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  • Andersson, Sarah, et al. (författare)
  • Malmbanan Diaries
  • 2010
  • Rapport (övrigt vetenskapligt)abstract
    • During an intense four day field trip, a group of nine PhD students and their supervisors – all part of the National Research School for Architecture and Planning in the Urban Landscape, APULA – set out to explore what may be considered the outback of Western Europe’s conurbations, the transnational region of Kiruna - Narvik. Both “remote” and “resourceful”, “threatened” and “thriving” (equally relative notions), this region seemed to offer possibilities to reflect upon many of the current tendencies influencing contemporary planning practice and research. And we were not disappointed. From the very first encounter with the municipality of Kiruna, whose foundation as an urban conglomeration is now literally cracking, to the last glimpses of cosmopolitan Narvik, competing for the cruiser ships’ attention, we found ourselves embedded in a multilayered urban narrative. Following the throbbing of the iron ore carriages running along Malmbanan, the rail link connecting Kiruna, Abisko and Narvik, we tried to get a grasp of what is both “the last wilderness of Europe” and perhaps its most important urban “testing grounds”. The aim of the field trip was to provide ample room for each and every participant to try out, interrogate and reflect upon their different research topics in relation to a totally new setting, as such also linking their subject matters and methods to the general conditions for spatial research. Through journalistic and improvisational approaches, a collaborative map emerged, not only actualizing a shifting and sprawling urbanity, but also the rambling and trailing of research as such. The result of the workshop is the following collaborative diaries; a composite travelogue of a thought provoking passage on the fringes of urbanity. Our guides throughout this dislocation have been Anders Johansson and Erik Wingquist of Testbedstudio, who both generously and enthusiastically shared their experience with us and competently and creatively coordinated the final outcome. Without Anders and Erik we would probably have gone astray, geographically as well as conceptually. But we got back safely, and if there is a conclusion to be formulated, it should be future oriented. The following is a narrative or a map, the outcomes and destinations of which hopefully are as numerous as its points of departure.
  • Aspegren, Anders, et al. (författare)
  • Novel non-coding RNAs in Dictyostelium discoideum and their expression during development
  • 2004
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 32:15, s. 4646-4656
  • Tidskriftsartikel (refereegranskat)abstract
    • The quest for non-coding RNAs (ncRNAs) in the last few years has revealed a surprisingly large number of small RNAs belonging to previously known as well as entirely novel classes. Computational and experimental approaches have uncovered new ncRNAs in all kingdoms of life. In this work, we used a shotgun cloning approach to construct full-length cDNA libraries of small RNAs from the eukaryotic model organism Dictyostelium discoideum. Interestingly, two entirely novel classes of RNAs were identified of which one is developmentally regulated. The RNAs within each class share conserved 5'- and 3'-termini that can potentially form stem structures. RNAs of both classes show predominantly cytoplasmic localization. In addition, based on conserved structure and/or sequence motifs, several of the identified ncRNAs could be divided into classes known from other organisms, e.g. 18 small nucleolar RNA candidates (17 box C/D, of which a few are developmentally regulated, and one box H/ACA). Two ncRNAs showed a high degree of similarity to the small nuclear U2 RNA and signal recognition particle RNA (SRP RNA), respectively. Furthermore, the majority of the regions upstream of the sequences encoding the isolated RNAs share conserved motifs that may constitute new promoter elements.
  • Engström, Linda, et al. (författare)
  • Lipopolysaccharide-Induced Fever Depends on Prostaglandin E2 Production Specifically in Brain Endothelial Cells
  • 2012
  • Ingår i: Endocrinology. - : Endocrine Society. - 0013-7227 .- 1945-7170. ; 153:10, s. 4849-4861
  • Tidskriftsartikel (refereegranskat)abstract
    • Immune-induced prostaglandin E2 (PGE2) synthesis is critical for fever and other centrally elicited disease symptoms. The production of PGE2 depends on cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1), but the identity of the cells involved has been a matter of controversy. We generated mice expressing mPGES-1 either in cells of hematopoietic or nonhematopoietic origin. Mice lacking mPGES-1 in hematopoietic cells displayed an intact febrile response to lipopolysaccharide, associated with elevated levels of PGE2 in the cerebrospinal fluid. In contrast, mice that expressed mPGES-1 only in hematopoietic cells, although displaying elevated PGE2 levels in plasma but not in the cerebrospinal fluid, showed no febrile response to lipopolysaccharide, thus pointing to the critical role of brain-derived PGE2 for fever. Immunohistochemical stainings showed that induced cyclooxygenase-2 expression in the brain exclusively occurred in endothelial cells, and quantitative PCR analysis on brain cells isolated by flow cytometry demonstrated that mPGES-1 is induced in endothelial cells and not in vascular wall macrophages. Similar analysis on liver cells showed induced expression in macrophages and not in endothelial cells, pointing at the distinct role for brain endothelial cells in PGE2 synthesis. These results identify the brain endothelial cells as the PGE2-producing cells critical for immune-induced fever.
  • Gertow, Karl, et al. (författare)
  • Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk
  • 2012
  • Ingår i: Circulation: Cardiovascular Genetics. - : American Heart Association. - 1942-325X .- 1942-3268. ; 5:6, s. 656-665
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. Methods and Results-To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMTmean, IMTmax, and IMTmean-max), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11 590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75x10(-7) for IMTmax; replication P=7.24x10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53x10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83x10(-4), n= 82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). Conclusions-This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent. (Circ Cardiovasc Genet. 2012;5:656-665.)
  • Lagedal, Rickard, et al. (författare)
  • Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients
  • 2022
  • Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March-September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5-34.4) and 4.2 (1.1-15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.
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