, shadows and lighting) may annoy or stress both wildlife and livestock. However, the few studies available suggest the lack of such effects, or a swift habituation to the disturbance, and therefore a limited impact.Animals may also get accustomed to the other disturbances from wind power. For example, both domestic and wild reindeer appear to remain in areas despite human presence, at least when no alternative areas are available. The ability to habituate varies with species, sex, age, individual, time of year, type of disturbance, and how frequent and predictable disturbances are, so overall, habituation cannot be presupposed.There may be differences in the response to disturbance, depending on landscape and current land use. In already disturbed areas, such as most agricultural landscapes, wind power may not affect the occurring species to the same extent as it would in more sparsely populated forest and mountain areas.The effects may also depand on the size of the wind farm. At the construction of large wind farms, even small and localised effects may sum up to significant impact, with consequences at the population level.Our summary highlights the large knowledge gaps in the field and indicates the need for research as well as for efficient environmental monitoring. Of particular need is to study the effects of noise and visual impacts from the turbines. Also studies are needed on the localisation of new wind power in relation to areas of particular value for ungulates and large predators. It is important that the potential cumulative impacts of wind power are considered, as these may lead to consequences at the population level and thus be most relevant from a conservation perspective.To address the large knowledge gaps, it is crucial that monitoring programs for new wind power are set up to create new, generalisable knowledge. We describe some principles that should be followed to achieve this. It is also important that monitoring programs are coordinated nationally and that the data are analysed on a comprehensive level.
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| 25. |
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| 26. |
- Horstkotte, Tim, 1981-, et al.
(författare)
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Semi-domesticated reindeer avoid winter habitats with exotic tree species Pinus contorta
- 2023
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Ingår i: Forest Ecology and Management. - : Elsevier. - 0378-1127 .- 1872-7042. ; 540
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of exotic tree species can have profound effects on the native environment, including habitat use and movement patterns of animals, as well as becoming a management challenge for other land users. Here, we used GPS data from reindeer (Rangifer tarandus) and remote sensing measurements of lichen cover and soil moisture to assess the effects of the exotic lodgepole pine (Pinus contorta) on reindeer husbandry by the Indigenous Sámi in northern Sweden. We used locational data from 67 reindeer for three winters to analyze their habitat selection at the second-order selection (placement of home range in the landscape) and third-order selection (selection of sites within the home range) in relation to land cover class, terricolous lichen cover as measure of winter forage abundance, topographic features, and distance to roads. We also analyzed remotely sensed abundance of lichens in different forest types, and the association between these forest types and soil moisture as measure of suitability as lichen habitat. Compared to native P. sylvestris, we found that reindeer avoided stands with P. contorta where trees were higher than three meters. If P. contorta was the dominant tree species, reindeer were 60 % less likely to select these stands compared to stands with P. sylvestris, and 40 % less likely if P. contorta was less dominant at both orders of selection. We also found that reindeer selected areas with higher lichen cover. Lichen cover was lower in P. contorta stands compared to stands of the native P. sylvestris, even though P. contorta occurred mainly on dry soils usually favorable for terricolous lichens. We conclude that planting P. contorta on soils suitable for terricolous lichens is likely to reduce forage availability for reindeer and turn habitats earlier preferred by reindeer into avoided habitat, resulting in an overall reduction of winter grazing grounds. The effects of stands with P. contorta, albeit covering a comparatively small percentage of the reindeer husbandry area, need to be seen in context with generally declining terricolous lichen abundance due to land uses like forestry and other cumulative effects by external pressures on reindeer husbandry.
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| 27. |
- Lederman, Judith S., et al.
(författare)
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Completing the progression establishing an international baseline of primary, middle and secondary students’ views of scientific inquiry
- 2023
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Ingår i: International Journal of Science Education. - : Routledge. - 0950-0693 .- 1464-5289.
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of scientific inquiry (SI) is considered essential to the development of an individual's Scientific Literacy (SL) and therefore, SI is included in many international science education reform documents. Two previous large scale international studies assessed the SI understandings of students entering middle school and secondary students at the end of their formal K-12 science education. The purpose of this international project was to use the VASI-E to collect data on what primary level students have learned about SI in their first few years of school. This study adds to previous research to bridge the landscape of SI understandings now with representation from primary, middle and high school samples. A total of 4,238 students from 35 countries/regions spanning six continents participated in the study. The results show that globally, primary students are not adequately informed about SI for their age group. However, when compared with the students in the previous international studies (grades seven and 12), the primary students' understandings were surprisingly closer to the levels of understanding of SI of the secondary school students than those in the seventh grade study.
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| 28. |
- Muhar, Matthias, et al.
(författare)
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SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 360:6390, s. 800-805
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Tidskriftsartikel (refereegranskat)abstract
- Defining direct targets of transcription factors and regulatory pathways is key to understanding their roles in physiology and disease. We combined SLAM-seq [thiol(SH)-linked alkylation for the metabolic sequencing of RNA], a method for direct quantification of newly synthesized messenger RNAs (mRNAs), with pharmacological and chemical-genetic perturbation in order to define regulatory functions of two transcriptional hubs in cancer, BRD4 and MYC, and to interrogate direct responses to BET bromodomain inhibitors (BETis). We found that BRD4 acts as general coactivator of RNA polymerase II-dependent transcription, which is broadly repressed upon high-dose BETi treatment. At doses triggering selective effects in leukemia, BETis deregulate a small set of hypersensitive targets including MYC. In contrast to BRD4, MYC primarily acts as a selective transcriptional activator controlling metabolic processes such as ribosome biogenesis and de novo purine synthesis. Our study establishes a simple and scalable strategy to identify direct transcriptional targets of any gene or pathway.
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| 29. |
- Neumann, Ariane, et al.
(författare)
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Immunoregulation of Neutrophil Extracellular Trap Formation by Endothelial-Derived p33 (gC1q Receptor)
- 2018
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 10:1, s. 30-43
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Tidskriftsartikel (refereegranskat)abstract
- The formation of neutrophil extracellular traps (NETs) is a host defence mechanism, known to facilitate the entrapment and growth inhibition of many bacterial pathogens. It has been implicated that the translocation of myeloperoxidase (MPO) from neutrophilic granules to the nucleus is crucial to this process. Under disease conditions, however, excessive NET formation can trigger self-destructive complications by releasing pathologic levels of danger-associated molecular pattern molecules (DAMPs). To counteract such devastating immune reactions, the host has to rely on precautions that help circumvent these deleterious effects. Though the induction of DAMP responses has been intensively studied, the mechanisms that are used by the host to down-regulate them are still not understood. In this study, we show that p33 is an endothelial-derived protein that has the ability to annul NET formation. We found that the expression of human p33 is up-regulated in endothelial cells upon infections with Streptococcus pyogenes bacteria. Using tissue biopsies from a patient with streptococcal necrotising fasciitis, we monitored co-localisation of p33 with MPO. Further in vitro studies revealed that p33 is able to block the formation of DAMP-induced NET formation by inhibiting the enzymatic activity of MPO. Additionally, mice challenged with S. pyogenes bacteria demonstrated diminished MPO activity when treated with p33. Together, our results demonstrate that host-derived p33 has an important immunomodulating function that helps to counterbalance an overwhelming DAMP response.
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| 30. |
- Neumann, Patrick, et al.
(författare)
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Consumer demand as a driver of improved working conditions : the 'Ergo-Brand' proposition
- 2014
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 57:8, s. 1113-1126
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Tidskriftsartikel (refereegranskat)abstract
- This paper develops and explores the “Ergo-Brand” proposition; which posits that consumersmay prefer to buy goods that are made under good working conditions (GWC). This preferencewould enhance a differentiation strategy for companies, thereby fostering the application ofergonomics in production. This proposition is developed in the context of a narrative review ofthe literature on ‘ethical consumerism’. This is supplemented with a small pilot survey study,conducted in both Canada and Sweden (n=141) to explore this proposition. Results indicate thatconsumers would prefer goods made under GWC, but not unconditionally as quality and priceconcerns were ranked higher. Access to information on the working conditions in productionwas seen as a barrier. Nevertheless, the Ergo-Brand concept may be a viable avenue topromoting attention to ergonomics in companies – particularly if consumer habits are subject tointervention by advertising. Further research on this strategy is warranted.
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| 31. |
- Neumann, Stephan, et al.
(författare)
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Modeling the German Legal Latitude Principles
- 2013
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Ingår i: ELECTRONIC PARTICIPATION, EPART 2013. - Berlin : Springer Berlin/Heidelberg. - 9783642403460 ; , s. 49-56
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Konferensbidrag (refereegranskat)abstract
- Postal voting was established in Germany in 1956. Based on the legal latitude of the national legislator, the Federal Constitutional Court confirmed the constitutionality of postal voting several times. In contrast, the constitutionality of electronic voting machines, which were used for federal elections from 2002 to 2005, was rejected as the possibility to control the essential steps in the election was not provided to all citizens. These two cases emphasize that the legal system allows to limit realization of election principles to the advantage of other election principles, but that there are limits. In order to introduce new voting systems, in particular Internet voting systems, it is essential to have guidelines on what is and what is not acceptable. This work provides such guidelines. It identifies the principles of the legal latitude in the German constitution, and captures this latitude in a model. This model enables a review of the constitutionality of new voting systems.
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| 32. |
- Reinbothe, Susann, et al.
(författare)
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EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation.
- 2014
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 445:1, s. 163-169
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Tidskriftsartikel (refereegranskat)abstract
- The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα(+)) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.
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| 33. |
- Shane, Dixon, et al.
(författare)
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Young consumers' considerations of healthy working conditions in purchasing decisions : a qualitative examination
- 2017
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Ingår i: Ergonomics. - : Taylor & Francis Group. - 0014-0139 .- 1366-5847. ; 60:5, s. 601-612
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Tidskriftsartikel (refereegranskat)abstract
- Research has suggested that products manufactured under healthy work conditions (HWC) may provide a marketing advantage to companies. This paper explores young consumers’ considerations of HWC in purchasing decisions using data from qualitative interviews with a sample of 21 university students. The results suggest that interviewees frequently considered the working conditions of those who produced the products they purchased. Participants reported a willingness to pay 17.5% more on a $100 product if it were produced under HWC compared to not. Their ability and willingness to act on this issue was, however, hampered a lack of credible information about working conditions in production, the limited availability of HWC goods and a presumed higher price of HWC goods. While caution should be applied when generalising from this targetable market segment to a general population, these results provide actionable direction for companies interested in using a HWC brand image to gain a strategic sales advantage.Practitioner Summary: This interview study shows that young consumers are interested in, and willing to pay a premium for, goods made under healthy working conditions (HWC). Reported barriers to acting on this impulse include a lack of credible information on working conditions. Ergonomics can help provide a strategic marketing advantage for companies.
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| 34. |
- Svensson, Johan, et al.
(författare)
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Landscape approaches to sustainability : aspects of conflict, integration and synergy in national public land-use interests
- 2020
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Strong land-use pressure challenges sustainable development and calls for landscape approaches that balance economic, ecological, and socio-cultural aspects and interests. In the boreal, sub-alpine, and alpine regions in Sweden, encompassing 32 million ha, many and different land-use interests overlap, which causes risks for conflict, but potentially also suggests integration and synergy opportunities. Based on geographic information system (GIS) analyses of geographically delineated national interests regulated in the Swedish Environmental Code, including, amongst others, Natura 2000, contiguous mountains, recreation, reindeer husbandry, and wind power, and based on forestry as a dominating land use, we found extensive overlap among similar but also between dissimilar types of interest. In some mountain municipalities, our results show that the designated national interest area is four times as large as the available terrestrial area. Moreover, the overlap is much higher in the alpine than in the boreal biome, and there is increasing designation for nature conservation and a decreasing designation for national interests for culture, recreation, and tourism from south to north. We interpret the results with reference to multiple-use needs and opportunities for landscape approaches to sustainable planning. Departing from biodiversity conservation values, we also discuss opportunities to focus planning strategies on assessing synergy, integration, and conflict based on nature-based and place-based land-use characteristics.
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| 35. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 36. |
- Thellbro, Camilla, et al.
(författare)
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Readiness and planning for more wind power : municipalities as key actors implementing national strategies
- 2022
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Ingår i: Cleaner energy systems. - : Elsevier. - 2772-7831. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- In the global context of rapidly developing wind-power technology, local governments have to balance local interests with larger scale targets when implementing national and international strategies. An implication of a new Swedish national strategy for wind-power development is considerable intrusion into natural resource-rich northern landscapes, where municipalities already strive to manage diverse surface demanding and legally valued land-use interests. Municipalities will thus play a key role in wind-power development. Results of our survey suggest that most municipalities have functioning wind-power plans, linked to their municipal comprehensive planning (MCP). However, so far, relatively few wind-power farms have been established, and municipalities have rarely used their right to veto, suggesting that most have not yet experienced significant problems linked to wind-power development. The municipalities rely on their right to veto, and only a third highlighted planning as a tool for handling the increasing demand for wind-power developments. Legislative changes regarding the right to veto and the status of MCP could affect local self-government considerably. Wind-power development could have major consequences for local landscapes and governments, and a municipal-wide policy regarding future wind-power development and MCP as a mediating tool must be secured to balance local interests with national ambitions.
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| 37. |
- Thurner, Lorenz, et al.
(författare)
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Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta' (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD(+) LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/kappa -type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD(+) B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-kappa B pathway and the proliferation of IgD(+) DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD(+) BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies. Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.
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| 38. |
- Waibel, S., et al.
(författare)
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Truncating mutations in FUS/TLS give rise to a more aggressive ALS-phenotype than missense mutations : a clinico-genetic study in Germany
- 2013
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 20:3, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Mutations in the FUS/TLS have been associated with amyotrophic lateral sclerosis (ALS) in a few percent of patients. Methods: We screened 184 familial (FALS) and 200 sporadic German patients with ALS for FUS/TLS mutations by sequence analysis of exons 5, 6 and 13-15. We compared the phenotypes of patients with different FUS/TLS mutations. Results: We identified three missense mutations p.K510R, p.R514G, p.R521H, and the two truncating mutations p.R495X and p.G478LfsX23 in samples from eight pedigrees. Both truncating mutations were associated with young onset and very aggressive disease courses, whereas the p.R521H, p.R514G and in particular the p. K510R mutation showed a milder phenotype with disease durations ranging from 3 years to more than 26 years, the longest reported for a patient with a FUS/TLS mutation. Also, in a pair of monozygous twins with the p.K510R mutation, a remarkable similar disease course was observed. Conclusions: Mutations in FUS/TLS account for 8.7% (16 of 184) of FALS in Germany. This is a higher prevalence than reported from other countries. Truncating FUS/TLS mutations result in a more severe phenotype than most missense mutations. The wide phenotypic differences have implications for genetic counselling.
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| 39. |
- Waldhuber, Anna, et al.
(författare)
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Uropathogenic Escherichia coli strain CFT073 disrupts NLRP3 inflammasome activation
- 2016
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 126:7, s. 36-2425
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Tidskriftsartikel (refereegranskat)abstract
- Successful bacterial pathogens produce an array of virulence factors that allow subversion of the immune system and persistence within the host. For example, uropathogenic Escherichia coli strains, such as CFT073, express Toll/IL-1 receptor-containing (TIR-containing) protein C (TcpC), which impairs TLR signaling, thereby suppressing innate immunity in the urinary tract and enhancing persistence in the kidneys. Here, we have reported that TcpC also reduces secretion of IL-1β by directly interacting with the NACHT leucin-rich repeat PYD protein 3 (NLRP3) inflammasome, which is crucial for recognition of pathogens within the cytosol. At a low MOI, IL-1β secretion was minimal in CFT073-infected macrophages; however, IL-1β release was markedly increased in macrophages infected with CFT073 lacking tcpC. Induction of IL-1β secretion by CFT073 and tcpC-deficient CFT073 required the NLRP3 inflammasome. TcpC attenuated activation of the NLRP3 inflammasome by binding both NLRP3 and caspase-1 and thereby preventing processing and activation of caspase-1. Moreover, in a murine urinary tract infection model, CFT073 infection rapidly induced expression of the NLRP3 inflammasome in the bladder mucosa; however, the presence of TcpC in WT CFT073 reduced IL-1β levels in the urine of infected mice. Together, these findings illustrate how uropathogenic E. coli use the multifunctional virulence factor TcpC to attenuate innate immune responses in the urinary tract.
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| 40. |
- Westman, Johannes, et al.
(författare)
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Protein SIC secreted from Streptococcus pyogenes forms complexes with extracellular histones that boost cytokine production
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:FEB, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Innate immunity relies on an effective recognition of the pathogenic microorganism as well as on endogenous danger signals. While bacteria in concert with their secreted virulence factors can cause a number of inflammatory reactions, danger signals released at the site of infection may in addition determine the amplitude of such responses and influence the outcome of the disease. Here, we report that protein SIC, Streptococcal Inhibitor of Complement, an abundant secreted protein from Streptococcus pyogenes, binds to extracellular histones, a group of danger signals released during necrotizing tissue damage. This interaction leads to the formation of large aggregates in vitro. Extracellular histones and SIC are abundantly expressed and seen colocalized in biopsies from patients with necrotizing soft-tissue infections caused by S. pyogenes. In addition, binding of SIC to histones neutralized their antimicrobial activity. Likewise, the ability of histones to induce hemolysis was inhibited in the presence of SIC. However, when added to whole blood, SIC was not able to block the pro-inflammatory effect of histones. Instead SIC boosted the histone-triggered release of a broad range of cytokines and chemokines, including IL-6, TNF-α, IL-8, IL-1β, IL-1ra, G-CSF, and IFN-γ. These results demonstrate that the interaction between SIC and histones has multiple effects on the host response to S. pyogenes infection.
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| 41. |
- Zachrisson, Anna, Docent, 1978-, et al.
(författare)
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Participatory comprehensive planning to handle competing land-use priorities in the sparsely populated rural context
- 2021
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Ingår i: Journal of Rural Studies. - : Elsevier. - 0743-0167 .- 1873-1392. ; 88, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Rural areas supply the planet's natural resources while simultaneously harbor refuges for most of the world's remaining biodiversity and intact, resilient ecosystems. Since traditional extractive activities must increasingly co-exist with non-exploitative activities such as tourism and conservation, sustainable land use planning is essential for managing trade-offs between incompatible interests in rural areas. With "communicative planning" being promoted since decades, participation is considered crucial for reconciling different planning interests. However, the implementation of participation remains patchy and uneven, not least in sparsely populated regions with low capacity where participation could be a game-changer. Here, we consider municipal comprehensive planning as an existing arena to explore participatory planning approaches potentially capable of simultaneously managing competing land uses and promoting sustainable development in sparsely populated rural contexts. Collaborative work between researchers and public managers resulted in the co-development of an approach based on qualitative village- and interest-based focus groups that facilitated the formulation, negotiation, and legitimization of concrete and detailed local guidelines that prioritize between different land uses. Consequently, the resulting comprehensive plan draft was more readily adopted than the output of a traditional planning process. We found that citizens in sparsely populated municipalities seem willing to actively contribute to rural development processes if they have significant influence.
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| 42. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813 .- 1089-490X. ; 92:3
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Tidskriftsartikel (refereegranskat)
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| 43. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :8
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Tidskriftsartikel (refereegranskat)
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| 44. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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